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Sample records for schizophrenia controls synaptic

  1. Dysregulations of Synaptic Vesicle Trafficking in Schizophrenia.

    Science.gov (United States)

    Egbujo, Chijioke N; Sinclair, Duncan; Hahn, Chang-Gyu

    2016-08-01

    Schizophrenia is a serious psychiatric illness which is experienced by about 1 % of individuals worldwide and has a debilitating impact on perception, cognition, and social function. Over the years, several models/hypotheses have been developed which link schizophrenia to dysregulations of the dopamine, glutamate, and serotonin receptor pathways. An important segment of these pathways that have been extensively studied for the pathophysiology of schizophrenia is the presynaptic neurotransmitter release mechanism. This set of molecular events is an evolutionarily well-conserved process that involves vesicle recruitment, docking, membrane fusion, and recycling, leading to efficient neurotransmitter delivery at the synapse. Accumulated evidence indicate dysregulation of this mechanism impacting postsynaptic signal transduction via different neurotransmitters in key brain regions implicated in schizophrenia. In recent years, after ground-breaking work that elucidated the operations of this mechanism, research efforts have focused on the alterations in the messenger RNA (mRNA) and protein expression of presynaptic neurotransmitter release molecules in schizophrenia and other neuropsychiatric conditions. In this review article, we present recent evidence from schizophrenia human postmortem studies that key proteins involved in the presynaptic release mechanism are dysregulated in the disorder. We also discuss the potential impact of dysfunctional presynaptic neurotransmitter release on the various neurotransmitter systems implicated in schizophrenia.

  2. Synaptic plasticity, neural circuits, and the emerging role of altered short-term information processing in schizophrenia.

    Science.gov (United States)

    Crabtree, Gregg W; Gogos, Joseph A

    2014-01-01

    Synaptic plasticity alters the strength of information flow between presynaptic and postsynaptic neurons and thus modifies the likelihood that action potentials in a presynaptic neuron will lead to an action potential in a postsynaptic neuron. As such, synaptic plasticity and pathological changes in synaptic plasticity impact the synaptic computation which controls the information flow through the neural microcircuits responsible for the complex information processing necessary to drive adaptive behaviors. As current theories of neuropsychiatric disease suggest that distinct dysfunctions in neural circuit performance may critically underlie the unique symptoms of these diseases, pathological alterations in synaptic plasticity mechanisms may be fundamental to the disease process. Here we consider mechanisms of both short-term and long-term plasticity of synaptic transmission and their possible roles in information processing by neural microcircuits in both health and disease. As paradigms of neuropsychiatric diseases with strongly implicated risk genes, we discuss the findings in schizophrenia and autism and consider the alterations in synaptic plasticity and network function observed in both human studies and genetic mouse models of these diseases. Together these studies have begun to point toward a likely dominant role of short-term synaptic plasticity alterations in schizophrenia while dysfunction in autism spectrum disorders (ASDs) may be due to a combination of both short-term and long-term synaptic plasticity alterations.

  3. Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons.

    Science.gov (United States)

    Eastwood, S L; Harrison, P J

    2005-03-01

    Synaptic protein gene expression is altered in schizophrenia. In the hippocampal formation there may be particular involvement of glutamatergic neurons and their synapses, but overall the profile remains unclear. In this in situ hybridization histochemistry (ISHH) study, we examined four informative synaptic protein transcripts: vesicular glutamate transporter (VGLUT) 1, VGLUT2, complexin I, and complexin II, in dorsolateral prefrontal cortex (DPFC), superior temporal cortex (STC), and hippocampal formation, in 13 subjects with schizophrenia and 18 controls. In these areas, VGLUT1 and complexin II are expressed primarily by excitatory neurons, whereas complexin I is mainly expressed by inhibitory neurons. In schizophrenia, VGLUT1 mRNA was decreased in hippocampal formation and DPFC, complexin II mRNA was reduced in DPFC and STC, and complexin I mRNA decreased in STC. Hippocampal VGLUT1 mRNA declined with age selectively in the schizophrenia group. VGLUT2 mRNA was not quantifiable due to its low level. The data provide additional evidence for a synaptic pathology in schizophrenia, in terms of a reduced expression of three synaptic protein genes. In the hippocampus, the loss of VGLUT1 mRNA supports data indicating that glutamatergic presynaptic deficits are prominent, whereas the pattern of results in temporal and frontal cortex suggests broadly similar changes may affect inhibitory and excitatory neurons. The impairment of synaptic transmission implied by the synaptic protein reductions may contribute to the dysfunction of cortical neural circuits that characterises the disorder.

  4. Synaptic control of motoneuronal excitability

    DEFF Research Database (Denmark)

    Rekling, J C; Funk, G D; Bayliss, D A

    2000-01-01

    Movement, the fundamental component of behavior and the principal extrinsic action of the brain, is produced when skeletal muscles contract and relax in response to patterns of action potentials generated by motoneurons. The processes that determine the firing behavior of motoneurons are therefore...... important in understanding the transformation of neural activity to motor behavior. Here, we review recent studies on the control of motoneuronal excitability, focusing on synaptic and cellular properties. We first present a background description of motoneurons: their development, anatomical organization...... current, hyperpolarization-activated inward current, Ca(2+) channels, or presynaptic release processes. Together, these numerous inputs mediate and modify incoming motor commands, ultimately generating the coordinated firing patterns that underlie muscle contractions during motor behavior....

  5. Exclusion of close linkage between the synaptic vesicular monoamine transporter locus and schizophrenia spectrum disorders

    Energy Technology Data Exchange (ETDEWEB)

    Persico, A.M.; Uhl, G.R. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); Wang, Zhe Wu [Universitario Campus Bio-Medico, Rome (Italy)] [and others

    1995-12-18

    The principal brain synaptic vesicular monoamine transporter (VMAT2) is responsible for the reuptake of serotonin, dopamine, norepinephrine, epinephrine, and histamine from the cytoplasm into synaptic vesicles, thus contributing to determination of the size of releasable neurotransmitter vesicular pools. Potential involvement of VMAT2 gene variants in the etiology of schizophrenia and related disorders was tested using polymorphic VMAT2 gene markers in 156 subjects from 16 multiplex pedigrees with schizophrenia, schizophreniform, schizoaffective, and schizotypal disorders and mood incongruent psychotic depression. Assuming genetic homogeneity, complete ({theta} = 0.0) linkage to the schizophrenia spectrum was excluded under both dominant and recessive models. Allelic variants at the VMAT2 locus do not appear to provide major genetic contributions to the etiology of schizophrenia spectrum disorders in these pedigrees. 16 refs.

  6. Mapping the Consequences of Impaired Synaptic Plasticity in Schizophrenia through Development: An Integrative Model for Diverse Clinical Features.

    Science.gov (United States)

    Forsyth, Jennifer K; Lewis, David A

    2017-10-01

    Schizophrenia is associated with alterations in sensory, motor, and cognitive functions that emerge before psychosis onset; identifying pathogenic processes that can account for this multi-faceted phenotype remains a challenge. Accumulating evidence suggests that synaptic plasticity is impaired in schizophrenia. Given the role of synaptic plasticity in learning, memory, and neural circuit maturation, impaired plasticity may underlie many features of the schizophrenia syndrome. Here, we summarize the neurobiology of synaptic plasticity, review evidence that plasticity is impaired in schizophrenia, and explore a framework in which impaired synaptic plasticity interacts with brain maturation to yield the emergence of sensory, motor, cognitive, and psychotic features at different times during development in schizophrenia. Key gaps in the literature and future directions for testing this framework are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Dynamic Control of Synaptic Adhesion and Organizing Molecules in Synaptic Plasticity

    Energy Technology Data Exchange (ETDEWEB)

    Rudenko, Gabby (Texas-MED)

    2017-01-01

    Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, formingtrans-complexes spanning the synaptic cleft orcis-complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well. SAMs are regulated through a portfolio of different mechanisms that affect their protein levels, precise localization, stability, and the availability of their partners at synapses. Interaction of SAMs with their partners can further be strengthened or weakened through alternative splicing, competing protein partners, ectodomain shedding, or astrocytically secreted factors. Given that numerous SAMs appear altered by synaptic activity, in vivo, these molecules may be used to dynamically scale up or scale down synaptic communication. Many SAMs, including neurexins, neuroligins, cadherins, and contactins, are now implicated in neuropsychiatric and neurodevelopmental diseases, such as autism spectrum disorder, schizophrenia, and bipolar disorder and studying their molecular mechanisms holds promise for developing novel therapeutics.

  8. Dynamic Control of Synaptic Adhesion and Organizing Molecules in Synaptic Plasticity

    Science.gov (United States)

    2017-01-01

    Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, forming trans-complexes spanning the synaptic cleft or cis-complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well. SAMs are regulated through a portfolio of different mechanisms that affect their protein levels, precise localization, stability, and the availability of their partners at synapses. Interaction of SAMs with their partners can further be strengthened or weakened through alternative splicing, competing protein partners, ectodomain shedding, or astrocytically secreted factors. Given that numerous SAMs appear altered by synaptic activity, in vivo, these molecules may be used to dynamically scale up or scale down synaptic communication. Many SAMs, including neurexins, neuroligins, cadherins, and contactins, are now implicated in neuropsychiatric and neurodevelopmental diseases, such as autism spectrum disorder, schizophrenia, and bipolar disorder and studying their molecular mechanisms holds promise for developing novel therapeutics. PMID:28255461

  9. Rare exonic deletions implicate the synaptic organizer Gephyrin (GPHN) in risk for autism, schizophrenia and seizures.

    Science.gov (United States)

    Lionel, Anath C; Vaags, Andrea K; Sato, Daisuke; Gazzellone, Matthew J; Mitchell, Elyse B; Chen, Hong Yang; Costain, Gregory; Walker, Susan; Egger, Gerald; Thiruvahindrapuram, Bhooma; Merico, Daniele; Prasad, Aparna; Anagnostou, Evdokia; Fombonne, Eric; Zwaigenbaum, Lonnie; Roberts, Wendy; Szatmari, Peter; Fernandez, Bridget A; Georgieva, Lyudmila; Brzustowicz, Linda M; Roetzer, Katharina; Kaschnitz, Wolfgang; Vincent, John B; Windpassinger, Christian; Marshall, Christian R; Trifiletti, Rosario R; Kirmani, Salman; Kirov, George; Petek, Erwin; Hodge, Jennelle C; Bassett, Anne S; Scherer, Stephen W

    2013-05-15

    The GPHN gene codes for gephyrin, a key scaffolding protein in the neuronal postsynaptic membrane, responsible for the clustering and localization of glycine and GABA receptors at inhibitory synapses. Gephyrin has well-established functional links with several synaptic proteins that have been implicated in genetic risk for neurodevelopmental disorders such as autism spectrum disorder (ASD), schizophrenia and epilepsy including the neuroligins (NLGN2, NLGN4), the neurexins (NRXN1, NRXN2, NRXN3) and collybistin (ARHGEF9). Moreover, temporal lobe epilepsy has been linked to abnormally spliced GPHN mRNA lacking exons encoding the G-domain of the gephyrin protein, potentially arising due to cellular stress associated with epileptogenesis such as temperature and alkalosis. Here, we present clinical and genomic characterization of six unrelated subjects, with a range of neurodevelopmental diagnoses including ASD, schizophrenia or seizures, who possess rare de novo or inherited hemizygous microdeletions overlapping exons of GPHN at chromosome 14q23.3. The region of common overlap across the deletions encompasses exons 3-5, corresponding to the G-domain of the gephyrin protein. These findings, together with previous reports of homozygous GPHN mutations in connection with autosomal recessive molybdenum cofactor deficiency, will aid in clinical genetic interpretation of the GPHN mutation spectrum. Our data also add to the accumulating evidence implicating neuronal synaptic gene products as key molecular factors underlying the etiologies of a diverse range of neurodevelopmental conditions.

  10. Glutamatergic postsynaptic density protein dysfunctions in synaptic plasticity and dendritic spines morphology: relevance to schizophrenia and other behavioral disorders pathophysiology, and implications for novel therapeutic approaches.

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    de Bartolomeis, Andrea; Latte, Gianmarco; Tomasetti, Carmine; Iasevoli, Felice

    2014-02-01

    Emerging researches point to a relevant role of postsynaptic density (PSD) proteins, such as PSD-95, Homer, Shank, and DISC-1, in the pathophysiology of schizophrenia and autism spectrum disorders. The PSD is a thickness, detectable at electronic microscopy, localized at the postsynaptic membrane of glutamatergic synapses, and made by scaffolding proteins, receptors, and effector proteins; it is considered a structural and functional crossroad where multiple neurotransmitter systems converge, including the dopaminergic, serotonergic, and glutamatergic ones, which are all implicated in the pathophysiology of psychosis. Decreased PSD-95 protein levels have been reported in postmortem brains of schizophrenia patients. Variants of Homer1, a key PSD protein for glutamate signaling, have been associated with schizophrenia symptoms severity and therapeutic response. Mutations in Shank gene have been recognized in autism spectrum disorder patients, as well as reported to be associated to behaviors reminiscent of schizophrenia symptoms when expressed in genetically engineered mice. Here, we provide a critical appraisal of PSD proteins role in the pathophysiology of schizophrenia and autism spectrum disorders. Then, we discuss how antipsychotics may affect PSD proteins in brain regions relevant to psychosis pathophysiology, possibly by controlling synaptic plasticity and dendritic spine rearrangements through the modulation of glutamate-related targets. We finally provide a framework that may explain how PSD proteins might be useful candidates to develop new therapeutic approaches for schizophrenia and related disorders in which there is a need for new biological treatments, especially against some symptom domains, such as negative symptoms, that are poorly affected by current antipsychotics.

  11. Fast synaptic subcortical control of hippocampal circuits.

    Science.gov (United States)

    Varga, Viktor; Losonczy, Attila; Zemelman, Boris V; Borhegyi, Zsolt; Nyiri, Gábor; Domonkos, Andor; Hangya, Balázs; Holderith, Noémi; Magee, Jeffrey C; Freund, Tamás F

    2009-10-16

    Cortical information processing is under state-dependent control of subcortical neuromodulatory systems. Although this modulatory effect is thought to be mediated mainly by slow nonsynaptic metabotropic receptors, other mechanisms, such as direct synaptic transmission, are possible. Yet, it is currently unknown if any such form of subcortical control exists. Here, we present direct evidence of a strong, spatiotemporally precise excitatory input from an ascending neuromodulatory center. Selective stimulation of serotonergic median raphe neurons produced a rapid activation of hippocampal interneurons. At the network level, this subcortical drive was manifested as a pattern of effective disynaptic GABAergic inhibition that spread throughout the circuit. This form of subcortical network regulation should be incorporated into current concepts of normal and pathological cortical function.

  12. Microglia Activation and Schizophrenia: Lessons From the Effects of Minocycline on Postnatal Neurogenesis, Neuronal Survival and Synaptic Pruning.

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    Inta, Dragos; Lang, Undine E; Borgwardt, Stefan; Meyer-Lindenberg, Andreas; Gass, Peter

    2017-05-01

    The implication of neuroinflammation in schizophrenia, sustained by recent genetic evidence, represents one of the most exciting topics in schizophrenia research. Drugs which inhibit microglia activation, especially the classical tetracycline antibiotic minocycline are currently under investigation as alternative antipsychotics. However, recent studies demonstrated that microglia activation is not only a hallmark of neuroinflammation, but plays important roles during brain development. Inhibition of microglia activation by minocycline was shown to induce extensive neuronal cell death and to impair subventricular zone (SVZ) neurogenesis and synaptic pruning in the early postnatal and adolescent rodent brain, respectively. These deleterious effects contrast with the neuroprotective actions of minocycline at adult stages. They are of potential importance for schizophrenia, since minocycline triggers similar pro-apoptotic effects in the developing brain as NMDA receptor (NMDAR) antagonists, known to induce long-term schizophrenia-like abnormalities. Moreover, altered postnatal neurogenesis, recently described in the human striatum, was proposed to induce striatal dopamine dysregulation associated with schizophrenia. Finally, the effect of minocycline on synapse remodeling is of interest considering the recently reported strong genetic association of the pruning-regulating complement factor gene C4A with schizophrenia. This raises the exciting possibility that in conditions of hyperactive synaptic pruning, as supposed in schizophrenia, the inhibitory action of minocycline turns into a beneficial effect, with relevance for early therapeutic interventions. Altogether, these data support a differential view on microglia activation and its inhibition. Further studies are needed to clarify the relevance of these results for the pathogenesis of schizophrenia and the use of minocycline as antipsychotic drug. © The Author 2016. Published by Oxford University Press on behalf of

  13. Synaptic Control of Secretory Trafficking in Dendrites

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    Cyril Hanus

    2014-06-01

    Full Text Available Localized signaling in neuronal dendrites requires tight spatial control of membrane composition. Upon initial synthesis, nascent secretory cargo in dendrites exits the endoplasmic reticulum (ER from local zones of ER complexity that are spatially coupled to post-ER compartments. Although newly synthesized membrane proteins can be processed locally, the mechanisms that control the spatial range of secretory cargo transport in dendritic segments are unknown. Here, we monitored the dynamics of nascent membrane proteins in dendritic post-ER compartments under regimes of low or increased neuronal activity. In response to activity blockade, post-ER carriers are highly mobile and are transported over long distances. Conversely, increasing synaptic activity dramatically restricts the spatial scale of post-ER trafficking along dendrites. This activity-induced confinement of secretory cargo requires site-specific phosphorylation of the kinesin motor KIF17 by Ca2+/calmodulin-dependent protein kinases (CaMK. Thus, the length scales of early secretory trafficking in dendrites are tuned by activity-dependent regulation of microtubule-dependent transport.

  14. Inhibition of 14-3-3 Proteins Leads to Schizophrenia-Related Behavioral Phenotypes and Synaptic Defects in Mice.

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    Foote, Molly; Qiao, Haifa; Graham, Kourtney; Wu, Yuying; Zhou, Yi

    2015-09-15

    The 14-3-3 family of proteins is implicated in the regulation of several key neuronal processes. Previous human and animal studies suggested an association between 14-3-3 dysregulation and schizophrenia. We characterized behavioral and functional changes in transgenic mice that express an isoform-independent 14-3-3 inhibitor peptide in the brain. We recently showed that 14-3-3 functional knockout mice (FKO) exhibit impairments in associative learning and memory. We report here that these 14-3-3 FKO mice display other behavioral deficits that correspond to the core symptoms of schizophrenia. These behavioral deficits may be attributed to alterations in multiple neurotransmission systems in the 14-3-3 FKO mice. In particular, inhibition of 14-3-3 proteins results in a reduction of dendritic complexity and spine density in forebrain excitatory neurons, which may underlie the altered synaptic connectivity in the prefrontal cortical synapse of the 14-3-3 FKO mice. At the molecular level, this dendritic spine defect may stem from dysregulated actin dynamics secondary to a disruption of the 14-3-3-dependent regulation of phosphorylated cofilin. Collectively, our data provide a link between 14-3-3 dysfunction, synaptic alterations, and schizophrenia-associated behavioral deficits. Published by Elsevier Inc.

  15. Cognitive control and discourse comprehension in schizophrenia.

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    Boudewyn, Megan A; Carter, Cameron S; Swaab, Tamara Y

    2012-01-01

    Cognitive deficits across a wide range of domains have been consistently observed in schizophrenia and are linked to poor functional outcome (Green, 1996; Carter, 2006). Language abnormalities are among the most salient and include disorganized speech as well as deficits in comprehension. In this review, we aim to evaluate impairments of language processing in schizophrenia in relation to a domain-general control deficit. We first provide an overview of language comprehension in the healthy human brain, stressing the role of cognitive control processes, especially during discourse comprehension. We then discuss cognitive control deficits in schizophrenia, before turning to evidence suggesting that schizophrenia patients are particularly impaired at processing meaningful discourse as a result of deficits in control functions. We conclude that domain-general control mechanisms are impaired in schizophrenia and that during language comprehension this is most likely to result in difficulties during the processing of discourse-level context, which involves integrating and maintaining multiple levels of meaning. Finally, we predict that language comprehension in schizophrenia patients will be most impaired during discourse processing. We further suggest that discourse comprehension problems in schizophrenia might be mitigated when conflicting information is absent and strong relations amongst individual words are present in the discourse context."There is no "centre of Speech" in the brain any more than there is a faculty of Speech in the mind.The entire brain, more or less, is at work in a man who uses language"William JamesFrom The Principles of Psychology, 1890"The mind in dementia praecox is like an orchestra without a conductor"Kraepelin, 1919.

  16. Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia

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    Chung Joo-Ho

    2005-08-01

    Full Text Available Abstract Background The occurrence of aberrant functional connectivity in the neuronal circuit is one of the integrative theories of the etiology of schizophrenia. Previous studies have reported that the protein and mRNA levels of the synapsin 2 (SYN2 and complexin 2 (CPLX2 genes were decreased in patients with schizophrenia. Synapsin 2 and complexin 2 are involved in synaptogenesis and the modulation of neurotransmitter release. This report presents a study of the association of polymorphisms of SYN2 and CPLX2 with schizophrenia in the Korean population. Methods Six single nucleotide polymorphisms (SNPs and one 5-bp insertion/deletion in SYN2 and five SNPs in CPLX2 were genotyped in 154 Korean patients with schizophrenia and 133 control patients using direct sequencing or restriction fragment length polymorphism analysis. An intermarker linkage disequilibrium map was constructed for each gene. Results Although there was no significant difference in the genotypic distributions and allelic frequencies of either SYN2 or CPLX2 polymorphisms between the schizophrenia and control groups, the two-way haplotype analyses revealed significant associations with the disease (P SYN2 with schizophrenia (P Conclusion These results suggest that both SYN2 and CPLX2 may confer susceptibility to schizophrenia in the Korean population.

  17. ADF/Cofilin Controls Synaptic Actin Dynamics and Regulates Synaptic Vesicle Mobilization and Exocytosis.

    Science.gov (United States)

    Wolf, Michael; Zimmermann, Anika-Maria; Görlich, Andreas; Gurniak, Christine B; Sassoè-Pognetto, Marco; Friauf, Eckhard; Witke, Walter; Rust, Marco B

    2015-09-01

    Actin is a regulator of synaptic vesicle mobilization and exocytosis, but little is known about the mechanisms that regulate actin at presynaptic terminals. Genetic data on LIMK1, a negative regulator of actin-depolymerizing proteins of the ADF/cofilin family, suggest a role for ADF/cofilin in presynaptic function. However, synapse physiology is fully preserved upon genetic ablation of ADF in mice, and n-cofilin mutant mice display defects in postsynaptic plasticity, but not in presynaptic function. One explanation for this phenomenon is overlapping functions of ADF and n-cofilin in presynaptic physiology. Here, we tested this hypothesis and genetically removed ADF together with n-cofilin from synapses. In double mutants for ADF and n-cofilin, synaptic actin dynamics was impaired and more severely affected than in single mutants. The resulting cytoskeletal defects heavily affected the organization, mobilization, and exocytosis of synaptic vesicles in hippocampal CA3-CA1 synapses. Our data for the first time identify overlapping functions for ADF and n-cofilin in presynaptic physiology and vesicle trafficking. We conclude that n-cofilin is a limiting factor in postsynaptic plasticity, a function which cannot be substituted by ADF. On the presynaptic side, the presence of either ADF or n-cofilin is sufficient to control actin remodeling during vesicle release. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Evaluation of Dream Content among Patients with Schizophrenia, their Siblings, Patients with Psychiatric Diagnoses other than Schizophrenia, and Healthy Control

    OpenAIRE

    Leeba Rezaie; Masoud Rezaei; Schwebel, David C.; Golrokh Younesi; Masoud Tahmasian; Habibolah Khazaie; Mehrak Mohamadi; Arezo Ghanbari

    2012-01-01

    Objective: Schizophrenia is a chronic psychotic disorder with unknown etiology that causes cognitive impairment, affecting thinking, behavior, social function, sleep and dream content. This study considered the dream content of patients with schizophrenia, siblings of patients with schizophrenia, patients with psychiatric diagnoses other than schizophrenia, and a group of healthy controls. The aim of this study was to compare the dream content of patients with schizophrenia with dream content...

  19. Bidirectional Control of Synaptic GABAAR Clustering by Glutamate and Calcium

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    Hiroko Bannai

    2015-12-01

    Full Text Available GABAergic synaptic transmission regulates brain function by establishing the appropriate excitation-inhibition (E/I balance in neural circuits. The structure and function of GABAergic synapses are sensitive to destabilization by impinging neurotransmitters. However, signaling mechanisms that promote the restorative homeostatic stabilization of GABAergic synapses remain unknown. Here, by quantum dot single-particle tracking, we characterize a signaling pathway that promotes the stability of GABAA receptor (GABAAR postsynaptic organization. Slow metabotropic glutamate receptor signaling activates IP3 receptor-dependent calcium release and protein kinase C to promote GABAAR clustering and GABAergic transmission. This GABAAR stabilization pathway counteracts the rapid cluster dispersion caused by glutamate-driven NMDA receptor-dependent calcium influx and calcineurin dephosphorylation, including in conditions of pathological glutamate toxicity. These findings show that glutamate activates distinct receptors and spatiotemporal patterns of calcium signaling for opposing control of GABAergic synapses.

  20. Disrupted-in-schizophrenia1 (DISC1) L100P mutation alters synaptic transmission and plasticity in the hippocampus and causes recognition memory deficits.

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    Cui, Lin; Sun, Wei; Yu, Ming; Li, Nan; Guo, Li; Gu, Huating; Zhou, Yu

    2016-10-12

    Disrupted-in-schizophrenia 1(DISC1) is a promising candidate susceptibility gene for a spectrum of psychiatric illnesses that share cognitive impairments in common, including schizophrenia, bipolar disorder and major depression. Here we report that DISC1 L100P homozygous mutant shows normal anxiety- and depression-like behavior, but impaired object recognition which is prevented by administration of atypical antipsychotic drug clozapine. Ca2+ image analysis reveals suppression of glutamate-evoked elevation of cytoplasmic [Ca2+] in L100P hippocampal slices. L100P mutant slices exhibit decreased excitatory synaptic transmission (sEPSCs and mEPSCs) in dentate gyrus (DG) and impaired long-term potentiation in the CA1 region of the hippocampus. L100P mutation does not alter proteins expression of the excitatory synaptic markers, PSD95 and synapsin-1; neither does it changes dendrites morphology of primary cultured hippocampal neurons. Our findings suggest that the existence of abnormal synaptic transmission and plasticity in hippocampal network may disrupt declarative information processing and contribute to recognition deficits in DISC1 L100P mutant mice.

  1. Schizophrenia

    Science.gov (United States)

    Schizophrenia is a serious brain illness. People who have it may hear voices that aren't there. ... job or take care of themselves. Symptoms of schizophrenia usually start between ages 16 and 30. Men ...

  2. Achieving High-Frequency Optical Control of Synaptic Transmission

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    Jackman, Skyler L.; Beneduce, Brandon M.; Drew, Iain R.

    2014-01-01

    The optogenetic tool channelrhodopsin-2 (ChR2) is widely used to excite neurons to study neural circuits. Previous optogenetic studies of synapses suggest that light-evoked synaptic responses often exhibit artificial synaptic depression, which has been attributed to either the inability of ChR2 to reliably fire presynaptic axons or to ChR2 elevating the probability of release by depolarizing presynaptic boutons. Here, we compare light-evoked and electrically evoked synaptic responses for high-frequency stimulation at three synapses in the mouse brain. At synapses from Purkinje cells to deep cerebellar nuclei neurons (PC→DCN), light- and electrically evoked synaptic currents were remarkably similar for ChR2 expressed transgenically or with adeno-associated virus (AAV) expression vectors. For hippocampal CA3→CA1 synapses, AAV expression vectors of serotype 1, 5, and 8 led to light-evoked synaptic currents that depressed much more than electrically evoked currents, even though ChR2 could fire axons reliably at up to 50 Hz. The disparity between optical and electrical stimulation was eliminated when ChR2 was expressed transgenically or with AAV9. For cerebellar granule cell to stellate cell (grc→SC) synapses, AAV1 also led to artificial synaptic depression and AAV9 provided superior performance. Artificial synaptic depression also occurred when stimulating over presynaptic boutons, rather than axons, at CA3→CA1 synapses, but not at PC→DCN synapses. These findings indicate that ChR2 expression methods and light stimulation techniques influence synaptic responses in a neuron-specific manner. They also identify pitfalls associated with using ChR2 to study synapses and suggest an approach that allows optogenetics to be applied in a manner that helps to avoid potential complications. PMID:24872574

  3. Achieving high-frequency optical control of synaptic transmission.

    Science.gov (United States)

    Jackman, Skyler L; Beneduce, Brandon M; Drew, Iain R; Regehr, Wade G

    2014-05-28

    The optogenetic tool channelrhodopsin-2 (ChR2) is widely used to excite neurons to study neural circuits. Previous optogenetic studies of synapses suggest that light-evoked synaptic responses often exhibit artificial synaptic depression, which has been attributed to either the inability of ChR2 to reliably fire presynaptic axons or to ChR2 elevating the probability of release by depolarizing presynaptic boutons. Here, we compare light-evoked and electrically evoked synaptic responses for high-frequency stimulation at three synapses in the mouse brain. At synapses from Purkinje cells to deep cerebellar nuclei neurons (PC→DCN), light- and electrically evoked synaptic currents were remarkably similar for ChR2 expressed transgenically or with adeno-associated virus (AAV) expression vectors. For hippocampal CA3→CA1 synapses, AAV expression vectors of serotype 1, 5, and 8 led to light-evoked synaptic currents that depressed much more than electrically evoked currents, even though ChR2 could fire axons reliably at up to 50 Hz. The disparity between optical and electrical stimulation was eliminated when ChR2 was expressed transgenically or with AAV9. For cerebellar granule cell to stellate cell (grc→SC) synapses, AAV1 also led to artificial synaptic depression and AAV9 provided superior performance. Artificial synaptic depression also occurred when stimulating over presynaptic boutons, rather than axons, at CA3→CA1 synapses, but not at PC→DCN synapses. These findings indicate that ChR2 expression methods and light stimulation techniques influence synaptic responses in a neuron-specific manner. They also identify pitfalls associated with using ChR2 to study synapses and suggest an approach that allows optogenetics to be applied in a manner that helps to avoid potential complications. Copyright © 2014 the authors 0270-6474/14/347704-11$15.00/0.

  4. Oxytocin administration enhances controlled social cognition in patients with schizophrenia.

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    Woolley, J D; Chuang, B; Lam, O; Lai, W; O'Donovan, A; Rankin, K P; Mathalon, D H; Vinogradov, S

    2014-09-01

    Individuals with schizophrenia have functionally significant deficits in automatic and controlled social cognition, but no currently available pharmacologic treatments reduce these deficits. The neuropeptide oxytocin has multiple prosocial effects when administered intranasally in humans and there is growing interest in its therapeutic potential in schizophrenia. We administered 40 IU of oxytocin and saline placebo intranasally to 29 male subjects with schizophrenia and 31 age-matched, healthy controls in a randomized, double-blind, placebo-controlled, cross-over study. Social cognition was assessed with The Awareness of Social Inference Test (TASIT) and the Reading the Mind in the Eyes Test (RMET). We examined the effects of oxytocin administration on automatic social cognition (the ability to rapidly interpret and understand emotional cues from the voice, face, and body); controlled social cognition (the ability to comprehend indirectly expressed emotions, thoughts, and intentions through complex deliberations over longer time periods); and a control task (the ability to comprehend truthful dialog and perform general task procedures) in individuals with and without schizophrenia using mixed factorial analysis of variance models. Patients with schizophrenia showed significant impairments in automatic and controlled social cognition compared to healthy controls, and administration of oxytocin significantly improved their controlled, but not automatic, social cognition, F(1, 58)=8.75; p=0.004. Conversely, oxytocin administration had limited effects on social cognition in healthy participants. Patients and controls performed equally well and there were no effects of oxytocin administration on the control task. Intact social cognitive abilities are associated with better functional outcomes in individuals with schizophrenia. Our data highlight the potentially complex effects of oxytocin on some but not all aspects of social cognition, and support the exploration of

  5. Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum.

    Directory of Open Access Journals (Sweden)

    Joann Mudge

    Full Text Available Schizophrenia (SCZ is a common, disabling mental illness with high heritability but complex, poorly understood genetic etiology. As the first phase of a genomic convergence analysis of SCZ, we generated 16.7 billion nucleotides of short read, shotgun sequences of cDNA from post-mortem cerebellar cortices of 14 patients and six, matched controls. A rigorous analysis pipeline was developed for analysis of digital gene expression studies. Sequences aligned to approximately 33,200 transcripts in each sample, with average coverage of 450 reads per gene. Following adjustments for confounding clinical, sample and experimental sources of variation, 215 genes differed significantly in expression between cases and controls. Golgi apparatus, vesicular transport, membrane association, Zinc binding and regulation of transcription were over-represented among differentially expressed genes. Twenty three genes with altered expression and involvement in presynaptic vesicular transport, Golgi function and GABAergic neurotransmission define a unifying molecular hypothesis for dysfunction in cerebellar cortex in SCZ.

  6. Schizophrenia

    Science.gov (United States)

    ... many people with schizophrenia. Behavioral techniques, such as social skills training, can help the person function better in social and work situations. Job training and relationship-building ...

  7. Control of synaptic plasticity in deep cortical networks

    NARCIS (Netherlands)

    Roelfsema, Pieter R; Holtmaat, Anthony J D G

    2018-01-01

    Humans and many other animals have an enormous capacity to learn about sensory stimuli and to master new skills. However, many of the mechanisms that enable us to learn remain to be understood. One of the greatest challenges of systems neuroscience is to explain how synaptic connections change to

  8. Body composition in patients with schizophrenia: Comparison with healthy controls

    Directory of Open Access Journals (Sweden)

    Sugawara Norio

    2012-05-01

    Full Text Available Abstract Background Recently, a relationship between obesity and schizophrenia has been reported. Although fat- mass and fat free mass have been shown to be more predictive of health risk than body mass index, there are limited findings about body composition among patients suffering from schizophrenia. The aim of this study is to compare the body composition of schizophrenia patients with that of healthy subjects in Japan. Methods We recruited patients (n = 204, aged 41.3 ± 13.8 (mean ± SD years old with the DSM-IV diagnosis of schizophrenia who were admitted to psychiatric hospital using a cross-sectional design. Subjects' anthropometric measurements including weight, height, body mass index (BMI, and medications were also collected. Body fat, percent (% body fat, fat- free mass, muscle mass, and body water were measured using the bioelectrical impedance analysis (BIA method. Comparative analysis was performed with schizophrenic subjects and 204 healthy control individuals. Results In a multiple regression model with age, body mass index, and dose in chlorpromazine equivalents, schizophrenia was a significantly linked with more body fat, higher % body fat, lower fat- free mass, lower muscle mass, and lower body water among males. In females, schizophrenia had a significant association with lower % body fat, higher fat- free mass, higher muscle mass, and higher body water. Conclusions Our data demonstrate gender differences with regard to changes in body composition in association with schizophrenia. These results indicate that intervention programs designed to fight obesity among schizophrenic patients should be individualized according to gender.

  9. Randomized Controlled Trials of Add-On Antidepressants in Schizophrenia.

    Science.gov (United States)

    Terevnikov, Viacheslav; Joffe, Grigori; Stenberg, Jan-Henry

    2015-05-19

    Despite adequate treatment with antipsychotics, a substantial number of patients with schizophrenia demonstrate only suboptimal clinical outcome. To overcome this challenge, various psychopharmacological combination strategies have been used, including antidepressants added to antipsychotics. To analyze the efficacy of add-on antidepressants for the treatment of negative, positive, cognitive, depressive, and antipsychotic-induced extrapyramidal symptoms in schizophrenia, published randomized controlled trials assessing the efficacy of adjunctive antidepressants in schizophrenia were reviewed using the following parameters: baseline clinical characteristics and number of patients, their on-going antipsychotic treatment, dosage of the add-on antidepressants, duration of the trial, efficacy measures, and outcomes. There were 36 randomized controlled trials reported in 41 journal publications (n=1582). The antidepressants used were the selective serotonin reuptake inhibitors, duloxetine, imipramine, mianserin, mirtazapine, nefazodone, reboxetin, trazodone, and bupropion. Mirtazapine and mianserin showed somewhat consistent efficacy for negative symptoms and both seemed to enhance neurocognition. Trazodone and nefazodone appeared to improve the antipsychotics-induced extrapyramidal symptoms. Imipramine and duloxetine tended to improve depressive symptoms. No clear evidence supporting selective serotonin reuptake inhibitors' efficacy on any clinical domain of schizophrenia was found. Add-on antidepressants did not worsen psychosis. Despite a substantial number of randomized controlled trials, the overall efficacy of add-on antidepressants in schizophrenia remains uncertain mainly due to methodological issues. Some differences in efficacy on several schizophrenia domains seem, however, to exist and to vary by the antidepressant subgroups--plausibly due to differences in the mechanisms of action. Antidepressants may not worsen the course of psychosis. Better designed

  10. Neurexin-Neuroligin Synaptic Complex Regulates Schizophrenia-Related DISC1/Kal-7/Rac1 “Signalosome”

    DEFF Research Database (Denmark)

    Jacobsen, Sylwia Owczarek; Bang, Marie Louise; Berezin, Vladimir

    2015-01-01

    Neurexins (NXs) and neuroligins (NLs) are cell adhesion molecules that are localized at opposite sites of synaptic membranes. They interact with each other to promote the assembly, maintenance, and function of synapses in the central nervous system. Both NX and NL are cleaved from a membrane...... downstream of DISC1. We also show that NL1 binds to a well-characterized DISC1 interaction partner, Kal-7, and this interaction can be compromised by DISC1. Our results indicate that the NX/NL synaptic complex is intrinsically involved in the regulation of DISC1 function, thus contributing to a better...

  11. Homeostatic Control of Synaptic Activity by Endogenous Adenosine is Mediated by Adenosine Kinase

    Science.gov (United States)

    Diógenes, Maria José; Neves-Tomé, Raquel; Fucile, Sergio; Martinello, Katiuscia; Scianni, Maria; Theofilas, Panos; Lopatář, Jan; Ribeiro, Joaquim A.; Maggi, Laura; Frenguelli, Bruno G.; Limatola, Cristina; Boison, Detlev; Sebastião, Ana M.

    2014-01-01

    Extracellular adenosine, a key regulator of neuronal excitability, is metabolized by astrocyte-based enzyme adenosine kinase (ADK). We hypothesized that ADK might be an upstream regulator of adenosine-based homeostatic brain functions by simultaneously affecting several downstream pathways. We therefore studied the relationship between ADK expression, levels of extracellular adenosine, synaptic transmission, intrinsic excitability, and brain-derived neurotrophic factor (BDNF)-dependent synaptic actions in transgenic mice underexpressing or overexpressing ADK. We demonstrate that ADK: 1) Critically influences the basal tone of adenosine, evaluated by microelectrode adenosine biosensors, and its release following stimulation; 2) determines the degree of tonic adenosine-dependent synaptic inhibition, which correlates with differential plasticity at hippocampal synapses with low release probability; 3) modulates the age-dependent effects of BDNF on hippocampal synaptic transmission, an action dependent upon co-activation of adenosine A2A receptors; and 4) influences GABAA receptor-mediated currents in CA3 pyramidal neurons. We conclude that ADK provides important upstream regulation of adenosine-based homeostatic function of the brain and that this mechanism is necessary and permissive to synaptic actions of adenosine acting on multiple pathways. These mechanistic studies support previous therapeutic studies and implicate ADK as a promising therapeutic target for upstream control of multiple neuronal signaling pathways crucial for a variety of neurological disorders. PMID:22997174

  12. Interaural Level Difference Dependent Gain Control and Synaptic Scaling Underlying Binaural Computation

    Science.gov (United States)

    Xiong, Xiaorui R.; Liang, Feixue; Li, Haifu; Mesik, Lukas; Zhang, Ke K.; Polley, Daniel B.; Tao, Huizhong W.; Xiao, Zhongju; Zhang, Li I.

    2013-01-01

    Binaural integration in the central nucleus of inferior colliculus (ICC) plays a critical role in sound localization. However, its arithmetic nature and underlying synaptic mechanisms remain unclear. Here, we showed in mouse ICC neurons that the contralateral dominance is created by a “push-pull”-like mechanism, with contralaterally dominant excitation and more bilaterally balanced inhibition. Importantly, binaural spiking response is generated apparently from an ipsilaterally-mediated scaling of contralateral response, leaving frequency tuning unchanged. This scaling effect is attributed to a divisive attenuation of contralaterally-evoked synaptic excitation onto ICC neurons with their inhibition largely unaffected. Thus, a gain control mediates the linear transformation from monaural to binaural spike responses. The gain value is modulated by interaural level difference (ILD) primarily through scaling excitation to different levels. The ILD-dependent synaptic scaling and gain adjustment allow ICC neurons to dynamically encode interaural sound localization cues while maintaining an invariant representation of other independent sound attributes. PMID:23972599

  13. Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain.

    Science.gov (United States)

    Bonansco, Christian; Fuenzalida, Marco

    2016-01-01

    Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I) balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks.

  14. Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain

    Directory of Open Access Journals (Sweden)

    Christian Bonansco

    2016-01-01

    Full Text Available Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks.

  15. Evaluation of Dream Content Among Patients with Schizophrenia, their Siblings, Patients with Psychiatric Diagnoses Other than Schizophrenia, and Healthy Control

    Directory of Open Access Journals (Sweden)

    Leeba Rezaie

    2012-04-01

    Full Text Available Objective: Schizophrenia is a chronic psychotic disorder with unknown etiology that causes cognitive impairment, affecting thinking, behavior, social function, sleep and dream content. This study considered the dream content of patients with schizophrenia, siblings of patients with schizophrenia, patients with psychiatric diagnoses other than schizophrenia, and a group of healthy controls. The aim of this study was to compare the dream content of patients with schizophrenia with dream content of individuals with other mental disorders, first degree relatives of patients with schizophrenia, and community controls . Method: Seventy-two patients were selected and placed in 4 groups. The first group consisted of 18 inpatients with schizophrenia whose medications were stable for at least four weeks; the second group consisted of 16 nonpsychotic mentally ill inpatients; the third group consisted of 18 individuals who were siblings of patients with schizophrenia; and the fourth group consisted of 20 healthy individuals in the community with no family history of mental or somatic disorders. The four groups were matched by age and gender. A 14-item dream content questionnaire was administered for all the participants, and the Positive and Negative Symptoms Scale (PANSS was also administered for the two groups of hospitalized patients . Results: Results showed that there were significant differences in dream content among groups included friends acquaintances, females and colorful components. No significant differences were found between the positive and negative subscales of PANSS and any of the dream questionnaire subscales. Conclusion: Our results suggest that there were a few changes in the dream content of the patients with schizophrenia compare to other groups.

  16. Electrophysiological Evidence for Impaired Control of Motor Output in Schizophrenia.

    Science.gov (United States)

    Kappenman, Emily S; Luck, Steven J; Kring, Ann M; Lesh, Tyler A; Mangun, George R; Niendam, Tara; Ragland, J Daniel; Ranganath, Charan; Solomon, Marjorie; Swaab, Tamara Y; Carter, Cameron S

    2016-05-01

    Previous research has demonstrated pervasive deficits in response-related processing in people with schizophrenia (PSZ). The present study used behavioral measures and event-related potentials (ERPs) to test the hypothesis that schizophrenia involves specific impairment in the ability to exert control over response-related processing. Twenty-two PSZ and 22 matched control participants completed a choice response task in counterbalanced testing sessions that emphasized only accuracy (the unspeeded condition) or emphasized speed and accuracy equally (the speeded condition). Control participants successfully modulated behavioral and ERP indices of response-related processing under speed pressure, as evidenced by faster and less variable reaction times (RTs) and an earlier onset and increased amplitude lateralized readiness potential (LRP). By contrast, PSZ were unable to improve RT speed or variability or to modulate the LRP under speed pressure, despite showing a decrease in accuracy. Notably, response-related deficits in PSZ emerged only in the speeded condition; behavioral and ERP measures did not differ between groups in the unspeeded condition. Together, these results indicate that impairment in the ability to exert control over response-related processing may underlie response-related deficits in schizophrenia. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Neuropsychological performance in patients with schizophrenia and controls as a function of cigarette smoking status

    Science.gov (United States)

    Wing, Victoria C.; Bacher, Ingrid; Sacco, Kristi A.; George, Tony P.

    2011-01-01

    Schizophrenia is associated with many neurocognitive deficits, some of which are improved by nicotine and cigarette smoking. To better understand the relationship between smoking and cognitive function in schizophrenia, cross-sectional assessment of neuropsychological performance as a function of smoking status (smoker or non-smoker) and smoking history (current, former or never-smoker) in clinically-stable outpatients with schizophrenia and controls was evaluated. Subjects (N=140) were divided into subgroups on the basis of self-report and biochemical verification of smoking history. Current smokers with schizophrenia (n=38), former smokers with schizophrenia (n=17), never-smokers with schizophrenia (n=12), control smokers (n=31), control former smokers (n=16), and control never-smokers (n=26) were administered a comprehensive neuropsychological battery. Smokers were studied under non-deprivation conditions. Comparison of neuropsychological performance in schizophrenia and control subjects revealed significant main effects of diagnosis. Analysis of the data as a function of smoking history demonstrated that never-smokers with schizophrenia performed the poorest on measures of sustained attention, processing speed and response inhibition, when compared to the other schizophrenia subgroups. Cigarette smoking did not alter neuropsychological performance in controls. Our findings suggest that smoking status and history differentially alters neuropsychological outcomes in schizophrenia compared to non-psychiatric controls, and that never-smokers may present with more severe neurocognitive impairments. PMID:21669462

  18. Lateral prefrontal cortex activity during cognitive control of emotion predicts response to social stress in schizophrenia

    Directory of Open Access Journals (Sweden)

    Laura M. Tully, PhD

    2014-01-01

    Full Text Available LPFC dysfunction is a well-established neural impairment in schizophrenia and is associated with worse symptoms. However, how LPFC activation influences symptoms is unclear. Previous findings in healthy individuals demonstrate that lateral prefrontal cortex (LPFC activation during cognitive control of emotional information predicts mood and behavior in response to interpersonal conflict, thus impairments in these processes may contribute to symptom exacerbation in schizophrenia. We investigated whether schizophrenia participants show LPFC deficits during cognitive control of emotional information, and whether these LPFC deficits prospectively predict changes in mood and symptoms following real-world interpersonal conflict. During fMRI, 23 individuals with schizophrenia or schizoaffective disorder and 24 healthy controls completed the Multi-Source Interference Task superimposed on neutral and negative pictures. Afterwards, schizophrenia participants completed a 21-day online daily-diary in which they rated the extent to which they experienced mood and schizophrenia-spectrum symptoms, as well as the occurrence and response to interpersonal conflict. Schizophrenia participants had lower dorsal LPFC activity (BA9 during cognitive control of task-irrelevant negative emotional information. Within schizophrenia participants, DLPFC activity during cognitive control of emotional information predicted changes in positive and negative mood on days following highly distressing interpersonal conflicts. Results have implications for understanding the specific role of LPFC in response to social stress in schizophrenia, and suggest that treatments targeting LPFC-mediated cognitive control of emotion could promote adaptive response to social stress in schizophrenia.

  19. Coordinated Regulation of Synaptic Plasticity at Striatopallidal and Striatonigral Neurons Orchestrates Motor Control

    Directory of Open Access Journals (Sweden)

    Massimo Trusel

    2015-11-01

    Full Text Available The basal ganglia play a critical role in shaping motor behavior. For this function, the activity of medium spiny neurons (MSNs of the striatonigral and striatopallidal pathways must be integrated. It remains unclear whether the activity of the two pathways is primarily coordinated by synaptic plasticity mechanisms. Using a model of Parkinson’s disease, we determined the circuit and behavioral effects of concurrently regulating cell-type-specific forms of corticostriatal long-term synaptic depression (LTD by inhibiting small-conductance Ca2+-activated K+ channels (SKs of the dorsolateral striatum. At striatopallidal synapses, SK channel inhibition rescued the disease-linked deficits in endocannabinoid (eCB-dependent LTD. At striatonigral cells, inhibition of these channels counteracted a form of adenosine-mediated LTD by activating the ERK cascade. Interfering with eCB-, adenosine-, and ERK signaling in vivo alleviated motor abnormalities, which supports that synaptic modulation of striatal pathways affects behavior. Thus, our results establish a central role of coordinated synaptic plasticity at MSN subpopulations in motor control.

  20. Robust differences in antisaccade performance exist between COGS schizophrenia cases and controls regardless of recruitment strategies

    OpenAIRE

    Radant, AD; Millard, SP; Braff, DL; Calkins, ME; Dobie, DJ; Freedman, R.; Green, MF; Greenwood, TA; Gur, RE; Gur, RC; Lazzeroni, LC; Light, GA; Meichle, SP; Nuechterlein, KH; Olincy, A.

    2015-01-01

    © 2014. The impaired ability to make correct antisaccades (i.e., antisaccade performance) is well documented among schizophrenia subjects, and researchers have successfully demonstrated that antisaccade performance is a valid schizophrenia endophenotype that is useful for genetic studies. However, it is unclear how the ascertainment biases that unavoidably result from recruitment differences in schizophrenia subjects identified in family versus case-control studies may influence patient-contr...

  1. Psychoeducation and the family burden in schizophrenia: a randomized controlled trial

    OpenAIRE

    Kausar Rukhsana; Nasr Tanveer

    2009-01-01

    Abstract Background The majority of patients with schizophrenia live with their relatives in Pakistan, thereby families experience a considerable burden. We aimed to study the impact of psychoeducation on the burden of schizophrenia on the family in a randomised controlled trial. Methods A total of 108 patients with schizophrenia and their family members from the outpatient department of a teaching hospital in Lahore, Pakistan were randomised. Both groups received psychotropic drugs but one g...

  2. Spared and impaired aspects of motivated cognitive control in schizophrenia.

    Science.gov (United States)

    Mann, Claire L; Footer, Owen; Chung, Yu Sun; Driscoll, Lori L; Barch, Deanna M

    2013-08-01

    The ability to upregulate cognitive control in motivationally salient situations was examined in individuals with schizophrenia (patients) and healthy controls. Fifty-four patients and 39 healthy controls were recruited. A computerized monetary response conflict task required participants to identity a picture, over which was printed a matching (congruent), neutral, or incongruent word. This baseline condition was followed by an incentive condition, in which participants were given the opportunity to win money on reward-cued trials. These reward-cued trials were interleaved with nonreward cued trials. Reaction times (RT) were examined for both incentive context effects (difference in RT between baseline and nonreward cue trials in the incentive condition) and incentive cue effects (difference in RT between nonreward and reward cue trials in the incentive condition). Compared with baseline, controls showed a speeding of responses during both the nonreward (incentive context effect) and reward cued (incentive cue effect) trials during the incentive condition, but with a larger incentive context than incentive cue effect, suggesting a reliance on proactive control strategies. Although patients also showed a speeding of responses to both nonreward and reward cued trials, they showed a significantly smaller incentive context effect than controls, suggesting a reduction in the use of proactive control and a greater reliance on the use of "just-in-time," reactive control strategies. These results are discussed in light of the relationship between motivation and cognitive impairments in schizophrenia, and the potential role of impairments in prefrontally mediated active maintenance mechanisms. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  3. Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons

    Science.gov (United States)

    Cristino, Luigia; Busetto, Giuseppe; Imperatore, Roberta; Ferrandino, Ida; Palomba, Letizia; Silvestri, Cristoforo; Petrosino, Stefania; Orlando, Pierangelo; Bentivoglio, Marina; Mackie, Kenneth; Di Marzo, Vincenzo

    2013-01-01

    Acute or chronic alterations in energy status alter the balance between excitatory and inhibitory synaptic transmission and associated synaptic plasticity to allow for the adaptation of energy metabolism to new homeostatic requirements. The impact of such changes on endocannabinoid and cannabinoid receptor type 1 (CB1)-mediated modulation of synaptic transmission and strength is not known, despite the fact that this signaling system is an important target for the development of new drugs against obesity. We investigated whether CB1-expressing excitatory vs. inhibitory inputs to orexin-A–containing neurons in the lateral hypothalamus are altered in obesity and how this modifies endocannabinoid control of these neurons. In lean mice, these inputs are mostly excitatory. By confocal and ultrastructural microscopic analyses, we observed that in leptin-knockout (ob/ob) obese mice, and in mice with diet-induced obesity, orexinergic neurons receive predominantly inhibitory CB1-expressing inputs and overexpress the biosynthetic enzyme for the endocannabinoid 2-arachidonoylglycerol, which retrogradely inhibits synaptic transmission at CB1-expressing axon terminals. Patch-clamp recordings also showed increased CB1-sensitive inhibitory innervation of orexinergic neurons in ob/ob mice. These alterations are reversed by leptin administration, partly through activation of the mammalian target of rapamycin pathway in neuropeptide-Y-ergic neurons of the arcuate nucleus, and are accompanied by CB1-mediated enhancement of orexinergic innervation of target brain areas. We propose that enhanced inhibitory control of orexin-A neurons, and their CB1-mediated disinhibition, are a consequence of leptin signaling impairment in the arcuate nucleus. We also provide initial evidence of the participation of this phenomenon in hyperphagia and hormonal dysregulation in obesity. PMID:23630288

  4. Risk-taking in schizophrenia and controls with and without cannabis dependence.

    Science.gov (United States)

    Fischer, Bernard A; McMahon, Robert P; Kelly, Deanna L; Wehring, Heidi J; Meyer, Walter A; Feldman, Stephanie; Carpenter, William T; Gorelick, David A

    2015-02-01

    Risk-based decision making is altered in people with schizophrenia and in people with cannabis use compared to healthy controls; the pattern of risk-assessment in people with co-occurring schizophrenia and cannabis dependence is poorly understood. This study examined measures of risk-taking and decision-making in people with and without schizophrenia and/or cannabis dependence. Participants with schizophrenia (n=24), cannabis dependence (n=23), schizophrenia and co-occurring cannabis dependence (n=18), and healthy controls (n=24) were recruited from the community via advertisements and completed a one-visit battery of symptom, risk-based decision making, gambling behavior, cognitive, and addiction assessments. This report presents self-assessments of self-mastery, optimism, impulsivity, and sensation seeking and a behavioral assessment of risk (Balloon Analog Risk Task [BART]). On self-report measures, participants with schizophrenia and co-occurring cannabis dependence were intermediate between those with only cannabis dependence or only schizophrenia on ratings of self-mastery, sensation-seeking, and impulsivity. There were no group differences on ratings of optimism. Their behavior on the BART was most similar to participants with only cannabis dependence or healthy controls, rather than to participants with only schizophrenia. People with schizophrenia and co-occurring cannabis dependence may represent a unique group in terms of risk-perception and risk-taking. This has implications for interventions designed to influence health behaviors such as motivational interviewing. Published by Elsevier B.V.

  5. Control of Homeostatic Synaptic Plasticity by AKAP-Anchored Kinase and Phosphatase Regulation of Ca2+-Permeable AMPA Receptors.

    Science.gov (United States)

    Sanderson, Jennifer L; Scott, John D; Dell'Acqua, Mark L

    2018-02-13

    Neuronal information processing requires multiple forms of synaptic plasticity mediated by NMDA and AMPA-type glutamate receptors (NMDAR, AMPAR). These plasticity mechanisms include long-term potentiation (LTP) and depression (LTD), which are Hebbian, homosynaptic mechanisms locally regulating synaptic strength of specific inputs, and homeostatic synaptic scaling, which is a heterosynaptic mechanism globally regulating synaptic strength across all inputs. In many cases, LTP and homeostatic scaling regulate AMPAR subunit composition to increase synaptic strength via incorporation of Ca 2+ -permeable receptors (CP-AMPAR) containing GluA1, but lacking GluA2, subunits. Previous work by our group and others demonstrated that anchoring of the kinase PKA and the phosphatase calcineurin (CaN) to A-kinase anchoring protein (AKAP) 150 play opposing roles in regulation of GluA1 Ser845 phosphorylation and CP-AMPAR synaptic incorporation during hippocampal LTP and LTD. Here, using both male and female knock-in mice that are deficient in PKA or CaN anchoring, we show that AKAP150-anchored PKA and CaN also play novel roles in controlling CP-AMPAR synaptic incorporation during homeostatic plasticity in hippocampal neurons. We found that genetic disruption of AKAP-PKA anchoring prevented increases in Ser845 phosphorylation and CP-AMPAR synaptic recruitment during rapid homeostatic synaptic scaling-up induced by combined blockade of action potential firing and NMDAR activity. In contrast, genetic disruption of AKAP-CaN anchoring resulted in basal increases in Ser845 phosphorylation and CP-AMPAR synaptic activity that blocked subsequent scaling-up by preventing additional CP-AMPAR recruitment. Thus, the balanced, opposing phospho-regulation provided by AKAP-anchored PKA and CaN is essential for control of both Hebbian and homeostatic plasticity mechanisms that require CP-AMPARs. Significance statement: Neuronal circuit function is shaped by multiple forms of activity

  6. Robust differences in antisaccade performance exist between COGS schizophrenia cases and controls regardless of recruitment strategies.

    Science.gov (United States)

    Radant, Allen D; Millard, Steven P; Braff, David L; Calkins, Monica E; Dobie, Dorcas J; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Light, Gregory A; Meichle, Sean P; Nuechterlein, Keith H; Olincy, Ann; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Stone, William S; Swerdlow, Neal R; Sugar, Catherine A; Tsuang, Ming T; Turetsky, Bruce I; Tsuang, Debby W

    2015-04-01

    The impaired ability to make correct antisaccades (i.e., antisaccade performance) is well documented among schizophrenia subjects, and researchers have successfully demonstrated that antisaccade performance is a valid schizophrenia endophenotype that is useful for genetic studies. However, it is unclear how the ascertainment biases that unavoidably result from recruitment differences in schizophrenia subjects identified in family versus case-control studies may influence patient-control differences in antisaccade performance. To assess the impact of ascertainment bias, researchers from the Consortium on the Genetics of Schizophrenia (COGS) compared antisaccade performance and antisaccade metrics (latency and gain) in schizophrenia and control subjects from COGS-1, a family-based schizophrenia study, to schizophrenia and control subjects from COGS-2, a corresponding case-control study. COGS-2 schizophrenia subjects were substantially older; had lower education status, worse psychosocial function, and more severe symptoms; and were three times more likely to be a member of a multiplex family than COGS-1 schizophrenia subjects. Despite these variations, which were likely the result of ascertainment differences (as described in the introduction to this special issue), the effect sizes of the control-schizophrenia differences in antisaccade performance were similar in both studies (Cohen's d effect size of 1.06 and 1.01 in COGS-1 and COGS-2, respectively). This suggests that, in addition to the robust, state-independent schizophrenia-related deficits described in endophenotype studies, group differences in antisaccade performance do not vary based on subject ascertainment and recruitment factors. Published by Elsevier B.V.

  7. Impaired theory of mind in first-episode schizophrenia: comparison with community, university and depressed controls.

    Science.gov (United States)

    Kettle, Jonathan W L; O'Brien-Simpson, Laurie; Allen, Nicholas B

    2008-02-01

    First order theory of mind, as measured by the 'Reading the Mind in the Eyes Test' Revised, is impaired in schizophrenia. However, no study has investigated whether this occurs in first-episode schizophrenia. Also, it is unclear whether such a deficit is specific to schizophrenia, and whether convenience control samples, particularly undergraduate university students, represent valid comparison groups. This study investigated theory of mind ability, measured by the 'Reading the Mind in the Eyes Test' Revised, in a group of first-episode schizophrenia outpatients (n=13) and three control groups: outpatients with non-psychotic major depression (n=14), individuals from the general community (n=16) and from an undergraduate university course (n=27). The schizophrenia group exhibited significant theory of mind impairments compared to both non-psychiatric control groups but not the depression group. Unexpectedly, the depression group was not significantly impaired compared to the community control group, and the university control group exhibited superior theory of mind ability relative to all three groups. The findings indicate theory of mind deficits in first episode schizophrenia and support the implementation of theory of mind interventions in first-episode schizophrenia treatment programs. Results also indicate that community rather than university control groups represent more valid comparison groups in first-episode schizophrenia research.

  8. Interaural level difference-dependent gain control and synaptic scaling underlying binaural computation.

    Science.gov (United States)

    Xiong, Xiaorui R; Liang, Feixue; Li, Haifu; Mesik, Lukas; Zhang, Ke K; Polley, Daniel B; Tao, Huizhong W; Xiao, Zhongju; Zhang, Li I

    2013-08-21

    Binaural integration in the central nucleus of inferior colliculus (ICC) plays a critical role in sound localization. However, its arithmetic nature and underlying synaptic mechanisms remain unclear. Here, we showed in mouse ICC neurons that the contralateral dominance is created by a "push-pull"-like mechanism, with contralaterally dominant excitation and more bilaterally balanced inhibition. Importantly, binaural spiking response is generated apparently from an ipsilaterally mediated scaling of contralateral response, leaving frequency tuning unchanged. This scaling effect is attributed to a divisive attenuation of contralaterally evoked synaptic excitation onto ICC neurons with their inhibition largely unaffected. Thus, a gain control mediates the linear transformation from monaural to binaural spike responses. The gain value is modulated by interaural level difference (ILD) primarily through scaling excitation to different levels. The ILD-dependent synaptic scaling and gain adjustment allow ICC neurons to dynamically encode interaural sound localization cues while maintaining an invariant representation of other independent sound attributes. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. The association between cannabis abuse and subsequent schizophrenia: a Swedish national co-relative control study.

    Science.gov (United States)

    Giordano, G N; Ohlsson, H; Sundquist, K; Sundquist, J; Kendler, K S

    2015-01-01

    Although cannabis abuse (CA) is known to be associated with schizophrenia, the causal nature of this association is unclear, with prodromal effects complicating its interpretation. From Swedish national registry databases, we used a co-relative case-control design with full-sibling, half-sibling and first-cousin comparisons, alongside a general Swedish population sample. Using ICD codes, 5456 individuals with an initial diagnosis of schizophrenia (2000-2010) were matched with five schizophrenia-free controls. We further identified first-cousin, half-sibling and full-sibling pairs discordant for CA and statistically extrapolated results for discordant monozygotic (MZ) twins. Within the general Swedish population, CA was strongly associated with later schizophrenia [odds ratio (OR) 10.44, 95% confidence interval (CI) 8.99-12.11]. This association was substantially attenuated both by increasing temporal delays between CA exposure and schizophrenia diagnosis and by controlling for increasing degrees of familial confounding. Extrapolated discordant MZ pairs suggested that fully controlling for confounding familial factors reduced the association between CA and later schizophrenia to more modest levels (ORs of approximately 3.3 and 1.6 with 3- and 7-year temporal delays respectively). Opiate, sedative, cocaine/stimulant and hallucinogen abuse were also strongly associated with subsequent schizophrenia in the general population. After controlling for familial confounding, only cocaine/stimulant exposure remained associated. CA has an appreciable causal impact on future risk for schizophrenia. However, population-based estimates of cannabis-schizophrenia co-morbidity substantially overestimate their causal association. Predictions of the cases of schizophrenia that might be prevented by reduced cannabis consumption based on population associations are therefore likely to be considerably overestimated.

  10. Specific Glial Functions Contribute to Schizophrenia Susceptibility

    NARCIS (Netherlands)

    Goudriaan, A.; de Leeuw, C.A.; Ripke, S.; Hultman, C. M.; Sklar, P.; Sullivan, P.F.; Smit, A.B.; Posthuma, D.; Verheijen, M.H.G.

    2014-01-01

    Schizophrenia is a highly polygenic brain disorder. The main hypothesis for disease etiology in schizophrenia primarily focuses on the role of dysfunctional synaptic transmission. Previous studies have therefore directed their investigations toward the role of neuronal dysfunction. However, recent

  11. Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controls

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    Eduardo Castro-Nallar

    2015-08-01

    Full Text Available The role of the human microbiome in schizophrenia remains largely unexplored. The microbiome has been shown to alter brain development and modulate behavior and cognition in animals through gut-brain connections, and research in humans suggests that it may be a modulating factor in many disorders. This study reports findings from a shotgun metagenomic analysis of the oropharyngeal microbiome in 16 individuals with schizophrenia and 16 controls. High-level differences were evident at both the phylum and genus levels, with Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria dominating both schizophrenia patients and controls, and Ascomycota being more abundant in schizophrenia patients than controls. Controls were richer in species but less even in their distributions, i.e., dominated by fewer species, as opposed to schizophrenia patients. Lactic acid bacteria were relatively more abundant in schizophrenia, including species of Lactobacilli and Bifidobacterium, which have been shown to modulate chronic inflammation. We also found Eubacterium halii, a lactate-utilizing species. Functionally, the microbiome of schizophrenia patients was characterized by an increased number of metabolic pathways related to metabolite transport systems including siderophores, glutamate, and vitamin B12. In contrast, carbohydrate and lipid pathways and energy metabolism were abundant in controls. These findings suggest that the oropharyngeal microbiome in individuals with schizophrenia is significantly different compared to controls, and that particular microbial species and metabolic pathways differentiate both groups. Confirmation of these findings in larger and more diverse samples, e.g., gut microbiome, will contribute to elucidating potential links between schizophrenia and the human microbiota.

  12. [Somatotype and schizophrenia. A case-control study].

    Science.gov (United States)

    Pailhez, G; Rodríguez, A; Ariza, J; Palomo, A L; Bulbena, A

    2009-01-01

    To compare somatotypes of schizophrenic patients and healthy controls and to examine some associations between somatic (joint mobility, somatotype) and psychopathological (anxiety, clinical seriousness and schizophrenic types) features. Thirty four in-patients with DSM-IV diagnosis of schizophrenia assessed by SCID-I, aged 18 to 50 years, were recruited as cases. Thirty two subjects of a general non-clinical population were recruited as controls. Heath-Carter method and 5 questions to detect joint hypermobility were used to assess both somatotype and joint hypermobility. Trait anxiety (STAI) and BPRS were assessed at medical discharge. There were no statistically significant differences between mean somatotype groups (cases: 4(1/2) 5(1/2) 1(1/2); controls: 5 - 5 - 1(1/2)). Schizophrenic patients showed significantly more divergence among themselves in relationship to their own common mean [t = 1.98; gl = 64; p = 0.05] and accounted for more ectomorphic categories than the control group. Somatotype means of paranoid and disorganized types were significantly more homogeneous (with greater values of ectomorphism) than undifferentiated type [X2 = 6.61; gl = 2; p = 0.037]. There was a tendency towards positive association between anxiety - joint hypermobility and anxiety- ectomorphism, but it did not reach a statistically significant level. In spite of their limitations, the results provide suggestive data for identification of subtypes in mental illnesses that can be used as a nosologic knowledge or as potential risk markers.

  13. Cannabis use and sensorimotor gating in patients with schizophrenia and healthy controls.

    Science.gov (United States)

    Scholes-Balog, Kirsty E; Martin-Iverson, Mathew T

    2011-08-01

    Schizophrenia patients and healthy cannabis users show different attention-dependant alterations in prepulse inhibition (PPI). It is of interest then to examine PPI in patients with schizophrenia who use cannabis, given the hypothesized association between cannabis use and schizophrenia. Prepulse inhibition was measured in 34 healthy cannabis users, 32 healthy non-using controls, 20 patients with schizophrenia who were current cannabis users, and 44 non-using patients with schizophrenia. PPI was measured across a range of startling stimulus intensities, during two attention set conditions. Curves of best fit were fitted to the startle magnitudes, across the stimulus intensities. A number of reflex parameters were extracted from these logistic functions. Similar to healthy cannabis users, cannabis-using patients showed altered PPI of Threshold, only when instructed to sustain attention to the auditory stimuli. Conversely, non-using patients with schizophrenia showed reduced PP of R(MAX) only when instructed to ignore the auditory stimuli. Cannabis use in patients with schizophrenia is associated with a similar pattern of attention-dependant alterations in PPI to that observed in healthy cannabis users. This is different to those observed in patients with schizophrenia who do not use cannabis and may be as a result of a dysfunction of sustained attention. Copyright © 2011 John Wiley & Sons, Ltd.

  14. Sleep disorders in patients with depression or schizophrenia: A randomized controlled trial using acupuncture treatment

    NARCIS (Netherlands)

    Bosch, M.P.C.; Noort, M.W.M.L. van den; Staudte, H.; Lim, S.; Yeo, S.; Coenen, A.M.L.; Luijtelaar, E.L.J.M. van

    2016-01-01

    Introduction: The purpose of this preliminary clinical trial was to investigate whether acupuncture has a positive influence on sleep and symptomatology in patients with schizophrenia or depression. Methods: A randomized controlled trial was used. One hundred participants were recruited: 40

  15. Body composition in patients with schizophrenia: Comparison with healthy controls

    OpenAIRE

    Sugawara Norio; Yasui-Furukori Norio; Tsuchimine Shoko; Fujii Akira; Sato Yasushi; Saito Manabu; Matsuzaka Masashi; Takahashi Ippei; Kaneko Sunao

    2012-01-01

    Abstract Background Recently, a relationship between obesity and schizophrenia has been reported. Although fat- mass and fat free mass have been shown to be more predictive of health risk than body mass index, there are limited findings about body composition among patients suffering from schizophrenia. The aim of this study is to compare the body composition of schizophrenia patients with that of healthy subjects in Japan. Methods We recruited patients (n = 204), aged 41.3 ± 13.8 (mean ± SD)...

  16. Association between schizophrenia and urinary calculi: a population-based case-control study.

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    Shih-Ping Liu

    Full Text Available BACKGROUND: People with schizophrenia have been demonstrated to have higher overall morbidity and all-cause mortality rates from general medical conditions. However, little attention has been given to the urinary system of people with schizophrenia. As no direct evidence has been reported demonstrating a link between schizophrenia and urinary calculi, this study utilized a population-based case-control study design to investigate the possibility of an association between schizophrenia and the occurrence of urinary calculi. METHOD: This study used data from the Taiwan Longitudinal Health Insurance Database. Cases consisted of 53,965 urinary calculi patients newly diagnosed between 2002 and 2008. In total, 269,825 controls were randomly selected and matched with the cases in terms of age and sex. Each person was traced to discern whether he had previously received a diagnosis of schizophrenia. Conditional logistic regression models were performed for the analysis. RESULTS: A total of 3,119 (1.0% subjects had been diagnosed with schizophrenia prior to the index date. This included 0.7% of the patients with urinary calculi, and 1.0% of the controls. A prior diagnosis of schizophrenia was independently associated with a 30% decrease (95% CI = 0.62-0.76 in the occurrence of urinary calculi. The reduction was even more remarkable in males (38%, 95% CI = 0.55-0.71 and in elder individuals independent of gender (48% in those aged >69, 95% CI = 0.36-0.77. CONCLUSION: Our findings suggest that there is an inverse association between schizophrenia and urinary calculi. Future studies are needed to elucidate the mechanisms by which schizophrenia negatively associates with urinary calculi.

  17. Endurance training in patients with schizophrenia and healthy controls: differences and similarities.

    Science.gov (United States)

    Keller-Varady, Katriona; Hasan, Alkomiet; Schneider-Axmann, Thomas; Hillmer-Vogel, Ursula; Adomßent, Björn; Wobrock, Thomas; Schmitt, Andrea; Niklas, Andree; Falkai, Peter; Malchow, Berend

    2016-08-01

    The aims were to examine the feasibility of and adaptations to endurance training in persons diagnosed with schizophrenia and to address the question whether the principles and beneficial effects of endurance training established in the healthy population apply also to patients with schizophrenia. In this controlled interventional study, 22 patients with schizophrenia and 22 healthy controls performed a standardized aerobic endurance training on bicycle ergometers over 12 weeks. Another group of 21 patients with schizophrenia played table soccer. Endurance capacity was measured with incremental cycle ergometry before and after the intervention and 3 months later. A specific set of outcome parameters was defined. The training stimuli can be assumed to be similar in both endurance groups. Endurance capacity improved significantly in the endurance groups, but not in the table soccer group. Patients and healthy controls showed comparable adaptations to endurance training, as assessed by physical working capacity and maximal achieved power. Differences were found in changes of performance at a lactate concentration of 3 mmol/l. Endurance training was feasible and effective in both groups. The principles and types of training that are usually applied to healthy controls need to be verified in patients with schizophrenia. Nevertheless, patients benefited from endurance training in terms of improvement of endurance capacity and reduction in the baseline deficit in comparison with healthy controls. Therefore, endurance training should be implemented in future therapy programs. These programs need to pay special attention to the differences between patients with schizophrenia and healthy controls.

  18. VRK2 gene expression in schizophrenia, bipolar disorder and healthy controls.

    Science.gov (United States)

    Tesli, Martin; Wirgenes, Katrine Verena; Hughes, Timothy; Bettella, Francesco; Athanasiu, Lavinia; Hoseth, Eva S; Nerhus, Mari; Lagerberg, Trine V; Steen, Nils E; Agartz, Ingrid; Melle, Ingrid; Dieset, Ingrid; Djurovic, Srdjan; Andreassen, Ole A

    2016-08-01

    Common variants in the Vaccinia-related kinase 2 (VRK2) gene have been associated with schizophrenia, but the relevance of its encoded protein VRK2 in the disorder remains unclear. To identify potential differences in VRK2 gene expression levels between schizophrenia, bipolar disorder, psychosis not otherwise specified (PNOS) and healthy controls. VRK2 mRNA level was measured in whole blood in 652 individuals (schizophrenia, n = 201; bipolar disorder, n = 167; PNOS, n = 61; healthy controls, n = 223), and compared across diagnostic categories and subcategories. Additionally, we analysed for association between 1566 VRK2 single nucleotide polymorphisms and mRNA levels. We found lower VRK2 mRNA levels in schizophrenia compared with healthy controls (Pdisorder (Pdisorder (P = 0.00026). Expression quantitative trait loci in close proximity to the transcription start site of the short isoforms of the VRK2 gene were identified. Altered VRK2 gene expression seems specific for schizophrenia and PNOS, which is in accordance with findings from genome-wide association studies. These results suggest that reduced VRK2 mRNA levels are involved in the underlying mechanisms in schizophrenia spectrum disorders. © The Royal College of Psychiatrists 2016.

  19. Auditory top-down control and affective theory of mind in schizophrenia with and without hallucinations.

    Science.gov (United States)

    Rominger, Christian; Bleier, Angelika; Fitz, Werner; Marksteiner, Josef; Fink, Andreas; Papousek, Ilona; Weiss, Elisabeth M

    2016-07-01

    Social cognitive impairments may represent a core feature of schizophrenia and above all are a strong predictor of positive psychotic symptoms. Previous studies could show that reduced inhibitory top-down control contributes to deficits in theory of mind abilities and is involved in the genesis of hallucinations. The current study aimed to investigate the relationship between auditory inhibition, affective theory of mind and the experience of hallucinations in patients with schizophrenia. In the present study, 20 in-patients with schizophrenia and 20 healthy controls completed a social cognition task (the Reading the Mind in the Eyes Test) and an inhibitory top-down Dichotic Listening Test. Schizophrenia patients with greater severity of hallucinations showed impaired affective theory of mind as well as impaired inhibitory top-down control. More dysfunctional top-down inhibition was associated with poorer affective theory of mind performance, and seemed to mediate the association between impairment to affective theory of mind and severity of hallucinations. The findings support the idea of impaired theory of mind as a trait marker of schizophrenia. In addition, dysfunctional top-down inhibition may give rise to hallucinations and may further impair affective theory of mind skills in schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Dental caries status of patients with schizophrenia in Seville, Spain: a case-control study.

    Science.gov (United States)

    Velasco-Ortega, Eugenio; Monsalve-Guil, L; Ortiz-Garcia, I; Jimenez-Guerra, A; Lopez-Lopez, J; Segura-Egea, J J

    2017-01-18

    The aim of this study was to assess the dental status (DMFT) in patients with schizophrenia compared with a control group. In this case-control study, 50 patients with schizophrenia attended in the Psychiatric Unit at the Virgen Macarena University Hospital of Seville were compared with 50 people (without systemic diseases and not taking psychotropic drugs) in a control group attended in the School of Dentistry of Seville. Decayed, missing and filled teeth (DMFT) were assessed according to the World Health Organization WHO criteria. Patients with schizophrenia showed a decayed teeth (DT) score of 7.26 ± 5.69 compared with 6.50 ± 4.37 for patients the control group. These differences were significant and suggest that dental caries are most prevalent in patients with schizophrenia. People who smoked showed significantly higher DT scores in both groups. Among patients with schizophrenia, smokers scored 9.34 ± 5.42 compared with 4.38 ± 4.82 for non-smokers. Among the healthy controls, smokers scored 6.88 ± 4.85 compared with 6.12 ± 3.85 for non-smokers (p schizophrenia showed a missing teeth (MT) score of 9.10 ± 8.56 compared with 5.38 ± 5.14 in control patients. MT scores increased significantly with age and with smoking in both groups of patients (p schizophrenia showed a filled teeth (FT) score of 1.38 ± 2.70 compared with 2.34 ± 3.48 in control patients. FT differences in gender and smoking habits between patients with schizophrenia and healthy control subjects were statistically significant (p schizophrenia have extensive untreated dental disease. Patients with schizophrenia constitute a high risk population for dental health. This group showed a greater prevalence of decayed and missing teeth and more extensive treatment needs.

  1. Control of submillisecond synaptic timing in binaural coincidence detectors by K(v)1 channels.

    Science.gov (United States)

    Mathews, Paul J; Jercog, Pablo E; Rinzel, John; Scott, Luisa L; Golding, Nace L

    2010-05-01

    Neurons in the medial superior olive process sound-localization cues via binaural coincidence detection, in which excitatory synaptic inputs from each ear are segregated onto different branches of a bipolar dendritic structure and summed at the soma and axon with submillisecond time resolution. Although synaptic timing and dynamics critically shape this computation, synaptic interactions with intrinsic ion channels have received less attention. Using paired somatic and dendritic patch-clamp recordings in gerbil brainstem slices together with compartmental modeling, we found that activation of K(v)1 channels by dendritic excitatory postsynaptic potentials (EPSPs) accelerated membrane repolarization in a voltage-dependent manner and actively improved the time resolution of synaptic integration. We found that a somatically biased gradient of K(v)1 channels underlies the degree of compensation for passive cable filtering during propagation of EPSPs in dendrites. Thus, both the spatial distribution and properties of K(v)1 channels are important for preserving binaural synaptic timing.

  2. Cognitive performance of long-term institutionalized elderly patients with schizophrenia: A case control study

    Directory of Open Access Journals (Sweden)

    Alexandre Paim Diaz

    Full Text Available Abstract Cognitive impairment is inherent to the ageing process. Several studies suggest that patients with late-life schizophrenia have more marked cognitive impairment. Objective: The aim of this study was to compare the cognitive performance of elderly institutionalized patients with schizophrenia and institutionalized elderly control patients without neurological or psychiatric diseases, matched for age, educational level and institutionalization time. Methods: The Cambridge Examination for Mental Disorders of the Elderly (CAMCOG was used to test 10 institutionalized elderly patients with schizophrenia. Results were compared with those of 10 institutionalized control patients with history of Hansen's disease. Results: Patients with schizophrenia showed a worse performance in terms of total CAMCOG score and on its subtests of orientation, language, abstraction, and memory (p≤0.05. Patients with schizophrenia also disclosed a non-significant trend toward lower scores on the MMSE and on calculus. Conclusion: Findings demonstrated that schizophrenia was associated to worse cognitive impairment in long-term institutionalized elderly patients compared with institutionalized patients without neurological or psychiatric diseases.

  3. A randomised, double-blind, placebo-controlled trial of tropisetron in patients with schizophrenia

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    Shiraishi Tetsuya

    2010-06-01

    Full Text Available Abstract Background Cognitive deficits in schizophrenia are associated with psychosocial deficits that are primarily responsible for the poor long-term outcome of this disease. Auditory sensory gating P50 deficits are correlated with neuropsychological deficits in attention, one of the principal cognitive disturbances in schizophrenia. Our studies suggest that the α7 nicotinic acetylcholine receptor (α7 nAChR agonist tropisetron might be a potential therapeutic drug for cognitive deficits in schizophrenia. Therefore, it is of particular interest to investigate the effects of tropisetron on the cognitive deficits in patients with schizophrenia. Methods A randomised, placebo-controlled trial of tropisetron in patients with schizophrenia was performed. A total of 40 patients with chronic schizophrenia who had taken risperidone (2 to 6 mg/day were enrolled. Subjects were randomly assigned to a fixed titration of tropisetron (n = 20, 10 mg/day or placebo (n = 20 in an 8-week double-blind trial. Auditory sensory gating P50 deficits and Quality of Life Scale (QLS, Cambridge Neuropsychological Test Automated Battery (CANTAB, and Positive and Negative Syndrome Scale (PANSS scores were measured. Results In all, 33 patients completed the trial. Tropisetron was well tolerated. Administration of tropisetron, but not placebo, significantly improved auditory sensory gating P50 deficits in non-smoking patients with schizophrenia. The score on the rapid visual information processing (sustained visual attention task of CANTAB was significantly improved by tropisetron treatment. Total and subscale scores of PANSS were not changed by this trial. QLS scores in the all patients, but not non-smoking patients, were significantly improved by tropisetron trial. Conclusions This first randomised, double-blind, placebo-controlled trial supports the safety and efficacy of adjunctive tropisetron for treatment of cognitive deficits in schizophrenia.

  4. Caffeine Controls Glutamatergic Synaptic Transmission and Pyramidal Neuron Excitability in Human Neocortex

    Science.gov (United States)

    Kerkhofs, Amber; Xavier, Ana C.; da Silva, Beatriz S.; Canas, Paula M.; Idema, Sander; Baayen, Johannes C.; Ferreira, Samira G.; Cunha, Rodrigo A.; Mansvelder, Huibert D.

    2018-01-01

    Caffeine is the most widely used psychoactive drug, bolstering attention and normalizing mood and cognition, all functions involving cerebral cortical circuits. Whereas studies in rodents showed that caffeine acts through the antagonism of inhibitory A1 adenosine receptors (A1R), neither the role of A1R nor the impact of caffeine on human cortical neurons is known. We here provide the first characterization of the impact of realistic concentrations of caffeine experienced by moderate coffee drinkers (50 μM) on excitability of pyramidal neurons and excitatory synaptic transmission in the human temporal cortex. Moderate concentrations of caffeine disinhibited several of the inhibitory A1R-mediated effects of adenosine, similar to previous observations in the rodent brain. Thus, caffeine restored the adenosine-induced decrease of both intrinsic membrane excitability and excitatory synaptic transmission in the human pyramidal neurons through antagonism of post-synaptic A1R. Indeed, the A1R-mediated effects of endogenous adenosine were more efficient to inhibit synaptic transmission than neuronal excitability. This was associated with a distinct affinity of caffeine for synaptic versus extra-synaptic human cortical A1R, probably resulting from a different molecular organization of A1R in human cortical synapses. These findings constitute the first neurophysiological description of the impact of caffeine on pyramidal neuron excitability and excitatory synaptic transmission in the human temporal cortex, providing adequate ground for the effects of caffeine on cognition in humans. PMID:29354052

  5. Caffeine Controls Glutamatergic Synaptic Transmission and Pyramidal Neuron Excitability in Human Neocortex

    Directory of Open Access Journals (Sweden)

    Amber Kerkhofs

    2018-01-01

    Full Text Available Caffeine is the most widely used psychoactive drug, bolstering attention and normalizing mood and cognition, all functions involving cerebral cortical circuits. Whereas studies in rodents showed that caffeine acts through the antagonism of inhibitory A1 adenosine receptors (A1R, neither the role of A1R nor the impact of caffeine on human cortical neurons is known. We here provide the first characterization of the impact of realistic concentrations of caffeine experienced by moderate coffee drinkers (50 μM on excitability of pyramidal neurons and excitatory synaptic transmission in the human temporal cortex. Moderate concentrations of caffeine disinhibited several of the inhibitory A1R-mediated effects of adenosine, similar to previous observations in the rodent brain. Thus, caffeine restored the adenosine-induced decrease of both intrinsic membrane excitability and excitatory synaptic transmission in the human pyramidal neurons through antagonism of post-synaptic A1R. Indeed, the A1R-mediated effects of endogenous adenosine were more efficient to inhibit synaptic transmission than neuronal excitability. This was associated with a distinct affinity of caffeine for synaptic versus extra-synaptic human cortical A1R, probably resulting from a different molecular organization of A1R in human cortical synapses. These findings constitute the first neurophysiological description of the impact of caffeine on pyramidal neuron excitability and excitatory synaptic transmission in the human temporal cortex, providing adequate ground for the effects of caffeine on cognition in humans.

  6. Flexibility and variability in lexicon usage among Yoruba-speaking Nigerian outpatients with schizophrenia: a controlled study.

    Science.gov (United States)

    Adewuya, Abiola O; Adewuya, Abiodun O

    2008-01-01

    The studies on language dysfunction in schizophrenia are few, inconclusive and have all been done in the western culture. There may be cross-cultural and cross-lingual differences in problems with speeches of patients with schizophrenia. This study aims to examine the flexibility or variability in the use of words among a group of Nigerian patients with schizophrenia compared with healthy controls. The spoken samples of 48 outpatients with schizophrenia and 48 matched controls were assessed using the mean segmental type-token ratio (MSTTR). The sociodemographic and clinical variables of the patients with schizophrenia were also compared with their MSTTR scores. The MSTTR score for the patients with schizophrenia was significantly lower compared with that of healthy controls (p < 0.001). The factors independently associated with a lower MSTTR in patients with schizophrenia include younger age at onset of illness, presence of negative formal thought disorder and simple or hebephrenic subtype of schizophrenia. The problem with flexibility and variability in lexicon usage among patients with schizophrenia is a cross-cultural phenomenon. The MSTTR may have value in predicting clinical judgements of thought disorder or in identifying deviant language. These may have broad potentials for application in longitudinal and pathogenetic studies of schizophrenia. (c) 2008 S. Karger AG, Basel.

  7. Fragile X mental retardation protein controls synaptic vesicle exocytosis by modulating N-type calcium channel density

    Science.gov (United States)

    Ferron, Laurent; Nieto-Rostro, Manuela; Cassidy, John S.; Dolphin, Annette C.

    2014-04-01

    Fragile X syndrome (FXS), the most common heritable form of mental retardation, is characterized by synaptic dysfunction. Synaptic transmission depends critically on presynaptic calcium entry via voltage-gated calcium (CaV) channels. Here we show that the functional expression of neuronal N-type CaV channels (CaV2.2) is regulated by fragile X mental retardation protein (FMRP). We find that FMRP knockdown in dorsal root ganglion neurons increases CaV channel density in somata and in presynaptic terminals. We then show that FMRP controls CaV2.2 surface expression by targeting the channels to the proteasome for degradation. The interaction between FMRP and CaV2.2 occurs between the carboxy-terminal domain of FMRP and domains of CaV2.2 known to interact with the neurotransmitter release machinery. Finally, we show that FMRP controls synaptic exocytosis via CaV2.2 channels. Our data indicate that FMRP is a potent regulator of presynaptic activity, and its loss is likely to contribute to synaptic dysfunction in FXS.

  8. Mechanisms of translation control underlying long-lasting synaptic plasticity and the consolidation of long-term memory.

    Science.gov (United States)

    Santini, Emanuela; Huynh, Thu N; Klann, Eric

    2014-01-01

    The complexity of memory formation and its persistence is a phenomenon that has been studied intensely for centuries. Memory exists in many forms and is stored in various brain regions. Generally speaking, memories are reorganized into broadly distributed cortical networks over time through systems level consolidation. At the cellular level, storage of information is believed to initially occur via altered synaptic strength by processes such as long-term potentiation. New protein synthesis is required for long-lasting synaptic plasticity as well as for the formation of long-term memory. The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of cap-dependent protein synthesis and is required for numerous forms of long-lasting synaptic plasticity and long-term memory. As such, the study of mTORC1 and protein factors that control translation initiation and elongation has enhanced our understanding of how the process of protein synthesis is regulated during memory formation. Herein we discuss the molecular mechanisms that regulate protein synthesis as well as pharmacological and genetic manipulations that demonstrate the requirement for proper translational control in long-lasting synaptic plasticity and long-term memory formation. © 2014 Elsevier Inc. All rights reserved.

  9. Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls.

    Science.gov (United States)

    Matsuzaka, Camila T; Christofolini, Denise; Ota, Vanessa K; Gadelha, Ary; Berberian, Arthur A; Noto, Cristiano; Mazzotti, Diego R; Spindola, Leticia M; Moretti, Patricia N; Smith, Marilia A C; Melaragno, Maria I; Belangero, Sintia I; Bressan, Rodrigo A

    2017-01-01

    Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs. We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype*group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients. These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.

  10. Catechol-O-methyltransferase (COMT polymorphisms modulate working memory in individuals with schizophrenia and healthy controls

    Directory of Open Access Journals (Sweden)

    Camila T. Matsuzaka

    2017-03-01

    Full Text Available Objective: Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC. It is hypothesized that functional single nucleotide polymorphism (SNP rs4680 of the catechol-O-methyltransferase (COMT gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. Methods: We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680 in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs were selected. The Visual Working Memory (VWM Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs. Results: We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599 exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype*group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients. Conclusion: These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.

  11. Dendritic mechanisms controlling the threshold and timing requirement of synaptic plasticity.

    Science.gov (United States)

    Zhao, Cuiping; Wang, Lang; Netoff, Theoden; Yuan, Li-Lian

    2011-03-01

    Active conductances located and operating on neuronal dendrites are expected to regulate synaptic integration and plasticity. We investigate how Kv4.2-mediated A-type K(+) channels and Ca(2+) -activated K(+) channels are involved in the induction process of Hebbian-type plasticity that requires correlated pre- and postsynaptic activities. In CA1 pyramidal neurons, robust long-term potentiation (LTP) induced by a theta burst pairing protocol usually occurred within a narrow window during which incoming synaptic potentials coincided with postsynaptic depolarization. Elimination of dendritic A-type K(+) currents in Kv4.2(-/-) mice, however, resulted in an expanded time window, making the induction of synaptic potentiation less dependent on the temporal relation of pre- and postsynaptic activity. For the other type of synaptic plasticity, long-term depression, the threshold was significantly increased in Kv4.2(-/-) mice. This shift in depression threshold was restored to normal when the appropriate amount of internal free calcium was chelated during induction. In concert with A-type channels, Ca(2+) -activated K(+) channels also exerted a sliding effect on synaptic plasticity. Blocking these channels in Kv4.2(-/-) mice resulted in an even larger potentiation while by contrast, the depression threshold was shifted further. In conclusion, dendritic A-type and Ca(2+) -activated K(+) channels dually regulate the timing-dependence and thresholds of synaptic plasticity in an additive way. Copyright © 2010 Wiley-Liss, Inc.

  12. Investigating consummatory and anticipatory pleasure across motivation deficits in schizophrenia and healthy controls.

    Science.gov (United States)

    Da Silva, Susana; Saperia, Sarah; Siddiqui, Ishraq; Fervaha, Gagan; Agid, Ofer; Daskalakis, Z Jeff; Ravindran, Arun; Voineskos, Aristotle N; Zakzanis, Konstantine K; Remington, Gary; Foussias, George

    2017-08-01

    Anhedonia has traditionally been considered a characteristic feature of schizophrenia, but the true nature of this deficit remains elusive. This study sought to investigate consummatory and anticipatory pleasure as it relates to motivation deficits. Eighty-four outpatients with schizophrenia and 81 healthy controls were administered the Temporal Experience of Pleasure Scale (TEPS), as well as a battery of clinical and cognitive assessments. Multivariate analyses of variance were used to examine the experience of pleasure as a function of diagnosis, and across levels of motivation deficits (i.e. low vs. moderate. vs. high) in schizophrenia. Hierarchical regression analyses were also conducted to evaluate the predictive value of amotivation in relation to the TEPS. There were no significant differences between schizophrenia and healthy control groups for either consummatory or anticipatory pleasure. Within the schizophrenia patients, only those with high levels of amotivation were significantly impaired in consummatory and anticipatory pleasure compared to low and moderate groups, and compared to healthy controls. Further, our results revealed that amotivation significantly predicts both consummatory and anticipatory pleasure, with no independent contribution of group. Utilizing study samples with a wide range of motivation deficits and incorporating objective paradigms may provide a more comprehensive understanding of hedonic deficits. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  13. Morphometrical and morphological analysis of lateral ventricles in schizophrenia patients versus healthy controls.

    Science.gov (United States)

    Meduri, Mario; Bramanti, Placido; Ielitro, Giuseppe; Favaloro, Angelo; Milardi, Demetrio; Cutroneo, Giuseppina; Muscatello, Maria Rosaria Anna; Bruno, Antonio; Micò, Umberto; Pandolfo, Gianluca; La Torre, Diletta; Vaccarino, Gianluigi; Anastasi, Giuseppe

    2010-07-30

    The goal of this report was to highlight lateral ventricle morphology and volume differences between schizophrenia patients and matched controls. Subjects identified as suitable for analysis comprised 15 schizophrenia patients and 15 healthy subjects. The method applied is three-dimensional (3D) volume rendering starting from structural magnetic resonance imaging (MRI) studies of selected ventricular regions. Differences between groups relative to the global ventricular system and its subdivisions were found. Total lateral ventricle volume, right ventricle volume and left ventricle volume were all higher in schizophrenia patients than in controls; unilateral differences between the two groups were also outlined (right ventricle volume>left ventricle volume in schizophrenia patients vs. healthy subjects). Furthermore, occipital and frontal horn enlargement was found in schizophrenia patients compared with normal controls, but the difference in the temporal horn was not statistically significant. A substantial difference was noted in lateral ventricle morphology between the two groups. Our findings were consistent with the literature and may shed light on some of the discrepancies in previous reports on differences in lateral ventricle volume enlargement. Copyright 2010. Published by Elsevier Ireland Ltd.

  14. Suicide risk in placebo vs active treatment in placebo-controlled trials for schizophrenia

    NARCIS (Netherlands)

    Storosum, Jitschak G.; van Zwieten, Barbara J.; Wohlfarth, Tamar; de Haan, Lieuwe; Khan, Arif; van den Brink, Wim

    2003-01-01

    Background: If there is an increased risk of suicide in the placebo arms of placebo-controlled studies in patients with schizophrenia, it would be a strong ethical argument against the conduct of placebo-controlled studies in this patient population. We tested whether the risk of suicide and

  15. Toxoplasmosis gondii and schizophrenia: a case control study in a low Toxoplasma gondii seroprevalence Mexican population

    Science.gov (United States)

    There are conflicting reports concerning the association of T. gondii infection and schizophrenia. Therefore, we determined such association in a Mexican population of Mestizo ethnicity. Through a case-control study design, 50 schizophrenic patients and 150 control subjects matched by gender, age, r...

  16. Turing mechanism for homeostatic control of synaptic density during C. elegans growth

    Science.gov (United States)

    Brooks, Heather A.; Bressloff, Paul C.

    2017-07-01

    We propose a mechanism for the homeostatic control of synapses along the ventral cord of Caenorhabditis elegans during development, based on a form of Turing pattern formation on a growing domain. C. elegans is an important animal model for understanding cellular mechanisms underlying learning and memory. Our mathematical model consists of two interacting chemical species, where one is passively diffusing and the other is actively trafficked by molecular motors, which switch between forward and backward moving states (bidirectional transport). This differs significantly from the standard mechanism for Turing pattern formation based on the interaction between fast and slow diffusing species. We derive evolution equations for the chemical concentrations on a slowly growing one-dimensional domain, and use numerical simulations to demonstrate the insertion of new concentration peaks as the length increases. Taking the passive component to be the protein kinase CaMKII and the active component to be the glutamate receptor GLR-1, we interpret the concentration peaks as sites of new synapses along the length of C. elegans, and thus show how the density of synaptic sites can be maintained.

  17. Fetal growth and schizophrenia: a nested case-control and case-sibling study.

    Science.gov (United States)

    Nielsen, Philip Rising; Mortensen, Preben Bo; Dalman, Christina; Henriksen, Tine Brink; Pedersen, Marianne Giørtz; Pedersen, Carsten Bøcker; Agerbo, Esben

    2013-11-01

    The association between low birth weight and schizophrenia has been suggested by many studies. Small for gestational age (SGA) is a measure used as a proxy for intrauterine growth restriction. We aim to examine if children who are born SGA are at increased risk of developing schizophrenia and whether an association may be explained by factors shared among siblings. We linked 3 population-based registers: the Danish National Medical Birth Register, the Danish Psychiatric Central Register, and the Danish Civil Registration register to identify all persons born between 1978 and 2000. A nested case-control study and a case-sibling study design were used. There were 4650 cases of schizophrenia. Incidence rate ratios (IRRs) were estimated using conditional logistic regression. SGA was defined as the lowest 10th birth weight percentile for a given sex and gestational age. SGA was associated with an IRR of 1.23 (95% CI: 1.11-1.37) for schizophrenia in the case-control study. An IRR of 1.28 (95% CI: 0.97-1.68) was found in the case-sibling study. There is a modest association between SGA and schizophrenia. Our results indicate that this association is due to an independent effect of factors associated with low birth weight for gestational age per se, rather than other factors shared by siblings.

  18. Attention, motor control and motor imagery in schizophrenia: implications for the role of the parietal cortex.

    Science.gov (United States)

    Danckert, James; Saoud, Mohamed; Maruff, Paul

    2004-10-01

    Many recent models of schizophrenia have attempted to explain the so-called first-rank symptoms in terms of a breakdown in the self-monitoring of thoughts and behaviours. These models have focused on the most common symptom of schizophrenia auditory hallucinations-suggesting that they may represent disordered self-monitoring of internal speech. As such, much attention has been given to the role of the temporal and frontal cortices in the clinical presentation of patients with schizophrenia. In this review, we examine the role of the posterior parietal cortex (PPC) in schizophrenia within the context of recent models of self-monitoring deficits in these patients. Attentional dysfunctions and certain impairments of motor control and motor imagery all point towards the involvement of the parietal cortex in the disorder. In particular, we suggest that patients experiencing passivity phenomena (e.g., delusions of control) may have particular impairments of parietal function related to poor utilisation of forward models of intended actions. We also present a novel hypothesis that suggests differential impairments of the left and right parietal cortices in schizophrenia may help explain many of the first-rank symptoms of the disorder.

  19. The Complement Control-Related Genes CSMD1 and CSMD2 Associate to Schizophrenia

    DEFF Research Database (Denmark)

    Håvik, Bjarte; Le Hellard, Stephanie; Rietschel, Marcella

    2011-01-01

    BACKGROUND: Patients with schizophrenia often suffer from cognitive dysfunction, including impaired learning and memory. We recently demonstrated that long-term potentiation in rat hippocampus, a mechanistic model of learning and memory, is linked to gene expression changes in immunity......-related processes involved in complement activity and antigen presentation. We therefore aimed to examine whether key regulators of these processes are genetic susceptibility factors in schizophrenia. METHODS: Analysis of genetic association was based on data mining of genotypes from a German genome......-wide association study and a multiplex GoldenGate tag single nucleotide polymorphism (SNP)-based assay of Norwegian and Danish case-control samples (Scandinavian Collaboration on Psychiatric Etiology), including 1133 patients with schizophrenia and 2444 healthy control subjects. RESULTS: Allelic associations were...

  20. Improving prefrontal cortex function in schizophrenia through focused training of cognitive control

    Directory of Open Access Journals (Sweden)

    Bethany G Edwards

    2010-04-01

    Full Text Available Previous research has shown that individuals with schizophrenia show deficits in cognitive control functions thought to depend on the lateral prefrontal cortex (PFC, and its interactions with related regions. The current study explored the effects of instructed strategy training on improving cognitive control functioning in patients with schizophrenia. Event-related fMRI was used to test whether effects of such training were associated with changes in brain activity dynamics during task performance. Patients with schizophrenia (N=22 performed the AX-CPT cognitive control task in two-sessions, with the first occurring pre-training and second following strategy training. The training protocol emphasized direct encoding of contextual cues and updating response selection goals in accordance with cue information. A matched group of healthy controls (N=14 underwent the same protocol but were only scanned in the pre-training session. In the pre-training session, patients exhibited behavioral evidence of impaired utilization of contextual cue information, along with reduced cue-related activity – but increased activation during probe and response periods – in a network of regions associated with cognitive control, centered on the lateral PFC. Following training, this pattern of activation dynamics significantly shifted, normalizing towards the pattern observed in controls. These activation effects were associated with both clinical symptoms and behavioral performance improvements. The results suggest that focused strategy training may facilitate cognitive task performance in patients with schizophrenia by changing the dynamics of activity within critical control-related brain regions.

  1. Hunger States Control the Directions of Synaptic Plasticity via Switching Cell Type-Specific Subunits of NMDA Receptors.

    Science.gov (United States)

    Qi, Yong; Yang, Yunlei

    2015-09-23

    It remains largely unknown whether and how hunger states control activity-dependent synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD). We here report that both LTP and LTD of excitatory synaptic strength within the appetite control circuits residing in hypothalamic arcuate nucleus (ARC) behave in a manner of hunger states dependence and cell type specificity. For instance, we find that tetanic stimulation induces LTP at orexigenic agouti-related protein (AgRP) neurons in ad libitum fed mice, whereas it induces LTD in food-deprived mice. In an opposite direction, the same induction protocol induces LTD at anorexigenic pro-opiomelanocortin (POMC) neurons in fed mice but weak LTP in deprived mice. Mechanistically, we also find that food deprivation increases the expressions of NR2C/NR2D/NR3-containing NMDA receptors (NMDARs) at AgRP neurons that contribute to the inductions of LTD, whereas it decreases their expressions at POMC neurons. Collectively, our data reveal that hunger states control the directions of activity-dependent synaptic plasticity by switching NMDA receptor subpopulations in a cell type-specific manner, providing insights into NMDAR-mediated interactions between energy states and associative memory. Significance statement: Based on the experiments performed in this study, we demonstrate that activity-dependent synaptic plasticity is also under the control of energy states by regulating NMDAR subpopulations in a cell type-specific manner. We thus propose a reversible memory configuration constructed from energy states-dependent cell type-specific bidirectional conversions of LTP and LTD. Together with the distinct functional roles played by NMDAR signaling in the control of food intake and energy states, these findings reveal a new reciprocal interaction between energy states and associative memory, one that might serve as a target for therapeutic treatments of the energy-related memory disorders or vice versa

  2. Role of the origin of glutamatergic synaptic inputs in controlling synaptic plasticity and its modulation by alcohol in mice nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Gilles Erwann Martin

    2015-07-01

    Full Text Available It is widely accepted that long-lasting changes of synaptic strength in the nucleus accumbens, a brain region involved in drug reward, mediate acute and chronic effects of alcohol. However, our understanding of the mechanisms underlying the effects of alcohol on synaptic plasticity is limited by the fact that the nucleus accumbens receives glutamatergic inputs from distinct brain regions (e.g. the prefrontal cortex, the amygdala and the hippocampus, each region providing different information (e.g. spatial, emotional and cognitive. Combining whole-cell patch-clamp recordings and the optogenetic technique, we examined synaptic plasticity, and its regulation by alcohol, at cortical, hippocampal and amygdala inputs in fresh slices of mouse tissue. We showed that the origin of synaptic inputs determines the basic properties of glutamatergic synaptic transmission, the expression of spike-timing dependent long-term depression (tLTD and long-term potentiation (tLTP and their regulation by alcohol. While we observed both tLTP and tLTD at amygadala and hippocampal synapses, we showed that cortical inputs only undergo tLTD. Functionally, we provide evidence that acute EtOH has little effects on higher order information coming from the prefrontal cortex (PFCx, while severely impacting the ability of emotional and contextual information to induce long-lasting changes of synaptic strength.

  3. Effects of endurance training on brain structures in chronic schizophrenia patients and healthy controls.

    Science.gov (United States)

    Malchow, Berend; Keeser, Daniel; Keller, Katriona; Hasan, Alkomiet; Rauchmann, Boris-Stephan; Kimura, Hiroshi; Schneider-Axmann, Thomas; Dechent, Peter; Gruber, Oliver; Ertl-Wagner, Birgit; Honer, William G; Hillmer-Vogel, Ursula; Schmitt, Andrea; Wobrock, Thomas; Niklas, Andree; Falkai, Peter

    2016-06-01

    The objective of this longitudinal magnetic resonance (MR) imaging study was to examine the effects of endurance training on hippocampal and grey matter volumes in schizophrenia patients and healthy controls. 20 chronic schizophrenia patients and 21 age- and gender-matched healthy controls underwent 3months of endurance training (30min, 3 times per week). 19 additionally recruited schizophrenia patients played table soccer ("foosball" in the USA) over the same period. MR imaging with 3D-volumetric T1-weighted sequences was performed on a 3T MR scanner at baseline, after 6weeks and after the 3-month intervention and 3 additional training-free months. In addition to voxel-based morphometry (VBM), we performed manual and automatic delineation of the hippocampus and its substructures. Endurance capacity and psychopathological symptoms were measured as secondary endpoints. No significant increases in the volumes of the hippocampus or hippocampal substructures were observed in schizophrenia patients or healthy controls. However, VBM analyses displayed an increased volume of the left superior, middle and inferior anterior temporal gyri compared to baseline in schizophrenia patients after the endurance training, whereas patients playing table soccer showed increased volumes in the motor and anterior cingulate cortices. After the additional training-free period, the differences were no longer present. While endurance capacity improved in exercising patients and healthy controls, psychopathological symptoms did not significantly change. The subtle changes in the left temporal cortex indicate an impact of exercise on brain volumes in schizophrenia. Subsequent studies in larger cohorts are warranted to address the question of response variability of endurance training. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Cortactin Is a Regulator of Activity-Dependent Synaptic Plasticity Controlled by Wingless.

    Science.gov (United States)

    Alicea, Daniel; Perez, Marizabeth; Maldonado, Carolina; Dominicci-Cotto, Carihann; Marie, Bruno

    2017-02-22

    Major signaling molecules initially characterized as key early developmental regulators are also essential for the plasticity of the nervous system. Previously, the Wingless (Wg)/Wnt pathway was shown to underlie the structural and electrophysiological changes during activity-dependent synaptic plasticity at the Drosophila neuromuscular junction. A challenge remains to understand how this signal mediates the cellular changes underlying this plasticity. Here, we focus on the actin regulator Cortactin, a major organizer of protrusion, membrane mobility, and invasiveness, and define its new role in synaptic plasticity. We show that Cortactin is present presynaptically and postsynaptically at the Drosophila NMJ and that it is a presynaptic regulator of rapid activity-dependent modifications in synaptic structure. Furthermore, animals lacking presynaptic Cortactin show a decrease in spontaneous release frequency, and presynaptic Cortactin is necessary for the rapid potentiation of spontaneous release frequency that takes place during activity-dependent plasticity. Most interestingly, Cortactin levels increase at stimulated synaptic terminals and this increase requires neuronal activity, de novo transcription and depends on Wg/Wnt expression. Because it is not simply the presence of Cortactin in the presynaptic terminal but its increase that is necessary for the full range of activity-dependent plasticity, we conclude that it probably plays a direct and important role in the regulation of this process. SIGNIFICANCE STATEMENT In the nervous system, changes in activity that lead to modifications in synaptic structure and function are referred to as synaptic plasticity and are thought to be the basis of learning and memory. The secreted Wingless/Wnt molecule is a potent regulator of synaptic plasticity in both vertebrates and invertebrates. Understanding the molecular mechanisms that underlie these plastic changes is a major gap in our knowledge. Here, we identify a

  5. Transcriptional Control of Synaptic Plasticity by Transcription Factor NF-κB

    Science.gov (United States)

    Engelmann, Christian; Haenold, Ronny

    2016-01-01

    Activation of nuclear factor kappa B (NF-κB) transcription factors is required for the induction of synaptic plasticity and memory formation. All components of this signaling pathway are localized at synapses, and transcriptionally active NF-κB dimers move to the nucleus to translate synaptic signals into altered gene expression. Neuron-specific inhibition results in altered connectivity of excitatory and inhibitory synapses and functionally in selective learning deficits. Recent research on transgenic mice with impaired or hyperactivated NF-κB gave important insights into plasticity-related target gene expression that is regulated by NF-κB. In this minireview, we update the available data on the role of this transcription factor for learning and memory formation and comment on cross-sectional activation of NF-κB in the aged and diseased brain that may directly or indirectly affect κB-dependent transcription of synaptic genes. PMID:26881128

  6. Karolinska Scales of Personality, cognition and psychotic symptoms in patients with schizophrenia and healthy controls.

    Science.gov (United States)

    Nilsson, Björn Mikael; Holm, Gunnar; Ekselius, Lisa

    2016-01-01

    Studies on both personality dimensions and cognition in schizophrenia are scarce. The objective of the present study was to examine personality traits and the relation to cognitive function and psychotic symptoms in a sample of patients with schizophrenia and healthy controls. In total 23 patients with schizophrenia and 14 controls were assessed with the Karolinska Scales of Personality (KSP). A broad cognitive test programme was used, including the Wechsler Adult Intelligence Scales, the Finger-Tapping Test, the Trail Making Test, the Verbal Fluency Test, the Benton Visual Retention Test, the Wisconsin Card Sorting Test and Rey Auditory Verbal Learning Test . Compared with controls, the patients exhibited prominent elevations on KSP scales measuring anxiety proneness and neuroticism (P = 0.000005-0.0001), on the Detachment scale (P Aggression, Suspicion, Guilt and Irritability scales (P = 0.002-0.03) while the remaining five scales did not differ between patients and controls. KSP anxiety-related scales correlated with the Positive and Negative Symptoms Scale (PANSS) general psychopathology subscale. Cognitive test results were uniformly lower in the patient group and correlated with PANSS negative symptoms subscale. There was no association between KSP scale scores and PANSS positive or negative symptoms. The patients revealed a highly discriminative KSP test profile with elevated scores in neuroticism- and psychoticism-related scales as compared to controls. Results support previous findings utilizing other personality inventories in patients with schizophrenia. Cognitive test performance correlated inversely with negative symptoms.

  7. Depersonalization in patients with schizophrenia spectrum disorders, first-degree relatives and normal controls.

    Science.gov (United States)

    Gonzalez-Torres, Miguel Angel; Inchausti, Lucía; Aristegui, Maialen; Ibañez, Berta; Diez, Luis; Fernandez-Rivas, Aranzazu; Bustamante, Sonia; Haidar, Karim; Rodríguez-Zabaleta, Maier; Mingo, Argiñe

    2010-01-01

    Depersonalization occurs in healthy individuals and across a broad range of psychiatric patients. Data on depersonalization in persons linked to patients through genetics, environment or education are scarce. Due to their higher risk of developing psychosis, first-degree healthy relatives might show differences with the general population. This study examines depersonalization in patients with schizophrenia or schizophrenia spectrum disorders, their first-degree healthy relatives and normal controls. The Cambridge Depersonalization Scale was used to measure depersonalization in a sample of 147 clinically stable patients with schizophrenia or schizophrenia spectrum disorders, 73 first-degree relatives with no psychiatric history and 172 healthy controls. Mixed effect models were used to account for both the familial structure of the data and the effect of sociodemographic characteristics. Patients obtained higher scores than relatives and controls for frequency and duration of depersonalization experiences, number of items responded positively and total depersonalization, while first-degree relatives obtained lower scores than patients and controls for all these characteristics. First-degree relatives of patients reported fewer episodes of depersonalization, which were less intense and of shorter duration, than healthy controls. This finding might be related to a protection mechanism that keeps first-degree relatives away from near-psychotic experiences. The nature of such a mechanism remains to be discovered. 2010 S. Karger AG, Basel.

  8. Differential effects of cannabis dependence on cortical inhibition in patients with schizophrenia and non-psychiatric controls.

    Science.gov (United States)

    Goodman, Michelle S; Bridgman, Alanna C; Rabin, Rachel A; Blumberger, Daniel M; Rajji, Tarek K; Daskalakis, Zafiris J; George, Tony P; Barr, Mera S

    Cannabis is the most commonly used illicit substance among patients with schizophrenia. Cannabis exacerbates psychotic symptoms and leads to poor functional outcomes. Dysfunctional cortical inhibition has been implicated in the pathophysiology of schizophrenia; however, the effects of cannabis on this mechanism have been relatively unexamined. The goal of this study was to index cortical inhibition from the motor cortex among 4 groups: schizophrenia patients and non-psychiatric controls dependent on cannabis as well as cannabis-free schizophrenia patients and non-psychiatric controls. In this cross-sectional study, GABA-mediated cortical inhibition was index with single- and paired-pulse transcranial magnetic stimulation (TMS) paradigms to the left motor cortex in 12 cannabis dependent and 11 cannabis-free schizophrenia patients, and in 10 cannabis dependent and 13 cannabis-free controls. Cannabis-dependent patients with schizophrenia displayed greater short-interval cortical inhibition (SICI) compared to cannabis-free schizophrenia patients (p = 0.029), while cannabis-dependent controls displayed reduced SICI compared to cannabis-free controls (p = 0.004). SICI did not differ between cannabis dependent patients and cannabis-free controls, or between dependent schizophrenia patients compared to dependent controls. No significant differences were found for long-interval cortical inhibition (LICI) or intra-cortical facilitation (ICF) receptor function, suggesting a selective effect on SICI. These findings suggest that cannabis dependence may have selective and differing effects on SICI in schizophrenia patients compared to controls, which may provide insight into the pathophysiology of co-morbid cannabis dependence in schizophrenia. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Pregabalin for anxiety in patients with schizophrenia - A randomized, double-blind placebo-controlled study

    DEFF Research Database (Denmark)

    Schjerning, Ole; Damkier, Per; Lykkegaard, Signe Engelhardt

    2017-01-01

    INTRODUCTION: Anxiety is frequent in patients with schizophrenia and poses a major impact on patients perceived quality of life, daily functioning and risk of suicide. Pregabalin has shown effective in the treatment of generalized anxiety disorder and has been suggested for the treatment of anxiety...... in patients with schizophrenia. As evidence is sparse regarding treatment of anxiety in this patient group, we aimed to investigate the use of pregabalin for anxiety in patients with schizophrenia. METHODS: A randomized, double-blind placebo controlled study was used. Patients were randomized to either...... placebo or pregabalin (≤600mg/d) as add-on treatment. Primary analyses were intention-to-treat based with change in Hamilton Anxiety Scale after 4 and 8weeks of treatment as primary outcome. Secondary outcomes were change in psychopathology, quality-of-life, cognitive functioning and sleep. The study used...

  10. A Meta-Analysis of Controlled Research on Social Skills Training for Schizophrenia

    Science.gov (United States)

    Kurtz, Matthew M.; Mueser, Kim T.

    2008-01-01

    A meta-analysis of randomized, controlled trials of social skills training for schizophrenia was conducted. Outcome measures from 22 studies including 1,521 clients were categorized according to a proximal-distal continuum in relation to the presumed site of action of skills training interventions, with content mastery tests and performance-based…

  11. Schizophrenia Spectrum and Attention-Deficit/Hyperactivity Disorder Symptoms in Autism Spectrum Disorder and Controls

    Science.gov (United States)

    Gadow, Kenneth D.

    2012-01-01

    Objective: This study compared the differential severity of specific symptoms of schizophrenia spectrum disorder (SSD) in children with autism spectrum disorder (ASD) and child psychiatry outpatient referrals (controls). Each group was further subdivided into subgroups with and without co-occurring attention-deficit/hyperactivity disorder (ADHD).…

  12. Kynurenine 3-monooxygenase polymorphisms: relevance for kynurenic acid synthesis in patients with schizophrenia and healthy controls

    DEFF Research Database (Denmark)

    Holtze, Maria; Saetre, Peter; Engberg, Göran

    2012-01-01

    on the activity of kynurenine 3-monooxygenase (KMO), the enzyme converting kynurenine to 3-hydroxykynurenine. Methods: We analyzed the association between KMO gene polymorphisms and CSF concentrations of KYNA in patients with schizophrenia and healthy controls. Fifteen single nucleotide polymorphisms (SNPs) were...

  13. A systematic review of controlled interventions to reduce overweight and obesity for people with schizophrenia

    DEFF Research Database (Denmark)

    Hjorth, P.; Davidsen, A.S.; Killian, R.

    2014-01-01

    with schizophrenia. METHOD: A systematic literature search was carried out in the bibliographic databases PubMed (MEDLINE), Embase (Ovid), PsycInfo (Ovid) and Cinahl (Ebsco). We included all randomised and non-randomised clinically controlled studies that compared a non-pharmacological intervention, aimed at weight...

  14. Synaptic control of the shape of the motoneuron pool input-output function.

    Science.gov (United States)

    Powers, Randall K; Heckman, Charles J

    2017-03-01

    Although motoneurons have often been considered to be fairly linear transducers of synaptic input, recent evidence suggests that strong persistent inward currents (PICs) in motoneurons allow neuromodulatory and inhibitory synaptic inputs to induce large nonlinearities in the relation between the level of excitatory input and motor output. To try to estimate the possible extent of this nonlinearity, we developed a pool of model motoneurons designed to replicate the characteristics of motoneuron input-output properties measured in medial gastrocnemius motoneurons in the decerebrate cat with voltage-clamp and current-clamp techniques. We drove the model pool with a range of synaptic inputs consisting of various mixtures of excitation, inhibition, and neuromodulation. We then looked at the relation between excitatory drive and total pool output. Our results revealed that the PICs not only enhance gain but also induce a strong nonlinearity in the relation between the average firing rate of the motoneuron pool and the level of excitatory input. The relation between the total simulated force output and input was somewhat more linear because of higher force outputs in later-recruited units. We also found that the nonlinearity can be increased by increasing neuromodulatory input and/or balanced inhibitory input and minimized by a reciprocal, push-pull pattern of inhibition. We consider the possibility that a flexible input-output function may allow motor output to be tuned to match the widely varying demands of the normal motor repertoire. NEW & NOTEWORTHY Motoneuron activity is generally considered to reflect the level of excitatory drive. However, the activation of voltage-dependent intrinsic conductances can distort the relation between excitatory drive and the total output of a pool of motoneurons. Using a pool of realistic motoneuron models, we show that pool output can be a highly nonlinear function of synaptic input but linearity can be achieved through adjusting the

  15. Can repetitive magnetic stimulation improve cognition in schizophrenia? Pilot data from a randomized controlled trial.

    Science.gov (United States)

    Barr, Mera S; Farzan, Faranak; Rajji, Tarek K; Voineskos, Aristotle N; Blumberger, Daniel M; Arenovich, Tamara; Fitzgerald, Paul B; Daskalakis, Zafiris J

    2013-03-15

    Working memory represents a core cognitive domain that is impaired in schizophrenia for which there are currently no satisfactory treatments. Repetitive transcranial magnetic stimulation (rTMS) targeted over the dorsolateral prefrontal cortex has been shown to modulate neurophysiological mechanisms linked to working memory in schizophrenia and improves working memory performance in healthy subjects and might therefore represent a treatment modality for schizophrenia patients. The objectives were to evaluate the effects of rTMS on working memory performance in schizophrenia patients and evaluate whether rTMS normalizes performance to healthy subject levels. In a 4-week randomized double-blind sham-controlled pilot study design, 27 medicated schizophrenia patients were tested at the Centre for Addiction and Mental Health (a university teaching hospital that provides psychiatric care to a large urban catchment area and serves as a tertiary referral center for the province of Ontario). Patients performed the verbal working memory n-back task before and after rTMS magnetic resonance image targeted bilaterally sequentially to left and right dorsolateral prefrontal cortex 750 pulses/side at 20 Hz for 20 treatments. The main outcome measure was mean magnitude of change in the n-back accuracy for target responses with active (n = 13) or sham (n = 12) rTMS treatment course. The rTMS significantly improved 3-back accuracy for targets compared with placebo sham (Cohen's d = .92). The improvement in 3-back accuracy was also found to be at a level comparable to healthy subjects. These pilot data suggest that bilateral rTMS might be a novel, efficacious, and safe treatment for working memory deficits in patients with schizophrenia. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Synapse pathology and translational applications for schizophrenia.

    Science.gov (United States)

    Hayashi-Takagi, Akiko

    2017-01-01

    Schizophrenia is a chronic, severe, and disabling brain disorder, with an estimated lifetime prevalence of 0.7%. Despite its relatively low prevalence, the onset of schizophrenia usually occurs early in life, resulting in a severe lifelong disability for patients and increasing the economic and care burden on their families. This makes schizophrenia one of the most catastrophic mental illnesses. Although the etiology of schizophrenia remains poorly understood, clinical, genetic, and pharmacological studies have indicated that its pathophysiology involves synaptic disturbances. Here, I review the evidence suggesting synaptic disturbance as the causal pathophysiology of schizophrenia and discuss the possible application of synaptic intervention as a novel therapeutic strategy for schizophrenia. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  17. Morbidity profile of first-degree relatives of probands with schizophrenia: a comparison with mood disorder and healthy control.

    Science.gov (United States)

    Okewole, Adeniran O; Adewuya, Abiodun O; Makanjuola, Roger O A; Owoeye, Olugbenga A

    2015-03-01

    There is a paucity of data on heritability of psychotic disorders in Africa. The study aimed to investigate morbid risk of schizophrenia and mood disorder among first-degree relatives of schizophrenia probands, compared with mood disorder and healthy controls. The study examined 330 first-degree relatives of probands with schizophrenia (n = 50), 350 first-degree relatives of probands with mood disorder (n = 50) and 387 first-degree relatives of healthy control (n = 50). The Schedules for Clinical Assessment in Neuropsychiatry, SCAN was used to ascertain diagnosis in ill subjects. To each subject, a socio-demographic questionnaire was administered. Family history was obtained using the Family History Schedule. Morbid risk estimates were calculated using the Weinberg shorter method. There was a significant difference between the mean age of relatives of schizophrenia probands compared to mood disorder (p = 0.01, 95 % CI 1.34-9.61) and healthy control (p schizophrenia probands and the number of children of normal control (p schizophrenia probands compared to normal control (p = 0.04, 95 % CI 0.01-0.94). Finally, there was a significant difference between the number of first-degree relatives of schizophrenia probands compared to the number of first-degree relatives of healthy control who were below the age of risk for schizophrenia (p = 0.01, 95 % CI -0.12 to -1.27). Morbid risks of 4.38 and 0.39 were obtained for schizophrenia among first-degree relatives of probands with schizophrenia and mood disorder, while first-degree relatives of probands with schizophrenia, mood disorder and healthy control had morbid risks for mood disorder of 0.42, 3.82 and 0.35, respectively. The study revealed excess mortality among first-degree relatives of schizophrenia patients. First-degree relatives of probands with schizophrenia and mood disorder also had higher morbid risks for these psychotic conditions than healthy control with some measure of overlap between the

  18. Prevalences of autoimmune diseases in schizophrenia, bipolar I and II disorder, and controls.

    Science.gov (United States)

    Cremaschi, Laura; Kardell, Mathias; Johansson, Viktoria; Isgren, Anniella; Sellgren, Carl M; Altamura, A Carlo; Hultman, Christina M; Landén, Mikael

    2017-12-01

    Previous studies on the relationship between autoimmune diseases, schizophrenia, and bipolar disorder are mainly based on hospital discharge registers with insufficient coverage of outpatient data. Furthermore, data is scant on the prevalence of autoimmune diseases in bipolar subgroups. Here we estimate the self-reported prevalences of autoimmune diseases in schizophrenia, bipolar disorder type I and II, and controls. Lifetime prevalence of autoimmune diseases was assessed through a structured interview in a sample of 9076 patients (schizophrenia N = 5278, bipolar disorder type I N = 1952, type II N = 1846) and 6485 controls. Comparative analyses were performed using logistic regressions. The prevalence of diabetes type 1 did not differ between groups. Hyperthyroidism, hypothyroidism regardless of lithium effects, rheumatoid arthritis, and polymyalgia rheumatica were most common in bipolar disorder. Systemic lupus erythematosus was less common in bipolar disorder than in the other groups. The rate of autoimmune diseases did not differ significantly between bipolar subgroups. We conclude that prevalences of autoimmune diseases show clear differences between schizophrenia and bipolar disorder, but not between the bipolar subgroups. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Examining frontotemporal connectivity and rTMS in healthy controls: implications for auditory hallucinations in schizophrenia.

    Science.gov (United States)

    Gromann, Paula M; Tracy, Derek K; Giampietro, Vincent; Brammer, Michael J; Krabbendam, Lydia; Shergill, Sukhwinder S

    2012-01-01

    Repetitive transcranial magnetic stimulation (rTMS) has been shown to have clinically beneficial effects in altering the perception of auditory hallucinations (AH) in patients with schizophrenia. However, the mode of action is not clear. Recent neuroimaging findings indicate that rTMS has the potential to induce not only local effects but also changes in remote, functionally connected brain regions. Frontotemporal dysconnectivity has been proposed as a mechanism leading to psychotic symptoms in schizophrenia. The current study examines functional connectivity between temporal and frontal brain regions after rTMS and the implications for AH in schizophrenia. A connectivity analysis was conducted on the fMRI data of 11 healthy controls receiving rTMS, compared with 11 matched subjects receiving sham TMS, to the temporoparietal junction, before engaging in a task associated with robust frontotemporal activation. Compared to the control group, the rTMS group showed an altered frontotemporal connectivity with stronger connectivity between the right temporoparietal cortex and the dorsolateral prefrontal cortex and the angular gyrus. This finding provides preliminary evidence for the hypothesis that normalizing the functional connectivity between the temporoparietal and frontal brain regions may underlie the therapeutic effect of rTMS on AH in schizophrenia.

  20. A Placebo-Controlled Study of Raloxifene Added to Risperidone in Men with Chronic Schizophrenia.

    Science.gov (United States)

    Khodaie-Ardakani, Mohammad-Reza; Khosravi, Mohsen; Zarinfard, Razieh; Nejati, Somayeh; Mohsenian, Ali; Tabrizi, Mina; Akhondzadeh, Shahin

    2015-01-01

    Selective estrogen receptor modulators (SERMs) such as raloxifene have already shown beneficial effects on negative, positive and general psychopathology symptoms in postmenopausal women with schizophrenia. The purpose of the present investigation was to assess the efficacy of raloxifene as an adjuvant agent in the treatment of men with chronic schizophrenia in an 8-week double-blind and placebo-controlled trial. In a randomized, double-blind and placebo-controlled study, forty-six male patients diagnosed with schizophrenia (DSM-IV-TR), were randomized to either raloxifene (120 mg/day) or placebo in addition to risperidone (6 mg/day) for eight weeks. The assessment was performed using the positive and negative symptom scale (PANSS) at baseline, and at weeks 2, 4, 6 and 8. Extrapyramidal symptom rating scale (ESRS) at baseline, weeks 1, 2, 4, 6, 8 and Hamilton depression rating scale (HDRS) at baseline and week 8 were also used to assess extrapyramidal symptoms and depression simultaneously. Forty-two patients completed the trial. The raloxifene group showed significantly greater improvement on the negative subscale (Praloxifene as a potential adjunctive treatment strategy for chronic schizophrenia in men.

  1. Psychiatrist's adherence: a new factor in relapse prevention of schizophrenia. A randomized controlled study on relapse control through telemedicine system.

    Science.gov (United States)

    Spaniel, F; Novak, T; Bankovska Motlova, L; Capkova, J; Slovakova, A; Trancik, P; Matejka, M; Höschl, C

    2015-12-01

    Exposure to psychotic states has detrimental effects on the long-term outcome of schizophrenia and brain integrity. Therefore, improving relapse prevention is a key component of long-term management of schizophrenia. Previous studies using continuous monitoring of an individual's early signs of relapse and adopting preventative pharmacological interventions, when early signs are detected, showed promising clinical results in terms of relapse risk reduction. This 18-month multi-centre parallel randomized controlled, open label, trial with telemedicine relapse prevention programme ITAREPS failed to show superiority of maintenance plus prodrome-based targeted medication strategy over treatment as usual. The study, marked by low investigator's adherence, confirmed that absence of pharmacological intervention at early stage of prodrome, critically influenced the risk of relapse. This and previous randomized controlled trials with telemedicine programme ITAREPS suggested that substantial improvement in relapse prevention in schizophrenia is likely to be unattainable under current clinical settings. Future preventive strategies in schizophrenia would require rapid pharmacological intervention upon occurrence of subclinical prodromal symptoms that are undetectable under conventional outpatient practice. Studies with ITAREPS suggested that integration of telemedicine relapse prevention systems and visiting nurse service might together represent practical solution capable to address those requirements. The Information Technology Aided Relapse Prevention Programme in Schizophrenia (ITAREPS) presents a telemedicine solution for weekly monitoring and management of schizophrenia. This study aims to evaluate the effectiveness of the programme in reducing the number of hospitalizations during the 18-month multi-centre parallel randomized controlled, open label, trial. Outpatients with schizophrenia or schizoaffective disorder were randomized to the active (n = 74) or control group

  2. Interaural Level Difference Dependent Gain Control and Synaptic Scaling Underlying Binaural Computation

    OpenAIRE

    Xiong, Xiaorui R.; Liang, Feixue; Li, Haifu; Mesik, Lukas; Zhang, Ke K.; Polley, Daniel B.; Tao, Huizhong W.; Xiao, Zhongju; Zhang, Li I.

    2013-01-01

    Binaural integration in the central nucleus of inferior colliculus (ICC) plays a critical role in sound localization. However, its arithmetic nature and underlying synaptic mechanisms remain unclear. Here, we showed in mouse ICC neurons that the contralateral dominance is created by a “push-pull”-like mechanism, with contralaterally dominant excitation and more bilaterally balanced inhibition. Importantly, binaural spiking response is generated apparently from an ipsilaterally-mediated scalin...

  3. UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis

    Directory of Open Access Journals (Sweden)

    Jiandong Sun

    2015-07-01

    Full Text Available Gated solely by activity-induced changes in intracellular calcium, small-conductance potassium channels (SKs are critical for a variety of functions in the CNS, from learning and memory to rhythmic activity and sleep. While there is a wealth of information on SK2 gating, kinetics, and Ca2+ sensitivity, little is known regarding the regulation of SK2 subcellular localization. We report here that synaptic SK2 levels are regulated by the E3 ubiquitin ligase UBE3A, whose deficiency results in Angelman syndrome and overexpression in increased risk of autistic spectrum disorder. UBE3A directly ubiquitinates SK2 in the C-terminal domain, which facilitates endocytosis. In UBE3A-deficient mice, increased postsynaptic SK2 levels result in decreased NMDA receptor activation, thereby impairing hippocampal long-term synaptic plasticity. Impairments in both synaptic plasticity and fear conditioning memory in UBE3A-deficient mice are significantly ameliorated by blocking SK2. These results elucidate a mechanism by which UBE3A directly influences cognitive function.

  4. Attitudes toward Placebo-Controlled Clinical Trials of Patients with Schizophrenia in Japan.

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    Norio Sugawara

    Full Text Available Although the use of placebo in clinical trials of schizophrenia patients is controversial because of medical and ethical concerns, placebo-controlled clinical trials are commonly used in the licensing of new drugs.The objective of this study was to assess the attitudes toward placebo-controlled clinical trials among patients with schizophrenia in Japan.Using a cross-sectional design, we recruited patients (n = 251 aged 47.7±13.2 (mean±SD with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were admitted to six psychiatric hospitals from December 2013 to March 2014. We employed a 14-item questionnaire specifically developed to survey patients' attitudes toward placebo-controlled clinical trials.The results indicated that 33% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for improvement of disease, a guarantee of hospital treatment continuation, and encouragement by family or friends were associated with the willingness to participate in such trials, whereas a belief of additional time required for medical examinations was associated with non-participation.Fewer than half of the respondents stated that they would be willing to participate in placebo-controlled clinical trials. Therefore, interpreting the results from placebo-controlled clinical trials could be negatively affected by selection bias.

  5. Olanzapine versus Placebo in Adolescents with Schizophrenia; a 6-Week, Randomized Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Kryzhanovskaya, Ludmila; Schulz, Charles; McDougle, Christopher; Frazier, Jean; Dittman, Ralf; Robertson-Plouch, Carol; Bauer, Theresa; Xu, Wen; Wang, Wei; Carlson, Janice; Tohen, Mauricio

    2009-01-01

    The efficacy of olanzapine in treating schizophrenia was tested through a placebo-controlled trial involving one hundred seven inpatient and outpatients adolescents. Patients who took olanzapine experienced significant symptom improvement.

  6. Working memory and processing speed training in schizophrenia: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Cassetta, Briana D; Goghari, Vina M

    2016-01-26

    In most domains of cognition, individuals with schizophrenia are generally found to be one standard deviation below the mean of the controls. As a result, examining the impact of cognitive remediation in individuals with schizophrenia has been a burgeoning area of research. However, the state of the literature remains unclear as to which domains of cognition should be targeted to produce the most widespread and durable benefits for individuals with schizophrenia. One suggestion is that targeting lower-level cognitive processes that are important for higher-level and more complex aspects of cognition may produce the most widespread benefits in cognition and everyday functioning. Relatively few studies have examined the effects of working memory or processing speed training in schizophrenia, as most studies examine broad-based remediation programs. Thus, a need exists for targeted working memory and processing speed training studies to better understand the mechanisms of cognitive enhancement in patients. This study aims to 1) investigate near-transfer gains (that is, the transfer of learning to related contexts) associated with working memory and processing speed training in schizophrenia patients; 2) investigate far-transfer gains (that is, the transfer of learning to new contexts) associated with working memory and processing speed training (that is, gains in other neurocognitive domains and social cognition); and 3) investigate real-world gains associated with training (that is, gains in daily functioning). A double-blind randomized controlled trial with a three parallel group design will be conducted. A random sample of 81 patients with schizophrenia or schizoaffective disorder will be recruited through outpatient clinics at Foothills Hospital and community support programs in Calgary, Alberta. Participants will be randomly assigned using a computer-generated program in a 1:1:1 ratio to a working memory-training group, a processing speed-training group, or a no

  7. Cigarette smoking and cognitive function in Chinese male schizophrenia: a case-control study.

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    Xiang Yang Zhang

    Full Text Available Schizophrenic patients have higher smoking rates than the general population. Studies show that smoking may be a form of self-medication in an attempt to alleviate cognitive deficits in schizophrenic patients of European background. This study examined the relationships between smoking and cognitive deficits in Chinese schizophrenic patients, which have previously received little systemic study. We recruited 580 male chronic patients meeting DSM-IV criteria for schizophrenia and 175 male control subjects who were matched on age and education. The subjects completed a detailed cigarette smoking questionnaire, the Fagerstrom Test for Nicotine Dependence (FTND, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS. Patients also were rated on the Positive and Negative Symptom Scale (PANSS, the Simpson and Angus Extrapyramidal Symptom Rating Scale (SAES, and the Abnormal Involuntary Movement Scale (AIMS. All five RBANS subscales except for the Visuospatial/Constructional index showed significantly lower cognitive performance for schizophrenics than normal controls. The schizophrenic smokers scored lower than the schizophrenic non-smokers on the RBANS total score and the Visuospatial/Constructional and Immediate Memory indices. Similarly, the control smokers scored lower than the control non-smokers on the RBANS total score and the Immediate Memory index . Also, the schizophrenic smokers consistently performed the poorest on the cognitive domains of the RBANS. Among the schizophrenic patients, smokers displayed significantly fewer negative symptoms than non-smokers. Using multivariate regression analysis the following variables were independently associated with the RBANS total score: years of education, PANSS negative symptom score, age at schizophrenia onset, and number of hospitalizations. Our results show that smoking is associated with significant cognitive impairment in both schizophrenic patients and normal controls

  8. Reversible optical switching memristors with tunable STDP synaptic plasticity: a route to hierarchical control in artificial intelligent systems.

    Science.gov (United States)

    Jaafar, Ayoub H; Gray, Robert J; Verrelli, Emanuele; O'Neill, Mary; Kelly, Stephen M; Kemp, Neil T

    2017-11-09

    Optical control of memristors opens the route to new applications in optoelectronic switching and neuromorphic computing. Motivated by the need for reversible and latched optical switching we report on the development of a memristor with electronic properties tunable and switchable by wavelength and polarization specific light. The device consists of an optically active azobenzene polymer, poly(disperse red 1 acrylate), overlaying a forest of vertically aligned ZnO nanorods. Illumination induces trans-cis isomerization of the azobenzene molecules, which expands or contracts the polymer layer and alters the resistance of the off/on states, their ratio and retention time. The reversible optical effect enables dynamic control of a memristor's learning properties including control of synaptic potentiation and depression, optical switching between short-term and long-term memory and optical modulation of the synaptic efficacy via spike timing dependent plasticity. The work opens the route to the dynamic patterning of memristor networks both spatially and temporally by light, thus allowing the development of new optically reconfigurable neural networks and adaptive electronic circuits.

  9. Association of SNPs in EGR3 and ARC with Schizophrenia Supports a Biological Pathway for Schizophrenia Risk.

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    Matthew J Huentelman

    Full Text Available We have previously hypothesized a biological pathway of activity-dependent synaptic plasticity proteins that addresses the dual genetic and environmental contributions to schizophrenia. Accordingly, variations in the immediate early gene EGR3, and its target ARC, should influence schizophrenia susceptibility. We used a pooled Next-Generation Sequencing approach to identify variants across these genes in U.S. populations of European (EU and African (AA descent. Three EGR3 and one ARC SNP were selected and genotyped for validation, and three SNPs were tested for association in a replication cohort. In the EU group of 386 schizophrenia cases and 150 controls EGR3 SNP rs1877670 and ARC SNP rs35900184 showed significant associations (p = 0.0078 and p = 0.0275, respectively. In the AA group of 185 cases and 50 controls, only the ARC SNP revealed significant association (p = 0.0448. The ARC SNP did not show association in the Han Chinese (CH population. However, combining the EU, AA, and CH groups revealed a highly significant association of ARC SNP rs35900184 (p = 2.353 x 10(-7; OR [95% CI] = 1.54 [1.310-1.820]. These findings support previously reported associations between EGR3 and schizophrenia. Moreover, this is the first report associating an ARC SNP with schizophrenia and supports recent large-scale GWAS findings implicating the ARC complex in schizophrenia risk. These results support the need for further investigation of the proposed pathway of environmentally responsive, synaptic plasticity-related, schizophrenia genes.

  10. UNC-18 and Tomosyn Antagonistically Control Synaptic Vesicle Priming Downstream of UNC-13 in Caenorhabditis elegans.

    Science.gov (United States)

    Park, Seungmee; Bin, Na-Ryum; Yu, Bin; Wong, Raymond; Sitarska, Ewa; Sugita, Kyoko; Ma, Ke; Xu, Junjie; Tien, Chi-Wei; Algouneh, Arash; Turlova, Ekaterina; Wang, Siyan; Siriya, Pranay; Shahid, Waleed; Kalia, Lorraine; Feng, Zhong-Ping; Monnier, Philippe P; Sun, Hong-Shuo; Zhen, Mei; Gao, Shangbang; Rizo, Josep; Sugita, Shuzo

    2017-09-06

    Munc18-1/UNC-18 is believed to prime SNARE-mediated membrane fusion, yet the underlying mechanisms remain enigmatic. Here, we examine how potential gain-of-function mutations of Munc18-1/UNC-18 affect locomotory behavior and synaptic transmission, and how Munc18-1-mediated priming is related to Munc13-1/UNC-13 and Tomosyn/TOM-1, positive and negative SNARE regulators, respectively. We show that a Munc18-1(P335A)/UNC-18(P334A) mutation leads to significantly increased locomotory activity and acetylcholine release in Caenorhabditis elegans, as well as enhanced synaptic neurotransmission in cultured mammalian neurons. Importantly, similar to tom-1 null mutants, unc-18(P334A) mutants partially bypass the requirement of UNC-13. Moreover, unc-18(P334A) and tom-1 null mutations confer a strong synergy in suppressing the phenotypes of unc-13 mutants. Through biochemical experiments, we demonstrate that Munc18-1(P335A) exhibits enhanced activity in SNARE complex formation as well as in binding to the preformed SNARE complex, and partially bypasses the Munc13-1 requirement in liposome fusion assays. Our results indicate that Munc18-1/UNC-18 primes vesicle fusion downstream of Munc13-1/UNC-13 by templating SNARE complex assembly and acts antagonistically with Tomosyn/TOM-1.SIGNIFICANCE STATEMENT At presynaptic sites, SNARE-mediated membrane fusion is tightly regulated by several key proteins including Munc18/UNC-18, Munc13/UNC-13, and Tomosyn/TOM-1. However, how these proteins interact with each other to achieve the precise regulation of neurotransmitter release remains largely unclear. Using Caenorhabditis elegans as an in vivo model, we found that a gain-of-function mutant of UNC-18 increases locomotory activity and synaptic acetylcholine release, that it partially bypasses the requirement of UNC-13 for release, and that this bypass is synergistically augmented by the lack of TOM-1. We also elucidated the biochemical basis for the gain-of-function caused by this mutation

  11. The effects of oxytocin on fear recognition in patients with schizophrenia and in healthy controls

    Directory of Open Access Journals (Sweden)

    Meytal eFischer-Shofty

    2013-07-01

    Full Text Available Individuals who suffer from schizophrenia often show a marked deficit in recognition of emotional facial expressions, as part of broader impairment of social cognition. Research has shown that recognition of negative emotions, specifically fear recognition, is particularly impaired among patients with schizophrenia. Recently we reported that intranasal administration of OT (IN OT increased the ability to correctly recognize fear in a group of healthy men. The aim of the current study was to examine the effects of IN OT administration on fear recognition among patients with schizophrenia. Based on previous research, we also sought to examine a possible selective effect of OT dependent on baseline performance, hypothesizing that IN OT would have a greater enhancement effect on less proficient individuals. It was thus hypothesized that patients will show more improvement in fear recognition following the administration of IN OT as compared to controls. Sixty six participants (31 schizophrenia patients, 35 healthy controls were enrolled in the current study. All participants received treatment of a single dose of 24 IU IN OT and an equivalent amount of placebo, one week apart. The participants’ ability to accurately recognize fear and happiness was evaluated using a face morphing task. Overall, as a group, both patients and healthy control participants were more accurate in recognizing fearful facial expressions, but not happy faces, following IN OT administration, as compared to their performance following placebo. IN OT did not differentially affect emotion recognition in patients and healthy controls. Yet, the results indicated a selective effect for IN OT, in which the hormone improves fear recognition only among individuals whose baseline performance was below the median, regardless of their psychiatric status.

  12. Personalized smoking environment cue reactivity in smokers with schizophrenia and controls: a pilot study

    OpenAIRE

    AhnAllen, Christopher G.; Tidey, Jennifer W.

    2011-01-01

    Exposure to smoking cues increases craving to smoke and negatively changes mood in smokers with schizophrenia (SWS). This pilot study compared reactivity to real-world smoking environments versus neutral environments in SWS (n = 10) and non-psychiatric control smokers (CON; n = 10). Results indicate that both SWS and CON experienced increases in smoking urges when viewing images of their smoking environments and that SWS tended to report greater increases in withdrawal-related negative mood t...

  13. Pre-synaptic control of remote fear extinction in the neocortex

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    Gisella eVetere

    2012-06-01

    Full Text Available Consolidation of remote memory enhances immediate early genes induction (IEGs, augments the expression of the presynaptic growth associated protein 43 (GAP-43, and increases the density and size of dendritic spines in anterior cingulate (aCC and infra-limbic (ILC cortices. Remote memory extinction, however, does not uniformly alter consolidation-induced structural changes. In the aCC, the density, but not the size, of spines is reset to pseudo-conditioning levels while novel thin spines are formed in the ILC. Whether IEGs and GAP-43 also undergo region-specific changes upon remote memory extinction is undetermined. Here we confirm in the same batch of mice that c-Fos induction and GAP-43 expression are increased in both the aCC and the ILC 36 days after contextual fear conditioning. We then show that, in both regions, remote memory extinction is associated with decrease of c-Fos induction but no change in GAP-43 expression thus revealing similar, although protein-specific, pre-synaptic adaptations in aCC and ILC neurons. These observations, in addition to our previous report of region-specific post-synaptic structural changes, disclose a complex pattern of extinction-driven neocortical alterations suitable to support erasure or reinstatement of fear according to the environment demand.

  14. A randomized, controlled trial of computer-assisted cognitive remediation for schizophrenia.

    Science.gov (United States)

    Dickinson, Dwight; Tenhula, Wendy; Morris, Sarah; Brown, Clayton; Peer, Jason; Spencer, Katrina; Li, Lan; Gold, James M; Bellack, Alan S

    2010-02-01

    There is considerable interest in cognitive remediation for schizophrenia, but its essential components are still unclear. The goal of the current study was to develop a broadly targeted computer-assisted cognitive remediation program and conduct a rigorous clinical trial in a large group of schizophrenia patients. Sixty-nine people with schizophrenia or schizoaffective disorder were randomly assigned to 36 sessions of computer-assisted cognitive remediation or an active control condition. Remediation broadly targeted cognitive and everyday performance by providing supportive, graduated training and practice in selecting, executing, and monitoring cognitive operations. It used engaging computer-based cognitive exercises and one-on-one training. A total of 61 individuals (34 in remediation group, 27 in control group) engaged in treatment, completed posttreatment assessments, and were included in intent-to-treat analyses. Primary outcomes were remediation exercise metrics, neuropsychological composites (episodic memory, working memory, attention, executive functioning, and processing speed), and proxy measures of community functioning. Regression modeling indicated that performance on eight of 10 exercise metrics improved significantly more in the remediation condition than in the control condition. The mean effect size, favoring the remediation condition, was 0.53 across all 10 metrics. However, there were no significant benefits of cognitive remediation on any neuropsychological or functional outcome measure, either immediately after treatment or at the 3-month follow-up. Cognitive remediation for people with schizophrenia was effective in improving performance on computer exercises, but the benefits of training did not generalize to broader neuropsychological or functional outcome measures. The evidence for this treatment approach remains mixed.

  15. Synaptic Plasticity and Translation Initiation

    Science.gov (United States)

    Klann, Eric; Antion, Marcia D.; Banko, Jessica L.; Hou, Lingfei

    2004-01-01

    It is widely accepted that protein synthesis, including local protein synthesis at synapses, is required for several forms of synaptic plasticity. Local protein synthesis enables synapses to control synaptic strength independent of the cell body via rapid protein production from pre-existing mRNA. Therefore, regulation of translation initiation is…

  16. Oxidative stress in schizophrenia: a case-control study on the effects on social cognition and neurocognition.

    Science.gov (United States)

    Gonzalez-Liencres, Cristina; Tas, Cumhur; Brown, Elliot C; Erdin, Soner; Onur, Ece; Cubukcoglu, Zeynep; Aydemir, Omer; Esen-Danaci, Aysen; Brüne, Martin

    2014-09-24

    Schizophrenia is a debilitating mental disorder that presents impairments in neurocognition and social cognition. Several studies have suggested that the etiology of schizophrenia can be partly explained by oxidative stress. However, our knowledge about the implications of oxidative stress on illness-related cognitive deficits is still far from being clear. The aim of this work was to study the role of oxidative stress molecules on social cognition and neurocognition in patients with schizophrenia. We assessed the peripheral levels of several molecules associated with oxidative stress, namely nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), homocysteine, superoxide dismutase (SOD) and neurotrophin 4/5 (NT4/5), in forty-one patients with schizophrenia and forty-three healthy participants. A battery of tests to measure neurocognition and social cognition was also administered to the schizophrenia group. We found that the schizophrenia group presented substantially higher levels of oxidative stress than the control group, as revealed by elevated quantities of the pro-oxidants NO and MDA, and decreased levels of the antioxidants GSH, SOD and NT4/5. Interestingly, the levels of NT4/5, which have been shown to have antioxidant effects, correlated with executive functioning, as measured by two distinct tests (WCST and TMT). However, social cognition and symptom severity were not found to be associated with oxidative stress. We propose a protective role of NT4/5 against oxidative stress, which appears to have a potentially beneficial impact on neurocognition in schizophrenia.

  17. Effects of Extended Cannabis Abstinence on Cognitive Outcomes in Cannabis Dependent Patients with Schizophrenia vs Non-Psychiatric Controls.

    Science.gov (United States)

    Rabin, Rachel A; Barr, Mera S; Goodman, Michelle S; Herman, Yarissa; Zakzanis, Konstantine K; Kish, Stephen J; Kiang, Michael; Remington, Gary; George, Tony P

    2017-10-01

    Cross-sectional studies of the effects of cannabis on cognition in schizophrenia have produced mixed results. Heavy and persistent cannabis use in schizophrenia is a common clinical problem, and effects of controlled abstinence from cannabis in these patients have not been carefully evaluated. The present study sought to determine the effects of cannabis abstinence on cognition in patients with schizophrenia and co-occurring cannabis dependence. We utilized a 28-day cannabis abstinence paradigm to investigate the state-dependent effects of cannabis on select cognitive outcomes in cannabis-dependent patients with schizophrenia and non-psychiatric controls. Nineteen patients and 20 non-psychiatric male cannabis-dependent participants underwent 28 days of cannabis abstinence. Cognition was assessed on day 0, 14, and 28 using a comprehensive neuropsychological battery. Clinical symptoms were assessed weekly. Abstinence was facilitated by contingency reinforcement confirmed by twice weekly urinalysis. Forty-two percent of patients and 55% of controls achieved end-point abstinence (p=0.53), which was biochemically-verified (day 28 urinary THC-COOH schizophrenia-abstainers demonstrated improvements in Hopkins Verbal Learning Test-Revised (HVLT-R) performance over time [F(2,14)=4.73, pschizophrenia and control subjects with cannabis abstinence, but larger more definitive studies are needed. Our findings underscore the importance of developing effective interventions for cannabis use disorders in schizophrenia.

  18. A Case-Control Study of the Association between Polymorphisms in the Fibrinogen Alpha Chain Gene and Schizophrenia

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    Wenwang Rao

    2017-01-01

    Full Text Available Our previous studies using the mass spectrum analysis provided evidence that fibrinopeptide A (FPA could be a potential biomarker for schizophrenia diagnosis. We sought further to demonstrate that variants in the fibrinogen alpha chain gene (FGA coded FPA might confer vulnerability to schizophrenia. 1,145 patients with schizophrenia and 1,016 healthy volunteers from the Han population in Northeast China were recruited. The association of three tag single nucleotide polymorphisms (SNPs (rs2070011 in the 5′UTR, rs2070016 in intron 4, and rs2070022 in the 3′UTR in FGA and schizophrenia was examined using a case-control study design. Genotypic distributions of these three SNPs were not found to be significantly different between cases and controls (rs2070011: χ2=1.28, P=0.528; rs2070016: χ2=4.11, P=0.128; rs2070022: χ2=1.23, P=0.541. There were also no significant differences in SNP allelic frequencies between cases and controls (all P>0.05. Additionally, the frequency of haplotypes consisting of alleles of these three SNPs was not significantly different between cases and healthy control subjects (global χ2=9.27, P=0.159. Our study did not show a significant association of FGA SNPs with schizophrenia. Future studies may need to test more FGA SNPs in a larger sample to identify those SNPs with a minor or moderate effect on schizophrenia.

  19. Effectiveness of humor intervention for patients with schizophrenia: a randomized controlled trial.

    Science.gov (United States)

    Cai, Chunfeng; Yu, Liping; Rong, Lan; Zhong, Hanling

    2014-12-01

    The primary aim of this pilot study was to evaluate the possible therapeutic effects of a 10-session humor intervention program in improving rehabilitative outcomes and the effects of the intervention on patients' sense of humor among patients with schizophrenia. Thirty subjects were randomly assigned into either the intervention (humor skill training) group (n = 15) or the control (doing handwork) group (n = 15). The results were analyzed using descriptive statistics, t-tests and ANOVA. Repeated measures analysis of variance (ANOVA) tests were conducted to examine the differences across conditions and time. A group by time interaction effect was observed on all of the outcomes, except positive symptoms of PANSS. The time main effect was also significant on the total score (p humor skill training in a mental health service can improve rehabilitative outcomes and sense of humor for schizophrenia patients who were in the rehabilitation stage. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Controlling the spotlight of attention: visual span size and flexibility in schizophrenia.

    Science.gov (United States)

    Elahipanah, Ava; Christensen, Bruce K; Reingold, Eyal M

    2011-10-01

    The current study investigated the size and flexible control of visual span among patients with schizophrenia during visual search performance. Visual span is the region of the visual field from which one extracts information during a single eye fixation, and a larger visual span size is linked to more efficient search performance. Therefore, a reduced visual span may explain patients' impaired performance on search tasks. The gaze-contingent moving window paradigm was used to estimate the visual span size of patients and healthy participants while they performed two different search tasks. In addition, changes in visual span size were measured as a function of two manipulations of task difficulty: target-distractor similarity and stimulus familiarity. Patients with schizophrenia searched more slowly across both tasks and conditions. Patients also demonstrated smaller visual span sizes on the easier search condition in each task. Moreover, healthy controls' visual span size increased as target discriminability or distractor familiarity increased. This modulation of visual span size, however, was reduced or not observed among patients. The implications of the present findings, with regard to previously reported visual search deficits, and other functional and structural abnormalities associated with schizophrenia, are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Progressive muscle relaxation in persons with schizophrenia: a systematic review of randomized controlled trials.

    Science.gov (United States)

    Vancampfort, Davy; Correll, Christoph U; Scheewe, Thomas W; Probst, Michel; De Herdt, Amber; Knapen, Jan; De Hert, Marc

    2013-04-01

    The aim of this systematic review was to assess the effectiveness of progressive muscle relaxation on psychological distress and anxiety symptoms and on response/remission for people with schizophrenia. Randomized controlled trials were considered if they investigated progressive muscle relaxation in patients with schizophrenia. EMBASE, PsycINFO, PubMed, ISI Web of Science, CINAHL, PEDro and Cochrane Library were searched. The selection of studies, data extraction and quality assessment were performed independently by two reviewers. Three randomized controlled trials involving 146 patients met the inclusion criteria. Progressive muscle relaxation can acutely reduce state anxiety and psychological distress and improve subjective well-being. No studies investigated the evidence for progressive muscle relaxation as an add-on treatment for general psychopathology and for positive or negative symptoms. Also, no studies assessed the value of progressive muscle relaxation in longer-term treatment and for relapse prevention. There were no data to draw any conclusions about progressive muscle relaxation in comparison with other treatment modalities. None of the studies encountered adverse events. Dose-response relationships could not be determined. Progressive muscle relaxation might be a useful add-on treatment to reduce state anxiety and psychological distress and improve subjective well-being in persons with schizophrenia.

  2. A Placebo-Controlled Study of Raloxifene Added to Risperidone in Men with Chronic Schizophrenia.

    Directory of Open Access Journals (Sweden)

    Mohammad-Reza Khodaie-Ardakani

    2015-06-01

    Full Text Available Selective estrogen receptor modulators (SERMs such as raloxifene have already shown beneficial effects on negative, positive and general psychopathology symptoms in postmenopausal women with schizophrenia. The purpose of the present investigation was to assess the efficacy of raloxifene as an adjuvant agent in the treatment of men with chronic schizophrenia in an 8-week double-blind and placebo-controlled trial. In a randomized, double-blind and placebo-controlled study, forty-six male patients diagnosed with schizophrenia (DSM-IV-TR, were randomized to either raloxifene (120 mg/day or placebo in addition to risperidone (6 mg/day for eight weeks. The assessment was performed using the positive and negative symptom scale (PANSS at baseline, and at weeks 2, 4, 6 and 8. Extrapyramidal symptom rating scale (ESRS at baseline, weeks 1, 2, 4, 6, 8 and Hamilton depression rating scale (HDRS at baseline and week 8 were also used to assess extrapyramidal symptoms and depression simultaneously. Forty-two patients completed the trial. The raloxifene group showed significantly greater improvement on the negative subscale (P<0.001, the general psychopathology subscale (P=0.002 and total PANSS score (P<0.001 in comparison to the placebo group at the endpoint. There was no significant difference in the reduction of positive symptoms score between the two group (P=0.525. Extrapyramidal symptom rating scale and Hamilton depression rating scale and frequency of other adverse effects were comparable between two groups.This study indicates raloxifene as a potential adjunctive treatment strategy for chronic schizophrenia in men.

  3. Early information processing deficit in schizophrenia. New findings using schizophrenic subgroups and manic control subjects.

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    Saccuzzo, D P; Braff, D L

    1981-02-01

    In recent years, the idea that schizophrenia involves a primary disturbance of the higher cognitive (ie, cortical) thinking processes has been challenged by investigators who have shown that there may be a primary disturbance in schizophrenia in the early stages of information processing that occurs during the first few hundred milliseconds after the stimulus reaches the sense organs. Among the hypothesized early information processing deficits are deficiencies in iconic storage (a brief peripheral memory store) and slowness of processing from iconic storage to a more permanent memory system. Three experiments were conducted using tachistoscopically presented stimuli in order to evaluate these two stages of information processing (iconic storage and speed of processing) in schizophrenic and control subjects. Results converged in supporting the hypothesis, that independent of iconic storage and sensory registration, slow information processing is a relatively stable deficit of schizophrenic patients with a poor prognosis. The schizophrenic patients with a good prognosis had a similar deficit, which was reversible. Results are discussed as they relate to the early information processing deficit theories of schizophrenia.

  4. Antipsychotic polypharmacy in clozapine resistant schizophrenia: a randomized controlled trial of tapering antipsychotic co-treatment

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    Jari Tiihonen

    2012-01-01

    Full Text Available There is a considerable disparity between clinical practice and recommendations based on meta-analyses of antipsychotic polypharmacy in clozapine resistant schizophrenia. For this reason, we investigated the clinical response to reducing the use olanzapine that had been previously added on clozapine treatment among seriously ill hospitalized patients. In a randomized controlled trial with crossover design, we studied volunteer patients (N = 15 who had olanzapine added on to clozapine in a state mental hospital. Clozapine monotherapy was just as effective as clozapine-olanzapine therapy, according to results from Clinical Global Impression Scale and Global Assessment of Functioning as primary outcome measures. Polypharmacy is widely used in treating schizophrenia, and usually, add-on medications are started because of worsening of the clinical state. A major confounding feature of these add-ons is whether observed improvements are caused by the medication or explained by the natural fluctuating course of the disorder. The present study, in spite of its small size, indicates the necessity of reconsidering the value of polypharmacy in treating schizophrenia.

  5. Imaging dopamine transmission in schizophrenia

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    Laruelle, M. [New York, Columbia Univ. College of Physicians and Surgeons, NY (United States). New York State Psychiatric Insitute. Brain Imaging Division

    1998-09-01

    Over the last ten years, several positron emission tomography (PET) and single photon computerized tomography (SPECT) studies of the dopamine (DA) system in patients with schizophrenia were performed to test the hypothesis that DA hyperactivity is associated with this illness. In this paper are reviewed the results of fifteen brain imaging studies comparing indices of DA function in drug naive or drug free patients with schizophrenia and healthy controls: thirteen studies included measurements of Da D{sub 2} receptor density, two studies compared amphetamine-induced DA release, and two studies measured DOPA decarboxylase activity, an enzyme involved in DA synthesis. It was conducted a meta-analysis of the studies measuring D{sub 2} receptor density parameters, under the assumption that all tracers labeled the same population of D{sub 2} receptors. This analysis revealed that, compared to healthy controls, patients with schizophrenia present a significant but mild elevation of D{sub 2} receptor density parameters and a significant larger variability of these indices. It was found no statistical evidence that studies performed with radiolabeled butyrophenones detected a larger increase in D{sub 2} receptor density parameters than studies performed with other radioligands, such as benzamides. Studies of presynaptic activity revealed an increase in DA transmission response to amphetamine challenge, and an increase in DOPA decarboxylase activity. Together, these data are compatible with both pre- and post-synaptic alterations of DA transmission in schizophrenia. Future studies should aim at a better characterization of these alterations, and at defining their role in the pathophysiology of the illness.

  6. Employment outcomes for people with schizophrenia spectrum disorder: A meta-analysis of randomized controlled trials.

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    Carmona, Viviana R; Gómez-Benito, Juana; Huedo-Medina, Tania B; Rojo, J Emilio

    2017-05-08

    Access to employment plays a critical role in the recovery and functioning of people with schizophrenia. We have investigated the effectiveness of treatments to enhance employment outcomes for people with schizophrenia and evaluated the potential moderators of these outcomes. A literature search was conducted in CINAHL, Cochrane Databases, MEDLINE, ProQuest XML, PsycINFO, Scopus, and Web of Science. Grey literature databases, references lists of the retrieved articles and specialized journals in the field were also inspected. Job placement, job tenure and wages earned were tested. Risk ratios were extracted for job placement and standardized mean differences were calculated for job tenure and wages earned. Twenty-five randomized controlled trials published between 1986 and December 2015 were analyzed. Engaging in a vocational intervention increases the likelihood of obtaining a competitive job (risk ratio (RR) = 2.31, 95% confidence interval (CI): 1.85-2.88) and has a positive impact on hours worked in any job (standardized mean difference (SMD) = 0.42, 95% CI: 0.16-0.68). There was no evidence of intervention efficacy with regard to wages earned from competitive employment. Participation in rehabilitative vocational treatment is not sufficient to ensure work participation for people with schizophrenia. Comprehensive treatments are necessary to address functional deficits that hinder labor stability and job performance for people with schizophrenia. Int J Occup Med Environ Health 2017;30(3):345-366. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  7. Event-related brain potentials to emotional images and gonadal steroid hormone levels in patients with schizophrenia and paired controls

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    Julie eChampagne

    2014-06-01

    Full Text Available Prominent disturbances in the experience, expression, and emotion recognition in patients with schizophrenia have been relatively well documented over the last few years. Furthermore, sex differences in behavior and brain activity, associated with the processing of various emotions, have been reported in the general population and in schizophrenia patients. Others proposed that sex differences should be rather attributed to testosterone, which may play a role in the etiology of schizophrenia. Also, it had been suggested that estradiol may play a protective role in schizophrenia. Surprisingly, few studies investigating this pathology have focused on both brain substrates and gonadal steroid hormone levels, in emotional processing. In the present study, we investigated electrocortical responses related to emotional valence and arousal as well as gonadal steroid hormone levels in patients with schizophrenia. Event-Related Potentials (ERP were recorded during exposition to emotional pictures in 18 patients with schizophrenia and in 24 control participants paired on intelligence, manual dominance and socioeconomic status. Given their previous sensitivity to emotional and attention processes, the P200, N200 and the P300 were selected for analysis. More precisely, emotional valence generally affects early components (N200, which reflect early process of selective attention, whereas emotional arousal and valence both influences the P300 component, which is related to memory context updating, and stimulus categorization. Results showed that, in the control group, the amplitude of the N200 was significantly more lateralized over the right hemisphere, while there was no such lateralization in patients with schizophrenia. In patients with schizophrenia, significantly smaller anterior P300 amplitude was observed to the unpleasant, compared to the pleasant. That anterior P300 reduction was also correlated with negative symptoms.

  8. Improving psychology students' attitudes toward people with schizophrenia: A quasi-randomized controlled study.

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    Magliano, Lorenza; Rinaldi, Angela; Costanzo, Regina; De Leo, Renata; Schioppa, Giustina; Petrillo, Miriam; Read, John

    2016-01-01

    Despite scientific evidence that the majority of people with schizophrenia (PWS) have personal histories of traumatic life events and adversities, their needs for psychological support often remain unmet. Poor availability of nonpharmacological therapies in schizophrenia may be partly because of professionals' attitudes toward people diagnosed with this disorder. As future health professionals, psychology students represent a target population for efforts to increase the probability that PWS will be offered effective psychological therapies. This quasi-randomized controlled study investigated the effect of an educational intervention, addressing common prejudices via scientific evidence and prerecorded audio-testimony from PWS, on the attitudes of psychology students toward PWS. Students in their fifth year of a master's degree in Psychology at the Second University of Naples, Italy were randomly assigned to an experimental group-which attended two 3-hr sessions a week apart-or to a control group. Compared with their baseline assessment, at 1-month reassessment the 76 educated students endorsed more psychosocial causes and more of them recommended psychologists in the treatment of schizophrenia. They were also more optimistic about recovery, less convinced that PWS are recognizable and unpredictable, and more convinced that treatments, pharmacological and psychological, are useful. No significant changes were found, from baseline to 1-month reassessment, in the 112 controls. At 1-month reassessment, educated students were more optimistic about recovery and less convinced that PWS are unpredictable than controls. These findings suggest that psychology students' attitudes toward PWS can be improved by training initiatives including education and indirect contact with users. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  9. Executive functions and cognitive deficits in schizophrenia: Comparisons between probands, parents and controls in India

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    Bhatia T

    2009-01-01

    Full Text Available Background: Cognitive impairment is said to be a core feature of schizophrenia. Executive function is an important cognitive domain. Aim: This study was undertaken to assess cognitive impairment among Indian patients with schizophrenia (Sz or schizoaffective disorder (SzA, compared with their parents and unaffected individuals (controls. Settings and Design: Executive functions as measured by Trail-making Test (TMT, of patients and their parents were compared with controls. The patients were recruited from the Outpatients′ Department (OPD of a government hospital. Materials and Methods: Patients diagnosed as Sz or SzA (n=172 and their parents (n=196: families n=132, 119 fathers and 77 mothers participated. We also included 120 persons with no history of psychiatric illness. Cognitive function was assessed with the TMT. The Information Score of the Post Graduate Institute Battery of Brain Dysfunction test, developed in India for Indian subjects was used as a proxy for general fixed knowledge. Statistical Analysis: Logistic and linear regression was used to compare cognitive deficits of cases, parents and controls. Results: Cases and their parents took significantly more time than controls on Part B of the TMT. There were no statistically significant differences between cases and parents on any of the TMT parameters. Using regression analysis, the most significant correlates of all TMT parameters among cases were with occurrence of auditory hallucinations and current age. Conclusion: Cases, as well as their parents showed more cognitive impairment than controls on the TMT.

  10. Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: a randomized, placebo-controlled trial.

    Science.gov (United States)

    Dickerson, Faith B; Stallings, Cassie; Origoni, Andrea; Katsafanas, Emily; Savage, Christina L G; Schweinfurth, Lucy A B; Goga, Joshana; Khushalani, Sunil; Yolken, Robert H

    2014-01-01

    A range of immune system abnormalities have been associated with schizophrenia. Probiotic compounds modulate the immune response and offer a potential treatment strategy for schizophrenia. Probiotic compounds have also been observed to improve gastrointestinal dysfunction, which is a common problem in individuals with schizophrenia. We performed a randomized, double-blind, placebo-controlled trial to examine whether probiotic supplementation can reduce symptom severity in patients with schizophrenia receiving antipsychotic treatment and also whether probiotics are associated with bowel functioning. Outpatients with schizophrenia (N = 65) meeting DSM-IV criteria and with at least moderately severe psychotic symptoms were enrolled in the study from December 2010-August 2012. Following a 2-week placebo run-in period, patients were randomly assigned to 14 weeks of double-blind adjunctive probiotic (combined Lactobacillus rhamnosus strain GG and Bifidobacterium animalis subsp. lactis strain Bb12) or placebo therapy. Psychiatric symptoms were assessed biweekly with the Positive and Negative Syndrome Scale (PANSS), and patients were queried weekly about their gastrointestinal functioning. Repeated-measures analysis of variance showed no significant differences in the PANSS total score between probiotic and placebo supplementation (F = 1.28, P = .25). However, patients in the probiotic group were less likely to develop severe bowel difficulty over the course of the trial (hazard ratio = 0.23; 95% CI, 0.09-0.61, P = .003). Probiotic supplementation may help prevent a common somatic symptom associated with schizophrenia. ClinicalTrials.gov identifier: NCT01242371.

  11. SNP8NRG433E1006 NEUREGULIN-1 GENETIC VARIATION IN BATAKS ETHNIC WITH SCHIZOPHRENIA PARANOID AND HEALTHY CONTROL

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    Elmeida Effendy

    2014-05-01

    Full Text Available The neuregulin 1 (NRG1 gene which influences the development of white matter connectivity has been associated with schizophrenia. It influences neuronal migration, synaptogenesis, gliogenesis, neuron-glia communication, myelination, and neurotransmission in the brain and others. NRG1 is located in 8p13, and it is frequently replicated in schizphrenia. SNP8NRG433E1006 gene NRG1 is one of core at risk haplotype of schizphrenia. This study looked forward differences SNP8NRG433E1006 neuregulin 1 between Bataks ethnic with schizophrenia paranoid and Bataks ethnic healthy control. Methods: Batak ethnic with schizophrenia paranoid were recruited and interviewed with semi-structured MINI ICD-X to establish the diagnosis. All the eligible subjects were requested their permission for blood sampling. Healthy Batak ethnic were also recruited by mathcing the age and gender. The blood samples went through DNA isolation, Nested PCR, and DNA sequencing. Results: Ninety three subjects were recruited, but only 74 blood samples were succesfully sequenced. We found three types of polymorphisms, i.e. G/A allele at base pair (bp 76, G/T allele at bp 112, and deletion at bp 110 in Batak ethnic with schizophrenia. There were two kind sequences at bp 113-116 in Batak ethnics, and Batak ethnics with ATCG were at higher risk for having schizophrenia. This study support that NRG1 is a schizophrenia-susceptibility gene.

  12. The Association between Intelligence Scores and Family History of Psychiatric Disorder in Schizophrenia Patients, Their Siblings and Healthy Controls

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    Verweij, Kim H. W.; Derks, Eske M.

    2013-01-01

    Background The degree of intellectual impairment in schizophrenia patients and their relatives has been suggested to be associated with the degree of familial loading for schizophrenia. Since other psychiatric disorders are also more present in relatives of schizophrenia patients, the definition of family history should be broadened. The association between family history for psychiatric disorder and intelligence scores was investigated in patients with non-affective psychosis, their unaffected siblings and controls. Methods A sample of 712 schizophrenia proband families (696 patients and 766 siblings) and 427 healthy control families (517 subjects) participated in this study. Family history of psychiatric disorder was determined while excluding the data of the participating schizophrenia patient. A dichotomous division was made between families with no first- or second degree relative with psychiatric disorder and families with one or more affected relatives. Total intelligence scores were estimated by admission of the short form of the Wechsler Adult Intelligence Scale III. Results A significant interaction was found between family history of psychiatric disorder and clinical status (F(2,1086.87)= 4.17; p=.016). Patients with a positive family history of psychiatric disorder obtained higher intelligence scores compared to patients with no family history (mean IQ scores are 95.52 and 92.72) with an opposite effect in controls (mean IQ scores are 108.71 and 111.19). No significant difference was found between siblings of schizophrenia patients with or without a positive family history (mean IQ scores are 102.98 and 103.24). Conclusion In patients with schizophrenia, a negative family history of psychiatric disorder was associated with relatively low IQ suggesting that the etiology in these patients may involve environmental or genetic factors which are unique to the patient and are not observed in other relatives. Possible factors include severe environmental

  13. Intranasal oxytocin increases facial expressivity, but not ratings of trustworthiness, in patients with schizophrenia and healthy controls.

    Science.gov (United States)

    Woolley, J D; Chuang, B; Fussell, C; Scherer, S; Biagianti, B; Fulford, D; Mathalon, D H; Vinogradov, S

    2017-05-01

    Blunted facial affect is a common negative symptom of schizophrenia. Additionally, assessing the trustworthiness of faces is a social cognitive ability that is impaired in schizophrenia. Currently available pharmacological agents are ineffective at improving either of these symptoms, despite their clinical significance. The hypothalamic neuropeptide oxytocin has multiple prosocial effects when administered intranasally to healthy individuals and shows promise in decreasing negative symptoms and enhancing social cognition in schizophrenia. Although two small studies have investigated oxytocin's effects on ratings of facial trustworthiness in schizophrenia, its effects on facial expressivity have not been investigated in any population. We investigated the effects of oxytocin on facial emotional expressivity while participants performed a facial trustworthiness rating task in 33 individuals with schizophrenia and 35 age-matched healthy controls using a double-blind, placebo-controlled, cross-over design. Participants rated the trustworthiness of presented faces interspersed with emotionally evocative photographs while being video-recorded. Participants' facial expressivity in these videos was quantified by blind raters using a well-validated manualized approach (i.e. the Facial Expression Coding System; FACES). While oxytocin administration did not affect ratings of facial trustworthiness, it significantly increased facial expressivity in individuals with schizophrenia (Z = -2.33, p = 0.02) and at trend level in healthy controls (Z = -1.87, p = 0.06). These results demonstrate that oxytocin administration can increase facial expressivity in response to emotional stimuli and suggest that oxytocin may have the potential to serve as a treatment for blunted facial affect in schizophrenia.

  14. Deficient grip force control in schizophrenia: behavioral and modeling evidence for altered motor inhibition and motor noise.

    Science.gov (United States)

    Teremetz, Maxime; Amado, Isabelle; Bendjemaa, Narjes; Krebs, Marie-Odile; Lindberg, Pavel G; Maier, Marc A

    2014-01-01

    Whether upper limb sensorimotor control is affected in schizophrenia and how underlying pathological mechanisms may potentially intervene in these deficits is still being debated. We tested voluntary force control in schizophrenia patients and used a computational model in order to elucidate potential cerebral mechanisms underlying sensorimotor deficits in schizophrenia. A visuomotor grip force-tracking task was performed by 17 medicated and 6 non-medicated patients with schizophrenia (DSM-IV) and by 15 healthy controls. Target forces in the ramp-hold-and-release paradigm were set to 5 N and to 10% maximal voluntary grip force. Force trajectory was analyzed by performance measures and Principal Component Analysis (PCA). A computational model incorporating neural control signals was used to replicate the empirically observed motor behavior and to explore underlying neural mechanisms. Grip task performance was significantly lower in medicated and non-medicated schizophrenia patients compared to controls. Three behavioral variables were significantly higher in both patient groups: tracking error (by 50%), coefficient of variation of force (by 57%) and duration of force release (up by 37%). Behavioral performance did not differ between patient groups. Computational simulation successfully replicated these findings and predicted that decreased motor inhibition, together with an increased signal-dependent motor noise, are sufficient to explain the observed motor deficits in patients. PCA also suggested altered motor inhibition as a key factor differentiating patients from control subjects: the principal component representing inhibition correlated with clinical severity. These findings show that schizophrenia affects voluntary sensorimotor control of the hand independent of medication, and suggest that reduced motor inhibition and increased signal-dependent motor noise likely reflect key pathological mechanisms of the sensorimotor deficit.

  15. Cognitive and neural strategies during control of the anterior cingulate cortex by fMRI neurofeedback in patients with schizophrenia.

    Science.gov (United States)

    Cordes, Julia S; Mathiak, Krystyna A; Dyck, Miriam; Alawi, Eliza M; Gaber, Tilman J; Zepf, Florian D; Klasen, Martin; Zvyagintsev, Mikhail; Gur, Ruben C; Mathiak, Klaus

    2015-01-01

    Cognitive functioning is impaired in patients with schizophrenia, leading to significant disabilities in everyday functioning. Its improvement is an important treatment target. Neurofeedback (NF) seems a promising method to address the neural dysfunctions underlying those cognitive impairments. The anterior cingulate cortex (ACC), a central hub for cognitive processing, is one of the brain regions known to be dysfunctional in schizophrenia. Here we conducted NF training based on real-time functional magnetic resonance imaging (fMRI) in patients with schizophrenia to enable them to control their ACC activity. Training was performed over 3 days in a group of 11 patients with schizophrenia and 11 healthy controls. Social feedback was provided in accordance with the evoked activity in the selected region of interest (ROI). Neural and cognitive strategies were examined off-line. Both groups learned to control the activity of their ACC but used different neural strategies: patients activated the dorsal and healthy controls the rostral subdivision. Patients mainly used imagination of music to elicit activity and the control group imagination of sports. In a stepwise regression analysis, the difference in neural control did not result from the differences in cognitive strategies but from diagnosis alone. Based on social reinforcers, patients with schizophrenia can learn to regulate localized brain activity. However, cognitive strategies and neural network location differ from healthy controls. These data emphasize that for therapeutic interventions in patients with schizophrenia compensatory strategies may emerge. Specific cognitive skills or specific dysfunctional networks should be addressed to train impaired skills. Social NF based on fMRI may be one method to accomplish precise learning targets.

  16. Cognitive and neural strategies during control of the anterior cingulate cortex by fMRI neurofeedback in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Julia S Cordes

    2015-06-01

    Full Text Available Cognitive functioning is impaired in patients with schizophrenia, leading to significant disabilities in everyday functioning. Its improvement is an important treatment target. Neurofeedback (NF seems a promising method to address the neural dysfunctions underlying those cognitive impairments. The anterior cingulate cortex (ACC, a central hub for cognitive processing, is one of the dysfunctional brain regions in schizophrenia. Here we conducted NF training based on real-time functional magnetic resonance imaging (fMRI in patients with schizophrenia to enable them to control their ACC activity. Training was performed over three days in a group of 11 patients with schizophrenia and 11 healthy controls. Social feedback was provided in accordance with the evoked activity in the selected region of interest (ROI. Neural and cognitive strategies were examined off-line. Both groups learned to control the activity of their ACC but used different neural strategies: Patients activated the dorsal and healthy controls the rostral subdivision. Patients mainly used imagination of music to elicit activity and the control group imagination of sports. However, the difference in neural control did not result from the differences in cognitive strategies but from diagnosis alone. Based on social reinforcers, schizophrenia patients can learn to regulate localized brain activity. Cognitive strategies and neural network location differ, however, from healthy controls. These data emphasize that for therapeutic interventions in schizophrenia compensatory strategies may emerge. Specific cognitive skills or specific dysfunctional networks should be addressed to train impaired skills. Social neurofeedback based on fMRI may be one method to accomplish precise learning targets.

  17. Antipsychotic Medications and Risk of Acute Coronary Syndrome in Schizophrenia: A Nested Case-Control Study.

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    Hsing-Cheng Liu

    Full Text Available This study assessed the risk of developing acute coronary syndrome requiring hospitalization in association with the use of certain antipsychotic medications in schizophrenia patients.A nationwide cohort of 31,177 inpatients with schizophrenia between the ages of 18 and 65 years whose records were enrolled in the National Health Insurance Research Database in Taiwan from 2000 to 2008 and were studied after encrypting the identifications. Cases (n = 147 were patients with subsequent acute coronary syndrome requiring hospitalization after their first psychiatric admission. Based on a nested case-control design, each case was matched with 20 controls for age, sex and the year of first psychiatric admission using risk-set sampling. The effects of antipsychotic agents on the development of acute coronary syndrome were assessed using multiple conditional logistic regression and sensitivity analyses to confirm any association.We found that current use of aripiprazole (adjusted risk ratio [RR] = 3.68, 95% CI: 1.27-10.64, p<0.05 and chlorpromazine (adjusted RR = 2.96, 95% CI: 1.40-6.24, p<0.001 were associated with a dose-dependent increase in the risk of developing acute coronary syndrome. Although haloperidol was associated with an increased risk (adjusted RR = 2.03, 95% CI: 1.20-3.44, p<0.01, there was no clear dose-dependent relationship. These three antipsychotic agents were also associated with an increased risk in the first 30 days of use, and the risk decreased as the duration of therapy increased. Sensitivity analyses using propensity score-adjusted modeling showed that the results were similar to those of multiple regression analysis.Patients with schizophrenia who received aripiprazole, chlorpromazine, or haloperidol could have a potentially elevated risk of developing acute coronary syndrome, particularly at the start of therapy.

  18. EDITORIAL: Synaptic electronics Synaptic electronics

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    Demming, Anna; Gimzewski, James K.; Vuillaume, Dominique

    2013-09-01

    Conventional computers excel in logic and accurate scientific calculations but make hard work of open ended problems that human brains handle easily. Even von Neumann—the mathematician and polymath who first developed the programming architecture that forms the basis of today's computers—was already looking to the brain for future developments before his death in 1957 [1]. Neuromorphic computing uses approaches that better mimic the working of the human brain. Recent developments in nanotechnology are now providing structures with very accommodating properties for neuromorphic approaches. This special issue, with guest editors James K Gimzewski and Dominique Vuillaume, is devoted to research at the serendipitous interface between the two disciplines. 'Synaptic electronics', looks at artificial devices with connections that demonstrate behaviour similar to synapses in the nervous system allowing a new and more powerful approach to computing. Synapses and connecting neurons respond differently to incident signals depending on the history of signals previously experienced, ultimately leading to short term and long term memory behaviour. The basic characteristics of a synapse can be replicated with around ten simple transistors. However with the human brain having around 1011 neurons and 1015 synapses, artificial neurons and synapses from basic transistors are unlikely to accommodate the scalability required. The discovery of nanoscale elements that function as 'memristors' has provided a key tool for the implementation of synaptic connections [2]. Leon Chua first developed the concept of the 'The memristor—the missing circuit element' in 1971 [3]. In this special issue he presents a tutorial describing how memristor research has fed into our understanding of synaptic behaviour and how they can be applied in information processing [4]. He also describes, 'The new principle of local activity, which uncovers a minuscule life-enabling "Goldilocks zone", dubbed the

  19. CANNABIS USE AND ASSOCIATED HARMS AMONG SCHIZOPHRENIA PATIENTS IN A NGERIAN CLINICAL SETTING: A CASE CONTROL STUDY

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    Victor Lasebikan

    2016-08-01

    Full Text Available Aim: The overall aim of this study was to determine the prevalence of cannabis use among patients with schizophrenia with associated levels of harm in a Nigerian clinical setting.Method: In this case-control study, consecutive 150 patients with schizophrenia were matched by age and gender with an equal number of patients that utilized the general outpatient department of the State Hospital, Ring Road Ibadan.The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST was used to obtain prevalence of cannabis use and level of health risk as determined by the ASSIST score. The Positive and Negative Syndrome Scale (PANSS was used to determine the severity of psychosis. Results: Prevalence of cannabis use among the cases was 10.0% and 2.7% among the control group, p = 0.03. Mean ASSIST score was significantly higher among the cases compared with the control, p < 0.001. Respondents of male gender and those who were not married were significantly more likely to be cannabis users among patients with schizophrenia, p < 0.001, p < 0.02 respectively. Conclusion: Cannabis use was prevalent among patients with schizophrenia and was associated with health risks. Thus, routine screening for cannabis use and brief intervention is suggested to be integrated into care for adolescents and adults with schizophrenia.

  20. Cannabis Use and Associated Harms among Schizophrenia Patients in a Nigerian Clinical Setting: A Case-Control Study.

    Science.gov (United States)

    Lasebikan, Victor; Aremu, Olaolu O

    2016-01-01

    The overall aim of this study was to determine the prevalence of cannabis use among patients with schizophrenia with associated levels of harm in a Nigerian clinical setting. In this case-control study, consecutive 150 patients with schizophrenia were matched by age and gender with an equal number of patients that utilized the general outpatient department of the State Hospital, Ring Road Ibadan. The alcohol, smoking and substance involvement screening test (ASSIST) was used to obtain prevalence of cannabis use and level of health risk as determined by the ASSIST score. The positive and negative syndrome scale was used to determine the severity of psychosis. Prevalence of cannabis use among the cases and control group was 10.0 and 2.7%, respectively, p = 0.03. Mean ASSIST score was significantly higher among the cases compared with the control, p cannabis users among patients with schizophrenia (p Cannabis use was prevalent among patients with schizophrenia and was associated with health risks. Thus, routine screening for cannabis use and brief intervention is suggested to be integrated into care for adolescents and adults with schizophrenia.

  1. Plasticity in respiratory motor neurons in response to reduced synaptic inputs: A form of homeostatic plasticity in respiratory control?

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    Braegelmann, K M; Streeter, K A; Fields, D P; Baker, T L

    2017-01-01

    For most individuals, the respiratory control system produces a remarkably stable and coordinated motor output-recognizable as a breath-from birth until death. Very little is understood regarding the processes by which the respiratory control system maintains network stability in the presence of changing physiological demands and network properties that occur throughout life. An emerging principle of neuroscience is that neural activity is sensed and adjusted locally to assure that neurons continue to operate in an optimal range, yet to date, it is unknown whether such homeostatic plasticity is a feature of the neurons controlling breathing. Here, we review the evidence that local mechanisms sense and respond to perturbations in respiratory neural activity, with a focus on plasticity in respiratory motor neurons. We discuss whether these forms of plasticity represent homeostatic plasticity in respiratory control. We present new analyses demonstrating that reductions in synaptic inputs to phrenic motor neurons elicit a compensatory enhancement of phrenic inspiratory motor output, a form of plasticity termed inactivity-induced phrenic motor facilitation (iPMF), that is proportional to the magnitude of activity deprivation. Although the physiological role of iPMF is not understood, we hypothesize that it has an important role in protecting the drive to breathe during conditions of prolonged or intermittent reductions in respiratory neural activity, such as following spinal cord injury or during central sleep apnea. Copyright © 2016. Published by Elsevier Inc.

  2. Neurocognitive function in clinically stable individuals with long-term bipolar I disorder: Comparisons with schizophrenia patients and controls.

    Science.gov (United States)

    Lin, Pei-Yun; Wang, Peng-Wei; Chen, Cheng-Sheng; Yen, Cheng-Fang

    2017-05-01

    This study compared the levels of the five domains of neurocognitive function-executive function, attention, memory, verbal comprehension, and perceptual organization-among clinically stable individuals with long-term bipolar I disorder, individuals with long-term schizophrenia, and a group of controls. We recruited a total of 93 clinically stable individuals with bipolar I disorder, 94 individuals with schizophrenia, and 106 controls in this study. Their neurocognitive function was measured using a series of neurocognitive function tests: the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), Line Cancellation Test, Visual Form Discrimination, Controlled Oral Word Association Test, Wisconsin Card Sorting Test, Continuous Performance Task, and Wechsler Memory Scale-Third Edition. Neurocognitive function was compared among the three groups through a multivariate analysis of variance. The results indicated that when the effect of age was controlled, clinically stable individuals with bipolar I disorder and those with schizophrenia demonstrated poor neurocognitive function on all tests except for the WAIS-III Similarity and Information and the Line Cancellation Test. The individuals with bipolar I disorder had similar levels of neurocognitive function compared with the schizophrenia group, but higher levels of neurocognitive function on the WAIS-III Comprehension, Controlled Oral Word Association Test, and Wechsler Memory Scale-Third Edition Auditory Immediate and Delayed Index and Visual Immediate and Delayed Index. The conclusions of this study suggest that compared with controls, individuals with long-term bipolar I disorder and those with long-term schizophrenia have poorer neurocognitive function, even when clinically stable. Individuals with long-term bipolar I disorder and those with long-term schizophrenia have similar levels of deficits in several domains of neurocognitive function. Copyright © 2017. Published by Elsevier Taiwan.

  3. Neurocognitive function in clinically stable individuals with long-term bipolar I disorder: Comparisons with schizophrenia patients and controls

    Directory of Open Access Journals (Sweden)

    Pei-Yun Lin

    2017-05-01

    Full Text Available This study compared the levels of the five domains of neurocognitive function—executive function, attention, memory, verbal comprehension, and perceptual organization—among clinically stable individuals with long-term bipolar I disorder, individuals with long-term schizophrenia, and a group of controls. We recruited a total of 93 clinically stable individuals with bipolar I disorder, 94 individuals with schizophrenia, and 106 controls in this study. Their neurocognitive function was measured using a series of neurocognitive function tests: the Wechsler Adult Intelligence Scale—Third Edition (WAIS-III, Line Cancellation Test, Visual Form Discrimination, Controlled Oral Word Association Test, Wisconsin Card Sorting Test, Continuous Performance Task, and Wechsler Memory Scale—Third Edition. Neurocognitive function was compared among the three groups through a multivariate analysis of variance. The results indicated that when the effect of age was controlled, clinically stable individuals with bipolar I disorder and those with schizophrenia demonstrated poor neurocognitive function on all tests except for the WAIS-III Similarity and Information and the Line Cancellation Test. The individuals with bipolar I disorder had similar levels of neurocognitive function compared with the schizophrenia group, but higher levels of neurocognitive function on the WAIS-III Comprehension, Controlled Oral Word Association Test, and Wechsler Memory Scale—Third Edition Auditory Immediate and Delayed Index and Visual Immediate and Delayed Index. The conclusions of this study suggest that compared with controls, individuals with long-term bipolar I disorder and those with long-term schizophrenia have poorer neurocognitive function, even when clinically stable. Individuals with long-term bipolar I disorder and those with long-term schizophrenia have similar levels of deficits in several domains of neurocognitive function.

  4. Foxp1 in Forebrain Pyramidal Neurons Controls Gene Expression Required for Spatial Learning and Synaptic Plasticity.

    Science.gov (United States)

    Araujo, Daniel J; Toriumi, Kazuya; Escamilla, Christine O; Kulkarni, Ashwinikumar; Anderson, Ashley G; Harper, Matthew; Usui, Noriyoshi; Ellegood, Jacob; Lerch, Jason P; Birnbaum, Shari G; Tucker, Haley O; Powell, Craig M; Konopka, Genevieve

    2017-11-08

    Genetic perturbations of the transcription factor Forkhead Box P1 (FOXP1) are causative for severe forms of autism spectrum disorder that are often comorbid with intellectual disability. Recent work has begun to reveal an important role for FoxP1 in brain development, but the brain-region-specific contributions of Foxp1 to autism and intellectual disability phenotypes have yet to be determined fully. Here, we describe Foxp1 conditional knock-out (Foxp1cKO) male and female mice with loss of Foxp1 in the pyramidal neurons of the neocortex and the CA1/CA2 subfields of the hippocampus. Foxp1cKO mice exhibit behavioral phenotypes that are of potential relevance to autism spectrum disorder, including hyperactivity, increased anxiety, communication impairments, and decreased sociability. In addition, Foxp1cKO mice have gross deficits in learning and memory tasks of relevance to intellectual disability. Using a genome-wide approach, we identified differentially expressed genes in the hippocampus of Foxp1cKO mice associated with synaptic function and development. Furthermore, using magnetic resonance imaging, we uncovered a significant reduction in the volumes of both the entire hippocampus as well as individual hippocampal subfields of Foxp1cKO mice. Finally, we observed reduced maintenance of LTP in area CA1 of the hippocampus in these mutant mice. Together, these data suggest that proper expression of Foxp1 in the pyramidal neurons of the forebrain is important for regulating gene expression pathways that contribute to specific behaviors reminiscent of those seen in autism and intellectual disability. In particular, Foxp1 regulation of gene expression appears to be crucial for normal hippocampal development, CA1 plasticity, and spatial learning.SIGNIFICANCE STATEMENT Loss-of-function mutations in the transcription factor Forkhead Box P1 (FOXP1) lead to autism spectrum disorder and intellectual disability. Understanding the potential brain-region-specific contributions of

  5. Sleep habits in middle-aged, non-hospitalized men and women with schizophrenia: a comparison with healthy controls.

    Science.gov (United States)

    Poulin, Julie; Chouinard, Sylvie; Pampoulova, Tania; Lecomte, Yves; Stip, Emmanuel; Godbout, Roger

    2010-10-30

    Patients with schizophrenia may have sleep disorders even when clinically stable under antipsychotic treatments. To better understand this issue, we measured sleep characteristics between 1999 and 2003 in 150 outpatients diagnosed with Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) schizophrenia or schizoaffective disorder and 80 healthy controls using a sleep habits questionnaire. Comparisons between both groups were performed and multiple comparisons were Bonferroni corrected. Compared to healthy controls, patients with schizophrenia reported significantly increased sleep latency, time in bed, total sleep time and frequency of naps during weekdays and weekends along with normal sleep efficiency, sleep satisfaction, and feeling of restfulness in the morning. In conclusion, sleep-onset insomnia is a major, enduring disorder in middle-aged, non-hospitalized patients with schizophrenia that are otherwise clinically stable under antipsychotic and adjuvant medications. Noteworthy, these patients do not complain of sleep-maintenance insomnia but report increased sleep propensity and normal sleep satisfaction. These results may reflect circadian disturbances in schizophrenia, but objective laboratory investigations are needed to confirm subjective sleep reports. Copyright © 2009 Elsevier Ltd. All rights reserved.

  6. Cognitive remediation therapy in adolescents with early-onset schizophrenia: a randomized controlled trial.

    Science.gov (United States)

    Puig, Olga; Penadés, Rafael; Baeza, Inmaculada; De la Serna, Elena; Sánchez-Gistau, Vanessa; Bernardo, Miquel; Castro-Fornieles, Josefina

    2014-08-01

    Cognitive impairment is an enduring and functionally relevant feature of early-onset schizophrenia (EOS). Cognitive remediation therapy (CRT) improves cognition and functional outcome in adults with schizophrenia, although data in adolescents with EOS remain scarce. The purpose of this study is to examine the efficacy of CRT in improving cognition and functional outcomes in a sample of symptomatically stable but cognitively disabled adolescents with EOS. We performed a randomized, controlled trial of individually delivered CRT plus treatment-as-usual compared with treatment-as-usual (TAU). Fifty adolescents with EOS were randomly assigned to receive CRT (n = 25) or TAU (n = 25) and were included in an intention-to-treat analysis. Clinical symptoms and cognitive and functional performance were assessed before and after treatment in both groups and after 3 months in the CRT group. Cognitive domains were defined according to the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus battery and averaged in a global cognitive composite score. After CRT, significant improvements were found in verbal memory and executive functions, with medium-to-large effect sizes (ES). The derived cognitive composite score showed an improvement after the treatment, with a large ES. This change was reliable in more than two-thirds of the treated patients. Medium-sized ES were found for improvements after CRT in daily living and adaptive functioning, whereas large ES were observed for improvements in family burden. With the exception of functional gains, these changes were maintained after 3 months. CRT appears to be a useful intervention strategy for adolescents with EOS. Cognitive improvements can be achieved through CRT, although further research is warranted to determine the durability of functional gains. Clinical trial registration information-Cognitive Remediation Therapy (CRT) in Adolescents With EOS; www.clinicaltrials.gov; NCT01701609

  7. Training patients with schizophrenia to share decisions with their psychiatrists: a randomized-controlled trial.

    Science.gov (United States)

    Hamann, Johannes; Parchmann, Anna; Sassenberg, Nina; Bronner, Katharina; Albus, Margot; Richter, Alwin; Hoppstock, Sandra; Kissling, Werner

    2017-02-01

    Many patients with schizophrenia have a desire for shared decision-making (SDM). However, in clinical practice SDM often does not take place. One cause might be that many patients behave passively in the medical encounter, therefore not facilitating SDM. It was the aim of the study to evaluate the effects of a patient directed SDM-training on patients' communicative behavior in the consultation, their attitudes towards decision-making and their long-term adherence. Randomized-controlled trial comparing a five-session SDM-training for inpatients with schizophrenia with five sessions of non-specific group training. The SDM-training sessions included motivational (e.g. prospects of participation, patient rights) and behavioral aspects (e.g. role plays) and addressed important aspects of the patient-doctor interaction such as question asking or giving feedback. N = 264 patients were recruited in four psychiatric hospitals in Germany. The SDM-training yielded no group differences regarding the main outcome measure (treatment adherence) at 6 and 12 months after discharge. However, there were short-term effects on patients' participation preferences, their wish to take over more responsibility for medical decisions and (according to their psychiatrists' estimate) their behavior in psychiatric consultations. While there was no effect regarding treatment adherence, the shared decision-making training for inpatients with schizophrenia has been shown to increase patients' active behavior in psychiatric consultations during their inpatient treatment. When implemented it should be combined with complementary SDM interventions (decision support tools and communication training for professionals) to yield maximum effects.

  8. Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials

    Directory of Open Access Journals (Sweden)

    Borrill Jo

    2005-10-01

    Full Text Available Abstract Background Chlorpromazine (CPZ remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo. Methods We sought all relevant randomised controlled trials (RCT comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR, the number needed to treat (NNT and their 95% confidence intervals (CI calculated. Results Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10, although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1 and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1. There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8, increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth. Conclusion It is understandable why the World Health Organization (WHO have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations.

  9. Social Cognition in Schizophrenia

    OpenAIRE

    Green, Michael F.; Leitman, David I.

    2008-01-01

    Impairments in social cognitions in schizophrenia are increasingly reported in the last decade but only a few studies have come from Asia. The objective of the study was to evaluated emotion perception, theory of mind and social knowledge in people with schizophrenia compared to healthy controls. Participants were 36 clinically stable outpatients with schizophrenia and 36 normal controls with comparable age and level of education. We administered general neurocognition test (the Addenbrooke’s...

  10. Combining social cognitive treatment, cognitive remediation, and functional skills training in schizophrenia: a randomized controlled trial.

    Science.gov (United States)

    Peña, Javier; Ibarretxe-Bilbao, Naroa; Sánchez, Pedro; Iriarte, Maria B; Elizagarate, Edorta; Garay, Maria A; Gutiérrez, Miguel; Iribarren, Aránzazu; Ojeda, Natalia

    2016-01-01

    This study examined the efficacy of an integrative cognitive remediation program (REHACOP) in improving cognition and functional outcome in patients with schizophrenia. The program combines cognitive remediation, social cognitive intervention, and functional skills training. Few studies have attempted this approach. One hundred and eleven patients diagnosed with schizophrenia were randomly assigned to either the cognitive remediation group (REHACOP) or an active control group (occupational activities) for 4 months (three sessions per week, 90 min). Primary outcomes were change on general neurocognitive performance and social cognition, including theory of mind (ToM), emotion perception (EP), attributional style, and social perception (SP). Secondary outcomes included changes on clinical symptoms (Positive and Negative Syndrome Scale) and functional outcome (UCSD Performance-Based Skills Assessment and the Global Assessment of Functioning). The trial was registered with clinicaltrials.gov (NCT02796417). No baseline group differences were found. Significant differences were found in the mean change between the REHACOP group and control group in neurocognition ([Formula: see text]), SP ([Formula: see text]), ToM ([Formula: see text]), EP ([Formula: see text]), negative symptoms ([Formula: see text]), emotional distress ([Formula: see text]), Global Assessment of Functioning ([Formula: see text]), and UCSD Performance-Based Skills Assessment ([Formula: see text]). The combination of cognitive remediation, social cognitive intervention, and functional skills training demonstrated statistically significant and clinically meaningful changes in neurocognition, social cognition, negative, and functional disability.

  11. Occipital bending in schizophrenia.

    Science.gov (United States)

    Maller, Jerome J; Anderson, Rodney J; Thomson, Richard H; Daskalakis, Zafiris J; Rosenfeld, Jeffrey V; Fitzgerald, Paul B

    2017-01-01

    To investigate the prevalence of occipital bending (an occipital lobe crossing or twisting across the midline) in subjects with schizophrenia and matched healthy controls. Occipital bending prevalence was investigated in 37 patients with schizophrenia and 44 healthy controls. Ratings showed that prevalence was nearly three times higher among schizophrenia patients (13/37 [35.1%]) than in control subjects (6/44 [13.6%]). Furthermore, those with schizophrenia had greater normalized gray matter volume but less white matter volume and had larger brain-to-cranial ratio. The results suggest that occipital bending is more prevalent among schizophrenia patients than healthy subjects and that schizophrenia patients have different gray matter-white matter proportions. Although the cause and clinical ramifications of occipital bending are unclear, the results infer that occipital bending may be a marker of psychiatric illness.

  12. Common and disease-specific dysfunctions of brain systems underlying attentional and executive control in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Melcher, Tobias; Wolter, Sarah; Falck, Stefanie; Wild, Eva; Wild, Florian; Gruber, Eva; Falkai, Peter; Gruber, Oliver

    2014-09-01

    Schizophrenia and bipolar disorder broadly overlap in multiple areas involving clinical phenomenology, genetics, and neurobiology. Still, the investigation into specific elementary (sub-)processes of executive functioning may help to define clear points of distinction between these categorical diagnoses to validate the nosological dichotomy and, indirectly, to further elucidate their pathophysiological underpinnings. In the present behavioral study, we sought to separate common from diagnosis-specific deficits in a series of specific elementary sub-functions of executive processing in patients with schizophrenia and bipolar disorder. For our purpose, we administered a modern and multi-purpose neuropsychological task paradigm to equal-sized and matched groups of schizophrenia patients, patients with bipolar disorder, and healthy control subjects. First, schizophrenia patients compared to the bipolar group exhibited a more pronounced deficit in general measures of task performance comprising both response speed and accuracy. Additionally, bipolar patients showed increased advance task preparation, i.e., were better able to compensate for response speed deficits when longer preparation intervals were provided. Set-shifting, on the other hand, was impaired to a similar degree in both patient groups. Finally, schizophrenia patients exhibited a specific deficit in conflict processing (inhibitory control) and the shielding of task-relevant processing from distraction (i.e., attentional maintenance). The present investigation suggests that specific neuropsychological measures of elementary executive functions may represent important points of dissociation between schizophrenia and bipolar disorder, which may help to differentiate the pathophysiological underpinnings of these major psychiatric disorders. In this context, the present findings highlight the measures of inhibitory control and attentional maintenance as promising candidates.

  13. Randomized controlled trial of computer-based treatment of social cognition in schizophrenia: the TRuSST trial protocol.

    Science.gov (United States)

    Rose, Annika; Vinogradov, Sophia; Fisher, Melissa; Green, Michael F; Ventura, Joseph; Hooker, Christine; Merzenich, Michael; Nahum, Mor

    2015-07-03

    Schizophrenia is a severe and chronic medical condition, characterized by positive and negative symptoms, as well as pervasive social cognitive deficits. Despite the functional significance of the social cognition deficits affecting many aspects of daily living, such as social relationships, occupational status, and independent living, there is still no effective treatment option for these deficits, which is applied as standard of care. To address this need, we developed a novel, internet-based training program that targets social cognition deficits in schizophrenia (SocialVille). Preliminary studies demonstrate the feasibility and initial efficacy of Socialville in schizophrenia patients (Nahum et al., 2014). The purpose of the current trial (referred to as the TReatment of Social cognition in Schizophrenia Trial or TRuSST) is to compare SocialVille to an active control training condition, include a larger sample of patients, and assess both social cognitive functioning, and functional outcomes. We will employ a multi-site, longitudinal, blinded, randomized controlled trial (RCT) design with a target sample of 128 patients with schizophrenia. Patients will perform, at their home or in clinic, 40 sessions of either the SocialVille training program or an active control computer game condition. Each session will last for 40-45 minutes/day, performed 3-5 days a week, over 10-12 weeks, totaling to 30 hours of training. Patients will be assessed on a battery of social cognitive, social functioning and functional outcomes immediately before training, mid-way through training (after 20 training sessions) and at the completion of the 40 training sessions. The strengths of this protocol are that it tests an innovative, internet-based treatment that targets fundamental social cognitive deficits in schizophrenia, employs a highly sensitive and extensive battery of functional outcome measures, and incorporates a large sample size in an RCT design. ClinicalTrials.gov NCT

  14. Exploring rationality in schizophrenia

    DEFF Research Database (Denmark)

    Revsbech, Rasmus; Mortensen, Erik Lykke; Owen, Gareth

    2015-01-01

    Background Empirical studies of rationality (syllogisms) in patients with schizophrenia have obtained different results. One study found that patients reason more logically if the syllogism is presented through an unusual content. Aims To explore syllogism-based rationality in schizophrenia. Method...... Thirty-eight first-admitted patients with schizophrenia and 38 healthy controls solved 29 syllogisms that varied in presentation content (ordinary v. unusual) and validity (valid v. invalid). Statistical tests were made of unadjusted and adjusted group differences in models adjusting for intelligence...... differences became non-significant. Conclusions When taking intelligence and neuropsychological performance into account, patients with schizophrenia and controls perform similarly on syllogism tests of rationality....

  15. Association of Schizophrenia Spectrum and Autism Spectrum Disorder (ASD) Symptoms in Children with ASD and Clinic Controls

    Science.gov (United States)

    Gadow, Kenneth D.

    2013-01-01

    Objective: This study examines relations between the severity of specific symptoms of schizophrenia spectrum disorder (SSD) and severity of the three defining symptom domains of autism spectrum disorder (ASD) in children with ASD (N = 147) and child psychiatry outpatient referrals (Controls; N = 339). Method: Participants were subdivided into four…

  16. A randomized, controlled trial of Social Cognition and Interaction Training (SCIT) for outpatients with schizophrenia spectrum disorders.

    Science.gov (United States)

    Roberts, David L; Combs, Dennis R; Willoughby, Michael; Mintz, Jim; Gibson, Clare; Rupp, Betty; Penn, David L

    2014-09-01

    In schizophrenia, the ability to adaptively infer the thoughts and feelings of others (i.e., social cognition) is strongly associated with community functioning. Researchers have designed psychosocial interventions to improve social cognition with the aim of improving downstream social functioning. Social Cognition and Interaction Training (SCIT) is one such intervention. Previous research on SCIT has been promising, but has consisted largely of smaller trials with insufficient experimental control. Randomized, controlled trial. The current article reports on a controlled trial of 66 adults with schizophrenia randomized to receive either SCIT (n = 33), delivered in weekly group sessions, or treatment as usual (n = 33) for 6 months. Participants completed assessments of social cognition, social functioning, neurocognition and symptoms at baseline, post-treatment, and 3-month follow-up. Primary analyses suggest that SCIT may improve social functioning, negative symptoms, and possibly hostile attributional bias. Post-hoc analyses suggest a dose-response effect. Findings are discussed in the context of continuing to refine and improve social cognitive interventions for schizophrenia. Social cognitive intervention is a feasible and promising approach to improving social functioning among individuals with schizophrenia-spectrum disorders. Dose-response findings suggest that delivering social cognitive interventions with greater frequency may maximize their benefit to patients. Research on social cognitive interventions is still young and effects from well-controlled trials have been inconsistent. It is not yet clear which components of social cognitive training may be the key active ingredients. © 2014 The British Psychological Society.

  17. Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with clozapine.

    Science.gov (United States)

    Yamamori, Hidenaga; Hashimoto, Ryota; Ishima, Tamaki; Kishi, Fukuko; Yasuda, Yuka; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Ito, Akira; Hashimoto, Kenji; Takeda, Masatoshi

    2013-11-27

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. Peripheral BDNF levels in patients with schizophrenia have been widely reported in the literature. However, it is still controversial whether peripheral levels of BDNF are altered in patients with schizophrenia. The peripheral BDNF levels previously reported in patients with schizophrenia were total BDNF (proBDNF and mature BDNF) as it was unable to specifically measure mature BDNF due to limited BDNF antibody specificity. In this study, we examined whether peripheral levels of mature BDNF were altered in patients with treatment-resistant schizophrenia. Matrix metalloproteinase-9 (MMP-9) levels were also measured, as MMP-9 plays a role in the conversion of proBDNF to mature BDNF. Twenty-two patients with treatment-resistant schizophrenia treated with clozapine and 22 age- and sex-matched healthy controls were enrolled. The plasma levels of mature BDNF and MMP-9 were measured using ELISA kits. No significant difference was observed for mature BDNF however, MMP-9 was significantly increased in patients with schizophrenia. The significant correlation was observed between mature BDNF and MMP-9 plasma levels. Neither mature BDNF nor MMP-9 plasma levels were associated clinical variables. Our results do not support the view that peripheral BDNF levels are associated with schizophrenia. MMP-9 may play a role in the pathophysiology of schizophrenia and serve as a biomarker for schizophrenia. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  18. A method to achieve extended cannabis abstinence in cannabis dependent patients with schizophrenia and non-psychiatric controls.

    Science.gov (United States)

    Rabin, Rachel A; Kozak, Karolina; Zakzanis, Konstantine K; Remington, Gary; Stefan, Cristiana; Budney, Alan J; George, Tony P

    2017-05-12

    Cannabis use disorders (CUD) are common in schizophrenia (~25%) compared to the general population (~3%). Tetrahydrocannabinol (THC), the principal psychoactive component in cannabis is fat-soluble, resulting in an extended period for cannabinoid elimination. While detection of cannabinoids in urine is indicative of prior cannabis exposure, time of last use is difficult to verify sustained abstinence for extended periods (e.g., 28-days) in chronic cannabis users. Therefore, we evaluated the utility of a sustained cannabis abstinence paradigm in patients with schizophrenia and non-psychiatric controls. Cannabis dependent patients (n=19) and controls (n=20) underwent 28-days of monitored cannabis abstinence facilitated with contingency management. Urine samples were taken twice weekly. Abstinence was evaluated using 1) Self-report; 2) Qualitative biochemical confirmation using MEDTOX; and 3) in a subset of participants (schizophrenia, n=13; controls, n=13) gas chromatography-mass spectrometry (GC-MS) was performed to obtain quantitative creatinine-normalized carboxy-THC (THC-COOH) metabolite levels cannabis abstinence and further supported time-dependent abstinence trajectories. Abstinence rates of 42.1% (8/19) in patients and 55% (11/19) in controls (p=0.53) were observed. Increased cannabis withdrawal symptoms in both patients and controls supported abstinence. Our results suggest a feasible method for identification of short-term cannabis abstinence in individuals with schizophrenia at rates comparable to controls. Monitoring sustained abstinence may have implications for potential interventions for CUDs in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Postural Stability of Patients with Schizophrenia during Challenging Sensory Conditions: Implication of Sensory Integration for Postural Control.

    Science.gov (United States)

    Teng, Ya-Ling; Chen, Chiung-Ling; Lou, Shu-Zon; Wang, Wei-Tsan; Wu, Jui-Yen; Ma, Hui-Ing; Chen, Vincent Chin-Hung

    2016-01-01

    Postural dysfunctions are prevalent in patients with schizophrenia and affect their daily life and ability to work. In addition, sensory functions and sensory integration that are crucial for postural control are also compromised. This study intended to examine how patients with schizophrenia coordinate multiple sensory systems to maintain postural stability in dynamic sensory conditions. Twenty-nine patients with schizophrenia and 32 control subjects were recruited. Postural stability of the participants was examined in six sensory conditions of different level of congruency of multiple sensory information, which was based on combinations of correct, removed, or conflicting sensory inputs from visual, somatosensory, and vestibular systems. The excursion of the center of pressure was measured by posturography. Equilibrium scores were derived to indicate the range of anterior-posterior (AP) postural sway, and sensory ratios were calculated to explore ability to use sensory information to maintain balance. The overall AP postural sway was significantly larger for patients with schizophrenia compared to the controls [patients (69.62±8.99); controls (76.53±7.47); t1,59 = -3.28, ppostural sway was significantly larger for patients compared to the controls in conditions containing unreliable somatosensory information either with visual deprivation or with conflicting visual information. Sensory ratios were not significantly different between groups, although small and non-significant difference in inefficiency to utilize vestibular information was also noted. No significant correlations were found between postural stability and clinical characteristics. To sum up, patients with schizophrenia showed increased postural sway and a higher rate of falls during challenging sensory conditions, which was independent of clinical characteristics. Patients further demonstrated similar pattern and level of utilizing sensory information to maintain balance compared to the controls.

  20. Postural Stability of Patients with Schizophrenia during Challenging Sensory Conditions: Implication of Sensory Integration for Postural Control.

    Directory of Open Access Journals (Sweden)

    Ya-Ling Teng

    Full Text Available Postural dysfunctions are prevalent in patients with schizophrenia and affect their daily life and ability to work. In addition, sensory functions and sensory integration that are crucial for postural control are also compromised. This study intended to examine how patients with schizophrenia coordinate multiple sensory systems to maintain postural stability in dynamic sensory conditions. Twenty-nine patients with schizophrenia and 32 control subjects were recruited. Postural stability of the participants was examined in six sensory conditions of different level of congruency of multiple sensory information, which was based on combinations of correct, removed, or conflicting sensory inputs from visual, somatosensory, and vestibular systems. The excursion of the center of pressure was measured by posturography. Equilibrium scores were derived to indicate the range of anterior-posterior (AP postural sway, and sensory ratios were calculated to explore ability to use sensory information to maintain balance. The overall AP postural sway was significantly larger for patients with schizophrenia compared to the controls [patients (69.62±8.99; controls (76.53±7.47; t1,59 = -3.28, p<0.001]. The results of mixed-model ANOVAs showed a significant interaction between the group and sensory conditions [F5,295 = 5.55, p<0.001]. Further analysis indicated that AP postural sway was significantly larger for patients compared to the controls in conditions containing unreliable somatosensory information either with visual deprivation or with conflicting visual information. Sensory ratios were not significantly different between groups, although small and non-significant difference in inefficiency to utilize vestibular information was also noted. No significant correlations were found between postural stability and clinical characteristics. To sum up, patients with schizophrenia showed increased postural sway and a higher rate of falls during challenging sensory

  1. Comparative Study of Neurological Soft Signs in Patients with Schizophrenia or Obsessive-compulsive Disorder, and Healthy Controls.

    Science.gov (United States)

    Tripathi, R; Soni, A; Tyagi, A; Mehta, S; Gupta, S

    2015-06-01

    The primary objective of this study was to examine neurological soft signs in patients with obsessive-compulsive disorder compared with patients with schizophrenia and a control group in the Indian setting. The secondary objective was to find any correlation between age at onset and neurological soft signs scores, as well as that between severity of obsessive-compulsive disorder symptoms (total Yale-Brown Obsessive Compulsive Scale score) and neurological soft signs scores. This was a cross-sectional hospital-based study of 135 individuals (45 patients with schizophrenia, 45 patients with obsessive-compulsive disorder who were attending the psychiatric outpatient department of Sawai Man Singh Medical College, Jaipur, India, and 45 matched healthy controls) from 20 June 2013 to 22 December 2014. After applying strict inclusion and exclusion criteria, the participants completed the study instruments (Cambridge Neurological Inventory [Part 2] and Yale-Brown Obsessive Compulsive Scale). Their socio-demographic data were also recorded. The neurological soft signs total score and domain scores (motor coordination, sensory integration, and disinhibition) were significantly higher in patients with schizophrenia (p disorder group or the control group. The obsessive-compulsive disorder group did not significantly differ from the control group in terms of neurological soft signs scores. No correlation was found between neurological soft signs scores and age at onset as well as that between neurological soft signs scores and total Yale-Brown Obsessive Compulsive Scale score. Neurological soft signs assessed by the Cambridge Neurological Inventory and Yale-Brown Obsessive Compulsive Scale, which discriminate patients with schizophrenia from controls, appear to be relatively specific to schizophrenia. Further studies are required to explore neurological soft signs in patients with obsessive-compulsive disorder.

  2. A randomized waitlist control community study of Social Cognition and Interaction Training for people with schizophrenia.

    Science.gov (United States)

    Gordon, Anne; Davis, Penelope J; Patterson, Susan; Pepping, Christopher A; Scott, James G; Salter, Kerri; Connell, Melissa

    2017-10-09

    Social Cognition and Interaction Training (SCIT) has demonstrated effectiveness in improving social cognition and functioning of people with schizophrenia. This pilot study examines the acceptability, feasibility, and effectiveness of SCIT with individuals who have schizophrenia-spectrum disorders and are receiving care through a public mental health service. In a pragmatic randomized waitlist controlled trial, 36 participants (aged 19-55 years) with a schizophrenia spectrum disorder were randomly allocated to SCIT or treatment as usual (TAU). Measures of theory of mind, emotion perception, attributional bias, social skills, quality of life, life skills, depression, anxiety, and stress were administered pre- and post-intervention with follow-up conducted 4 months later. All wait-list controls subsequently received the intervention and a secondary within-group analysis was conducted including these participants. While no significant differences were found between groups on any outcomes, there was strong engagement with the SCIT intervention. Of the 21 participants in the intervention group, the completion rate was 85.71% with a median attendance rate of 17 sessions. Within subject analyses of SCIT participants over time showed significant improvements in quality of life, emotion recognition, social skills, and a trend towards better life skills from pre- to post-intervention. These gains were sustained at the 4-month follow-up time. Although this study showed limited benefits in outcomes associated with SCIT compared with TAU, it demonstrated the acceptability of SCIT to participants in a real world public health setting shown by high retention, attendance, and positive feedback. This pilot shows SCIT can be implemented in routine clinical practice and lays the foundation for a larger pragmatic study. SCIT can be implemented successfully in a real-world community mental health setting. SCIT had high levels of acceptability to these participants. Limitations The

  3. Feasibility of reducing the duration of placebo-controlled trials in schizophrenia research.

    Science.gov (United States)

    McMahon, Robert P; Kelly, Deanna L; Boggs, Douglas L; Li, Lan; Hu, Qiaoyan; Davis, John M; Carpenter, William T

    2008-03-01

    Use of placebo-controlled trials in medical and psychiatric research has been controversial, although a consensus is emerging about conditions under which placebo-controlled trials are ethical. In schizophrenia research, the paradigm of slow onset of antipsychotic effects has led to a model in which placebo-controlled trials of 6-8 weeks duration have been used to demonstrate efficacy. Recent evidence that the largest symptom reductions are typically seen in the first weeks of treatment suggests that shorter placebo-controlled studies to demonstrate antipsychotic efficacy are possible. In a pilot study of the feasibility of shortening placebo-controlled studies, we reanalyzed data from placebo-controlled registry trials of olanzapine and risperidone and found that trials as short as 4 weeks could have similar power to longer term 6-8 week studies, given the estimated time course of treatment effects. Although fuller evaluation is required, the results suggest future antipsychotic trials could be shortened from 6-8 weeks to 3-4 weeks with a relatively low increase in sample size requirements. Shortening placebo-controlled trials would reduce patient burden and ethical objections to prolonged administration of placebo and reduce potential bias due to high dropout rates in longer clinical trials.

  4. Modafinil and cognitive enhancement in schizophrenia and healthy volunteers: the effects of test battery in a randomised controlled trial.

    Science.gov (United States)

    Lees, J; Michalopoulou, P G; Lewis, S W; Preston, S; Bamford, C; Collier, T; Kalpakidou, A; Wykes, T; Emsley, R; Pandina, G; Kapur, S; Drake, R J

    2017-10-01

    Cognitive deficits in schizophrenia have major functional impacts. Modafinil is a cognitive enhancer whose effect in healthy volunteers is well-described, but whose effects on the cognitive deficits of schizophrenia appear to be inconsistent. Two possible reasons for this are that cognitive test batteries vary in their sensitivity, or that the phase of illness may be important, with patients early in their illness responding better. A double-blind, randomised, placebo-controlled single-dose crossover study of modafinil 200 mg examined this with two cognitive batteries [MATRICS Consensus Cognitive Battery (MCCB) and Cambridge Neuropsychological Test Automated Battery (CANTAB)] in 46 participants with under 3 years' duration of DSM-IV schizophrenia, on stable antipsychotic medication. In parallel, the same design was used in 28 age-, sex-, and education-matched healthy volunteers. Uncorrected p values were calculated using mixed effects models. In patients, modafinil significantly improved CANTAB Paired Associate Learning, non-significantly improved efficiency and significantly slowed performance of the CANTAB Stockings of Cambridge spatial planning task. There was no significant effect on any MCCB domain. In healthy volunteers, modafinil significantly increased CANTAB Rapid Visual Processing, Intra-Extra Dimensional Set Shifting and verbal recall accuracy, and MCCB social cognition performance. The only significant differences between groups were in MCCB visual learning. As in earlier chronic schizophrenia studies, modafinil failed to produce changes in cognition in early psychosis as measured by MCCB. CANTAB proved more sensitive to the effects of modafinil in participants with early schizophrenia and in healthy volunteers. This confirms the importance of selecting the appropriate test battery in treatment studies of cognition in schizophrenia.

  5. Course of intelligence deficits in early onset, first episode schizophrenia: a controlled, 5-year longitudinal study

    DEFF Research Database (Denmark)

    Jepsen, Jens Richardt Møllegaard; Fagerlund, Birgitte; Pagsberg, Anne Katrine

    2010-01-01

    predominantly been characterized as relatively stable in these studies. However, comparisons of IQs from different test versions based on the different norms may not permit unequivocal interpretations. The objective of the current study was to compare the development of intelligence in EOS patients (N = 10......Only few prospective longitudinal studies have assessed the course of intelligence deficits in early onset schizophrenia (EOS), and these have used different age appropriate versions of Wechsler Intelligence Scales and age appropriate norms. The post-psychotic development of intelligence in EOS has......) from their first psychotic episode to 5 years of post onset with that of healthy controls (N = 35) and patients who at baseline had been diagnosed with other non-affective psychoses (N = 8). The same version of a Wechsler Intelligence Scale was administered at both baseline and follow-up assessments...

  6. Group art therapy as an adjunctive treatment for people with schizophrenia: a randomised controlled trial (MATISSE).

    Science.gov (United States)

    Crawford, M J; Killaspy, H; Barnes, T R; Barrett, B; Byford, S; Clayton, K; Dinsmore, J; Floyd, S; Hoadley, A; Johnson, T; Kalaitzaki, E; King, M; Leurent, B; Maratos, A; O'Neill, F A; Osborn, D; Patterson, S; Soteriou, T; Tyrer, P; Waller, D

    2012-01-01

    To examine the clinical effectiveness and cost-effectiveness of referral to group art therapy plus standard care, compared with referral to an activity group plus standard care and standard care alone, among people with schizophrenia. A three-arm, parallel group, single-blind, pragmatic, randomised controlled trial. Participants were randomised via an independent and remote telephone randomisation service using permuted blocks, stratified by study centre. Study participants were recruited from secondary care mental health and social services in four UK centres. Potential participants were aged 18 years or over, had a clinical diagnosis of schizophrenia, confirmed by an examination of case notes, and provided written informed consent. We excluded those who were unable to speak sufficient English to complete the baseline assessment, those with severe cognitive impairment and those already receiving arts therapy. Group art therapy was delivered by registered art therapists according to nationally agreed standards. Groups had up to eight members, lasted for 90 minutes and ran for 12 months. Members were given access to a range of art materials and encouraged to use these to express themselves freely. Activity groups were designed to control for the non-specific effects of group art therapy. Group facilitators offered various activities and encouraged participants to collectively select those they wanted to pursue. Standard care involved follow-up from secondary care mental health services and the option of referral to other services, except arts therapies, as required. Our co-primary outcomes were global functioning (measured using the Global Assessment of Functioning Scale - GAF) and mental health symptoms (measured using the Positive and Negative Syndrome Scale - PANSS) at 24 months. The main secondary outcomes were level of group attendance, social functioning, well-being, health-related quality of life, service utilisation and other costs measured 12 and 24 months

  7. Differential effects of common variants in SCN2A on general cognitive ability, brain physiology, and messenger RNA expression in schizophrenia cases and control individuals.

    Science.gov (United States)

    Dickinson, Dwight; Straub, Richard E; Trampush, Joey W; Gao, Yuan; Feng, Ningping; Xie, Bin; Shin, Joo Heon; Lim, Hun Ki; Ursini, Gianluca; Bigos, Kristin L; Kolachana, Bhaskar; Hashimoto, Ryota; Takeda, Masatoshi; Baum, Graham L; Rujescu, Dan; Callicott, Joseph H; Hyde, Thomas M; Berman, Karen F; Kleinman, Joel E; Weinberger, Daniel R

    2014-06-01

    One approach to understanding the genetic complexity of schizophrenia is to study associated behavioral and biological phenotypes that may be more directly linked to genetic variation. To identify single-nucleotide polymorphisms associated with general cognitive ability (g) in people with schizophrenia and control individuals. Genomewide association study, followed by analyses in unaffected siblings and independent schizophrenia samples, functional magnetic resonance imaging studies of brain physiology in vivo, and RNA sequencing in postmortem brain samples. The discovery cohort and unaffected siblings were participants in the National Institute of Mental Health Clinical Brain Disorders Branch schizophrenia genetics studies. Additional schizophrenia cohorts were from psychiatric treatment settings in the United States, Japan, and Germany. The discovery cohort comprised 339 with schizophrenia and 363 community control participants. Follow-up analyses studied 147 unaffected siblings of the schizophrenia cases and independent schizophrenia samples including a total of an additional 668 participants. Imaging analyses included 87 schizophrenia cases and 397 control individuals. Brain tissue samples were available for 64 cases and 61 control individuals. We studied genomewide association with g, by group, in the discovery cohort. We used selected genotypes to test specific associations in unaffected siblings and independent schizophrenia samples. Imaging analyses focused on activation in the prefrontal cortex during working memory. Brain tissue studies yielded messenger RNA expression levels for RefSeq transcripts. The schizophrenia discovery cohort showed genomewide-significant association of g with polymorphisms in sodium channel gene SCN2A, accounting for 10.4% of g variance (rs10174400, P = 9.27 × 10(-10)). Control individuals showed a trend for g/genotype association with reversed allelic directionality. The genotype-by-group interaction was also genomewide

  8. Foxp2 Controls Synaptic Wiring of Corticostriatal Circuits and Vocal Communication by Opposing Mef2C

    OpenAIRE

    Chen, Yi-Chuan; Kuo, Hsiao-Ying; Bornschein, Ulrich; Takahashi, Hiroshi; Chen, Shih-Yun; Lu, Kuan-Ming; Yang, Hao-Yu; Chen, Gui-May; Lin, Jing-Ruei; Lee, Yi-Hsin; Chou, Yun-Chia; Cheng, Sin-Jhong; Chien, Cheng-Ting; Enard, Wolfgang; Hevers, Wulf

    2016-01-01

    Cortico-basal ganglia circuits are critical for speech and language and are implicated in autism spectrum disorder (ASD), in which language function can be severely affected. We demonstrate that in the striatum, the gene, Foxp2, negatively interacts with the synapse suppressor, Mef2C. We present causal evidence that Mef2C inhibition by Foxp2 in neonatal mouse striatum controls synaptogenesis of corticostriatal inputs and vocalization in neonates. Mef2C suppresses corticostriatal synapse forma...

  9. Synaptic Regulation of a Thalamocortical Circuit Controls Depression-Related Behavior

    OpenAIRE

    Miller, Oliver H; Andreas Bruns; Imen Ben Ammar; Thomas Mueggler; Hall, Benjamin J

    2017-01-01

    The NMDA receptor (NMDAR) antagonist ketamine elicits a long-lasting antidepressant response in patients with treatment-resistant depression. Understanding how antagonism of NMDARs alters synapse and circuit function is pivotal to developing circuit-based therapies for depression. Using virally induced gene deletion, ex vivo optogenetic-assisted circuit analysis, and in vivo chemogenetics and fMRI, we assessed the role of NMDARs in the medial prefrontal cortex (mPFC) in controlling depression...

  10. Synaptic Regulation of a Thalamocortical Circuit Controls Depression-Related Behavior

    Directory of Open Access Journals (Sweden)

    Oliver H. Miller

    2017-08-01

    Full Text Available The NMDA receptor (NMDAR antagonist ketamine elicits a long-lasting antidepressant response in patients with treatment-resistant depression. Understanding how antagonism of NMDARs alters synapse and circuit function is pivotal to developing circuit-based therapies for depression. Using virally induced gene deletion, ex vivo optogenetic-assisted circuit analysis, and in vivo chemogenetics and fMRI, we assessed the role of NMDARs in the medial prefrontal cortex (mPFC in controlling depression-related behavior in mice. We demonstrate that post-developmental genetic deletion of the NMDAR subunit GluN2B from pyramidal neurons in the mPFC enhances connectivity between the mPFC and limbic thalamus, but not the ventral hippocampus, and reduces depression-like behavior. Using intersectional chemogenetics, we show that activation of this thalamocortical circuit is sufficient to elicit a decrease in despair-like behavior. Our findings reveal that GluN2B exerts input-specific control of pyramidal neuron innervation and identify a medial dorsal thalamus (MDT→mPFC circuit that controls depression-like behavior.

  11. A Molecular Circuit Composed of CPEB-1 and c-Jun Controls Growth Hormone-Mediated Synaptic Plasticity in the Mouse Hippocampus

    OpenAIRE

    Zearfoss, N. Ruth; Alarcon, Juan Marcos; Trifilieff, Pierre; Kandel, Eric; Richter, Joel D.

    2008-01-01

    Cytoplasmic polyadenylation element binding protein 1 (CPEB-1) resides at postsynaptic sites in hippocampal neurons in which it controls polyadenylation-induced translation. CPEB-1 knock-out (KO) mice display defects in some forms of synaptic plasticity and hippocampal-dependent memories. To identify CPEB-1-regulated mRNAs, we used proteomics to compare polypeptides in wild-type (WT) and CPEB-1 KO hippocampus. Growth hormone (GH) was reduced in the KO hippocampus, as were the GH signaling mol...

  12. Brain Oscillatory Correlates of Altered Executive Functioning in Positive and Negative Symptomatic Schizophrenia Patients and Healthy Controls.

    Science.gov (United States)

    Berger, Barbara; Minarik, Tamas; Griesmayr, Birgit; Stelzig-Schoeler, Renate; Aichhorn, Wolfgang; Sauseng, Paul

    2016-01-01

    Working Memory and executive functioning deficits are core characteristics of patients suffering from schizophrenia. Electrophysiological research indicates that altered patterns of neural oscillatory mechanisms underpinning executive functioning are associated with the psychiatric disorder. Such brain oscillatory changes have been found in local amplitude differences at gamma and theta frequencies in task-specific cortical areas. Moreover, interregional interactions are also disrupted as signified by decreased phase coherence of fronto-posterior theta activity in schizophrenia patients. However, schizophrenia is not a one-dimensional psychiatric disorder but has various forms and expressions. A common distinction is between positive and negative symptomatology but most patients have both negative and positive symptoms to some extent. Here, we examined three groups-healthy controls, predominantly negative, and predominantly positive symptomatic schizophrenia patients-when performing a working memory task with increasing cognitive demand and increasing need for executive control. We analyzed brain oscillatory activity in the three groups separately and investigated how predominant symptomatology might explain differences in brain oscillatory patterns. Our results indicate that differences in task specific fronto-posterior network activity (i.e., executive control network) expressed by interregional phase synchronization are able to account for working memory dysfunctions between groups. Local changes in the theta and gamma frequency range also show differences between patients and healthy controls, and more importantly, between the two patient groups. We conclude that differences in oscillatory brain activation patterns related to executive processing can be an indicator for positive and negative symptomatology in schizophrenia. Furthermore, changes in cognitive and especially executive functioning in patients are expressed by alterations in a task-specific fronto

  13. Effects of extended cannabis abstinence on clinical symptoms in cannabis dependent schizophrenia patients versus non-psychiatric controls.

    Science.gov (United States)

    Rabin, Rachel A; Kozak, Karolina; Zakzanis, Konstantine K; Remington, Gary; George, Tony P

    2017-03-08

    Rates of cannabis use among patients with schizophrenia are high, however little is understood about clinical effects of continued cannabis use and cessation after illness onset. Therefore, we investigated the effects of 28-days of cannabis abstinence on psychotic and depressive symptomatology in cannabis dependent patients with schizophrenia. Males with cannabis dependence and co-morbid schizophrenia (n=19) and non-psychiatric controls (n=20) underwent 28-days of monitored cannabis abstinence. Clinical symptoms were assessed at baseline and then weekly. Abstinence was encouraged using weekly therapy sessions and contingency reinforcement, confirmed by twice-weekly urine assays. Forty-two percent (8/19) of patients and 55% (11/20) of controls achieved 28-days of sustained cannabis abstinence. In patients, PANSS subscores did not change over time irrespective of abstinence status. In contrast, patient abstainers demonstrated a more pronounced reduction in depression scores compared to non-abstainers, however, the Abstinence Status x Time interaction was non-significant. Short-term (28-days) cannabis abstinence is not associated with improvement in psychotic symptoms, but may be associated with improvement in depressive symptomatology in patients with schizophrenia. Future studies employing larger samples as well as a continuous cannabis-using group may help to better characterize the causal effects of cannabis on symptom outcomes in this disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Tai-Chi for Residential Patients with Schizophrenia on Movement Coordination, Negative Symptoms, and Functioning: A Pilot Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Rainbow T. H. Ho

    2012-01-01

    Full Text Available Objective. Patients with schizophrenia residing at institutions often suffer from negative symptoms, motor, and functional impairments more severe than their noninstitutionalized counterparts. Tai-chi emphasizes body relaxation, alertness, and movement coordination with benefits to balance, focus, and stress relief. This pilot study explored the efficacy of Tai-chi on movement coordination, negative symptoms, and functioning disabilities towards schizophrenia. Methods. A randomized waitlist control design was adopted, where participants were randomized to receive either the 6-week Tai-chi program and standard residential care or only the latter. 30 Chinese patients with schizophrenia were recruited from a rehabilitation residency. All were assessed on movement coordination, negative symptoms, and functional disabilities at baseline, following intervention and 6 weeks after intervention. Results. Tai-chi buffered from deteriorations in movement coordination and interpersonal functioning, the latter with sustained effectiveness 6 weeks after the class was ended. Controls showed marked deteriorations in those areas. The Tai-chi group also experienced fewer disruptions to life activities at the 6-week maintenance. There was no significant improvement in negative symptoms after Tai-chi. Conclusions. This study demonstrated encouraging benefits of Tai-chi in preventing deteriorations in movement coordination and interpersonal functioning for residential patients with schizophrenia. The ease of implementation facilitates promotion at institutional psychiatric services.

  15. Dynamic Connectivity States Estimated from Resting fMRI Identify Differences among Schizophrenia, Bipolar Disorder, and Healthy Control Subjects

    Directory of Open Access Journals (Sweden)

    Barnaly eRashid

    2014-11-01

    Full Text Available Schizophrenia and bipolar disorder share significant overlap in clinical symptoms, brain characteristics, and risk genes, and both are associated with dysconnectivity among large-scale brain networks. Resting state functional magnetic resonance imaging (rsfMRI data facilitates studying macroscopic connectivity among distant brain regions. Standard approaches to identifying such connectivity include seed-based correlation and data-driven clustering methods such as independent component analysis (ICA but typically focus on average connectivity. In this study, we utilize ICA on rsfMRI data to obtain intrinsic connectivity networks (ICNs in cohorts of healthy controls (HC and age matched schizophrenia and bipolar disorder patients. Subsequently, we investigated difference in functional network connectivity (FNC, defined as pairwise correlations among the timecourses of ICNs, between healthy controls and patients. We quantified differences in both static (average and dynamic (windowed connectivity during the entire scan duration. Disease-specific differences were identified in connectivity within different dynamic states. Schizophrenia patients showed more differences from healthy subjects than did bipolars, including both hyper and hypo connectivity in one common connectivity state (dynamic state 3. Also group differences between schizophrenia and bipolar patients were identified in patterns (states of connectivity involving the frontal (dynamic state 1 and frontal-parietal regions (dynamic state 3. Our results provide new information about these illnesses and strongly suggest that state-based analyses are critical to avoid averaging together important factors that can help distinguish these clinical groups.

  16. Preserved Learning during the Symbol–Digit Substitution Test in Patients with Schizophrenia, Age-Matched Controls, and Elderly

    Science.gov (United States)

    Cornelis, Claudia; De Picker, Livia J.; Hulstijn, Wouter; Dumont, Glenn; Timmers, Maarten; Janssens, Luc; Sabbe, Bernard G. C.; Morrens, Manuel

    2015-01-01

    Objective: Speed of processing, one of the main cognitive deficits in schizophrenia is most frequently measured with a digit–symbol-coding test. Performance on this test is additionally affected by writing speed and the rate at which symbol–digit relationships are learned, two factors that may be impaired in schizophrenia. This study aims to investigate the effects of sensorimotor speed, short-term learning, and long-term learning on task performance in schizophrenia. In addition, the study aims to explore differences in learning effects between patients with schizophrenia and elderly individuals. Methods: Patients with schizophrenia (N = 30) were compared with age-matched healthy controls (N = 30) and healthy elderly volunteers (N = 30) during the Symbol–Digit Substitution Test (SDST). The task was administered on a digitizing tablet, allowing precise measurements of the time taken to write each digit (writing time) and the time to decode symbols into their corresponding digits (matching time). The SDST was administered on three separate days (day 1, day 2, day 7). Symbol–digit repetitions during the task represented short-term learning and repeating the task on different days represented long-term learning. Results: The repetition of the same symbol–digit combinations within one test and the repetition of the test over days resulted in significant decreases in matching time. Interestingly, these short-term and long-term learning effects were about equal among the three groups. Individual participants showed a large variation in the rate of short-term learning. In general, patients with schizophrenia had the longest matching time whereas the elderly had the longest writing time. Writing time remained the same over repeated testing. Conclusion: The rate of learning and sensorimotor speed was found to have a substantial influence on the SDST score. However, a large individual variation in learning rate should be taken into account in the

  17. Regulation of extrasynaptic signaling by polysialylated NCAM: Impact for synaptic plasticity and cognitive functions.

    Science.gov (United States)

    Varbanov, Hristo; Dityatev, Alexander

    2017-06-01

    The activation of synaptic N-methyl-d-aspartate-receptors (NMDARs) is crucial for induction of synaptic plasticity and supports cell survival, whereas activation of extrasynaptic NMDARs inhibits long-term potentiation and triggers neurodegeneration. A soluble polysialylated form of the neural cell adhesion molecule (polySia-NCAM) suppresses signaling through peri-/extrasynaptic GluN2B-containing NMDARs. Genetic or enzymatic manipulations blocking this mechanism result in impaired synaptic plasticity and learning, which could be repaired by reintroduction of polySia, or inhibition of either GluN1/GluN2B receptors or downstream signaling through RasGRF1 and p38 MAP kinase. Ectodomain shedding of NCAM, and hence generation of soluble NCAM, is controlled by metalloproteases of a disintegrin and metalloprotease (ADAM) family. As polySia-NCAM is predominantly associated with GABAergic interneurons in the prefrontal cortex, it is noteworthy that EphrinA5/EphA3-induced ADAM10 activity promotes polySia-NCAM shedding in these neurons. Thus, in addition to the well-known regulation of synaptic NMDARs by the secreted molecule Reelin, shed polySia-NCAM may restrain activation of extrasynaptic NMDARs. These data support a concept that GABAergic interneuron-derived extracellular proteins control the balance in synaptic/extrasynaptic NMDAR-mediated signaling in principal cells. Strikingly, dysregulation of Reelin or polySia expression is linked to schizophrenia. Thus, targeting of the GABAergic interneuron-principle cell communication and restoring the balance in synaptic/extrasynaptic NMDARs represent promising strategies for treatment of psychiatric diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Overcoming Disembodiment: The Effect of Movement Therapy on Negative Symptoms in Schizophrenia- A Multicenter Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Lily Anna Lina Martin

    2016-03-01

    Full Text Available AbstractObjective. Negative symptoms of patients with Schizophrenia are resistant to medical treatment or conventional group therapy. Understanding schizophrenia as a form of disembodiment of the self, a number of scientists have argued that the approach of embodiment and associated embodied therapies, such as Dance and Movement Therapy (DMT or Body Psychotherapy (BPT, may be more suitable to explain the psychopathology underlying the mental illness and to address its symptoms. Hence the present randomized controlled trial (DRKS00009828, http://apps.who.int/trialsearch/ aimed to examine the effectiveness of manualized movement therapy (BPT/DMT on the negative symptoms of patients with schizophrenia.Method. A total of 68 out-patients with a diagnosis of a schizophrenia spectrum disorder were randomly allocated to either the treatment (n = 44, 20 sessions of BPT/DMT or the control condition (n = 24, treatment as usual (TAU. Changes in negative symptom scores on the Scale for the Assessment of Negative Symptoms (SANS were analyzed using Analysis of Covariance (ANCOVA with Simpson-Angus Scale (SAS scores as covariates in order to control for side effects of antipsychotic medication.Results. After twenty sessions of treatment (BPT/DMT or TAU, patients receiving movement therapy had significantly lower negative symptom scores (SANS total score, blunted affect, attention. Effect sizes were moderate and mean symptom reduction in the treatment group was 20.65%.Conclusion. The study demonstrates that embodied therapies, such as BPT/DMT, are highly effective in the treatment of patients with schizophrenia. Results strongly suggest that BPT/DMT should be embedded in the daily clinical routine.

  19. Physical Exercise Keeps the Brain Connected: Biking Increases White Matter Integrity in Patients With Schizophrenia and Healthy Controls.

    Science.gov (United States)

    Svatkova, Alena; Mandl, René C W; Scheewe, Thomas W; Cahn, Wiepke; Kahn, René S; Hulshoff Pol, Hilleke E

    2015-07-01

    It has been shown that learning a new skill leads to structural changes in the brain. However, it is unclear whether it is the acquisition or continuous practicing of the skill that causes this effect and whether brain connectivity of patients with schizophrenia can benefit from such practice. We examined the effect of 6 months exercise on a stationary bicycle on the brain in patients with schizophrenia and healthy controls. Biking is an endemic skill in the Netherlands and thus offers an ideal situation to disentangle the effects of learning vs practice. The 33 participating patients with schizophrenia and 48 healthy individuals were assigned to either one of two conditions, ie, physical exercise or life-as-usual, balanced for diagnosis. Diffusion tensor imaging brain scans were made prior to and after intervention. We demonstrate that irrespective of diagnosis regular physical exercise of an overlearned skill, such as bicycling, significantly increases the integrity, especially of motor functioning related, white matter fiber tracts whereas life-as-usual leads to a decrease in fiber integrity. Our findings imply that exercise of an overlearned physical skill improves brain connectivity in patients and healthy individuals. This has important implications for understanding the effect of fitness programs on the brain in both healthy subjects and patients with schizophrenia. Moreover, the outcome may even apply to the nonphysical realm. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Smoking and schizophrenia in population cohorts of Swedish women and men: a prospective co-relative control study.

    Science.gov (United States)

    Kendler, Kenneth S; Lönn, Sara Larsson; Sundquist, Jan; Sundquist, Kristina

    2015-11-01

    The purpose of this study was to clarify the causes of the smoking-schizophrenia association. Using Cox proportional hazard and co-relative control models, the authors predicted future risk for a diagnosis of schizophrenia or nonaffective psychosis from the smoking status of 1,413,849 women and 233,879 men from, respectively, the Swedish birth and conscript registries. Smoking was assessed in women at a mean age of 27 and in men at a mean age of 18. The mean age at end of follow-up was 46 for women and 26 for men. Hazard ratios for first-onset schizophrenia were elevated both for light smoking (2.21 [95% CI=1.90-2.56] for women and 2.15 [95% CI=1.25-3.44] for men) and heavy smoking (3.45 [95% CI=2.95-4.03] for women and 3.80 [95% CI=1.19-6.60] for men). These associations did not decline when schizophrenia onsets 3-5 years after smoking assessment were censored. When age, socioeconomic status, and drug abuse were controlled for, hazard ratios declined only modestly in both samples. Women who smoked into late pregnancy had a much higher risk for schizophrenia than those who quit early. Hazard ratios predicting nonaffective psychosis in the general population, in cousins, in half siblings, and in full siblings discordant for heavy smoking were, respectively, 2.67, 2.71, 2.54, and 2.18. A model utilizing all relative pairs predicted a hazard ratio of 1.69 (95% CI=1.17-2.44) for nonaffective psychosis in the heavy-smoking member of discordant monozygotic twin pairs. Smoking prospectively predicts risk for schizophrenia. This association does not arise from smoking onset during a schizophrenic prodrome and demonstrates a clear dose-response relationship. While little of this association is explained by epidemiological confounders, a portion arises from common familial/genetic risk factors. However, in full siblings and especially monozygotic twins discordant for smoking, risk for nonaffective psychosis is appreciably higher in the smoking member. These results can help

  1. Association between a disrupted-in-schizophrenia 1 (DISC1) single nucleotide polymorphism and schizophrenia in a combined Scandinavian case-control sample

    DEFF Research Database (Denmark)

    Saetre, Peter; Agartz, Ingrid; De Franciscis, Alessandra

    2008-01-01

    Disrupted-in-schizophrenia-1 (DISC1), located on chromosome 1q42.1, is linked to rare familial schizophrenia in a large Scottish family. The chromosomal translocation that segregates with the disease results in a truncated protein that impairs neurite outgrowth and proper development of the cereb......Disrupted-in-schizophrenia-1 (DISC1), located on chromosome 1q42.1, is linked to rare familial schizophrenia in a large Scottish family. The chromosomal translocation that segregates with the disease results in a truncated protein that impairs neurite outgrowth and proper development...

  2. The Structure of Neurexin 1[alpha] Reveals Features Promoting a Role as Synaptic Organizer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Fang; Venugopal, Vandavasi; Murray, Beverly; Rudenko, Gabby (Michigan)

    2014-10-02

    {alpha}-Neurexins are essential synaptic adhesion molecules implicated in autism spectrum disorder and schizophrenia. The {alpha}-neurexin extracellular domain consists of six LNS domains interspersed by three EGF-like repeats and interacts with many different proteins in the synaptic cleft. To understand how {alpha}-neurexins might function as synaptic organizers, we solved the structure of the neurexin 1{alpha} extracellular domain (n1{alpha}) to 2.65 {angstrom}. The L-shaped molecule can be divided into a flexible repeat I (LNS1-EGF-A-LNS2), a rigid horseshoe-shaped repeat II (LNS3-EGF-B-LNS4) with structural similarity to so-called reelin repeats, and an extended repeat III (LNS5-EGF-B-LNS6) with controlled flexibility. A 2.95 {angstrom} structure of n1{alpha} carrying splice insert SS3 in LNS4 reveals that SS3 protrudes as a loop and does not alter the rigid arrangement of repeat II. The global architecture imposed by conserved structural features enables {alpha}-neurexins to recruit and organize proteins in distinct and variable ways, influenced by splicing, thereby promoting synaptic function.

  3. Implicit and explicit affective associations towards cannabis use in patients with recent-onset schizophrenia and healthy controls.

    Science.gov (United States)

    Dekker, N; Smeerdijk, A M; Wiers, R W; Duits, J H; van Gelder, G; Houben, K; Schippers, G; Linszen, D H; de Haan, L

    2010-08-01

    Cannabis use is common in patients with recent-onset schizophrenia and this is associated with poor disease outcome. More insight in the cognitive-motivational processes related to cannabis use in schizophrenia may inform treatment strategies. The present study is the first known to compare implicit and explicit cannabis associations in individuals with and without psychotic disorder. Participants consisted of 70 patients with recent-onset psychotic disorder and 61 healthy controls with various levels of cannabis use. Three Single-Category Implicit Association Tests (SC-IAT) were used to assess 'relaxed', 'active' and 'negative' implicit associations towards cannabis use. Explicit expectancies of cannabis use were assessed with a questionnaire using the same words as the SC-IAT. There were no differences in implicit associations between patients and controls; however, patients scored significantly higher on explicit negative affect expectancies than controls. Both groups demonstrated strong negative implicit associations towards cannabis use. Explicit relaxed expectancies were the strongest predictors of cannabis use and craving. There was a trend for implicit active associations to predict craving. The findings indicate that patients suffering from schizophrenia have associations towards cannabis similar to controls, but they have stronger negative explicit cannabis associations. The strong negative implicit associations towards cannabis could imply that users of cannabis engage in a behaviour they do not implicitly like. Explicit relaxing expectancies of cannabis might be an important mediator in the continuation of cannabis use in patients and controls.

  4. Demodex Parazytes in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Mehmet Hanifi Kokacya

    2016-04-01

    Full Text Available Aim: Demodex parazytes are commonly present all over the world, especially in facial region of humans. Demodex spp. are assumed to be more common in schizophrenia due to partial suppression of immune system and lack of good self-care. The present study aimed to investigate the prevalence of Demodex ectoparasites in schizophrenia patients. Material and Method: In the study, 31 patients with a diagnosis of schizophrenia and 30 subjects without any psychiatric disorder or skin disease were subjected to standard superficial skin biopsy technique to determine Demodex spp. Results: Demodex spp. were found positive in nine schizophrenia patients and it was found positive in two healthy controls. Considering the prevalence of Demodex spp., a significant relationship is found between schizophrenia patients and normal controls (p

  5. Add-on fluvoxamine treatment for schizophrenia: an updated meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Kishi, Taro; Hirota, Tomoya; Iwata, Nakao

    2013-12-01

    We performed an updated meta-analysis of fluvoxamine add-on therapy in patients with schizophrenia treated with antipsychotics based on two previous meta-analyses (Sepehry et al., in J Clin Psychiatry 68:604-610, 2007 and Singh et al., in Br J Psychiatry J Mental Sci 197:174-179, 2010). We searched PubMed, the Cochrane Library database, and PsycINFO up to January 2013. We conducted a systematic review and meta-analysis of individual patient data from randomized controlled trials comparing fluvoxamine add-on therapy with placebo. The risk ratio (RR), 95 % confidence intervals (CI), and standardized mean difference (SMD) were calculated. Seven studies (total n = 272) were identified. These included two clozapine studies, one olanzapine study, one second-generation antipsychotic (SGA) monotherapy study, and three first-generation antipsychotics (FGAs) monotherapy studies. There were significant effect of fluvoxamine add-on therapy on overall (SMD = -0.46, CI = -0.75 to -0.16, p = 0.003, I (2) = 0 %, 5 studies, n = 180) and negative symptoms (SMD = -0.44, CI = -0.74 to -0.14, p = 0.004, I (2) = 0 %, 5 studies, n = 180). However, fluvoxamine add-on therapy showed no significant effects on positive symptoms, depressive symptoms, and discontinuations from any cause or adverse events. Fluvoxamine add-on therapy in patients primarily treated with SGAs improved overall (p = 0.02) but not negative symptoms (p = 0.31). On the other hand, fluvoxamine add-on therapy in patients primarily treated with FGAs improved both overall (p = 0.04) and negative symptoms (p = 0.004) compared with control groups. Our results suggest that fluvoxamine add-on therapy is more beneficial on the psychopathology (especially negative symptoms) than controls in patients with schizophrenia who are primarily treated with FGAs. Given that a small number of studies were included in this meta-analysis, the results should be treated with caution.

  6. Emerging Links between Homeostatic Synaptic Plasticity and Neurological Disease

    Directory of Open Access Journals (Sweden)

    Dion eDickman

    2013-11-01

    Full Text Available Homeostatic signaling systems are ubiquitous forms of biological regulation, having been studied for hundreds of years in the context of diverse physiological processes including body temperature and osmotic balance. However, only recently has this concept been brought to the study of excitatory and inhibitory electrical activity that the nervous system uses to establish and maintain stable communication. Synapses are a primary target of neuronal regulation with a variety of studies over the past 15 years demonstrating that these cellular junctions are under bidirectional homeostatic control. Recent work from an array of diverse systems and approaches has revealed exciting new links between homeostatic synaptic plasticity and a variety of seemingly disparate neurological and psychiatric diseases. These include autism spectrum disorders, intellectual disabilities, schizophrenia, and Fragile X Syndrome. Although the molecular mechanisms through which defective homeostatic signaling may lead to disease pathogenesis remain unclear, rapid progress is likely to be made in the coming years using a powerful combination of genetic, imaging, electrophysiological, and next generation sequencing approaches. Importantly, understanding homeostatic synaptic plasticity at a cellular and molecular level may lead to developments in new therapeutic innovations to treat these diseases. In this review we will examine recent studies that demonstrate homeostatic control of postsynaptic protein translation, retrograde signaling, and presynaptic function that may contribute to the etiology of complex neurological and psychiatric diseases.

  7. The role of dehydroepiandrosterone (DHEA) in schizophrenia.

    Science.gov (United States)

    Vuksan-Ćusa, Bjanka; Šagud, Marina; Radoš, Iva

    2016-03-01

    Neurosteroid dehydropiandrosterone (DHEA) and its sulphate (DHEAS) are reported to have modulatory effects on neuronal excitabillity and synaptic plasticity. DHEA and DHEAS are synthesized in central and peripheral nervous system from cholesterol or steroidal precursors imported from peripheral sources. There is accumulating evidence that alterations in DHEA(S) levels may be involved in the pathophysiology of schizophrenia. The possible effects of DHEA(S) as augmentation therapy in schizophrenia, related to psychological and somatic aspects of this disease, are discussed.

  8. Thought Disorder in Schizophrenia and Bipolar Disorder Probands, Their Relatives, and Nonpsychiatric Controls.

    Science.gov (United States)

    Morgan, Charity J; Coleman, Michael J; Ulgen, Ayse; Boling, Lenore; Cole, Jonathan O; Johnson, Frederick V; Lerbinger, Jan; Bodkin, J Alexander; Holzman, Philip S; Levy, Deborah L

    2017-05-01

    Thought disorder (TD) has long been associated with schizophrenia (SZ) and is now widely recognized as a symptom of mania and other psychotic disorders as well. Previous studies have suggested that the TD found in the clinically unaffected relatives of SZ, schizoaffective and bipolar probands is qualitatively similar to that found in the probands themselves. Here, we examine which quantitative measures of TD optimize the distinction between patients with diagnoses of SZ and bipolar disorder with psychotic features (BP) from nonpsychiatric controls (NC) and from each other. In addition, we investigate whether these same TD measures also distinguish their respective clinically unaffected relatives (RelSZ, RelBP) from controls as well as from each other. We find that deviant verbalizations are significantly associated with SZ and are co-familial in clinically unaffected RelSZ, but are dissociated from, and are not co-familial for, BP disorder. In contrast, combinatory thinking was nonspecifically associated with psychosis, but did not aggregate in either group of relatives. These results provide further support for the usefulness of TD for identifying potential non-penetrant carriers of SZ-risk genes, in turn enhancing the power of genetic analyses. These findings also suggest that further refinement of the TD phenotype may be needed in order to be suitable for use in genetic studies of bipolar disorder. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Alcohol use is associated with thinner cerebral cortex and larger ventricles in schizophrenia, bipolar disorder and healthy controls.

    Science.gov (United States)

    Lange, E H; Nerland, S; Jørgensen, K N; Mørch-Johnsen, L; Nesvåg, R; Hartberg, C B; Haukvik, U K; Osnes, K; Melle, I; Andreassen, O A; Agartz, I

    2017-03-01

    Excessive alcohol use is associated with brain damage but less is known about brain effects from moderate alcohol use. Previous findings indicate that patients with severe mental illness, particularly schizophrenia, are vulnerable to alcohol-related brain damage. We investigated the association between levels of alcohol consumption and cortical and subcortical brain structures in schizophrenia and bipolar disorder patients and healthy controls, and investigated for group differences for this association. 1.5 T structural magnetic resonance images were acquired of 609 alcohol-using participants (165 schizophrenia patients, 172 bipolar disorder patients, 272 healthy controls), mean (s.d.) age 34.2 (9.9) years, 52% men. Past year alcohol use was assessed with the Alcohol Use Disorder Identification Test - Consumption part (AUDIT-C). General linear models were used to investigate associations between AUDIT-C score and cortical thickness, surface area, and total brain and subcortical volumes. Increasing AUDIT-C score was linearly associated with thinner cortex in medial and dorsolateral frontal and parieto-occipital regions, and with larger left lateral ventricle volume. There was no significant interaction between AUDIT-C score and diagnostic group. The findings remained significant after controlling for substance use disorders, antipsychotic medication and illness severity. The results show a dose-dependent relationship between alcohol use and thinner cortex and ventricular expansion. The findings are present also at lower levels of alcohol consumption and do not differ between schizophrenia or bipolar disorder patients compared to healthy controls. Our results do not support previous findings of increased vulnerability for alcohol-related brain damage in severe mental illness.

  10. Schizophrenia and Mitochondrial Dysfunction

    Directory of Open Access Journals (Sweden)

    Suleyman Akarsu

    2014-08-01

    Full Text Available Genetic factors play an important role in the development of schizophrenia that the etiology is clearly not known. However, specific inheritance mechanism of this disorder is still unclear. Inheritance of schizophrenia is thought to be polygenic or multifactorial. In the recent studies, mitochondrial function and cerebral energy metabolism abnormalities have been identified in patients with schizophrenia. Cognitive deficits and behavioral abnormalities evident as typically found in the clinical course of schizophrenia may develop due to the affection of neuronal plasticity and brain circuits by impaired function of mitochondria. Some changes were found in patients with schizophrenia compared with control subjects in the researches examining both brain and peripheral tissues. Also, it was seen that antipsychotics used in the treatment of schizophrenia might lead to a progressive reduction in oxidative phosphorylation capacity of mitochondria by inhibition of respiratory chain. Especially the findings of the peripheral tissues in patients with schizophrenia were considered to be used as a biological marker for schizophrenia in these studies. Changes in the mitochondria of platelets are considered as a peripheral model for the neurons because of the lack of the platelets' own DNA. These changes reflect the findings of the brain in a variety of neuropsychiatric disorders. At the present time, making the diagnosis of schizophrenia based on only clinical criteria reveal the necessity of finding peripheral biological marker for schizophrenia. Thus further systematic studies investigating the relationship between schizophrenia and changes in mitochondrial electron transport chain are required. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 340-354

  11. ADHD and nicotine use in schizophrenia or Asperger syndrome: a controlled study.

    Science.gov (United States)

    Hallerbäck, Maria Unenge; Lugnegård, Tove; Gillberg, Christopher

    2014-07-01

    To examine ADHD prevalence, rating scales, and relationship to nicotine use in adults with schizophrenia or Asperger syndrome. Ninety-five individuals, 41 with schizophrenia and 54 with Asperger syndrome, were included. Self-rating of adult ADHD symptoms with the Wender-Reimherr Adult Attention Deficit Diagnostic Rating Scale (WRAADDS), parent rating of proband's ADHD childhood and adult life symptoms using the Swanson, Nolan, and Pelham Questionnaire (SNAP), and report of clinical ADHD diagnosis were included as ADHD measures. Nicotine use data were compared with data from a population sample. In all, 10% of the schizophrenia group and 30% of the Asperger syndrome group had a clinical ADHD diagnosis. Nicotine dependency in the whole sample was closely linked to ADHD. The prevalence of comorbid ADHD was high in schizophrenia and Asperger syndrome. The WRAADDS self-rating scale for ADHD can be one useful tool for assessing comorbid ADHD in these patient groups. © 2012 SAGE Publications.

  12. Immunomodulatory effects of probiotic supplementation in schizophrenia patients: A randomized, placebo-controlled trial

    NARCIS (Netherlands)

    J.J. Tomasik (Jakub); R.H. Yolken (Robert); S. Bahn (Sabine); F. Dickerson (Faith)

    2015-01-01

    textabstractAlthough peripheral immune system abnormalities have been linked to schizophrenia pathophysiology, standard antipsychotic drugs show limited immunological effects. Thus, more effective treatment approaches are required. Probiotics are microorganisms that modulate the immune response of

  13. Epigenetic mechanisms in schizophrenia.

    Science.gov (United States)

    Akbarian, Schahram

    2014-09-01

    Schizophrenia is a major psychiatric disorder that lacks a unifying neuropathology, while currently available pharmacological treatments provide only limited benefits to many patients. This review will discuss how the field of neuroepigenetics could contribute to advancements of the existing knowledge on the neurobiology and treatment of psychosis. Genome-scale mapping of DMA methylation, histone modifications and variants, and chromosomal loopings for promoter-enhancer interactions and other epigenetic determinants of genome organization and function are likely to provide important clues about mechanisms contributing to dysregulated expression of synaptic and metabolic genes in schizophrenia brain, including the potential links to the underlying genetic risk architecture and environmental exposures. In addition, studies in animal models are providing a rapidly increasing list of chromatin-regulatory mechanisms with significant effects on cognition and complex behaviors, thereby pointing to the therapeutic potential of epigenetic drug targets in the nervous system.

  14. [Metabolic Control, Evaluation and Follow-up Interventions in Patients With Schizophrenia].

    Science.gov (United States)

    Oviedo, Gabriel Fernando; Gómez Restrepo, Carlos; Bohórquez Peñaranda, Adriana; García Valencia, Jenny; Jaramillo, Luis Eduardo; Tamayo, Nathalie; Arenas, María Luisa; Vélez Fernández, Carolina

    2015-01-01

    To determine the laboratory tests, related to metabolic risk that should be practiced to adult patients diagnosed with schizophrenia. To assist the clinician decision-making process about complementary diagnostic evaluation strategies in adult diagnosed with schizophrenia. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. The risk of overall mortality in schizophrenia is higher than in the general population excluding suicide. Results related with mortality associated to antipsychotics showed contradictory results. Metabolic outcomes showed a higher incidence and association with schizophrenia and treatment with antipsychotics (AP). The diagnosis of dyslipidemia in men with schizophrenia appears to be lower in comparison with the general population. However, changes in weight, blood sugar levels, HDL cholesterol and triglycerides are influenced by the use of antipsychotics in general there is a higher risk of developing diabetes mellitus in adults with schizophrenia. Based on the evidence found a plan was formulated for the evaluation of physiological and paraclinical variables during and before the management with AP in adult diagnosed with schizophrenia. The overall quality of evidence is low considering that most of the reports come from observational studies that have risk of bias and some designs have methodological limitations. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  15. Associations between olfactory identification and verbal memory in patients with schizophrenia, first-degree relatives, and non-psychiatric controls.

    Science.gov (United States)

    Compton, Michael T; McKenzie Mack, LaTasha; Esterberg, Michelle L; Bercu, Zachary; Kryda, Aimee D; Quintero, Luis; Weiss, Paul S; Walker, Elaine F

    2006-09-01

    Olfactory identification deficits and verbal memory impairments may represent trait markers for schizophrenia. The aims of this study were to: (1) assess olfactory identification in patients, first-degree relatives, and non-psychiatric controls, (2) determine differences in verbal memory functioning in these three groups, and (3) study correlations between olfactory identification and three specific verbal memory domains. A total of 106 participants-41 patients with schizophrenia or related disorders, 27 relatives, and 38 controls-were assessed with the University of Pennsylvania Smell Identification Test (UPSIT) and the Wechsler Memory Scale-Third Edition. Linear mixed models, accounting for clustering within families and relevant covariates, were used to compare scores across groups and to examine associations between olfactory identification ability and the three verbal memory domains. A group effect was apparent for all four measures, and relatives scored midway between patients and controls on all three memory domains. UPSIT scores were significantly correlated with all three forms of verbal memory. Age, verbal working memory, and auditory recognition delayed memory were independently predictive of UPSIT scores. Impairments in olfactory identification and verbal memory appear to represent two correlated risk markers for schizophrenia, and frontal-temporal deficits likely account for both impairments.

  16. Nicotine and behavioral markers of risk for schizophrenia: a double-blind, placebo-controlled, cross-over study.

    Science.gov (United States)

    Dépatie, Lana; O'Driscoll, Gillian A; Holahan, Anne-Lise V; Atkinson, Victoria; Thavundayil, Joseph X; Kin, N Ng Ying; Lal, Samarthji

    2002-12-01

    We investigated the effect of nicotine on three behavioral markers of risk for schizophrenia: sustained attention (using the Continuous Performance Task (CPT)), antisaccade performance, and smooth pursuit. Smooth pursuit was investigated in two conditions, one in which attention was enhanced (monitoring target changes) and one in which attention was not enhanced (no monitoring). Patients with schizophrenia (n = 15) and controls (n = 14) were given a 14-mg nicotine patch in a double-blind, placebo-controlled, crossover design and plasma nicotine concentrations were monitored. Nicotine concentrations were similar in both groups. A Group x Drug interaction (p interaction (p pursuit gain indicated that nicotine significantly increased pursuit gain in the no-monitoring condition in patients and controls equally, but did not improve pursuit in the monitoring condition. Thus, improvement in pursuit may have been mediated via an effect on attention rather than by an effect on oculomotor function per se. In patients, the magnitude of improvement in attention on nicotine was correlated with the improvement on eye movement tasks. Thus, nicotine improves performance on both attention and oculomotor markers of risk for schizophrenia, possibly via common mechanisms.

  17. Cognitive effects of very low nicotine content cigarettes, with and without nicotine replacement, in smokers with schizophrenia and controls.

    Science.gov (United States)

    AhnAllen, Christopher G; Bidwell, L Cinnamon; Tidey, Jennifer W

    2015-05-01

    Beneficial effects of nicotine on cognitive functioning may contribute to the markedly high rates of smoking among people with schizophrenia. A reduction in the nicotine content of cigarettes to non-addictive levels is being considered as a regulatory strategy for reducing tobacco dependence in the United States. We examined whether switching to very low nicotine content (VLNC) cigarettes impairs cognitive functioning in smokers with and without schizophrenia, andwhether nicotine replacement reverses these effects. Smokers with schizophrenia (SS, n = 29) and control smokers matched on smoking rate but without psychiatric illness (CS, n = 28) smoked usual-brand cigarettes, VLNC cigarettes while wearing 2 placebo patches (PLA), or VLNC cigarettes while wearing 2 nicotine patches totaling 42mg (NIC) for 5hr, and then completed computerized assessments of visual sustained attention, motor speed, visual working memory, processing speed, inhibitory control, and response variability. Across conditions, SS were slower than CS in tasks of motor speed and visual working memory, and had poorer target detectability on a visual sustained attention task. Across groups, functioning in domains of visual sustained attention, inhibitory control, processing speed, and response variability was impaired in the VLNC + PLA condition relative to the usual-brand and VLNC + NIC conditions. Dramatically reducing the nicotine content of cigarettes may impair cognitive functioning in heavy smokers with and without schizophrenia, but the use of nicotine replacement while smoking VLNC cigarettes may preserve cognitive functioning in these smokers. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Synaptic Vesicle Endocytosis

    Science.gov (United States)

    Saheki, Yasunori; De Camilli, Pietro

    2012-01-01

    Neurons can sustain high rates of synaptic transmission without exhausting their supply of synaptic vesicles. This property relies on a highly efficient local endocytic recycling of synaptic vesicle membranes, which can be reused for hundreds, possibly thousands, of exo-endocytic cycles. Morphological, physiological, molecular, and genetic studies over the last four decades have provided insight into the membrane traffic reactions that govern this recycling and its regulation. These studies have shown that synaptic vesicle endocytosis capitalizes on fundamental and general endocytic mechanisms but also involves neuron-specific adaptations of such mechanisms. Thus, investigations of these processes have advanced not only the field of synaptic transmission but also, more generally, the field of endocytosis. This article summarizes current information on synaptic vesicle endocytosis with an emphasis on the underlying molecular mechanisms and with a special focus on clathrin-mediated endocytosis, the predominant pathway of synaptic vesicle protein internalization. PMID:22763746

  19. Reduced heart rate variability in schizophrenia and bipolar disorder compared to healthy controls.

    Science.gov (United States)

    Quintana, D S; Westlye, L T; Kaufmann, T; Rustan, Ø G; Brandt, C L; Haatveit, B; Steen, N E; Andreassen, O A

    2016-01-01

    Despite current diagnostic systems distinguishing schizophrenia (SZ) and bipolar disorder (BD) as separate diseases, emerging evidence suggests they share a number of clinical and epidemiological features, such as increased cardiovascular disease (CVD) risk. It is not well understood if poor cardiac autonomic nervous system regulation, which can be indexed non-invasively by the calculation of heart rate variability (HRV), contributes to these common CVD risk factors in both diseases. We calculated HRV in 47 patients with SZ, 33 patients with BD and 212 healthy controls. Measures of symptom severity were also collected from the patient groups. Heart rate variability was significantly reduced in both these disorders in comparison with the healthy participants; however, there were no HRV differences between disorders. Importantly, these reductions were independent of the medication, age or body mass index effects. There was also preliminary evidence that patients with reduced HRV had increased overall and negative psychosis symptom severity regardless of SZ or BD diagnosis. We suggest that HRV may provide a possible biomarker of CVD risk and symptom severity in severe mental illness. Thus, our results highlight the importance of cardiometabolic screening across SZ and bipolar spectrum disorders. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Ras and Rap signaling in synaptic plasticity and mental disorders.

    Science.gov (United States)

    Stornetta, Ruth L; Zhu, J Julius

    2011-02-01

    The Ras family GTPases (Ras, Rap1, and Rap2) and their downstream mitogen-activated protein kinases (ERK, JNK, and p38MAPK) and PI3K signaling cascades control various physiological processes. In neuronal cells, recent studies have shown that these parallel cascades signal distinct forms of AMPA-sensitive glutamate receptor trafficking during experience-dependent synaptic plasticity and adaptive behavior. Interestingly, both hypo- and hyperactivation of Ras/ Rap signaling impair the capacity of synaptic plasticity, underscoring the importance of a "happy-medium" dynamic regulation of the signaling. Moreover, accumulating reports have linked various genetic defects that either up- or down-regulate Ras/Rap signaling with several mental disorders associated with learning disability (e.g., Alzheimer's disease, Angelman syndrome, autism, cardio-facio-cutaneous syndrome, Coffin-Lowry syndrome, Costello syndrome, Cowden and Bannayan-Riley-Ruvalcaba syndromes, fragile X syndrome, neurofibromatosis type 1, Noonan syndrome, schizophrenia, tuberous sclerosis, and X-linked mental retardation), highlighting the necessity of happy-medium dynamic regulation of Ras/Rap signaling in learning behavior. Thus, the recent advances in understanding of neuronal Ras/Rap signaling provide a useful guide for developing novel treatments for mental diseases.

  1. Effects of sertindole on cognition in clozapine-treated schizophrenia patients - a double-blinded, randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Nielsen, R E; Levander, S; Nielsen, Jimmi

    . Method:  A 12-week, double-blinded, randomized, placebo-controlled, augmentation study of patients treated with clozapine. Participants were randomized 1:1 to receive 16 mg of sertindole or placebo as adjunctive treatment to clozapine. Results:  Participants displayed substantial cognitive deficits......Nielsen RE, Levander S, Thode D, Nielsen J. Effects of sertindole on cognition in clozapine-treated schizophrenia patients. Objective:  To assess the cognitive effects of sertindole augmentation in clozapine-treated patients diagnosed with schizophrenia. Cognition is secondary outcome of the trial...... changes in cognitive test performance, and found no significant correlations. Conclusion:  The clozapine-treated patients displayed marked cognitive deficits at baseline. Adding sertindole did not improve or worsen cognitive functioning, which is in line with previous negative studies of the effect...

  2. Comprehensive treatments for social cognitive deficits in schizophrenia: A critical review and effect-size analysis of controlled studies.

    Science.gov (United States)

    Kurtz, Matthew M; Gagen, Emily; Rocha, Nuno B F; Machado, Sergio; Penn, David L

    2016-02-01

    Recent advances in psychosocial treatments for schizophrenia have targeted social cognitive deficits. A critical literature review and effect-size (ES) analysis was conducted to investigate the efficacy of comprehensive programs of social cognitive training in schizophrenia. Results revealed 16 controlled studies consisting of seven models of comprehensive treatment with only three of these treatment models investigated in more than one study. The effects of social cognitive training were reported in 11/15 studies that included facial affect recognition skills (ES=.84) and 10/13 studies that included theory-of-mind (ES=.70) as outcomes. Less than half (4/9) of studies that measured attributional style as an outcome reported effects of treatment, but effect sizes across studies were significant (ESs=.30-.52). The effect sizes for symptoms were modest, but, with the exception of positive symptoms, significant (ESs=.32-.40). The majority of trials were randomized (13/16), selected active control conditions (11/16) and included at least 30 participants (12/16). Concerns for this area of research include the absence of blinded outcome raters in more than 50% of trials and low rates of utilization of procedures for maintaining treatment fidelity. These findings provide preliminary support for the broader use of comprehensive social cognitive training procedures as a psychosocial intervention for schizophrenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. In and out of control: brain mechanisms linking fluency of action selection to self-agency in patients with schizophrenia.

    Science.gov (United States)

    Voss, Martin; Chambon, Valérian; Wenke, Dorit; Kühn, Simone; Haggard, Patrick

    2017-08-01

    Sense of agency refers to the feeling of control over one's actions, and their consequences. It involves both predictive processes linked to action control, and retrospective 'sense-making' causal inferences. Schizophrenia has been associated with impaired predictive processing, but the underlying mechanisms that impair patients' sense of agency remain unclear. We introduce a new 'prospective' aspect of agency and show that subliminally priming an action not only influences response times, but also influences reported sense of agency over subsequent action outcomes. This effect of priming was associated with altered connectivity between frontal areas and the angular gyrus. The effects on response times and on frontal action selection mechanisms were similar in patients with schizophrenia and in healthy volunteers. However, patients showed no effects of priming on sense of agency, no priming-related activation of angular gyrus, and no priming-related changes in fronto-parietal connectivity. We suggest angular gyrus activation reflects the experiences of agency, or non-agency, in part by processing action selection signals generated in the frontal lobes. The altered action awareness that characterizes schizophrenia may be due to impaired communication between these areas. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. A 20-week program of resistance or concurrent exercise improves symptoms of schizophrenia: results of a blind, randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Bruna Andrade e Silva

    2015-01-01

    Full Text Available Objective:To evaluate the effects of 20 weeks of resistance and concurrent training on psychotic and depressive symptoms, quality of life outcomes, and serum IGF-1, IGFBP-3, and brain-derived neurotrophic factor (BDNF concentrations in patients with schizophrenia.Methods:In this blind, randomized controlled clinical trial, 34 patients with schizophrenia were assigned to one of three groups: control (CTRL, n=13, resistance exercise (RESEX, n=12, or concurrent exercise (CONCEX, n=9. Symptoms, quality of life, strength, and other variables were assessed.Results:A significant time-by-group interaction was found for the RESEX and CONCEX groups on the Positive and Negative Syndrome Scale (PANSS total score for disease symptoms (p = 0.007, positive symptoms (p = 0.003, and on the arm extension one-repetition maximum (1RM test (p = 0.016. In addition, significant improvements on negative symptoms (p = 0.027, on the role-physical domain of the Short Form-36 Health Survey (p = 0.019, and on the chest press 1RM test (p = 0.040 were observed in the RESEX group. No changes were observed for the other variables investigated.Conclusions:In this sample of patients with schizophrenia, 20 weeks of resistance or concurrent exercise program improved disease symptoms, strength, and quality of life. ClinicalTrials.gov: NCT01674543.

  5. Persistent deficits in hippocampal synaptic plasticity accompany losses of hippocampus-dependent memory in a rodent model of psychosis.

    Science.gov (United States)

    Wiescholleck, Valentina; Manahan-Vaughan, Denise

    2013-01-01

    Irreversible N-methyl-D-aspartate receptor (NMDAR) antagonism is known to provoke symptoms of psychosis and schizophrenia in healthy humans. NMDAR hypofunction is believed to play a central role in the pathophysiology of both disorders and in an animal model of psychosis, that is based on irreversible antagonism of NMDARs, pronounced deficits in hippocampal synaptic plasticity have been reported shortly after antagonist treatment. Here, we examined the long-term consequences for long-term potentiation (LTP) of a single acute treatment with an irreversible antagonist and investigated whether deficits are associated with memory impairments. The ability to express LTP at the perforant pathway - dentate gyrus synapse, as well as object recognition memory was assessed 1, 2, 3, and 4 weeks after a single treatment of the antagonist, MK801. Here, LTP in freely behaving rats was significantly impaired at all time-points compared to control LTP before treatment. Object recognition memory was also significantly poorer in MK801-treated compared to vehicle-treated animals for several weeks after treatment. Histological analysis revealed no changes in brain tissue. Taken together, these data support that acute treatment with an irreversible NMDAR-antagonist persistently impairs hippocampal functioning on behavioral, as well as synaptic levels. The long-term deficits in synaptic plasticity may underlie the cognitive impairments that are associated with schizophrenia-spectrum disorders.

  6. Persistent deficits in hippocampal synaptic plasticity accompany losses of hippocampus-dependent memory in a rodent model of psychosis

    Directory of Open Access Journals (Sweden)

    Valentina eWiescholleck

    2013-03-01

    Full Text Available Irreversible N-methyl-D-aspartate receptor (NMDAR antagonism is known to provoke symptoms of psychosis and schizophrenia in healthy humans. NMDAR hypofunction is believed to play a central role in the pathophysiology of both disorders and in an animal model of psychosis, that is based on irreversible antagonism of NMDARs, pronounced deficits in hippocampal synaptic plasticity have been reported shortly after antagonist treatment. Here, we examined the long-term consequences for long-term potentiation (LTP of a single acute treatment with an irreversible antagonist and investigated whether deficits are associated with memory impairments.The ability to express long-term potentiation (LTP at the perforant pathway – dentate gyrus synapse, as well as object recognition memory was assessed 1, 2, 3 and 4 weeks after a single -treatment of the antagonist, MK801. Here, LTP in freely behaving rats was significantly impaired at all time-points compared to control LTP before treatment. Object recognition memory was also significantly poorer in MK801-treated compared to vehicle-treated animals for several weeks after treatment. Histological analysis revealed no changes in brain tissue.Taken together, these data support that acute treatment with an irreversible NMDAR antagonist persistently impairs hippocampal functioning on behavioral, as well as synaptic levels. The long-term deficits in synaptic plasticity may underlie the cognitive impairments that are associated with schizophrenia-spectrum disorders.

  7. CACNA1C risk variant and amygdala activity in bipolar disorder, schizophrenia and healthy controls.

    Directory of Open Access Journals (Sweden)

    Martin Tesli

    Full Text Available OBJECTIVES: Several genetic studies have implicated the CACNA1C SNP rs1006737 in bipolar disorder (BD and schizophrenia (SZ pathology. This polymorphism was recently found associated with increased amygdala activity in healthy controls and patients with BD. We performed a functional Magnetic Resonance Imaging (fMRI study in a sample of BD and SZ cases and healthy controls to test for altered amygdala activity in carriers of the rs1006737 risk allele (AA/AG, and to investigate if there were differences across the diagnostic groups. METHODS: Rs1006737 was genotyped in 250 individuals (N = 66 BD, 61 SZ and 123 healthy controls, all of Northern European origin, who underwent an fMRI negative faces matching task. Statistical tests were performed with a model correcting for sex, age, diagnostic category and medication status in the total sample, and then in each diagnostic group. RESULTS: In the total sample, carriers of the risk allele had increased activation in the left amygdala. Group-wise analyses showed that this effect was significant in the BD group, but not in the other diagnostic groups. However, there was no significant interaction effect for the risk allele between BD and the other groups. CONCLUSIONS: These results indicate that CACNA1C SNP rs1006737 affects amygdala activity during emotional processing across all diagnostic groups. The current findings add to the growing body of knowledge of the pleiotropic effect of this polymorphism, and further support that ion channel dysregulation is involved in the underlying mechanisms of BD and SZ.

  8. Decreased expression of Sprouty2 in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder: a correlation with BDNF expression.

    Directory of Open Access Journals (Sweden)

    Anilkumar Pillai

    Full Text Available BACKGROUND: Current theories on the pathophysiology of schizophrenia suggest altered brain plasticity such as decreased neural proliferation and migration, delayed myelination, and abnormal synaptic modeling, in the brain of subjects with schizophrenia. Though functional alterations in BDNF, which plays important role in neuroplasticity, are implicated in many abnormalities found in schizophrenia, the regulatory mechanism(s involved in the abnormal signaling of BDNF in schizophrenia is not clear. The present study investigated whether Sprouty2, a regulator of growth factor signaling, is abnormally expressed in schizophrenia, and is associated with the changes in BDNF mRNA in this disorder. The potential effect of antipsychotic drugs on Sprouty2 expression was tested in adult rats. METHODS AND FINDINGS: Sprouty2 and BDNF gene expression were analyzed in dorsolateral prefrontal cortex samples from the Stanley Array Collection. Quantitative real-time PCR analysis of RNA in 100 individuals (35 with schizophrenia, 31 with bipolar disorder, and 34 psychiatrically normal controls showed significantly decreased expression of Sprouty2 and BDNF in both schizophrenia and bipolar disorder. Moreover, a significant correlation between these two genes existed in control, schizophrenia and bipolar subjects. Long-term treatment with antipsychotic drugs, haloperidol and olanzapine, showed differential effects on both Sprouty2 and BDNF mRNA and protein levels in the frontal cortex of rats. CONCLUSION: These findings demonstrating decreased expression of Sprouty2 associated with changes in BDNF, suggest the possibility that these decreases are secondary to treatment rather than to factors that are significant in the disease process of either schizophrenia and/or bipolar disorder. Further exploration of Sprouty2-related signal transduction pathways may be helpful to design novel treatment strategies for these disorders.

  9. Decreased expression of Sprouty2 in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder: a correlation with BDNF expression.

    Science.gov (United States)

    Pillai, Anilkumar

    2008-03-12

    Current theories on the pathophysiology of schizophrenia suggest altered brain plasticity such as decreased neural proliferation and migration, delayed myelination, and abnormal synaptic modeling, in the brain of subjects with schizophrenia. Though functional alterations in BDNF, which plays important role in neuroplasticity, are implicated in many abnormalities found in schizophrenia, the regulatory mechanism(s) involved in the abnormal signaling of BDNF in schizophrenia is not clear. The present study investigated whether Sprouty2, a regulator of growth factor signaling, is abnormally expressed in schizophrenia, and is associated with the changes in BDNF mRNA in this disorder. The potential effect of antipsychotic drugs on Sprouty2 expression was tested in adult rats. Sprouty2 and BDNF gene expression were analyzed in dorsolateral prefrontal cortex samples from the Stanley Array Collection. Quantitative real-time PCR analysis of RNA in 100 individuals (35 with schizophrenia, 31 with bipolar disorder, and 34 psychiatrically normal controls) showed significantly decreased expression of Sprouty2 and BDNF in both schizophrenia and bipolar disorder. Moreover, a significant correlation between these two genes existed in control, schizophrenia and bipolar subjects. Long-term treatment with antipsychotic drugs, haloperidol and olanzapine, showed differential effects on both Sprouty2 and BDNF mRNA and protein levels in the frontal cortex of rats. These findings demonstrating decreased expression of Sprouty2 associated with changes in BDNF, suggest the possibility that these decreases are secondary to treatment rather than to factors that are significant in the disease process of either schizophrenia and/or bipolar disorder. Further exploration of Sprouty2-related signal transduction pathways may be helpful to design novel treatment strategies for these disorders.

  10. Childhood Schizophrenia

    Science.gov (United States)

    ... of onset presents special challenges for diagnosis, treatment, education, and emotional and social development. Schizophrenia is a chronic condition that requires lifelong treatment. Identifying and starting treatment for childhood schizophrenia ...

  11. 5-HT3 antagonist for cognition improvement in schizophrenia: a double blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Neyousha Mohammadi

    2010-01-01

    Full Text Available   Abstract   Introduction: Patients with schizophrenia characteristically exhibit cognitive deficits. The level of cognitive impairment is found to predict the functional outcome of the illness more strongly than the severity of positive or negative symptoms. The purpose of this study was to assess the efficacy of ondansetron, a 5-HT3 receptor antagonist as an adjuvant agent in the treatment of chronic schizophrenia in particular for cognitive impairments.   Methods: This investigation was a 12-week, double blind study of parallel groups of patients with stable chronic schizophrenia. Thirty patients were recruited from inpatient and outpatient departments. All participants met Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR criteria for schizophrenia. To be eligible, patients were required to have been treated with a stable dose of risperidone as their primary antipsychotic treatment for a minimum period of 8 weeks. The subjects were randomized to receive ondansetron (8 mg/day or the placebo in addition to risperidone. Cognition was measured by a cognitive battery. Patients were assessed at baseline and after 8, and 12 weeks after the medication started.   Results: Administration of ondansetron significantly improved visual memory based on improvement on visual reproduction, visual paired associate and figural memory sub tests of Wechsler Memory Scale Revised.  Discussion: The present study indicates ondansetron as potential adjunctive treatment strategy for chronic schizophrenia particularly for cognitive impairments.

  12. Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Jing Qin Wu

    Full Text Available While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression.The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22 from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDR<0.05. Both types of transcriptional isoforms were exemplified by reads aligned to the neurodevelopmentally significant doublecortin-like kinase 1 (DCLK1 gene.This study provided the first deep and un-biased analysis of schizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia.

  13. Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia

    Science.gov (United States)

    Subotnik, Kenneth L.; Casaus, Laurie R.; Ventura, Joseph; Luo, John S.; Hellemann, Gerhard S.; Gretchen-Doorly, Denise; Marder, Stephen; Nuechterlein, Keith H.

    2016-01-01

    IMPORTANCE Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However, long-acting medications are rarely used following a first episode of schizophrenia. OBJECTIVE To compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-to-treat analysis was performed between October 4, 2012, and November 12, 2014. INTERVENTIONS A 12-month trial comparing the long-acting injectable vs oral risperidone and cognitive remediation vs healthy-behaviors training. MAIN OUTCOMES AND MEASURES Psychotic relapse and control of breakthrough psychotic symptoms. RESULTS Of the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; χ21 = 11.1; P risperidone better controlled mean levels of hallucinations and delusions throughout follow-up (β = −0.30; t68 = −2.6, P = .01). The cognitive remediation and healthy-behaviors training groups did not differ significantly regarding psychotic relapse, psychotic symptom control, or hospitalization rates, and there were no significant interactions between the 2 medications and the 2 psychosocial treatments. Discontinuations owing to inadequate clinical response were more common in the oral group than in the long

  14. More evidence on additive antipsychotic effect of adjunctive mirtazapine in schizophrenia: an extension phase of a randomized controlled trial.

    Science.gov (United States)

    Terevnikov, Viacheslav; Stenberg, Jan-Henry; Joffe, Marina; Tiihonen, Jari; Burkin, Mark; Tchoukhine, Evgueni; Joffe, Grigori

    2010-08-01

    Adjunctive mirtazapine improved negative symptoms of schizophrenia in several studies. Recently, we found an improvement also in positive symptoms when mirtazapine was added to first generation antipsychotics (FGAs) in a 6 week randomized controlled trial (RCT). The short duration of that trial was its limitation. This study aimed to explore whether longer treatment is worthwhile. Completers of the RCT (n = 39) received open-label add-on mirtazapine for additional 6 weeks. The Positive and Negative Syndrome Scale (PANSS) total score (primary outcome) and several other clinical parameters were measured prospectively. During the open-label phase, significant improvement was achieved in all parameters, with an effect size of 0.94 (CI 95% = 0.45-1.43) on the primary outcome and an impressive additive antipsychotic effect. Patients who received mirtazapine during both phases demonstrated greater improvement in positive symptoms (29.6% versus 21.2%, p = 0.027) than those who received mirtazapine during open-label extension phase only. These findings support our previous data on the additive antipsychotic effect of mirtazapine in FGAs-treated schizophrenia. Mirtazapine may be effective in other symptom domains, too. Longer duration of mirtazapine treatment may yield additional benefits. If these results will be confirmed in larger studies, add-on mirtazapine may become a feasible option in difficult-to-treat schizophrenia. Copyright 2010 John Wiley & Sons, Ltd.

  15. A virtual reality application in role-plays of social skills training for schizophrenia: a randomized, controlled trial.

    Science.gov (United States)

    Park, Kyung-Min; Ku, Jeonghun; Choi, Soo-Hee; Jang, Hee-Jeong; Park, Ji-Yeon; Kim, Sun I; Kim, Jae-Jin

    2011-09-30

    Although social skills training (SST) is an effective approach for improving social skills for schizophrenia, the motivational deficit attenuates its efficacy. Virtual reality (VR) applications have allowed individuals with mental disabilities to enhance their motivation for rehabilitation. We compared SST using VR role-playing (SST-VR) to SST using traditional role-playing (SST-TR). This randomized, controlled trial included 91 inpatients with schizophrenia who were assigned to either SST-VR (n=46) or SST-TR (n=45). Both groups were administered over 10 semiweekly group sessions. An experienced, blinded rater assessed vocal, nonverbal and conversational skills. We also obtained data on motivation for SST and various social abilities. Throughout the 10 sessions, the SST-VR group (n=33) showed greater interest in SST and generalization of the skills than the SST-TR group (n=31). After SST, the SST-VR group improved more in conversational skills and assertiveness than the SST-TR group, but less in nonverbal skills. The VR application in role-plays of SST for schizophrenia may be particularly beneficial in terms of improving the conversational skills and assertiveness, possibly through its advantages in enhancing motivation for SST and generalization of the skills, and thus it may be a useful supplement to traditional SST. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Dopamine Receptors Differentially Control Binge Alcohol Drinking-Mediated Synaptic Plasticity of the Core Nucleus Accumbens Direct and Indirect Pathways.

    Science.gov (United States)

    Ji, Xincai; Saha, Sucharita; Kolpakova, Jenya; Guildford, Melissa; Tapper, Andrew R; Martin, Gilles E

    2017-05-31

    Binge alcohol drinking, a behavior characterized by rapid repeated alcohol intake, is most prevalent in young adults and is a risk factor for excessive alcohol consumption and alcohol dependence. Although the alteration of synaptic plasticity is thought to contribute to this behavior, there is currently little evidence that this is the case. We used drinking in the dark (DID) as a model of binge alcohol drinking to assess its effects on spike timing-dependent plasticity (STDP) in medium spiny neurons (MSNs) of the core nucleus accumbens (NAc) by combining patch-clamp recordings with calcium imaging and optogenetics. After 2 weeks of daily alcohol binges, synaptic plasticity was profoundly altered. STDP in MSNs expressing dopamine D1 receptors shifted from spike-timing-dependent long-term depression (tLTD), the predominant form of plasticity in naive male mice, to spike-timing-dependent long-term potentiation (tLTP) in DID mice, an effect that was totally reversed in the presence of 4 μm SCH23390, a dopamine D1 receptor antagonist. In MSNs presumably expressing dopamine D2 receptors, tLTP, the main form of plasticity in naive mice, was inhibited in DID mice. Interestingly, 1 μm sulpiride, a D2 receptor antagonist, restored tLTP. Although we observed no alterations of AMPA and NMDA receptor properties, we found that the AMPA/NMDA ratio increased at cortical and amygdaloid inputs but not at hippocampal inputs. Also, DID effects on STDP were accompanied by lower dendritic calcium transients. These data suggest that the role of dopamine in mediating the effects of binge alcohol drinking on synaptic plasticity of NAc MSNs differs markedly whether these neurons belong to the direct or indirect pathways. SIGNIFICANCE STATEMENT We examined the relationship between binge alcohol drinking and spike timing-dependent plasticity in nucleus accumbens (NAc) neurons. We found that repeated drinking bouts modulate differently synaptic plasticity in medium spiny neurons of the

  17. The effect of cariprazine on hostility associated with schizophrenia: post hoc analyses from 3 randomized controlled trials.

    Science.gov (United States)

    Citrome, Leslie; Durgam, Suresh; Lu, Kaifeng; Ferguson, Paul; Laszlovszky, István

    2016-01-01

    Although most patients with schizophrenia are not aggressive, individuals with the disorder have increased risk of hostile behavior. Cariprazine, a dopamine D3 and D2 receptor partial agonist antipsychotic with preferential binding to D3 receptors, was evaluated for antihostility effects in patients with schizophrenia. Post hoc analyses were conducted using pooled data from 3 positive randomized, placebo-controlled, phase 2/3 studies in inpatients (18-60 years) with acute exacerbation of schizophrenia according to DSM-IV-TR criteria; data were collected between 2008 and 2011. The principal post hoc outcome was mean change from baseline to week 6 on the Positive and Negative Syndrome Scale (PANSS) hostility item (P7); separate analyses adjusted for certain PANSS positive symptoms and sedation covariates. Analyses were based on the pooled intent-to-treat population (N = 1,466) using a mixed-effects model for repeated measures approach; separate analyses were conducted in subgroups categorized by baseline hostility item scores (P7: ≥ 2, ≥ 3, ≥ 4). The least squares mean difference (LSMD) in change from baseline to week 6 was statistically significant on all PANSS hostility item analyses in favor of cariprazine versus placebo: unadjusted (-0.28; P < .0001), adjusted for PANSS positive symptoms (-0.12; P < .05), adjusted for positive symptoms plus sedation (-0.12; P < .05). The magnitude of change for cariprazine increased with greater baseline hostility (LSMD vs placebo for ≥ 2, ≥ 3, ≥ 4 subgroups: -0.32, -0.37, -0.51, respectively; P < .01 all). Significant improvement on the hostility item was seen in cariprazine- versus placebo-treated patients with schizophrenia; the effect of cariprazine increased with greater levels of baseline hostility. ClinicalTrials.gov identifiers: NCT00694707, NCT01104766, and NCT01104779. © Copyright 2016 Physicians Postgraduate Press, Inc.

  18. Effects of add-on mirtazapine on neurocognition in schizophrenia: a double-blind, randomized, placebo-controlled study.

    Science.gov (United States)

    Stenberg, Jan-Henry; Terevnikov, Viatcheslav; Joffe, Marina; Tiihonen, Jari; Tchoukhine, Evgueni; Burkin, Mark; Joffe, Grigori

    2010-05-01

    Mirtazapine added to antipsychotics appears to improve the clinical picture of schizophrenia, including both negative and positive symptoms. This study explored the effect of adjunctive mirtazapine on neurocognition in patients with schizophrenia who had shown an insufficient response to first-generation antipsychotics (FGAs). Thirty-seven schizophrenia patients, who were at least moderately ill despite their FGA treatment, received add-on mirtazapine (n=19) or placebo (n=18) in a 6-wk double-blind, randomized trial. Widely used neuropsychological tests were performed to explore visual-spatial functions, verbal and visual memory, executive functions, verbal fluency and general mental and psychomotor speed. The data were analysed on the modified intent-to-treat basis with last observation carried forward. False discovery rate was applied to correct for multiple testing. Mirtazapine outperformed placebo in the domains of visual-spatial ability and general mental speed/attentional control as assessed by, correspondingly, Block Design and Stroop dots. The difference in the degree of change (i.e. change while on mirtazapine minus that on placebo) was 18.6% (p=0.044) and 11.1% (p=0.044), respectively. Adjunctive mirtazapine might offer a safe, effective and cost-saving option as a neurocognitive enhancer for FGA-treated schizophrenia patients. Mirtazapine+FGA combinations may become especially useful in light of the currently increasing attention towards FGAs. Larger and longer studies that incorporate functional outcomes, as well as comparisons with second-generation antipsychotics are, however, still needed for more definite conclusions.

  19. Effects of raloxifene on cognition in postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Huerta-Ramos, Elena; Iniesta, Raquel; Ochoa, Susana; Cobo, Jesús; Miquel, Eva; Roca, Mercedes; Serrano-Blanco, Antoni; Teba, Fernando; Usall, Judith

    2014-02-01

    Studies of estrogen therapy in postmenopausal women provide evidence of an effect of sex hormones on cognitive function. Estrogen has demonstrated some utility in the prevention of normal, age-related decline in cognitive functions, especially in memory. The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator (SERM), appears to act similarly to conjugated estrogens on dopamine and serotonin brain systems, and may be a better option since it lacks the possible negative effects of estrogen on breast and uterine tissue. We assessed the utility of raloxifene as an adjuvant treatment for cognitive symptoms in postmenopausal women with schizophrenia in a 12-week, double-blind, randomized, placebo-controlled study. Patients were recruited from both the inpatient and outpatient departments. Thirty-three postmenopausal women with schizophrenia (DSM-IV) were randomized to receive either adjuvant raloxifene (16 women) or adjuvant placebo (17 women) for three months. The main outcome measures were: Memory, attention and executive functions. Assessment was conducted at baseline and week 12. The total sample is homogenous with respect to: age, years of schooling, illness duration, baseline symptomatology and pharmacological treatment. The addition of raloxifene (60 mg) to regular antipsychotic treatment showed: we found significant differences in some aspects of memory and executive function in patients treated with raloxifene. This improvement does not correlate with clinical improvement. The use of raloxifene as an adjuvant treatment in postmenopausal women with schizophrenia seems to be useful in improving cognitive symptoms. © 2013 Published by Elsevier B.V. and ECNP.

  20. Synaptic vesicle proteins and active zone plasticity

    Directory of Open Access Journals (Sweden)

    Robert J Kittel

    2016-04-01

    Full Text Available Neurotransmitter is released from synaptic vesicles at the highly specialized presynaptic active zone. The complex molecular architecture of active zones mediates the speed, precision and plasticity of synaptic transmission. Importantly, structural and functional properties of active zones vary significantly, even for a given connection. Thus, there appear to be distinct active zone states, which fundamentally influence neuronal communication by controlling the positioning and release of synaptic vesicles. Vice versa, recent evidence has revealed that synaptic vesicle components also modulate organizational states of the active zone.The protein-rich cytomatrix at the active zone (CAZ provides a structural platform for molecular interactions guiding vesicle exocytosis. Studies in Drosophila have now demonstrated that the vesicle proteins Synaptotagmin-1 (Syt1 and Rab3 also regulate glutamate release by shaping differentiation of the CAZ ultrastructure. We review these unexpected findings and discuss mechanistic interpretations of the reciprocal relationship between synaptic vesicles and active zone states, which has heretofore received little attention.

  1. Klotho regulates CA1 hippocampal synaptic plasticity.

    Science.gov (United States)

    Li, Qin; Vo, Hai T; Wang, Jing; Fox-Quick, Stephanie; Dobrunz, Lynn E; King, Gwendalyn D

    2017-04-07

    Global klotho overexpression extends lifespan while global klotho-deficiency shortens it. As well, klotho protein manipulations inversely regulate cognitive function. Mice without klotho develop rapid onset cognitive impairment before they are 2months old. Meanwhile, adult mice overexpressing klotho show enhanced cognitive function, particularly in hippocampal-dependent tasks. The cognitive enhancing effects of klotho extend to humans with a klotho polymorphism that increases circulating klotho and executive function. To affect cognitive function, klotho could act in or on the synapse to modulate synaptic transmission or plasticity. However, it is not yet known if klotho is located at synapses, and little is known about its effects on synaptic function. To test this, we fractionated hippocampi and detected klotho expression in both pre and post-synaptic compartments. We find that loss of klotho enhances both pre and post-synaptic measures of CA1 hippocampal synaptic plasticity at 5weeks of age. However, a rapid loss of synaptic enhancement occurs such that by 7weeks, when mice are cognitively impaired, there is no difference from wild-type controls. Klotho overexpressing mice show no early life effects on synaptic plasticity, but decreased CA1 hippocampal long-term potentiation was measured at 6months of age. Together these data suggest that klotho affects cognition, at least in part, by regulating hippocampal synaptic plasticity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Iloperidone for schizophrenia.

    Science.gov (United States)

    Rado, Jeffrey; Janicak, Philip G

    2010-08-01

    No existing antipsychotic adequately controls all symptoms associated with schizophrenia. Also, no antipsychotic adequately benefits most patients with this disorder. Finally, the safety and tolerability of each antipsychotic frequently dictate the choice of agent. The mechanism of action of iloperidone, its efficacy and its safety and tolerability when used to treat patients with schizophrenia. An appreciation of the potential advantages and disadvantages of iloperidone when used for the treatment of schizophrenia. Iloperidone is a recent addition to the current group of second-generation antipsychotics. While it may share many qualities with other agents in this class, its unique neuroreceptor signature and adverse-effect profile may prove beneficial in clinical practice.

  3. Effect of an art brut therapy program called go beyond the schizophrenia (GBTS) on prison inmates with schizophrenia in mainland China-A randomized, longitudinal, and controlled trial.

    Science.gov (United States)

    Qiu, Hong-Zhong; Ye, Zeng-Jie; Liang, Mu-Zi; Huang, Yue-Qun; Liu, Wei; Lu, Zhi-Dong

    2017-09-01

    Creative arts therapies are proven to promote an interconnection between body and mind, but there are major obstacles for providing therapeutic services in prisons due to inmates' inherent mistrust for verbal disclosure and rigid self-defenses, especially among inmates with schizophrenia. Thus, we developed a structured and quantitative art brut therapy program called go beyond the schizophrenia to actually measure the benefits of art therapy on prison inmates in mainland China. Upon completion of the program, the intervention group reported a decrease in anxiety, depression, anger, and negative psychiatric symptoms and showed better compliance with rules, socialization with peers, compliance with medications, and regular sleeping patterns after 16 weekly sessions of go beyond the schizophrenia. This article concludes that the art brut therapy was effective for the inmates with schizophrenia in mainland China and provides encouraging data on how to enhance mental health for inmates with schizophrenia. Art brut therapy can reduce emotional distress and negative psychiatric symptoms among Chinese inmates. Arts brut therapy can enhance Chinese inmates' compliance with rules, socialization with peers, compliance with medicines, and regular sleeping patterns. Arts brut therapy in conjunction with medication is highly recommended for recovery of Chinese inmates with schizophrenia, especially for patients with negative symptoms. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Selective optical control of synaptic transmission in the subcortical visual pathway by activation of viral vector-expressed halorhodopsin.

    Directory of Open Access Journals (Sweden)

    Katsuyuki Kaneda

    Full Text Available The superficial layer of the superior colliculus (sSC receives visual inputs via two different pathways: from the retina and the primary visual cortex. However, the functional significance of each input for the operation of the sSC circuit remains to be identified. As a first step toward understanding the functional role of each of these inputs, we developed an optogenetic method to specifically suppress the synaptic transmission in the retino-tectal pathway. We introduced enhanced halorhodopsin (eNpHR, a yellow light-sensitive, membrane-targeting chloride pump, into mouse retinal ganglion cells (RGCs by intravitreously injecting an adeno-associated virus serotype-2 vector carrying the CMV-eNpHR-EYFP construct. Several weeks after the injection, whole-cell recordings made from sSC neurons in slice preparations revealed that yellow laser illumination of the eNpHR-expressing retino-tectal axons, putatively synapsing onto the recorded cells, effectively inhibited EPSCs evoked by electrical stimulation of the optic nerve layer. We also showed that sSC spike activities elicited by visual stimulation were significantly reduced by laser illumination of the sSC in anesthetized mice. These results indicate that photo-activation of eNpHR expressed in RGC axons enables selective blockade of retino-tectal synaptic transmission. The method established here can most likely be applied to a variety of brain regions for studying the function of individual inputs to these regions.

  5. BISPHENOL A INTERFERES WITH SYNAPTIC REMODELING

    Science.gov (United States)

    Hajszan, Tibor; Leranth, Csaba

    2010-01-01

    The potential adverse effects of Bisphenol A (BPA), a synthetic xenoestrogen, have long been debated. Although standard toxicology tests have revealed no harmful effects, recent research highlighted what was missed so far: BPA-induced alterations in the nervous system. Since 2004, our laboratory has been investigating one of the central effects of BPA, which is interference with gonadal steroid-induced synaptogenesis and the resulting loss of spine synapses. We have shown in both rats and nonhuman primates that BPA completely negates the ~70–100% increase in the number of hippocampal and prefrontal spine synapses induced by both estrogens and androgens. Synaptic loss of this magnitude may have significant consequences, potentially causing cognitive decline, depression, and schizophrenia, to mention those that our laboratory has shown to be associated with synaptic loss. Finally, we discuss why children may particularly be vulnerable to BPA, which represents future direction of research in our laboratory. PMID:20609373

  6. Effect of a System-Oriented Intervention on Compliance Problems in Schizophrenia: A Pragmatic Controlled Trial

    Directory of Open Access Journals (Sweden)

    Hanne Skarsholm

    2014-01-01

    Full Text Available Background. Numerous studies have been conducted with a view to developing strategies for improvement of medical compliance in patients with schizophrenia. All of the studies conducted so far have had an individual approach to compliance based on the assumption that noncompliance is determined individually due to inappropriate behavior in the patient. We conducted a pragmatic controlled trial with a system-oriented approach, to provide a new perspective on compliance and test the efficacy of a multifactorial intervention at the system level in a routine clinical setting, an approach that has not previously been used for the improvement of compliance. Methods. 30 patients were allocated to the system-oriented therapy and 40 patients were allocated to the reference intervention, which consisted of individually based compliance therapy. The follow-up period was six months. Primary endpoint was improvement in compliance, measured by improvement in a compliance scale specifically developed for the project. Results. When accounting for missing values with a multiple imputation approach, we found a tendency toward a difference in both the compliance scale and PANSS favoring the system-oriented therapy, although it did not reach statistical significance. A significant difference in incidence of adverse events and time to first readmission was found. Attrition rates were significantly higher in the reference group and nonsignificant among individuals with lower compliance, which may have diluted effect estimates. This was reflected by significant differences found in an analysis based on a last observation carried forward approach. Conclusion. This study suggests that compliance problems are better solved by a multifactorial intervention at the system level than at the individual level.

  7. Blonanserin for schizophrenia: systematic review and meta-analysis of double-blind, randomized, controlled trials.

    Science.gov (United States)

    Kishi, Taro; Matsuda, Yuki; Nakamura, Hiroshi; Iwata, Nakao

    2013-02-01

    There is uncertainty about the efficacy and tolerability of blonanserin in schizophrenia. PubMed, the Cochrane Library databases, PsycINFO, and Google Scholar were searched up to September 2012. A systematic review and meta-analysis of individual patient data from randomized, controlled trials comparing blonanserin with other antipsychotics were conducted. The risk ratio (RR), 95% confidence intervals (CI), numbers-needed-to-harm (NNH), and weighted mean difference (WMD) were calculated. Four studies (total n = 1080) were identified (vs. risperidone studies [n = 508], vs. haloperidol studies [n = 572]). Comparing blonanserin with other pooled antipsychotics, there were no significant differences in the Positive and Negative Syndrome Scale (PANSS) total score (p = 0.75), PANSS positive (p = 0.41), PANSS negative (p = 0.09), and PANSS general psychopathology subscale scores (p = 0.96), and response rate (p = 0.72). However, blonanserin showed greater efficacy in PANSS negative subscale scores compared with haloperidol (WMD = -1.29, CI = -2.29 to -0.30, p = 0.01, I(2) = 0%). No significant differences were found in discontinuation rates between blonanserin and other pooled antipsychotics (due to any cause: p = 0.29, inefficacy: p = 0.32, adverse events: p = 0.56). Blonanserin had a 0.31 lower risk of hyperprolactinemia than the other pooled antipsychotics (CI = 0.20-0.49, NNH = not significant). While dizziness (RR = 0.47, CI = 0.23-0.93, NNH = not significant) and akathisia (RR = 0.54, CI = 0.32-0.90, NNH = 7) occurred significantly less often with blonanserin than with haloperidol, blonanserin had a 1.62 higher risk of akathisia than risperidone (CI = 1.18-2.22, NNH = 8) [corrected]. Our results suggest that although blonanserin has a more beneficial effect on negative symptoms than haloperidol, there was a significant difference in the adverse events profile between blonanserin and other antipsychotics. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Personality features in ultra-high risk for psychosis: a comparative study with schizophrenia and control subjects using the Temperament and Character Inventory-Revised (TCI-R).

    Science.gov (United States)

    Fresán, Ana; León-Ortiz, Pablo; Robles-García, Rebeca; Azcárraga, Mariana; Guizar, Diana; Reyes-Madrigal, Francisco; Tovilla-Zárate, Carlos Alfonso; de la Fuente-Sandoval, Camilo

    2015-02-01

    Several variables have been identified as risk factors for conversion to overt psychosis in ultra-high risk for psychosis (UHR) individuals. Although almost two-thirds of them do not experience a transition to psychosis, they still exhibit functional disabilities. Other subjective developmental features may be useful for a more precise identification of individuals at UHR. Avoidant behaviors are consistently reported in schizophrenia and in UHR individuals and may be the reflection of a pattern of personality. Thus, personality features in UHR individuals deserves further research. The objective of the present study was to compare temperament and character dimensions between UHR individuals, patients with schizophrenia and healthy controls. One hundred participants (25 UHR individuals, 25 schizophrenia patients and 50 control subjects) where evaluated with the Temperament and Character Inventory-Revised (TCI-R). Univariate ANOVAs followed by Bonferroni tests were used. UHR individuals and schizophrenia patients exhibited higher levels of Harm Avoidance (HA) when compared to control subjects. For HA1 Anticipatory worry vs Uninhibited optimism and HA4 Fatigability & asthenia, UHR and schizophrenia groups showed similar scores and both groups were higher compared to control subjects. With respect to Cooperativeness (CO), UHR and schizophrenia reported lower scores than control subjects, in particular CO2 Empathy vs Social disinterest and CO3 Helpfulness vs unhelpfulness. This study replicates and extends the consideration of HA as a psychopathological related endophenotype and gives us further information of the possible role of personality features in the expression of some of the social dysfunctions observed both in prodromal subjects and schizophrenia patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. The role of ubiquitin‐mediated pathways in regulating synaptic development, axonal degeneration and regeneration: insights from fly and worm

    National Research Council Canada - National Science Library

    Tian, Xiaolin; Wu, Chunlai

    2013-01-01

    ...‐mediated pathways play important roles in controlling the presynaptic size, synaptic elimination and stabilization, synaptic transmission, postsynaptic receptor abundance, axonal degeneration and regeneration...

  10. Rare UNC13B variations and risk of schizophrenia: Whole-exome sequencing in a multiplex family and follow-up resequencing and a case-control study.

    Science.gov (United States)

    Egawa, Jun; Hoya, Satoshi; Watanabe, Yuichiro; Nunokawa, Ayako; Shibuya, Masako; Ikeda, Masashi; Inoue, Emiko; Okuda, Shujiro; Kondo, Kenji; Saito, Takeo; Kaneko, Naoshi; Muratake, Tatsuyuki; Igeta, Hirofumi; Iwata, Nakao; Someya, Toshiyuki

    2016-09-01

    Rare genomic variations inherited in multiplex schizophrenia families are suggested to play a role in the genetic etiology of the disease. To identify rare variations with large effects on the risk of developing schizophrenia, we performed whole-exome sequencing (WES) in two affected and one unaffected individual of a multiplex family with 10 affected individuals. We also performed follow-up resequencing of the unc-13 homolog B (Caenorhabditis elegans) (UNC13B) gene, a potential risk gene identified by WES, in the multiplex family and undertook a case-control study to investigate association between UNC13B and schizophrenia. UNC13B coding regions (39 exons) from 15 individuals of the multiplex family and 111 affected offspring for whom parental DNA samples were available were resequenced. Rare missense UNC13B variations identified by resequencing were further tested for association with schizophrenia in two independent case-control populations comprising a total of 1,753 patients and 1,602 controls. A rare missense variation (V1525M) in UNC13B was identified by WES in the multiplex family; this variation was present in five of six affected individuals, but not in eight unaffected individuals or one individual of unknown disease status. Resequencing UNC13B coding regions identified five rare missense variations (T103M, M813T, P1349T, I1362T, and V1525M). In the case-control study, there was no significant association between rare missense UNC13B variations and schizophrenia, although single-variant meta-analysis indicated that M813T was nominally associated with schizophrenia. These results do not support a contribution of rare missense UNC13B variations to the genetic etiology of schizophrenia in the Japanese population. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Visual-Perceptual Abilities in Healthy Controls, Depressed Patients, and Schizophrenia Patients

    Science.gov (United States)

    Cavezian, Celine; Danckert, James; Lerond, Jerome; Dalery, Jean; d'Amato, Thierry; Saoud, Mohamed

    2007-01-01

    Previous studies have suggested a right hemineglect in schizophrenia, however few assessed possible visual-perceptual implication in this lateralized anomaly. A manual line bisection without (i.e., lines presented on their own) or with a local cueing paradigm (i.e., a number placed at one or both ends of the line) and the Motor-free Visual…

  12. Examining frontotemporal connectivity and rTMS in healthy controls: implications for auditory hallucinations in schizophrenia.

    NARCIS (Netherlands)

    Gromann, P.M.; Tracy, D.K.; Giampietro, V.; Brammer, M.J.; Krabbendam, A.C.; Shergill, S.S.

    2012-01-01

    Objective: Repetitive transcranial magnetic stimulation (rTMS) has been shown to have clinically beneficial effects in altering the perception of auditory hallucinations (AH) in patients with schizophrenia. However, the mode of action is not clear. Recent neuroimaging findings indicate that rTMS has

  13. Cannabis use and genetic predisposition for schizophrenia : a case-control study

    NARCIS (Netherlands)

    Veling, W; Mackenbach, J P; van Os, J; Hoek, H W

    BACKGROUND: Cannabis use may be a risk factor for schizophrenia. Part of this association may be explained by genotype-environment interaction, and part of it by genotype-environment correlation. The latter issue has not been explored. We investigated whether cannabis use is associated with

  14. Exercise therapy improves mental and physical health in schizophrenia: a randomised controlled trial.

    Science.gov (United States)

    Scheewe, T W; Backx, F J G; Takken, T; Jörg, F; van Strater, A C P; Kroes, A G; Kahn, R S; Cahn, W

    2013-06-01

    The objective of this multicenter randomised clinical trial was to examine the effect of exercise versus occupational therapy on mental and physical health in schizophrenia patients. Sixty-three patients with schizophrenia were randomly assigned to 2 h of structured exercise (n = 31) or occupational therapy (n = 32) weekly for 6 months. Symptoms (Positive and Negative Syndrome Scale) and cardiovascular fitness levels (Wpeak and VO2peak ), as assessed with a cardiopulmonary exercise test, were the primary outcome measures. Secondary outcome measures were the Montgomery and Åsberg Depression Rating Scale, Camberwell Assessment of Needs, body mass index, body fat percentage, and metabolic syndrome (MetS). Intention-to-treat analyses showed exercise therapy had a trend-level effect on depressive symptoms (P = 0.07) and a significant effect on cardiovascular fitness, measured by Wpeak (P occupational therapy. Per protocol analyses showed that exercise therapy reduced symptoms of schizophrenia (P = 0.001), depression (P = 0.012), need of care (P = 0.050), and increased cardiovascular fitness (P occupational therapy. No effect for MetS (factors) was found except a trend reduction in triglycerides (P = 0.08). Exercise therapy, when performed once to twice a week, improved mental health and cardiovascular fitness and reduced need of care in patients with schizophrenia. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Perceived discrimination and the risk of schizophrenia in ethnic minorities : a case-control study

    NARCIS (Netherlands)

    Veling, Wim; Hoek, H. W.; Mackenbach, J. P.

    2008-01-01

    BACKGROUND: Previous studies have reported a very high incidence of schizophrenia for immigrant ethnic groups in Western Europe. The explanation of these findings is unknown, but is likely to involve social stress inherent to the migrant condition. A previous study reported that the incidence of

  16. A randomised controlled trial of positive memory training for the treatment of depression within schizophrenia

    NARCIS (Netherlands)

    Steel, Craig; van der Gaag, Mark; Korrelboom, Kees; Simon, Judit; Phiri, Peter; Baksh, M. Fazil; Wykes, Til; Rose, Diana; Rose, Suzanna; Hardcastle, Mark; Enright, Simon; Evans, Gareth; Kingdon, David

    2015-01-01

    Background Depression is highly prevalent within individuals diagnosed with schizophrenia, and is associated with an increased risk of suicide. There are no current evidence based treatments for low mood within this group. The specific targeting of co-morbid conditions within complex mental health

  17. Ethnic identity and the risk of schizophrenia in ethnic minorities : a case-control study

    NARCIS (Netherlands)

    Veling, Wim; Hoek, Hans W.; Wiersma, Durk; Mackenbach, Johan P.

    2010-01-01

    OBJECTIVES: The high incidence of schizophrenia in immigrant ethnic groups in Western Europe may be explained by social stress associated with ethnic minority status. Positive identification with one's own ethnic group is a strong predictor of mental health in immigrants. We investigated whether

  18. Impaired glutathione synthesis in schizophrenia

    DEFF Research Database (Denmark)

    Gysin, René; Kraftsik, Rudolf; Sandell, Julie

    2007-01-01

    Schizophrenia is a complex multifactorial brain disorder with a genetic component. Convergent evidence has implicated oxidative stress and glutathione (GSH) deficits in the pathogenesis of this disease. The aim of the present study was to test whether schizophrenia is associated with a deficit...... of GSH synthesis. Cultured skin fibroblasts from schizophrenia patients and control subjects were challenged with oxidative stress, and parameters of the rate-limiting enzyme for the GSH synthesis, the glutamate cysteine ligase (GCL), were measured. Stressed cells of patients had a 26% (P = 0.......002) decreased GCL activity as compared with controls. This reduction correlated with a 29% (P schizophrenia in two...

  19. The Secreted Protein C1QL1 and Its Receptor BAI3 Control the Synaptic Connectivity of Excitatory Inputs Converging on Cerebellar Purkinje Cells

    Directory of Open Access Journals (Sweden)

    Séverine M. Sigoillot

    2015-02-01

    Full Text Available Precise patterns of connectivity are established by different types of afferents on a given target neuron, leading to well-defined and non-overlapping synaptic territories. What regulates the specific characteristics of each type of synapse, in terms of number, morphology, and subcellular localization, remains to be understood. Here, we show that the signaling pathway formed by the secreted complement C1Q-related protein C1QL1 and its receptor, the adhesion-GPCR brain angiogenesis inhibitor 3 (BAI3, controls the stereotyped pattern of connectivity established by excitatory afferents on cerebellar Purkinje cells. The BAI3 receptor modulates synaptogenesis of both parallel fiber and climbing fiber afferents. The restricted and timely expression of its ligand C1QL1 in inferior olivary neurons ensures the establishment of the proper synaptic territory for climbing fibers. Given the broad expression of C1QL and BAI proteins in the developing mouse brain, our study reveals a general mechanism contributing to the formation of a functional brain.

  20. Association analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample

    DEFF Research Database (Denmark)

    Tesli, Martin; Athanasiu, Lavinia; Mattingsdal, Morten

    2010-01-01

    A recent genome-wide association study (GWAS) found significant association between the PALB2 SNP rs420259 and bipolar disorder (BD). The intracellular functions of the expressed proteins from the breast cancer risk genes PALB2 and BRCA2 are closely related. Therefore, we investigated the relation...... between genetic variants in PALB2 and BRCA2 and BD. Due to increasing evidence of genetic overlap between BD and schizophrenia (SCZ), we also investigated association with SCZ. In a Scandinavian case-control sample (n¿=¿686/2,538) we found the BRCA2 SNP rs9567552 to be significantly associated with BD...

  1. Imaging synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Padamsey Zahid

    2011-09-01

    Full Text Available Abstract Over the past decade, the use and development of optical imaging techniques has advanced our understanding of synaptic plasticity by offering the spatial and temporal resolution necessary to examine long-term changes at individual synapses. Here, we review the use of these techniques in recent studies of synaptic plasticity and, in particular, long-term potentiation in the hippocampus.

  2. Efficacy and Safety of Yokukansan in Treatment-Resistant Schizophrenia: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Miyaoka

    2015-01-01

    Full Text Available Objectives. We aimed at evaluating both the efficacy and safety of TJ-54 (Yokukansan in patients with treatment-resistant schizophrenia. This randomized, multicenter, double-blind, placebo-controlled study was conducted. Methods. One hundred and twenty antipsychotic-treated inpatients were included. Patients were randomized to adjuvant treatment with TJ-54 or placebo. During a 4-week follow-up, psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS. Results. TJ-54 showed a tendency of being superior to placebo in reduction total, positive, and general PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant in both per-protocol set (PPS and intention-to-treat (ITT. However, in PPS analysis, compared to the placebo group, the TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores for lack of spontaneity and flow of conversation (TJ-54: −0.23±0.08; placebo: −0.03±0.08, P<0.018, tension (TJ-54: −0.42±0.09; placebo: −0.18±0.09, P<0.045, and poor impulse control (TJ-54: −0.39±0.10; placebo: −0.07±0.10, P<0.037. Conclusions. The results of the present study indicate that TJ-54 showed a tendency of being superior to placebo in reduction PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant. However, compared to the placebo group, TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores.

  3. Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex.

    Science.gov (United States)

    Xing, Bo; Li, Yan-Chun; Gao, Wen-Jun

    2016-06-15

    Among the neuromodulators that regulate prefrontal cortical circuit function, the catecholamine transmitters norepinephrine (NE) and dopamine (DA) stand out as powerful players in working memory and attention. Perturbation of either NE or DA signaling is implicated in the pathogenesis of several neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), schizophrenia, and drug addiction. Although the precise mechanisms employed by NE and DA to cooperatively control prefrontal functions are not fully understood, emerging research indicates that both transmitters regulate electrical and biochemical aspects of neuronal function by modulating convergent ionic and synaptic signaling in the prefrontal cortex (PFC). This review summarizes previous studies that investigated the effects of both NE and DA on excitatory and inhibitory transmissions in the prefrontal cortical circuitry. Specifically, we focus on the functional interaction between NE and DA in prefrontal cortical local circuitry, synaptic integration, signaling pathways, and receptor properties. Although it is clear that both NE and DA innervate the PFC extensively and modulate synaptic function by activating distinctly different receptor subtypes and signaling pathways, it remains unclear how these two systems coordinate their actions to optimize PFC function for appropriate behavior. Throughout this review, we provide perspectives and highlight several critical topics for future studies. This article is part of a Special Issue entitled SI: Noradrenergic System. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. A case-control study of the relationship between the metabotropic glutamate receptor 3 gene and schizophrenia in the Chinese population.

    Science.gov (United States)

    Chen, Qi; He, Guang; Chen, Qingying; Wu, Shengnan; Xu, Yifeng; Feng, Guoyin; Li, Yucheng; Wang, Lijun; He, Lin

    2005-02-01

    Recent studies of the association between the metabotropic glutamate receptor 3 gene (GRM3) and schizophrenia have produced conflicting results, although GRM3 is a promising candidate gene. Fujii et al. found a single nuclear polymorphism (SNP) for within this gene, rs1468412 to have a positive association to schizophrenia in Japanese patients. To investigate this further, we genotyped 7 SNPs around GRM3 including rs1468412, in 752 Chinese patients with schizophrenia and 752 controls using Taqman technology. We did not detect any association between rs1468412 and schizophrenia, however we found differences in the allele frequency distribution of SNP rs2299225 (p=0.0297, odds ration [OR]=1.44, 95% confidence interval 1.05-1.99) between cases and controls. Moreover, the overall frequency of haplotypes constructed from three SNPs including rs2299225 showed significant differences between cases and controls (p=0.0017). Our results partially support the previous studies in other ethnic groups and indicate that the GRM3 gene may play an important role in the etiology of schizophrenia in the Han Chinese.

  5. Demand and modality of directed attention modulate "pre-attentive" sensory processes in schizophrenia patients and nonpsychiatric controls.

    Science.gov (United States)

    Rissling, Anthony J; Park, Sung-Hyouk; Young, Jared W; Rissling, Michelle B; Sugar, Catherine A; Sprock, Joyce; Mathias, Daniel J; Pela, Marlena; Sharp, Richard F; Braff, David L; Light, Gregory A

    2013-05-01

    Mismatch negativity (MNN) and P3a are event related potential (ERP) measures of early sensory information processing. These components are usually conceptualized as being "pre-attentive" and therefore immune to changes with variations in attentional functioning. This study aimed to determine whether manipulations of attention influence the amplitudes and latencies of MMN and P3a and, if so, the extent to which these early sensory processes govern concurrent behavioral vigilance performance in schizophrenia patients and normal subjects. Schizophrenia patients (SZ; n = 20) and Nonpsychiatric Control Subjects (NCS; n = 20) underwent auditory ERP testing to assess MMN and P3a across 4 EEG recording sessions in which attentional demand (low vs. high) and sensory modality of directed attention (visual vs. auditory) were experimentally varied. Across conditions, SZ patients exhibited deficits in MMN and P3a amplitudes. Significant amplitude and latency modulation were observed in both SZ and NCS but there were no group-by-condition interactions. The amount of MMN amplitude attenuation from low- to high-demand tasks was significantly associated with increased vigilance performance in both SZ and NCS groups (r = -0.67 and r = -0.60). Several other robust associations were also observed among neurophysiologic, clinical and cognitive variables. Attentional demand and modality of directed attention significantly influence the amplitude and latencies of "pre-attentive" ERP components in both SZ and NCS. Deficits in MMN and P3a were not "normalized" when attention was directed to the auditory stimuli in schizophrenia patients. The adaptive modulation of early sensory information processing appears to govern concurrent attentional task performance. The temporal window reflecting automatic sensory discrimination as indexed as MMN and P3a may serve as a gateway to some higher order cognitive operations necessary for psychosocial functioning. Published by Elsevier B.V.

  6. Demand and Modality of Directed Attention Modulate “Pre-attentive” Sensory Processes in Schizophrenia Patients and Nonpsychiatric Controls

    Science.gov (United States)

    Rissling, Anthony J.; Park, Sung-Hyouk; Young, Jared W.; Rissling, Michelle B.; Sugar, Catherine A.; Sprock, Joyce; Mathias, Daniel J.; Pela, Marlena; Sharp, Richard F.; Braff, David L.; Light, Gregory A.

    2013-01-01

    Background Mismatch negativity (MNN) and P3a are event related potential (ERP) measures of early sensory information processing. These components are usually conceptualized as being “pre-attentive” and therefore immune to changes with variations in attentional functioning. This study aimed to determine whether manipulations of attention influence the amplitudes and latencies of MMN and P3a and, if so, the extent to which these early sensory processes govern concurrent behavioral vigilance performance in schizophrenia patients and normal subjects. Methods Schizophrenia patients (SZ; n=20) and Nonpsychiatric Control Subjects (NCS; n=20) underwent auditory ERP testing to assess MMN and P3a across 4 EEG recording sessions in which attentional demand (low vs. high) and sensory modality of directed attention (visual vs. auditory) were experimentally varied. Results Across conditions, SZ patients exhibited deficits in MMN and P3a amplitudes. Significant amplitude and latency modulation were observed in both SZ and NCS but there were no group-by- condition interactions. The amount of MMN amplitude attenuation from low- to-high-demand tasks was significantly associated with increased vigilance performance in both SZ and NCS groups (r=-0.67 and r=-0.60). Conclusions Attentional demand and modality of directed attention significantly influence the amplitude and latencies of “pre-attentive” ERP components in both SZ and NCS. Deficits in MMN and P3a were not “normalized” when attention was directed to the auditory stimuli in schizophrenia patients. The adaptive modulation of early sensory information processing appears to govern concurrent attentional task performance. MMN and P3a may serve as a gateway to some higher order cognitive operations necessary for psychosocial functioning. PMID:23490760

  7. Cardiac complications associated with short-term mortality in schizophrenia patients hospitalized for pneumonia: a nationwide case-control study.

    Directory of Open Access Journals (Sweden)

    Ya-Tang Liao

    Full Text Available BACKGROUND: Pneumonia is one of most prevalent infectious diseases worldwide and is associated with considerable mortality. In comparison to general population, schizophrenia patients hospitalized for pneumonia have poorer outcomes. We explored the risk factors of short-term mortality in this population because the information is lacking in the literature. METHODS: In a nationwide schizophrenia cohort, derived from the National Health Insurance Research Database in Taiwan, that was hospitalized for pneumonia between 2000 and 2008 (n = 1,741, we identified 141 subjects who died during their hospitalizations or shortly after their discharges. Based on risk-set sampling in a 1∶4 ratio, 468 matched controls were selected from the study cohort (i.e., schizophrenia cohort with pneumonia. Physical illnesses were categorized as pre-existing and incident illnesses that developed after pneumonia respectively. Exposures to medications were categorized by type, duration, and defined daily dose. We used stepwise conditional logistic regression to explore the risk factors for short-term mortality. RESULTS: Pre-existing arrhythmia was associated with short-term mortality (adjusted risk ratio [RR] = 4.99, p<0.01. Several variables during hospitalization were associated with increased mortality risk, including incident arrhythmia (RR = 7.44, p<0.01, incident heart failure (RR = 5.49, p = 0.0183 and the use of hypoglycemic drugs (RR = 2.32, p<0.01. Furthermore, individual antipsychotic drugs (such as clozapine known to induce pneumonia were not significantly associated with the risk. CONCLUSIONS: Incident cardiac complications following pneumonia are associated with increased short-term mortality. These findings have broad implications for clinical intervention and future studies are needed to clarify the mechanisms of the risk factors.

  8. Evolution of substance use, neurological and psychiatric symptoms in schizophrenia and substance use disorder patients: a 12-week, pilot, case-control trial with quetiapine

    Directory of Open Access Journals (Sweden)

    Simon eZhornitsky

    2011-05-01

    Full Text Available Neurological and psychiatric symptoms are consequences of substance abuse in schizophrenia and non-schizophrenia patients. The present case-control study examined changes in substance abuse/dependence and neurological and psychiatric symptoms in substance abusers with (DD group, n=26 and without schizophrenia (SUD group, n=24 and in non-abusing schizophrenia patients (SCZ group, n=23 undergoing 12-week treatment with the atypical antipsychotic, quetiapine. Neurological and psychiatric symptoms were evaluated with the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, the Extrapyramidal Symptoms Rating Scale and the Barnes Akathisia Rating Scale. At endpoint, DD and SCZ patients were receiving significantly higher doses of quetiapine (mean = 554mg/d and 478mg/d, respectively, relative to SUD patients (mean = 150mg/d. We found that SUD patients showed greater improvement in weekly dollars spent on alcohol and drugs and SUD severity, compared to DD patients. At endpoint, there was no significant difference in dollars spent, but DD patients still had a higher mean SUD severity. Interestingly, DD patients had significantly higher Parkinsonism and depression than SCZ patients at baseline and endpoint. On the other hand, we found that SUD patients had significantly more akathisia at baseline, improved more than SCZ patients and this was related to cannabis abuse/dependence. Finally, SUD patients improved more in PANSS positive scores than DD and SCZ patients. Taken together, our results provide evidence for increased vulnerability to the adverse effects of alcohol and drugs in schizophrenia patients. They also suggest that substance abuse/withdrawal may mimic some symptoms of schizophrenia. Future studies will need to determine the role quetiapine played in these improvements.

  9. Association analysis of schizophrenia on 18 genes involved in neuronal migration

    DEFF Research Database (Denmark)

    Kähler, Anna K; Djurovic, Srdjan; Kulle, Bettina

    2008-01-01

    Several lines of evidence support the theory of schizophrenia (SZ) being a neurodevelopmental disorder. The structural, cytoarchitectural and functional brain abnormalities reported in patients with SZ, might be due to aberrant neuronal migration, since the final position of neurons affects...... neuronal function, morphology, and formation of synaptic connections. We have investigated the putative association between SZ and gene variants engaged in the neuronal migration process, by performing an association study on 839 cases and 1,473 controls of Scandinavian origin. Using a gene-wide approach...

  10. Neurodevelopmental correlates in schizophrenia

    Directory of Open Access Journals (Sweden)

    Ivković Maja

    2003-01-01

    Full Text Available Contemporary aetiopathogenetic considerations, based on neuro-imaging genetic and developmental neurobiology studies, suggest neurodevelopmental origin of schizophrenia. Several lines of evidence including structural abnormalities on in vivo brain imaging, the excess of prenatal and obstetric complications and the association of congenital and minor physical anomalies with schizophrenia, strongly indicate the neurodevelopmental pathogenesis of schizophrenia. On the other hand, controversial concept of psychotic continuum suggests schizophrenia and depression sharing the same genetic contribution to the pathogenesis. If this would be the case, depression could also be considered as neuro developmental disorder. The aims of the study were to investigate the association between: a pregnancy and birth complications (PBC, and b minor physical anomalies (MPA and schizophrenia or depression. Experimental groups consisted of 60 schizophrenic, 28 major depression patients and 30 healthy controls. All patients were diagnosed according to DSM-IV. Schizophrenic group was divided with regard to PANSS score into positive (n=32 and negative form (n=28 subgroups. PBC information were gathered from maternal recall while MPA were examined by using Waldrop scale for adults. The results showed that negative and positive schizophrenic subgroups had significantly more PBC than depressive group (p<0,05, as well than controls (p<0,001; p<0,05; respectively. There was no significant trend for more PBC in negative than in positive subgroup. All schizophrenic patients had higher rates of MPA than depressives (p<0,05. This trend for more MPA was not significant in comparison with healthy controls. These findings suggest that schizophrenia, especially its negative forms, could be considered as a member of the spectrum of neuro developmental disorders, which does not seem to be the case with depression. PBC and MPA could also be valuable in evaluation of risks for

  11. The effect of sodium nitroprusside on psychotic symptoms and spatial working memory in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Stone, J M; Morrison, P D; Koychev, I; Gao, F; Reilly, T J; Kolanko, M; Mohammadinasab, A; Kapur, S; McGuire, P K

    2016-12-01

    Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms in patients with schizophrenia. This has the potential to revolutionize treatment for schizophrenia. In this study, we tested the hypothesis that SNP leads to a reduction in psychotic symptoms and an improvement in spatial working memory (SWM) performance in patients with schizophrenia. This was a single-centre, randomized, double-blind, placebo-controlled trial performed from 27 August 2014 to 10 February 2016 (clinicaltrials.gov identifier: NCT02176044). Twenty patients with schizophrenia aged 18-60 years with a diagnosis of schizophrenia or schizoaffective disorder were recruited from psychiatric outpatient clinics in the South London and Maudsley NHS Trust, London, UK. Baseline symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18), and SWM was assessed using the CANTAB computerized test. Participants received either an infusion of SNP (0.5 μg/kg per min for 4 h) or placebo and were re-assessed for symptoms and SWM performance immediately after the infusion, and 4 weeks later. SNP did not lead to any reduction in psychotic symptoms or improvement in SWM performance compared to placebo. Although this study was negative, it is possible that the beneficial effects of SNP may occur in patients with a shorter history of illness, or with more acute exacerbation of symptoms.

  12. Add-on mirtazapine improves depressive symptoms in schizophrenia: a double-blind randomized placebo-controlled study with an open-label extension phase.

    Science.gov (United States)

    Terevnikov, Viacheslav; Stenberg, Jan-Henry; Tiihonen, Jari; Joffe, Marina; Burkin, Mark; Tchoukhine, Evgueni; Joffe, Grigori

    2011-04-01

    Depression is common in schizophrenia and worsens its course. The role of antidepressants for schizophrenic depression remains unclear. In this study, the efficacy of add-on mirtazapine on depression in schizophrenia was explored in a subsidiary arm of a recent randomized controlled trial. Patients (n = 41) with chronic but stable schizophrenia and inadequate response to stable doses of different first-generation antipsychotics were treated with add-on mirtazapine 30 mg or placebo during a 6-week double-blind phase and with open-label add-on mirtazapine during a 6-week extension phase. Efficacy measures were the Calgary Depression Scale for Schizophrenia (CDSS) and the Positive and Negative Syndrome Scale depression item. During the double-blind phase, both measures' scores decreased significantly in the mirtazapine group but not in the placebo group (for the CDSS, 52.0% vs 19.6%, respectively). During the open‐label phase, both groups demonstrated significant improvements. In between‐group comparison, a trend favoring mirtazapine did not reach statistical significance. The changes in the CDSS correlated positively with those in the Positive and Negative Syndrome Scale negative, positive and total (sub)scales for mirtazapine‐treated patients during the double‐blind phase. Depressed patients with schizophrenia may benefit from mirtazapine–first‐generation antipsychotics combination, with no increased risk for psychosis. However, more studies are needed.

  13. Modular organization of functional network connectivity in healthy controls and patients with schizophrenia during the resting state

    Directory of Open Access Journals (Sweden)

    Qingbao eYu

    2012-01-01

    Full Text Available Neuroimaging studies have shown that functional brain networks composed from select regions of interest (ROIs have a modular community structure. However, the organization of functional network connectivity (FNC, comprising a purely data-driven network built from spatially independent brain components, is not yet clear. The aim of this study is to explore the modular organization of FNC in both healthy controls (HCs and patients with schizophrenia (SZs. Resting state functional magnetic resonance imaging (R-fMRI data of HCs and SZs were decomposed into independent components (ICs by group independent component analysis (ICA. Then weighted brain networks (in which nodes are brain components were built based on correlations among of ICA time courses. Clustering coefficients and connectivity strength of the networks were computed. A dynamic branch cutting algorithm was used to identify modules of the FNC in HCs and SZs. Results show stronger connectivity strength and higher clustering coefficient in HCs with more and smaller modules in SZs. In addition, HCs and SZs had some different hubs. Our findings demonstrate altered modular architecture of the FNC in schizophrenia and provide insights into abnormal topological organization of intrinsic brain networks in this mental illness.

  14. Metformin for Weight Loss and Metabolic Control in Overweight Outpatients With Schizophrenia and Schizoaffective Disorder

    Science.gov (United States)

    Jarskog, L. Fredrik; Hamer, Robert M.; Catellier, Diane J.; Stewart, Dawn D.; LaVange, Lisa; Ray, Neepa; Golden, Lauren H.; Lieberman, Jeffrey A.; Stroup, T. Scott

    2013-01-01

    Objective The purpose of this study was to determine whether metformin promotes weight loss in overweight out-patients with chronic schizophrenia or schizoaffective disorder. Method In a double-blind study, 148 clinically stable, overweight (body mass index [BMI] ≥27) outpatients with chronic schizophrenia or schizoaffective disorder were randomly assigned to receive 16 weeks of metformin or placebo. Metformin was titrated up to 1,000 mg twice daily, as tolerated. All patients continued to receive their prestudy medications, and all received weekly diet and exercise counseling. The primary outcome measure was change in body weight from baseline to week 16. Results Fifty-eight (77.3%) patients who received metformin and 58 (81.7%) who received placebo completed 16 weeks of treatment. Mean change in body weight was −3.0 kg (95% CI=−4.0 to −2.0) for the metformin group and −1.0 kg (95% CI= −2.0 to 0.0) for the placebo group, with a between-group difference of −2.0 kg (95% CI=−3.4 to −0.6). Metformin also demonstrated a significant between-group advantage for BMI (−0.7; 95% CI=−1.1 to −0.2), triglyceride level (−20.2 mg/dL; 95% CI=−39.2 to −1.3), and hemoglobin A1c level (−0.07%; 95% CI=−0.14 to −0.004). Metformin-associated side effects were mostly gastrointestinal and generally transient, and they rarely led to treatment discontinuation. Conclusions Metformin was modestly effective in reducing weight and other risk factors for cardiovascular disease in clinically stable, overweight outpatients with chronic schizophrenia or schizoaffective disorder over 16 weeks. A significant time-by-treatment interaction suggests that benefits of metformin may continue to accrue with longer treatment. Metformin may have an important role in diminishing the adverse consequences of obesity and metabolic impairments in patients with schizophrenia. PMID:23846733

  15. "Hitting" voices of schizophrenia patients may lastingly reduce persistent auditory hallucinations and their burden : 18-month outcome of a randomized controlled trial

    NARCIS (Netherlands)

    Jenner, JA; Nienhuis, FJ; van de Willige, G; Wiersma, D

    Objective: This study aimed to investigate the outcome of an 18-month randomized controlled trial (RCT) on subjective burden and psychopathology of patients suffering from schizophrenia. Method: An RCT was used to compare hallucination-focused integrative treatment (HIT) and routine treatment (RT)

  16. The gene encoding the melanin-concentrating hormone receptor 1 is associated with schizophrenia in a Danish case-control sample

    DEFF Research Database (Denmark)

    Demontis, Ditte; Nyegaard, Mette; Christensen, Jane H

    2012-01-01

    OBJECTIVE: The MCHR1 gene encoding the melanin-concentrating hormone receptor 1 is located on chromosome 22q13.2 and has previously been associated with schizophrenia in a study of cases and controls from the Faroe Islands and Scotland. Herein we report an association between variations in the MCHR...

  17. Executive function predicts response to antiaggression treatment in schizophrenia: a randomized controlled trial.

    Science.gov (United States)

    Krakowski, Menahem I; Czobor, Pal

    2012-01-01

    Despite extensive experience with antipsychotic medications, we have limited capacity to predict which patients will benefit from which medications and for what symptoms. Such prediction is of particular importance for the proper treatment of violence. Our goal was to determine whether executive function predicts outcome of treatment for aggressive behavior and whether such prediction varies across medication groups. Ninety-nine physically aggressive inpatients (aged 18-60 years) with schizophrenia or schizoaffective disorder (diagnosed according to DSM-IV) who completed tests of executive function were randomly assigned in a double-blind, parallel-group, 12-week trial to clozapine (n = 32), olanzapine (n = 32), or haloperidol (n = 35). The number and severity of aggressive events as measured by the Modified Overt Aggression Scale (MOAS) were the outcome measures. Psychopathology and medication side effects were also assessed. The study was conducted from 1999 to 2004. Poor executive function predicted higher levels of aggression, as measured by MOAS scores over the 12-week period, in all 3 medication groups (F(1,98) = 222.2, P aggression in patients with schizophrenia. clinicaltrials.gov Identifier: NCT01123408. © Copyright 2012 Physicians Postgraduate Press, Inc.

  18. Planning and problem-solving training for patients with schizophrenia: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Backenstraß Matthias

    2011-04-01

    Full Text Available Abstract Background The purpose of this study was to assess whether planning and problem-solving training is more effective in improving functional capacity in patients with schizophrenia than a training program addressing basic cognitive functions. Methods Eighty-nine patients with schizophrenia were randomly assigned either to a computer assisted training of planning and problem-solving or a training of basic cognition. Outcome variables included planning and problem-solving ability as well as functional capacity, which represents a proxy measure for functional outcome. Results Planning and problem-solving training improved one measure of planning and problem-solving more strongly than basic cognition training, while two other measures of planning did not show a differential effect. Participants in both groups improved over time in functional capacity. There was no differential effect of the interventions on functional capacity. Conclusion A differential effect of targeting specific cognitive functions on functional capacity could not be established. Small differences on cognitive outcome variables indicate a potential for differential effects. This will have to be addressed in further research including longer treatment programs and other settings. Trial registration ClinicalTrials.gov NCT00507988

  19. A pilot six-week randomized controlled trial of oxytocin on social cognition and social skills in schizophrenia.

    Science.gov (United States)

    Gibson, Clare M; Penn, David L; Smedley, Kelly L; Leserman, Jane; Elliott, Tonya; Pedersen, Cort A

    2014-07-01

    The current study explored whether oxytocin can improve social cognition and social skills in individuals with schizophrenia using a six-week, double-blind design. Fourteen participants with schizophrenia were randomized to receive either intranasal oxytocin or a placebo solution and completed a battery of social cognitive, social skills and clinical psychiatric symptom measures. Results showed within group improvements in fear recognition, perspective taking, and a reduction in negative symptoms in the oxytocin group. These preliminary findings indicate oxytocin treatment may help improve certain components of functioning in schizophrenia. Implications for the treatment of social functioning in schizophrenia are discussed. Published by Elsevier B.V.

  20. Exploring social cognition in schizophrenia

    DEFF Research Database (Denmark)

    Revsbech, R.; Mortensen, E. L.; Nordgaard, J.

    2017-01-01

    The aim of the study was to compare social cognition between groups of patients diagnosed with schizophrenia and healthy controls and to replicate two previous studies using tests of social cognition that may be particularly sensitive to social cognitive deficits in schizophrenia. Thirty...... nonsignificant. When intelligence and global cognitive functioning is taken into account, schizophrenia patients and healthy controls perform similarly on social cognitive tests....... for intelligence and neuropsychological test performance. Healthy controls performed better than patients on all types of social cognitive tests, particularly on “psychological understanding.” However, after adjusting for intelligence and neuropsychological test performance, all group differences became...

  1. Exploring social cognition in schizophrenia

    DEFF Research Database (Denmark)

    Revsbech, Rasmus; Mortensen, Erik Lykke; Frederiksen, Julie Elisabeth Nordgaard

    2017-01-01

    The aim of the study was to compare social cognition between groups of patients diagnosed with schizophrenia and healthy controls and to replicate two previous studies using tests of social cognition that may be particularly sensitive to social cognitive deficits in schizophrenia. Thirty...... nonsignificant. When intelligence and global cognitive functioning is taken into account, schizophrenia patients and healthy controls perform similarly on social cognitive tests. © 2016 Springer-Verlag Berlin Heidelberg...... for intelligence and neuropsychological test performance. Healthy controls performed better than patients on all types of social cognitive tests, particularly on “psychological understanding.” However, after adjusting for intelligence and neuropsychological test performance, all group differences became...

  2. The impact of eszopiclone on sleep and cognition in patients with schizophrenia and insomnia: a double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Tek, Cenk; Palmese, Laura B; Krystal, Andrew D; Srihari, Vinod H; DeGeorge, Pamela C; Reutenauer, Erin L; Guloksuz, Sinan

    2014-12-01

    Insomnia is frequent in schizophrenia and may contribute to cognitive impairment as well as overuse of weight inducing sedative antipsychotics. We investigated the effects of eszopiclone on sleep and cognition for patients with schizophrenia-related insomnia in a double-blind placebo controlled study, followed by a two-week, single-blind placebo phase. Thirty-nine clinically stable outpatients with schizophrenia or schizoaffective disorder and insomnia were randomized to either 3mg eszopiclone (n=20) or placebo (n=19). Primary outcome measure was change in Insomnia Severity Index (ISI) over 8 weeks. Secondary outcome measure was change in MATRICS Consensus Cognitive Battery (MATRICS). Sleep diaries, psychiatric symptoms, and quality of life were also monitored. ISI significantly improved more in eszopiclone (mean=-10.7, 95% CI=-13.2; -8.2) than in placebo (mean=-6.9, 95% CI=-9.5; -4.3) with a between-group difference of -3.8 (95% CI=-7.5; -0.2). MATRICS score change did not differ between groups. On further analysis there was a significant improvement in the working memory test, letter-number span component of MATRICS (mean=9.8±9.2, z=-2.00, p=0.045) only for subjects with schizophrenia on eszopiclone. There were improvements in sleep diary items in both groups with no between-group differences. Psychiatric symptoms remained stable. Discontinuation rates were similar. Sleep remained improved during single-blind placebo phase after eszopiclone was stopped, but the working memory improvement in patients with schizophrenia was not durable. Eszopiclone stands as a safe and effective alternative for the treatment of insomnia in patients with schizophrenia. Its effects on cognition require further study. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. To tweet or not to tweet about schizophrenia systematic reviews (TweetSz): study protocol for a randomised controlled trial

    Science.gov (United States)

    Jayaram, Mahesh; Bodart, Angelique Y M; Sampson, Stephanie; Zhao, Sai; Montgomery, Alan A; Adams, Clive E

    2015-01-01

    Introduction The Cochrane Schizophrenia Group (CSzG) has produced and maintained systematic reviews of effects of interventions for schizophrenia and related illness. Each review has a Plain Language Summary (PLS), for those without specialised knowledge, and an abstract, which are freely available from The Cochrane Library (https://summaries.cochrane.org). Increasingly, evidence is being distributed using social media such as Twitter and Weibo (in China) alongside traditional publications. Methods and analysis In a prospective two-arm, parallel, open randomised controlled trial with a 1:1 allocation ratio, we will allocate 170 published systematic reviews into the intervention group (tweeting arm/Weibo arm) versus the control group (non-tweeting arm). Reviews will be stratified by baseline access activity, defined as high (≥19 views per week, n=14), medium (4.3 to 18.99 views per week, n=72) or low (tweets daily using Hootsuite with a slightly different accompanying text (written by CEA and AB) and a shortened Uniform Resource Locator (URL) to the PLS: a) The review title as it appears in summaries.cochrane.org, b) A pertinent extract from results or discussion sections of the abstract and c) An intriguing question or pithy statement related to the evidence in the abstract. The primary outcome will be: total number of visits to a PLS in 7 days following the tweet. Secondary outcomes will include % new visits, bounce rate, pages per visit, visit duration, page views, unique page views, time on page, entrances, exiting behaviour and country distribution. Ethics and dissemination This study does not involve living participants, and uses information available in the public domain. Participants are published systematic reviews, hence, no ethical approval is required. Dissemination will be via Twitter, Weibo and traditional academic means. Trial registration number ISRCTN84658943. PMID:26159452

  4. Effectiveness of a peer-led self-management programme for people with schizophrenia: protocol for a randomized controlled trial.

    Science.gov (United States)

    Chan, Sally Wai Chi; Li, Ziqiang; Klainin-Yobas, Piyanee; Ting, Steven; Chan, Moon Fai; Eu, Pui-Wai

    2014-06-01

    To determine the effectiveness of a peer-led self-management programme for people with schizophrenia in reducing psychotic symptom severity, hospital readmission and psychiatric consultation and in enhancing cognition, empowerment, functioning level, medication adherence, perceived recovery, quality of life and social support. Several self-management programmes have been developed to empower patients with severe mental illness in achieving recovery. Research suggests that peer-led self-management programmes have positive effects on patient recovery. However, the existing evidence is inconclusive, due to a lack of credible evidence and long-term follow-up evaluations. A stratified randomized controlled trial will be conducted at six community mental health rehabilitation centres A sample of 242 adults with schizophrenia will be recruited. A peer-led self-management programme, comprising six 2-hour sessions, will be implemented in the intervention group and a standard rehabilitation programme in the control group. Outcomes will be measured at baseline, postintervention and at the 6- and 12-month follow-ups. The measures will include cognition, empowerment, functioning level, medication adherence, perceived recovery, quality of life, social support, symptom severity, hospital readmission and psychiatric consultation. A mixed effects model will be used to analyse the results. Semi-structured interviews will be conducted to explore the peer-trainers' and participants' perspectives on the programme. Research Ethics Committee approval was obtained in December 2011 and funding was obtained in January 2012. This study will provide evidence on the effectiveness of a peer-led self-management programme for patient recovery. It will identify a clinically useful and potentially effective intervention that incorporates empowerment concept. © 2013 John Wiley & Sons Ltd.

  5. Electrophysiological evidence for detrimental impact of a reappraisal emotion regulation strategy on subsequent cognitive control in schizophrenia.

    Science.gov (United States)

    Sullivan, Sara K; Strauss, Gregory P

    2017-07-01

    In healthy individuals, there is evidence that effective implementation of an emotion regulation strategy has beneficial effects on temporally proximal cognitive control task performance. This effect occurs because both of these processes rely heavily on the prefrontal cortex. Individuals with schizophrenia (SZ) have impairments in both emotion regulation and cognitive control that are driven by structural and functional abnormalities of the prefrontal cortex; however, it is unknown whether emotion regulation attempts fail to benefit subsequently performed cognitive control tasks in people with SZ. The present study examined whether attempts to increase or decrease negative emotion via reappraisal have differential effects on subsequent cognitive control in a sample of outpatients diagnosed with SZ (n = 30) and demographically matched healthy controls (CN; n = 29). Participants completed a combined emotion regulation and cognitive control task in which numerical Stroop trials were presented immediately after unpleasant or neutral images that were either increased via reappraisal, decreased via reappraisal, or passively viewed. The electroencephalogram was recorded while participants performed the reappraisal-Stroop task and event related potentials (ERPs) were used to index emotion regulation effectiveness (late positive potential: LPP) and cognitive control (sustained potential: SP). Both CN and SZ evidenced higher LPP amplitude for unpleasant than neutral stimuli consistent with robust neural response to unpleasant stimuli. Although CN demonstrated neurophysiological evidence of effective use of reappraisal to increase and decrease negative emotion, SZ only showed an effective ability to increase negative emotion via reappraisal. CN displayed enhanced cognitive control following increase trials and impaired cognitive control following decrease trials, as indicated by modulation of SP amplitude. In SZ, increase instructions impaired cognitive control and decrease

  6. Cognitive analysis of schizophrenia risk genes that function as epigenetic regulators of gene expression.

    Science.gov (United States)

    Whitton, Laura; Cosgrove, Donna; Clarkson, Christopher; Harold, Denise; Kendall, Kimberley; Richards, Alex; Mantripragada, Kiran; Owen, Michael J; O'Donovan, Michael C; Walters, James; Hartmann, Annette; Konte, Betina; Rujescu, Dan; Gill, Michael; Corvin, Aiden; Rea, Stephen; Donohoe, Gary; Morris, Derek W

    2016-12-01

    Epigenetic mechanisms are an important heritable and dynamic means of regulating various genomic functions, including gene expression, to orchestrate brain development, adult neurogenesis, and synaptic plasticity. These processes when perturbed are thought to contribute to schizophrenia pathophysiology. A core feature of schizophrenia is cognitive dysfunction. For genetic disorders where cognitive impairment is more severe such as intellectual disability, there are a disproportionally high number of genes involved in the epigenetic regulation of gene transcription. Evidence now supports some shared genetic aetiology between schizophrenia and intellectual disability. GWAS have identified 108 chromosomal regions associated with schizophrenia risk that span 350 genes. This study identified genes mapping to those loci that have epigenetic functions, and tested the risk alleles defining those loci for association with cognitive deficits. We developed a list of 350 genes with epigenetic functions and cross-referenced this with the GWAS loci. This identified eight candidate genes: BCL11B, CHD7, EP300, EPC2, GATAD2A, KDM3B, RERE, SATB2. Using a dataset of Irish psychosis cases and controls (n = 1235), the schizophrenia risk SNPs at these loci were tested for effects on IQ, working memory, episodic memory, and attention. Strongest associations were for rs6984242 with both measures of IQ (P = 0.001) and episodic memory (P = 0.007). We link rs6984242 to CHD7 via a long range eQTL. These associations were not replicated in independent samples. Our study highlights that a number of genes mapping to risk loci for schizophrenia may function as epigenetic regulators of gene expression but further studies are required to establish a role for these genes in cognition. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Astrocytes: Orchestrating synaptic plasticity?

    Science.gov (United States)

    De Pittà, M; Brunel, N; Volterra, A

    2016-05-26

    Synaptic plasticity is the capacity of a preexisting connection between two neurons to change in strength as a function of neural activity. Because synaptic plasticity is the major candidate mechanism for learning and memory, the elucidation of its constituting mechanisms is of crucial importance in many aspects of normal and pathological brain function. In particular, a prominent aspect that remains debated is how the plasticity mechanisms, that encompass a broad spectrum of temporal and spatial scales, come to play together in a concerted fashion. Here we review and discuss evidence that pinpoints to a possible non-neuronal, glial candidate for such orchestration: the regulation of synaptic plasticity by astrocytes. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. [Astrocytes and microglia: active players in synaptic plasticity].

    Science.gov (United States)

    Ronzano, Rémi

    2017-12-01

    Synaptic plasticity consists in a change in structure and composition of presynaptic and postsynaptic compartments. For a long time, synaptic plasticity had been thought as a neuronal mechanism only under the control of neural network activity. However, recently, with the growing knowledge about glial physiology, plasticity has been reviewed as a mechanism influenced by the synaptic environment. Thus, it appears that astrocytes and microglia modulate these mechanisms modifying neural environment by clearance of neurotransmitters, releasing essential factors and modulating inflammation. Moreover, glia can change its own activity and the expression pattern of many factors that modulate synaptic plasticity according to the environment. Hence, these populations of "non-neuronal" cells in the central nervous system seem to be active players in synaptic plasticity. This review discusses how glia modulates synaptic plasticity focusing on long-term potentiation and depression, and questions the role of the signaling processes between astrocytes and microglia in these mechanisms. © 2017 médecine/sciences – Inserm.

  9. Paliperidone extended-release tablets in Chinese patients with schizophrenia: meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Cai SL

    2015-07-01

    Full Text Available Shangli Cai,1,2 Huafei Lu,2 Zhihua Bai,2 Renrong Wu,1 Jingping Zhao1 1Mental Health Institute of the Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Hunan, 2Janssen Research and Development, Beijing, People’s Republic of China Background: Previous meta-analyses have compared paliperidone extended-release (ER tablets with other antipsychotics, but none have involved Chinese patients or studies from People’s Republic of China. Further, the results of these meta-analyses may not be applicable to Chinese patients. In the present study, we evaluated the efficacy, safety, and acceptability of paliperidone ER compared with other second-generation antipsychotics (SGAs for Chinese patients with schizophrenia.Methods: Randomized controlled studies of paliperidone ER and other SGAs as oral monotherapy in the acute phase treatment of schizophrenia were retrieved from Medline, Embase, and the Cochrane Library (CENTRAL, as well as from Chinese databases including the China National Knowledge Infrastructure, Wanfang, and VIP Information/Chinese Scientific Journals Database. We pooled data on response rates, chance of withdrawal due to adverse events, probability of adverse events, and odds of withdrawal for any reason.Results: Fifty randomized controlled trials were identified. The response rate for paliperidone ER was significantly higher than that of other pooled SGAs (risk ratio [RR] 0.83, 95% confidence interval [CI] 0.72–0.96 and ziprasidone (RR 0.57, 95% CI 0.39–0.82. Paliperidone ER significantly reduced the chance of withdrawal due to adverse events and the chance of any adverse events compared with other pooled SGAs (RR 0.32, 95% CI 0.17–0.58 and RR 0.88, 95% CI 0.79–0.97 and risperidone (RR 0.31, 95% CI 0.14–0.67 and RR 0.70, 95% CI 0.57–0.86. The incidence of extrapyramidal symptoms on paliperidone ER was comparable with

  10. Implicit and explicit affective associations towards cannabis use in patients with recent-onset schizophrenia and healthy controls

    NARCIS (Netherlands)

    Dekker, N. [=Nienke; Smeerdijk, A. M.; Wiers, R. W.; Duits, J. H.; van Gelder, G.; Houben, K.; Schippers, G.; Linszen, D. H.; de Haan, L.

    2010-01-01

    Background. Cannabis use is common in patients with recent-onset schizophrenia and this is associated with poor disease outcome. More insight in the cognitive-motivational processes related to cannabis use in schizophrenia may inform treatment strategies. The present study is the first known to

  11. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium

    NARCIS (Netherlands)

    van Erp, T. G. M.; Hibar, D. P.; Rasmussen, J. M.; Glahn, D. C.; Pearlson, G. D.; Andreassen, O. A.; Agartz, I.; Westlye, L. T.; Haukvik, U. K.; Dale, A. M.; Melle, I.; Hartberg, C. B.; Gruber, O.; Kraemer, B.; Zilles, D.; Donohoe, G.; Kelly, S.; McDonald, C.; Morris, D. W.; Cannon, D. M.; Corvin, A.; Machielsen, M. W. J.; Koenders, L.; de Haan, L.; Veltman, D. J.; Satterthwaite, T. D.; Wolf, D. H.; Gur, R. C.; Gur, R. E.; Potkin, S. G.; Mathalon, D. H.; Mueller, B. A.; Preda, A.; Macciardi, F.; Ehrlich, S.; Walton, E.; Hass, J.; Calhoun, V. D.; Bockholt, H. J.; Sponheim, S. R.; Shoemaker, J. M.; van Haren, N. E. M.; Pol, H. E. H.; Ophoff, R. A.; Kahn, R. S.; Roiz-Santianez, R.; Crespo-Facorro, B.; Wang, L.; Alpert, K. I.; Jonsson, E. G.; Dimitrova, R.; Bois, C.; Whalley, H. C.; McIntosh, A. M.; Lawrie, S. M.; Hashimoto, R.; Thompson, P. M.; Turner, J. A.; Oosterwijk, J.C.

    The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and

  12. Experimental Implementation of a Biometric Laser Synaptic Sensor

    Directory of Open Access Journals (Sweden)

    Alexander N. Pisarchik

    2013-12-01

    Full Text Available We fabricate a biometric laser fiber synaptic sensor to transmit information from one neuron cell to the other by an optical way. The optical synapse is constructed on the base of an erbium-doped fiber laser, whose pumped diode current is driven by a pre-synaptic FitzHugh–Nagumo electronic neuron, and the laser output controls a post-synaptic FitzHugh–Nagumo electronic neuron. The implemented laser synapse displays very rich dynamics, including fixed points, periodic orbits with different frequency-locking ratios and chaos. These regimes can be beneficial for efficient biorobotics, where behavioral flexibility subserved by synaptic connectivity is a challenge.

  13. A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia.

    Science.gov (United States)

    Bentsen, H; Osnes, K; Refsum, H; Solberg, D K; Bøhmer, T

    2013-12-17

    Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia. We examined the clinical effect of adding an omega-3 fatty acid and/or vitamins E+C to antipsychotics. It was hypothesized that lower baseline levels of polyunsaturated fatty acids (PUFAs) would predict more benefit from the add-on treatment. The trial had a multicenter, randomized, double-blind, placebo-controlled 2 × 2 factorial design. Patients aged 18-39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway. They received active or placebo ethyl-eicosapentaenoate (EPA) 2 g day⁻¹ and active or placebo vitamin E 364 mg day⁻¹+vitamin C 1000 mg day⁻¹ (vitamins) for 16 weeks. The main outcome measures were Positive and Negative Syndrome Scale (PANSS) total and subscales scores, analyzed by linear mixed models. Ninety-nine patients were included. At baseline, erythrocyte PUFA were measured in 97 subjects. Given separately, EPA and vitamins increased drop-out rates, whereas when combined they did not differ from placebo. In low PUFA patients, EPA alone impaired the course of total PANSS (Cohen's d=0.29; P=0.03) and psychotic symptoms (d=0.40; P=0.003), especially persecutory delusions (d=0.48; P=0.0004). Vitamins alone impaired the course of psychotic symptoms (d= 0.37; P=0.005), especially persecutory delusions (d=0.47; P=0.0005). Adding vitamins to EPA neutralized the detrimental effect on psychosis (interaction d=0.31; P=0.02). In high PUFA patients, there were no significant effects of trial drugs on PANSS scales. In conclusion, given separately during an acute episode, EPA and vitamins E+C induce psychotic symptoms in patients with low levels of PUFA. Combined, these agents seem safe.

  14. [Subjective cognition in schizophrenia].

    Science.gov (United States)

    Potvin, S; Aubin, G; Stip, E

    2017-02-01

    Given the extent, magnitude and functional significance of the neurocognitive deficits of schizophrenia, growing attention has been paid recently to patients' self-awareness of their own deficits. Thus far, the literature has shown either that patients fail to recognize their cognitive deficits or that the association between subjective and objective cognition is weak in schizophrenia. The reasons for this lack of consistency remain unexplained but may have to do, among others, with the influence of potential confounding clinical variables and the choice of the scale used to measure self-awareness of cognitive deficits. In the current study, we sought to examine the relationships between subjective and objective cognitive performance in schizophrenia, while controlling for the influence of sociodemographic and psychiatric variables. Eighty-two patients with a schizophrenia-spectrum disorder (DSM-IV criteria) were recruited. Patients' subjective cognitive complaints were evaluated with the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS), the most frequently used scale to measure self-awareness of cognitive deficits in schizophrenia. Neurocognition was evaluated with working memory, planning and visual learning tasks taken from Cambridge Neuropsychological Tests Automated Battery. The Stroop Color-Word test was also administered. Psychiatric symptoms were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. The relationships between subjective and objective cognition were evaluated with multivariate hierarchic linear regression analyses, taking into consideration potential confounders such as sociodemographic and psychiatric variables. Finally, a factor analysis of the SSTICS was performed. For the SSTICS total score, the regression analysis produced a model including two predictors, namely visual learning and Stoop interference performance, explaining a moderate portion of the variance

  15. Empathy in schizophrenia: impaired resonance.

    Science.gov (United States)

    Haker, Helene; Rössler, Wulf

    2009-09-01

    Resonance is the phenomenon of one person unconsciously mirroring the motor actions as basis of emotional expressions of another person. This shared representation serves as a basis for sharing physiological and emotional states of others and is an important component of empathy. Contagious laughing and contagious yawning are examples of resonance. In the interpersonal contact with individuals with schizophrenia we can often experience impaired empathic resonance. The aim of this study is to determine differences in empathic resonance-in terms of contagion by yawning and laughing-in individuals with schizophrenia and healthy controls in the context of psychopathology and social functioning. We presented video sequences of yawning, laughing or neutral faces to 43 schizophrenia outpatients and 45 sex- and age-matched healthy controls. Participants were video-taped during the stimulation and rated regarding contagion by yawning and laughing. In addition, we assessed self-rated empathic abilities (Interpersonal Reactivity Index), psychopathology (Positive and Negative Syndrome Scale in the schizophrenia group resp. Schizotypal Personality Questionnaire in the control group), social dysfunction (Social Dysfunction Index) and executive functions (Stroop, Fluency). Individuals with schizophrenia showed lower contagion rates for yawning and laughing. Self-rated empathic concern showed no group difference and did not correlate with contagion. Low rate of contagion by laughing correlated with the schizophrenia negative syndrome and with social dysfunction. We conclude that impaired resonance is a handicap for individuals with schizophrenia in social life. Blunted observable resonance does not necessarily reflect reduced subjective empathic concern.

  16. Altered Cortico-Striatal Connectivity in Offspring of Schizophrenia Patients Relative to Offspring of Bipolar Patients and Controls.

    Directory of Open Access Journals (Sweden)

    Cristina Solé-Padullés

    Full Text Available Schizophrenia (SZ and bipolar disorder (BD share clinical features, genetic risk factors and neuroimaging abnormalities. There is evidence of disrupted connectivity in resting state networks in patients with SZ and BD and their unaffected relatives. Resting state networks are known to undergo reorganization during youth coinciding with the period of increased incidence for both disorders. We therefore focused on characterizing resting state network connectivity in youth at familial risk for SZ or BD to identify alterations arising during this period. We measured resting-state functional connectivity in a sample of 106 youth, aged 7-19 years, comprising offspring of patients with SZ (N = 27, offspring of patients with BD (N = 39 and offspring of community control parents (N = 40. We used Independent Component Analysis to assess functional connectivity within the default mode, executive control, salience and basal ganglia networks and define their relationship to grey matter volume, clinical and cognitive measures. There was no difference in connectivity within any of the networks examined between offspring of patients with BD and offspring of community controls. In contrast, offspring of patients with SZ showed reduced connectivity within the left basal ganglia network compared to control offspring, and they showed a positive correlation between connectivity in this network and grey matter volume in the left caudate. Our findings suggest that dysconnectivity in the basal ganglia network is a robust correlate of familial risk for SZ and can be detected during childhood and adolescence.

  17. An interactive sports video game as an intervention for rehabilitation of community-living patients with schizophrenia: A controlled, single-blind, crossover study.

    Science.gov (United States)

    Shimizu, Nobuko; Umemura, Tomohiro; Matsunaga, Masahiro; Hirai, Takayoshi

    2017-01-01

    Hypofrontality is a state of decreased cerebral blood flow in the prefrontal cortex during executive function performance; it is commonly observed in patients with schizophrenia. Cognitive dysfunction, as well as the psychological symptoms of schizophrenia, influences the ability of patients to reintegrate into society. The current study investigated the effects of an interactive sports video game (IVG; Nintendo Wii™ Sports Resort) on frontal lobe function of patients with schizophrenia. A sample of eight patients (6 male and 2 female; mean age = 46.7 years, standard deviation (SD) = 13.7) engaged in an IVG every week for 3 months in a controlled, single-blind, crossover study. Before and after the intervention we examined frontal lobe blood-flow volume using functional near-infrared spectroscopy (fNIRS), and assessed functional changes using the Frontal Assessment Battery, Health-Related Quality of Life scale, and behaviorally-assessed physical function tests. fNIRS revealed that prefrontal activity during IVG performance significantly increased in the IVG period compared with the control period. Furthermore, significant correlations between cerebral blood flow changes in different channels were observed during IVG performance. In addition, we observed intervention-related improvement in health-related quality of life following IVG. IVG intervention was associated with increased prefrontal cortex activation and improved health-related quality of life performance in patients with schizophrenia. Patients with chronic schizophrenia are characterized by withdrawal and a lack of social responsiveness or interest in others. Interventions using IVG may provide a useful low-cost rehabilitation method for such patients, without the need for specialized equipment.

  18. An interactive sports video game as an intervention for rehabilitation of community-living patients with schizophrenia: A controlled, single-blind, crossover study

    Science.gov (United States)

    Umemura, Tomohiro; Matsunaga, Masahiro; Hirai, Takayoshi

    2017-01-01

    Hypofrontality is a state of decreased cerebral blood flow in the prefrontal cortex during executive function performance; it is commonly observed in patients with schizophrenia. Cognitive dysfunction, as well as the psychological symptoms of schizophrenia, influences the ability of patients to reintegrate into society. The current study investigated the effects of an interactive sports video game (IVG; Nintendo Wii™ Sports Resort) on frontal lobe function of patients with schizophrenia. A sample of eight patients (6 male and 2 female; mean age = 46.7 years, standard deviation (SD) = 13.7) engaged in an IVG every week for 3 months in a controlled, single-blind, crossover study. Before and after the intervention we examined frontal lobe blood-flow volume using functional near-infrared spectroscopy (fNIRS), and assessed functional changes using the Frontal Assessment Battery, Health-Related Quality of Life scale, and behaviorally-assessed physical function tests. fNIRS revealed that prefrontal activity during IVG performance significantly increased in the IVG period compared with the control period. Furthermore, significant correlations between cerebral blood flow changes in different channels were observed during IVG performance. In addition, we observed intervention-related improvement in health-related quality of life following IVG. IVG intervention was associated with increased prefrontal cortex activation and improved health-related quality of life performance in patients with schizophrenia. Patients with chronic schizophrenia are characterized by withdrawal and a lack of social responsiveness or interest in others. Interventions using IVG may provide a useful low-cost rehabilitation method for such patients, without the need for specialized equipment. PMID:29131826

  19. An interactive sports video game as an intervention for rehabilitation of community-living patients with schizophrenia: A controlled, single-blind, crossover study.

    Directory of Open Access Journals (Sweden)

    Nobuko Shimizu

    Full Text Available Hypofrontality is a state of decreased cerebral blood flow in the prefrontal cortex during executive function performance; it is commonly observed in patients with schizophrenia. Cognitive dysfunction, as well as the psychological symptoms of schizophrenia, influences the ability of patients to reintegrate into society. The current study investigated the effects of an interactive sports video game (IVG; Nintendo Wii™ Sports Resort on frontal lobe function of patients with schizophrenia. A sample of eight patients (6 male and 2 female; mean age = 46.7 years, standard deviation (SD = 13.7 engaged in an IVG every week for 3 months in a controlled, single-blind, crossover study. Before and after the intervention we examined frontal lobe blood-flow volume using functional near-infrared spectroscopy (fNIRS, and assessed functional changes using the Frontal Assessment Battery, Health-Related Quality of Life scale, and behaviorally-assessed physical function tests. fNIRS revealed that prefrontal activity during IVG performance significantly increased in the IVG period compared with the control period. Furthermore, significant correlations between cerebral blood flow changes in different channels were observed during IVG performance. In addition, we observed intervention-related improvement in health-related quality of life following IVG. IVG intervention was associated with increased prefrontal cortex activation and improved health-related quality of life performance in patients with schizophrenia. Patients with chronic schizophrenia are characterized by withdrawal and a lack of social responsiveness or interest in others. Interventions using IVG may provide a useful low-cost rehabilitation method for such patients, without the need for specialized equipment.

  20. ATA homozigosity in the IL-10 gene promoter is a risk factor for schizophrenia in Spanish females: a case control study

    Directory of Open Access Journals (Sweden)

    Fernandez-Piqueras Jose

    2011-06-01

    Full Text Available Abstract Background Three IL-10 gene promoter single nucleotide polymorphisms -1082G > A, -819C > T and -592C > A and the haplotypes they define in Caucasians, GCC, ACC, ATA, associated with different IL-10 production rates, have been linked to schizophrenia in some populations with conflicting results. On the basis of the evidence of the sex-dependent effect of certain genes in many complex diseases, we conducted a sex-stratified case-control association study to verify the linkage of the IL-10 gene promoter SNPs and haplotypes with schizophrenia and the possible sex-specific genetic effect in a Spanish schizophrenic population. Methods 241 DSM-IV diagnosed Spanish schizophrenic patients and 435 ethnically matched controls were genotyped for -1082G > A and -592C > A SNPs. Chi squared tests were performed to assess for genetic association of alleles, genotypes and haplotypes with the disease. Results The -1082A allele (p = 0.027, A/A (p = 0.008 and ATA/ATA (p = 0.003 genotypes were significantly associated with schizophrenia in females while neither allelic nor genotypic frequencies reached statistical significance in the male population. Conclusions Our results highlight the hypothesis of an imbalance towards an inflammatory syndrome as the immune abnormality of schizophrenia. Anyway, a better understanding of the involvement of the immune system would imply the search of immune abnormalities in endophenotypes in whose sex and ethnicity might be differential factors. It also reinforces the need of performing complex gene studies based on multiple cytokine SNPs, including anti and pro-inflammatory, to clarify the immune system abnormalities direction in the etiology of schizophrenia.

  1. Raloxifene Plus Antipsychotics Versus Placebo Plus Antipsychotics in Severely Ill Decompensated Postmenopausal Women With Schizophrenia or Schizoaffective Disorder: A Randomized Controlled Trial.

    Science.gov (United States)

    Weiser, Mark; Levi, Linda; Burshtein, Shimon; Hagin, Michal; Matei, Valentin P; Podea, Delia; Micluția, Ioana; Tiugan, Alexandru; Păcală, Bogdan; Grecu, Iosif Gabos; Noy, Adam; Zamora, Daisy; Davis, John M

    2017-07-01

    Several single-center studies have found raloxifene, an estrogen agonist, to be effective in ameliorating symptoms of schizophrenia in stable patients as augmentation of antipsychotics. This multicenter study assessed whether raloxifene plus antipsychotic treatment, in comparison to placebo plus antipsychotics, improves symptoms or cognition in severely ill decompensated schizophrenia patients. In this 16-week, double-blind, randomized, placebo-controlled study, 200 severely ill, decompensated postmenopausal women who met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder were recruited from January 2011 to December 2012 and were randomized to receive either raloxifene 120 mg/d plus antipsychotics or placebo plus antipsychotics. The primary outcome measure was Positive and Negative Syndrome Scale (PANSS) total score at the end of the trial. The placebo plus antipsychotics group experienced statistically significant improvement in PANSS total score (P raloxifene plus antipsychotics group, using mixed models for repeated measures, with results favoring placebo by 4.5 points (95% CI, 2.3-6.7). These results were clearly outside the 95% confidence interval. This negative effect was more pronounced in patients who had more frequent relapses and in those with baseline PANSS scores of 100 or higher. There were no differences between groups in Clinical Global Impression Scale-Severity scores or Composite Brief Assessment of Cognition in Schizophrenia scores at 16 weeks (P > .3). Baseline follicle-stimulating hormone and estradiol levels did not alter the drug-placebo differences. Individuals in the active treatment arm showed worse outcome than those in the placebo arm, most likely as a result of chance variation, but the results unequivocally show no benefit of antipsychotics plus raloxifene versus antipsychotics plus placebo in this large randomized, double-blind, placebo-controlled trial in postmenopausal women. These data do not support the use of

  2. Neuromodulation and Synaptic Plasticity for the Control of Fast Periodic Movement:Energy Efficiency in Coupled Compliant Joints via PCA

    Directory of Open Access Journals (Sweden)

    Philipp eStratmann

    2016-03-01

    Full Text Available There are multiple indications that the nervous system of animals tunes muscle output to exploit natural dynamics of the elastic locomotor system and the environment. This is an advantageous strategy especially in fast periodic movements, since the elastic elements store energy and increase energy efficiency and movement speed.Experimental evidence suggests that coordination among joints involves proprioceptive input and neuromodulatory influence originating in the brain stem. However, the neural strategies underlying the coordination of fast periodic movements remain poorly understood.Based on robotics control theory, we suggest that the nervous system implements a mechanism to accomplish coordination between joints by a linear coordinate transformation from the multi-dimensional space representing proprioceptive input at the joint level into a one-dimensional controller space. In this one-dimensional subspace, the movements of a whole limb can be driven by a single oscillating unit as simple as a reflex interneuron. The output of the oscillating unit is transformed back to joint space via the same transformation. The transformation weights correspond to the dominant principal component of the movement.In this study, we propose a biologically plausible neural network to exemplify that the central nervous system may encode our controller design. Using theoretical considerations and computer simulations, we demonstrate that spike-timing-dependent plasticity for the input mapping and serotonergic neuromodulation for the output mapping can extract the dominant principal component of sensory signals. Our simulations show that our network can reliably control mechanical systems of different complexity and increase the energy efficiency of ongoing cyclic movements.The proposed network is simple and consistent with previous biologic experiments. Thus, our controller could serve as a candidate to describe the neural control of fast, energy

  3. The Ubiquitin-Proteasome Pathway and Synaptic Plasticity

    Science.gov (United States)

    Hegde, Ashok N.

    2010-01-01

    Proteolysis by the ubiquitin-proteasome pathway (UPP) has emerged as a new molecular mechanism that controls wide-ranging functions in the nervous system, including fine-tuning of synaptic connections during development and synaptic plasticity in the adult organism. In the UPP, attachment of a small protein, ubiquitin, tags the substrates for…

  4. Neuroplasticity Signaling Pathways Linked to the Pathophysiology of Schizophrenia

    Science.gov (United States)

    Balu, Darrick T.; Coyle, Joseph T.

    2010-01-01

    Schizophrenia is a severe mental illness that afflicts nearly 1% of the world's population. One of the cardinal pathological features of schizophrenia is perturbation in synaptic connectivity. Although the etiology of schizophrenia is unknown, it appears to be a developmental disorder involving the interaction of a potentially large number of risk genes, with no one gene producing a strong effect except rare, highly penetrant copy number variants. The purpose of this review is to detail how putative schizophrenia risk genes (DISC-1, neuregulin/ErbB4, dysbindin, Akt1, BDNF, and NMDA receptor) are involved in regulating neuroplasticity and how alterations in their expression may contribute to the disconnectivity observed in schizophrenia. Moreover, this review highlights how many of these risk genes converge to regulate common neurotransmitter systems and signaling pathways. Future studies aimed at elucidating the functions of these risk genes will provide new insights into the pathophysiology of schizophrenia and will likely lead to the nomination of novel therapeutic targets for restoring proper synaptic connectivity in the brain in schizophrenia and related disorders. PMID:20951727

  5. Group cognitive remediation therapy for chronic schizophrenia: A randomized controlled trial.

    Science.gov (United States)

    Tan, Shuping; Zou, Yizhuang; Wykes, Til; Reeder, Clare; Zhu, Xiaolin; Yang, Fude; Zhao, Yanli; Tan, Yunlong; Fan, Fengmei; Zhou, Dongfeng

    2016-07-28

    Individual-level cognitive remediation therapy (CRT) has been shown to be effective for cognitive improvement and social function amelioration. Here, we aimed to test the efficacy of group-based CRT in Chinese subjects with schizophrenia. One-hundred and four inpatients were randomly assigned to either 40 sessions of small-group CRT therapy or therapeutic contact-matched Musical and Dancing Therapy (MDT). Cognitive and social functioning, as well as clinical symptoms, were evaluated over the course of treatment. Specifically, cognitive function was evaluated using a battery of cognitive measurements, clinical symptoms were evaluated using the Positive and Negative Syndrome Scale, and social function was evaluated using the Nurse's Observation Scale for Inpatient Evaluation-30. All patients were evaluated pre- and post-treatment. Forty-four individuals in the CRT group and 46 in the MDT group completed all of the planned treatments and analyses. Cognitive functions, especially cognitive flexibility and memory, showed significant improvement in the CRT group over the course of the study. The MDT group also showed improvement in several cognitive flexibility assessments, but the degree of improvement was significantly greater in the CRT group. Several social-function factors exhibited a significant improvement in the CRT group, but not in the MDT group. Cognitive function improvement correlated positively with social function without predicting social function change. We conclude that group-based CRT is an effective and promising therapy. Copyright © 2016. Published by Elsevier Ireland Ltd.

  6. Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials.

    Science.gov (United States)

    Iwata, Y; Nakajima, S; Suzuki, T; Keefe, R S E; Plitman, E; Chung, J K; Caravaggio, F; Mimura, M; Graff-Guerrero, A; Uchida, H

    2015-10-01

    Hypofunction of N-methyl-d-aspartate (NMDA) receptors has been proposed to have an important role in the cognitive impairments observed in schizophrenia. Although glutamate modulators may be effective in reversing such difficult-to-treat conditions, the results of individual studies thus far have been inconsistent. We conducted a systematic review and meta-analysis to examine whether glutamate positive modulators have beneficial effects on cognitive functions in patients with schizophrenia. A literature search was conducted to identify double-blind randomized placebo-controlled trials in schizophrenia or related disorders, using Embase, Medline, and PsycINFO (last search: February 2015). The effects of glutamate positive modulators on cognitive deficits were evaluated for overall cognitive function and eight cognitive domains by calculating standardized mean differences (SMDs) between active drugs and placebo added to antipsychotics. Seventeen studies (N=1391) were included. Glutamate positive modulators were not superior to placebo in terms of overall cognitive function (SMD=0.08, 95% confidence interval=-0.06 to 0.23) (11 studies, n=858) nor each of eight cognitive domains (SMDs=-0.03 to 0.11) (n=367-940) in this population. Subgroup analyses by diagnosis (schizophrenia only studies), concomitant antipsychotics, or pathway of drugs to enhance the glutamatergic neurotransmission (glycine allosteric site of NMDA receptors or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors) suggested no procognitive effect of glutamate positive modulators. Further, no effect was found in individual compounds on cognition. In conclusion, glutamate positive modulators may not be effective in reversing overall cognitive impairments in patients with schizophrenia as adjunctive therapies.

  7. Moderating factors for the effectiveness of group art therapy for schizophrenia: secondary analysis of data from the MATISSE randomised controlled trial.

    Science.gov (United States)

    Leurent, Baptiste; Killaspy, Helen; Osborn, David P; Crawford, Mike J; Hoadley, Angela; Waller, Diane; King, Michael

    2014-11-01

    Although some studies suggest that art therapy may be useful in the treatment of negative symptoms of schizophrenia, a recent large trial of group art therapy found no clinical advantage over standard care, but the study population was heterogeneous and uptake of the intervention was poor. This study aimed to investigate whether art therapy was more effective for specific subgroups of patients. Secondary analysis of data from a randomised controlled trial of group art therapy as an adjunctive treatment for schizophrenia (n = 140) versus standard care alone (n = 137). Positive and Negative Syndrome Scale scores at 12 months were compared between trial arms. Interaction between intervention effect and different subgroups, including those with more severe negative symptoms of schizophrenia, and those who expressed a preference for art therapy prior to randomisation, was tested using a linear mixed model. The clinical effectiveness of group art therapy did not significantly differ between participants with more or less severe negative symptoms [interaction for difference in PANSS = 1.7, 95 % CI (-8.6 to 12.1), P = 0.741], or between those who did and did not express a preference for art therapy [interaction = 3.9, 95 % CI (-6.7 to 14.5), P = 0.473]. None of the other exploratory subgroups suggested differences in intervention effect. There was no evidence of greater improvement in clinical symptoms of schizophrenia for those with more severe negative symptoms or those with a preference for art therapy. Identification of patients with schizophrenia who may benefit most from group art therapy remains elusive.

  8. Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study.

    Science.gov (United States)

    Takiguchi, Kazuo; Uezato, Akihito; Itasaka, Michio; Atsuta, Hidenori; Narushima, Kenji; Yamamoto, Naoki; Kurumaji, Akeo; Tomita, Makoto; Oshima, Kazunari; Shoda, Kosaku; Tamaru, Mai; Nakataki, Masahito; Okazaki, Mitsutoshi; Ishiwata, Sayuri; Ishiwata, Yasuyoshi; Yasuhara, Masato; Arima, Kunimasa; Ohmori, Tetsuro; Nishikawa, Toru

    2017-07-12

    It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity. UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 2006.

  9. Neural control of left ventricular contractility in the dog heart: synaptic interactions of negative inotropic vagal preganglionic neurons in the nucleus ambiguus with tyrosine hydroxylase immunoreactive terminals.

    Science.gov (United States)

    Massari, V J; Dickerson, L W; Gray, A L; Lauenstein, J M; Blinder, K J; Newsome, J T; Rodak, D J; Fleming, T J; Gatti, P J; Gillis, R A

    1998-08-17

    Recent physiological evidence indicates that vagal postganglionic control of left ventricular contractility is mediated by neurons found in a ventricular epicardial fat pad ganglion. In the dog this region has been referred to as the cranial medial ventricular (CMV) ganglion [J.L. Ardell, Structure and function of mammalian intrinsic cardiac neurons, in: J.A. Armour, J.L. Ardell (Eds.). Neurocardiology, Oxford Univ. Press, New York, 1994, pp. 95-114; B.X. Yuan, J.L. Ardell, D.A. Hopkins, A.M. Losier, J.A. Armour, Gross and microscopic anatomy of the canine intrinsic cardiac nervous system, Anat. Rec., 239 (1994) 75-87]. Since activation of the vagal neuronal input to the CMV ganglion reduces left ventricular contractility without influencing cardiac rate or AV conduction, this ganglion contains a functionally selective pool of negative inotropic parasympathetic postganglionic neurons. In the present report we have defined the light microscopic distribution of preganglionic negative inotropic neurons in the CNS which are retrogradely labeled from the CMV ganglion. Some tissues were also processed for the simultaneous immunocytochemical visualization of tyrosine hydroxylase (TH: a marker for catecholaminergic neurons) and examined with both light microscopic and electron microscopic methods. Histochemically visualized neurons were observed in a long slender column in the ventrolateral nucleus ambiguus (NA-VL). The greatest number of retrogradely labeled neurons were observed just rostral to the level of the area postrema. TH perikarya and dendrites were commonly observed interspersed with vagal motoneurons in the NA-VL. TH nerve terminals formed axo-dendritic synapses upon negative inotropic vagal motoneurons, however the origin of these terminals remains to be determined. We conclude that synaptic interactions exist which would permit the parasympathetic preganglionic vagal control of left ventricular contractility to be modulated monosynaptically by

  10. Effects of rapamycin treatment after controlled cortical impact injury on neurogenesis and synaptic reorganization in the mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Corwin R Butler

    2015-11-01

    Full Text Available Post-traumatic epilepsy (PTE is one consequence of traumatic brain injury (TBI. A prominent cell signaling pathway activated in animal models of both TBI and epilepsy is the mammalian target of rapamycin (mTOR. Inhibition of mTOR with rapamycin has shown promise as a potential modulator of epileptogenesis in several animal models of epilepsy, but cellular mechanisms linking mTOR expression and epileptogenesis are unclear. In this study, the role of mTOR in modifying functional hippocampal circuit reorganization after focal TBI induced by controlled cortical impact was investigated. Rapamycin (3 or 10 mg/kg, an inhibitor of mTOR signaling, was administered by intraperitoneal injection beginning on the day of injury and continued daily until tissue collection. Relative to controls, rapamycin treatment reduced dentate granule cell area in the hemisphere ipsilateral to the injury two weeks post-injury. Brain injury resulted in a significant increase in doublecortin immunolabeling in the dentate gyrus ipsilateral to the injury, indicating increased neurogenesis shortly after TBI. Rapamycin treatment prevented the increase in doublecortin labeling, with no overall effect on Fluoro-Jade B staining in the ipsilateral hemisphere, suggesting that rapamycin treatment reduced posttraumatic neurogenesis but did not prevent cell loss after injury. At later times post-injury (8-13 weeks, evidence of mossy fiber sprouting and increased recurrent excitation of dentate granule cells was detected, which were attenuated by rapamycin treatment. Rapamycin treatment also diminished seizure prevalence relative to vehicle-treated controls after TBI. Collectively, these results support a role for adult neurogenesis in PTE development and suggest that suppression of epileptogenesis by mTOR inhibition includes effects on post-injury neurogenesis.

  11. Association between upstream purine complexes of human caveolin-1 gene and schizophrenia in qazvin province of iran.

    Science.gov (United States)

    Najafipour, Reza; Heidari, Abolfazl; Alizadeh, Safar Ali; Ghafelebashi, Hannaneh; Rashvand, Zahra; Javadi, Amir; Moradi, Mohammad; Afshar, Hosein

    2014-12-01

    Caveolin is a multifunctional and scaffolding membrane protein, which involves cholesterol trafficking to plasma lipid microdomain. It organizes and targets synaptic parts of the neurotransmitter and neurotrophic receptor signaling pathways. Caveolins are encoded by CAV-1, 2 and 3 genes. Disruption of the CAV1 would likely ruin the neuronal signaling, which leads to symptoms of schizophrenia in predisposed individuals. The upper area of CAV-1 gene is highly conserved and can have a regulatory role in neurodegenerative diseases. This study was designed to find out the possible association of polymorphisms of this area and schizophrenia. In a case-control study, 254 blood samples were obtained from 127 patients with schizophrenia and 127 well matched controls referred to 22 Bahman Hospital of Qazvin University of Medical Sciences (QUMS) in Qazvin province, Iran, using simple random sampling method. After extracting DNA, the upper region of the human CAV1- gene was amplified by PCR in all collected samples. The products were visualized by silver staining in 10% polyacrylamide gel and then sequenced. We detected nine homozygotes in patients and 15 in control subjects. Homozygosity was 7.08% and 11.8% in cases and control, respectively. Nine types homozygote haplotype were detected in upper region of the CAV1 gene in cases and controls. Three haplotypes were common in cases and controls; four haplotypes were seen in controls only and two in cases. Our findings implied a significant correlation between some haplotypes of upper region of CAV1 gene and schizophrenia. Existence of some haplotypes and lack of another in CAV1 upstream can suggest a significant correlation between schizophrenia and some haplotypes.

  12. COMT (Val158Met and BDNF (Val66Met Genes Polymorphism in Schizophrenia: A Case-Control Report

    Directory of Open Access Journals (Sweden)

    ramin saravani

    2017-10-01

    Full Text Available Objective: The effects of human brain-derived neurotropic factor (BDNF Val66Met (G>A and the human Catechol-O-methylTransferase (COMT Val158Met (G>A polymorphisms on Schizophrenia (SCZ risk were evaluated.Methods: This case control study included 92 SCZ patients and 92 healthy controls (HCs. Genotyping of both variants were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR.Results: The findings showed that BDNF Val66Met (G>A variant increased the risk of SCZ (OR=2.008 95%CI=1.008-4.00, P=0.047, GA vs. GG, OR=3.876 95%CI=1.001-14.925, P=0.049. AA vs. GG, OR=2.272. 95%CI=1.204-4.347, P=0.011, GA+AA vs. GG, OR=2.22 95%CI=1.29-3.82. P=0.005, A vs. G. COMT Val158Met (G>A polymorphism was not associated with the risk/protective of SCZ.Conclusion: The results proposed that BDNF Val66Met (G>A polymorphism may increase the risk of SCZ development and did not support an association between COMT Val158Met (G>A variant and risk/protective of SCZ. Further studies and different ethnicities are recommended to confirm the findings.

  13. Reduced sleep spindles and spindle coherence in schizophrenia: mechanisms of impaired memory consolidation?

    Science.gov (United States)

    Wamsley, Erin J; Tucker, Matthew A; Shinn, Ann K; Ono, Kim E; McKinley, Sophia K; Ely, Alice V; Goff, Donald C; Stickgold, Robert; Manoach, Dara S

    2012-01-15

    Sleep spindles are thought to induce synaptic changes and thereby contribute to memory consolidation during sleep. Patients with schizophrenia show dramatic reductions of both spindles and sleep-dependent memory consolidation, which may be causally related. To examine the relations of sleep spindle activity to sleep-dependent consolidation of motor procedural memory, 21 chronic, medicated schizophrenia outpatients and 17 healthy volunteers underwent polysomnography on two consecutive nights. On the second night, participants were trained on the finger-tapping motor sequence task (MST) at bedtime and tested the following morning. The number, density, frequency, duration, amplitude, spectral content, and coherence of stage 2 sleep spindles were compared between groups and examined in relation to overnight changes in MST performance. Patients failed to show overnight improvement on the MST and differed significantly from control participants who did improve. Patients also exhibited marked reductions in the density (reduced 38% relative to control participants), number (reduced 36%), and coherence (reduced 19%) of sleep spindles but showed no abnormalities in the morphology of individual spindles or of sleep architecture. In patients, reduced spindle number and density predicted less overnight improvement on the MST. In addition, reduced amplitude and sigma power of individual spindles correlated with greater severity of positive symptoms. The observed sleep spindle abnormalities implicate thalamocortical network dysfunction in schizophrenia. In addition, the findings suggest that abnormal spindle generation impairs sleep-dependent memory consolidation in schizophrenia, contributes to positive symptoms, and is a promising novel target for the treatment of cognitive deficits in schizophrenia. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Distributed Recurrent Neural Forward Models with Synaptic Adaptation and CPG-based control for Complex Behaviors of Walking Robots

    Directory of Open Access Journals (Sweden)

    Sakyasingha eDasgupta

    2015-09-01

    Full Text Available Walking animals, like stick insects, cockroaches or ants, demonstrate a fascinating range of locomotive abilities and complex behaviors. The locomotive behaviors can consist of a variety of walking patterns along with adaptation that allow the animals to deal with changes in environmental conditions, like uneven terrains, gaps, obstacles etc. Biological study has revealed that such complex behaviors are a result of a combination of biomechanics and neural mechanism thus representing the true nature of embodied interactions. While the biomechanics helps maintain flexibility and sustain a variety of movements, the neural mechanisms generate movements while making appropriate predictions crucial for achieving adaptation. Such predictions or planning ahead can be achieved by way of internal models that are grounded in the overall behavior of the animal. Inspired by these findings, we present here, an artificial bio-inspired walking system which effectively combines biomechanics (in terms of the body and leg structures with the underlying neural mechanisms. The neural mechanisms consist of 1 central pattern generator based control for generating basic rhythmic patterns and coordinated movements, 2 distributed (at each leg recurrent neural network based adaptive forward models with efference copies as internal models for sensory predictions and instantaneous state estimations, and 3 searching and elevation control for adapting the movement of an individual leg to deal with different environmental conditions. Using simulations we show that this bio-inspired approach with adaptive internal models allows the walking robot to perform complex locomotive behaviors as observed in insects, including walking on undulated terrains, crossing large gaps as well as climbing over high obstacles. Furthermore we demonstrate that the newly developed recurrent network based approach to sensorimotor prediction outperforms the previous state of the art adaptive neuron

  15. Distributed recurrent neural forward models with synaptic adaptation and CPG-based control for complex behaviors of walking robots.

    Science.gov (United States)

    Dasgupta, Sakyasingha; Goldschmidt, Dennis; Wörgötter, Florentin; Manoonpong, Poramate

    2015-01-01

    Walking animals, like stick insects, cockroaches or ants, demonstrate a fascinating range of locomotive abilities and complex behaviors. The locomotive behaviors can consist of a variety of walking patterns along with adaptation that allow the animals to deal with changes in environmental conditions, like uneven terrains, gaps, obstacles etc. Biological study has revealed that such complex behaviors are a result of a combination of biomechanics and neural mechanism thus representing the true nature of embodied interactions. While the biomechanics helps maintain flexibility and sustain a variety of movements, the neural mechanisms generate movements while making appropriate predictions crucial for achieving adaptation. Such predictions or planning ahead can be achieved by way of internal models that are grounded in the overall behavior of the animal. Inspired by these findings, we present here, an artificial bio-inspired walking system which effectively combines biomechanics (in terms of the body and leg structures) with the underlying neural mechanisms. The neural mechanisms consist of (1) central pattern generator based control for generating basic rhythmic patterns and coordinated movements, (2) distributed (at each leg) recurrent neural network based adaptive forward models with efference copies as internal models for sensory predictions and instantaneous state estimations, and (3) searching and elevation control for adapting the movement of an individual leg to deal with different environmental conditions. Using simulations we show that this bio-inspired approach with adaptive internal models allows the walking robot to perform complex locomotive behaviors as observed in insects, including walking on undulated terrains, crossing large gaps, leg damage adaptations, as well as climbing over high obstacles. Furthermore, we demonstrate that the newly developed recurrent network based approach to online forward models outperforms the adaptive neuron forward models

  16. A microstructural study of sleep instability in drug-naive patients with schizophrenia and healthy controls: sleep spindles, rapid eye movements, and muscle atonia.

    Science.gov (United States)

    Guénolé, Fabian; Chevrier, Elyse; Stip, Emmanuel; Godbout, Roger

    2014-05-01

    This study aimed at characterizing the functional stability of sleep in schizophrenia by quantifying dissociated stages of sleep (DSS), and to explore their correlation with psychopathology. The sleep of 10 first-break, drug-naive young adults with schizophrenia and 10 controls was recorded. Four basic DSS patterns were scored: 1) the transitional EEG-mixed intermediate stage (EMIS); 2) Rapid-eye-movement (REM) sleep without rapid eye movement (RSWR); 3) REM sleep without atonia (RSWA); and 4) non-REM sleep with rapid eye movements. An intermediate sleep (IS) score was calculated by summing EMIS and RSWR scores, and the durations of intra-REM sleep periods IS (IRSPIS) and IS scored "at the expense" of REM sleep (ISERS) were determined. Patients were administered the Brief Psychiatric Rating Scale (BPRS) at the time of recording. Proportions of each DSS variables over total sleep time and proportions of IRSPIS and ISERS over REM sleep duration were compared between patients and controls. Correlation coefficients between DSS variables and BPRS total scores were calculated. The proportion of total DSS did not differ between patients and controls. Among DSS subtypes, RSWA was significantly increased in patients while other comparisons showed no significant differences. Significant positive correlations were found between BPRS scores and proportions of DSS, IS, RSWR, IRSPIS and ISERS over total sleep and REM sleep durations. These results demonstrate the functional instability of REM sleep in first-break, drug naive young adults with schizophrenia and unveil a pattern reminiscent of REM sleep behavior disorder. The significant correlation suggests that schizophrenia and REM sleep share common neuronal control mechanisms. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Personality traits in established schizophrenia: aspects of usability and differences between patients and controls using the Swedish universities Scales of Personality

    OpenAIRE

    Fagerberg, Tomas; S?derman, Erik; Gustavsson, J. Petter; Agartz, Ingrid; J?nsson, Erik G

    2016-01-01

    Abstract Background: Personality is considered as an important aspect that can affect symptoms and social function in persons with schizophrenia. The personality questionnaire Swedish universities Scales of Personality (SSP) has not previously been used in psychotic disorder. Aims: To investigate if SSP has a similar internal consistency and factor structure in a psychosis population as among healthy controls and if patients with psychotic disorders differ from non-psychotic individuals in th...

  18. Dynamic connectivity states estimated from resting fMRI Identify differences among Schizophrenia, bipolar disorder, and healthy control subjects

    National Research Council Canada - National Science Library

    Rashid, Barnaly; Damaraju, Eswar; Pearlson, Godfrey D; Calhoun, Vince D

    2014-01-01

    Schizophrenia (SZ) and bipolar disorder (BP) share significant overlap in clinical symptoms, brain characteristics, and risk genes, and both are associated with dysconnectivity among large-scale brain networks...

  19. Neurocognitive, Neuroprotective, and Cardiometabolic Effects of Raloxifene: Potential for Improving Therapeutic Outcomes in Schizophrenia.

    Science.gov (United States)

    Khan, Mohammad M

    2016-07-01

    Raloxifene is a selective estrogen receptor modulator that has been approved for treating osteoporosis and breast cancer in high-risk postmenopausal women. However, recent evidence suggests that raloxifene adjunct therapy improves cognition and reduces symptom severity in men and women with schizophrenia. In animal models, raloxifene increases forebrain neurogenesis and enhances working memory and synaptic plasticity. It may consequently repair the neuronal and synaptic connectivity that is disrupted in schizophrenia. It also reduces oxidative stress and neuroinflammation, which are potent etiological factors in the neuropathology of schizophrenia. Furthermore, in postmenopausal women, raloxifene reduces the risks for atherosclerosis, diabetes mellitus, and weight gain, which are serious adverse effects associated with long-term antipsychotic treatment in schizophrenia; therefore, it may improve the safety and efficacy of antipsychotic drugs. In this review, recent insights into the neurocognitive, neuroprotective, and cardiometabolic effects of raloxifene in relation to therapeutic outcomes in schizophrenia are discussed.

  20. Effects of progressive muscle relaxation on state anxiety and subjective well-being in people with schizophrenia: a randomized controlled trial.

    Science.gov (United States)

    Vancampfort, Davy; De Hert, Marc; Knapen, Jan; Maurissen, Katrien; Raepsaet, Julie; Deckx, Seppe; Remans, Sander; Probst, Michel

    2011-06-01

    To examine the efficacy of a single progressive muscle relaxation session compared with a control condition on state anxiety, psychological stress, fatigue and subjective well-being in patients with schizophrenia. Randomized controlled trial. An acute inpatient care unit of an University Psychiatric Centre. Sixty-four out of 88 eligible patients with schizophrenia. Patients were randomly assigned to either a single progressive muscle relaxation session during 25 minutes or a resting control condition with the opportunity to read for an equal amount of time. Before and after the single interventions the State anxiety inventory and the Subjective exercise experiences scale were completed. Effect sizes were calculated. Only within progressive muscle relaxation, participants (n=27) showed decreased state anxiety, psychological stress and fatigue and increased subjective well-being. Between-group differences in post scores were found for state anxiety, subjective well-being and psychological stress, but not for fatigue. The effect size favouring progressive muscle relaxation was 1.26 for subjective well-being and -1.25 and -1.02 for respectively state anxiety and psychological stress. Progressive muscle relaxation is highly effective in reducing acute feelings of stress and anxiety in patients with schizophrenia. A reduction in stress and state anxiety is associated with an increase in subjective well-being.

  1. Connectivity of the anterior insula differentiates participants with first-episode schizophrenia spectrum disorders from controls: a machine-learning study.

    Science.gov (United States)

    Mikolas, P; Melicher, T; Skoch, A; Matejka, M; Slovakova, A; Bakstein, E; Hajek, T; Spaniel, F

    2016-10-01

    Early diagnosis of schizophrenia could improve the outcomes and limit the negative effects of untreated illness. Although participants with schizophrenia show aberrant functional connectivity in brain networks, these between-group differences have a limited diagnostic utility. Novel methods of magnetic resonance imaging (MRI) analyses, such as machine learning (ML), may help bring neuroimaging from the bench to the bedside. Here, we used ML to differentiate participants with a first episode of schizophrenia-spectrum disorder (FES) from healthy controls based on resting-state functional connectivity (rsFC). We acquired resting-state functional MRI data from 63 patients with FES who were individually matched by age and sex to 63 healthy controls. We applied linear kernel support vector machines (SVM) to rsFC within the default mode network, the salience network and the central executive network. The SVM applied to the rsFC within the salience network distinguished the FES from the control participants with an accuracy of 73.0% (p = 0.001), specificity of 71.4% and sensitivity of 74.6%. The classification accuracy was not significantly affected by medication dose, or by the presence of psychotic symptoms. The functional connectivity within the default mode or the central executive networks did not yield classification accuracies above chance level. Seed-based functional connectivity maps can be utilized for diagnostic classification, even early in the course of schizophrenia. The classification was probably based on trait rather than state markers, as symptoms or medications were not significantly associated with classification accuracy. Our results support the role of the anterior insula/salience network in the pathophysiology of FES.

  2. Sudden death due to paralysis and synaptic and behavioral deficits when Hip14/Zdhhc17 is deleted in adult mice

    OpenAIRE

    Sanders, Shaun S.; Parsons, Matthew P.; Katherine K N Mui; Southwell, Amber L.; Franciosi, Sonia; Cheung, Daphne; Waltl, Sabine; Raymond, Lynn A.; Hayden, Michael R.

    2016-01-01

    Background Palmitoylation, the addition of palmitate to proteins by palmitoyl acyltransferases (PATs), is an important regulator of synaptic protein localization and function. Many palmitoylated proteins and PATs have been implicated in neuropsychiatric diseases, including Huntington disease, schizophrenia, amyotrophic lateral sclerosis, Alzheimer disease, and X-linked intellectual disability. HIP14/DHHC17 is the most conserved PAT that palmitoylates many synaptic proteins. Hip14 hypomorphic ...

  3. Selective Loss of Smaller Spines in Schizophrenia.

    Science.gov (United States)

    MacDonald, Matthew L; Alhassan, Jamil; Newman, Jason T; Richard, Michelle; Gu, Hong; Kelly, Ryan M; Sampson, Alan R; Fish, Kenneth N; Penzes, Peter; Wills, Zachary P; Lewis, David A; Sweet, Robert A

    2017-06-01

    Decreased density of dendritic spines in adult schizophrenia subjects has been hypothesized to result from increased pruning of excess synapses in adolescence. In vivo imaging studies have confirmed that synaptic pruning is largely driven by the loss of large or mature synapses. Thus, increased pruning throughout adolescence would likely result in a deficit of large spines in adulthood. Here, the authors examined the density and volume of dendritic spines in deep layer 3 of the auditory cortex of 20 schizophrenia and 20 matched comparison subjects as well as aberrant voltage-gated calcium channel subunit protein expression linked to spine loss. Primary auditory cortex deep layer 3 spine density and volume was assessed in 20 pairs of schizophrenia and matched comparison subjects in an initial and replication cohort (12 and eight pairs) by immunohistochemistry-confocal microscopy. Targeted mass spectrometry was used to quantify postsynaptic density and voltage-gated calcium channel protein expression. The effect of increased voltage-gated calcium channel subunit protein expression on spine density and volume was assessed in primary rat neuronal culture. Only the smallest spines are lost in deep layer 3 of the primary auditory cortex in subjects with schizophrenia, while larger spines are retained. Levels of the tryptic peptide ALFDFLK, found in the schizophrenia risk gene CACNB4, are inversely correlated with the density of smaller, but not larger, spines in schizophrenia subjects. Consistent with this observation, CACNB4 overexpression resulted in a lower density of smaller spines in primary neuronal cultures. These findings require a rethinking of the overpruning hypothesis, demonstrate a link between small spine loss and a schizophrenia risk gene, and should spur more in-depth investigations of the mechanisms that govern new or small spine generation and stabilization under normal conditions as well as how this process is impaired in schizophrenia.

  4. Synaptic Scaling in Combination with Many Generic Plasticity Mechanisms Stabilizes Circuit Connectivity

    Science.gov (United States)

    Tetzlaff, Christian; Kolodziejski, Christoph; Timme, Marc; Wörgötter, Florentin

    2011-01-01

    Synaptic scaling is a slow process that modifies synapses, keeping the firing rate of neural circuits in specific regimes. Together with other processes, such as conventional synaptic plasticity in the form of long term depression and potentiation, synaptic scaling changes the synaptic patterns in a network, ensuring diverse, functionally relevant, stable, and input-dependent connectivity. How synaptic patterns are generated and stabilized, however, is largely unknown. Here we formally describe and analyze synaptic scaling based on results from experimental studies and demonstrate that the combination of different conventional plasticity mechanisms and synaptic scaling provides a powerful general framework for regulating network connectivity. In addition, we design several simple models that reproduce experimentally observed synaptic distributions as well as the observed synaptic modifications during sustained activity changes. These models predict that the combination of plasticity with scaling generates globally stable, input-controlled synaptic patterns, also in recurrent networks. Thus, in combination with other forms of plasticity, synaptic scaling can robustly yield neuronal circuits with high synaptic diversity, which potentially enables robust dynamic storage of complex activation patterns. This mechanism is even more pronounced when considering networks with a realistic degree of inhibition. Synaptic scaling combined with plasticity could thus be the basis for learning structured behavior even in initially random networks. PMID:22203799

  5. Prediction of Neurocognitive Deficits by Parkinsonian Motor Impairment in Schizophrenia: A Study in Neuroleptic-Naïve Subjects, Unaffected First-Degree Relatives and Healthy Controls From an Indigenous Population.

    Science.gov (United States)

    Molina, Juan L; González Alemán, Gabriela; Florenzano, Néstor; Padilla, Eduardo; Calvó, María; Guerrero, Gonzalo; Kamis, Danielle; Stratton, Lee; Toranzo, Juan; Molina Rangeon, Beatriz; Hernández Cuervo, Helena; Bourdieu, Mercedes; Sedó, Manuel; Strejilevich, Sergio; Cloninger, Claude Robert; Escobar, Javier I; de Erausquin, Gabriel A

    2016-11-01

    Neurocognitive deficits are among the most debilitating and pervasive symptoms of schizophrenia, and are present also in unaffected first-degree relatives. Also, multiple reports reveal parkisonian motor deficits in untreated subjects with schizophrenia and in first-degree relatives of affected subjects. Yet, the relation between motor and cognitive impairment and its value as a classifier of endophenotypes has not been studied. To test the efficacy of midbrain hyperechogenicity (MHE) and parkinsonian motor impairment (PKM) as predictors of neurocognitive impairment in subjects with or at risk for schizophrenia, that could be used to segregate them from first-degree relatives and healthy controls. Seventy-six subjects with chronic schizophrenia never exposed to antipsychotic medication, 106 unaffected first-degree relatives, and 62 healthy controls were blindly assessed for cognitive and motor function, and transcranial ultrasound. Executive function, fluid intelligence, motor planning, and hand coordination showed group differences. PKM and MHE were significantly higher in untreated schizophrenia and unaffected relatives. Unaffected relatives showed milder impairment, but were different from controls. PKM and MHE predict cognitive impairment in neuroleptic-naive patients with schizophrenia and their unaffected first-degree relatives and may be used to segregate them from first-degree relatives and healthy controls. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. The tryptophan hydroxylase 1 (TPH1) gene, schizophrenia susceptibility, and suicidal behavior: a multi-centre case-control study and meta-analysis

    DEFF Research Database (Denmark)

    Saetre, Peter; Lundmark, Per; Wang, August

    2010-01-01

    .07-1.29). Association studies on suicide attempts are however conflicting (heterogeneity index I(2) = 0.54) and do not support the A218C/A779C polymorphisms being a susceptibility locus for suicidal behavior among individuals diagnosed with a psychiatric disorder (OR = 0.96 [0.80-1.16]). We conclude that the TPH1 A218....../A779 locus increases the susceptibility of schizophrenia in Caucasian and Asian populations. In addition, the data at hand suggest that the locus contributes to the liability of psychiatric disorders characterized by elevated suicidal rates, rather than affecting suicidal behavior of individuals...... associated with schizophrenia. The minor allele (A) of this polymorphism (A218C) is also more frequent in patients who have attempted suicide and individuals who died by suicide, than in healthy control individuals. In an attempt to replicate previous findings, five single nucleotide polymorphisms (SNPs...

  7. Genetics Home Reference: schizophrenia

    Science.gov (United States)

    ... Share: Email Facebook Twitter Home Health Conditions Schizophrenia Schizophrenia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Schizophrenia is a brain disorder classified as a psychosis, ...

  8. Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility.

    LENUS (Irish Health Repository)

    O'Dushlaine, C

    2011-03-01

    Susceptibility to schizophrenia and bipolar disorder may involve a substantial, shared contribution from thousands of common genetic variants, each of small effect. Identifying whether risk variants map to specific molecular pathways is potentially biologically informative. We report a molecular pathway analysis using the single-nucleotide polymorphism (SNP) ratio test, which compares the ratio of nominally significant (P<0.05) to nonsignificant SNPs in a given pathway to identify the \\'enrichment\\' for association signals. We applied this approach to the discovery (the International Schizophrenia Consortium (n=6909)) and validation (Genetic Association Information Network (n=2729)) of schizophrenia genome-wide association study (GWAS) data sets. We investigated each of the 212 experimentally validated pathways described in the Kyoto Encyclopaedia of Genes and Genomes in the discovery sample. Nominally significant pathways were tested in the validation sample, and five pathways were found to be significant (P=0.03-0.001); only the cell adhesion molecule (CAM) pathway withstood conservative correction for multiple testing. Interestingly, this pathway was also significantly associated with bipolar disorder (Wellcome Trust Case Control Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three samples (NRXN1 and CNTNAP2), which were previously implicated in specific language disorder, autism and schizophrenia. The CAM pathway functions in neuronal cell adhesion, which is critical for synaptic formation and normal cell signaling. Similar pathways have also emerged from a pathway analysis of autism, suggesting that mechanisms involved in neuronal cell adhesion may contribute broadly to neurodevelopmental psychiatric phenotypes.

  9. Growth hormone rescues hippocampal synaptic function after sleep deprivation

    Science.gov (United States)

    Kim, Eunyoung; Bertolotti, Don; Green, Todd L.

    2010-01-01

    Sleep is required for, and sleep loss impairs, normal hippocampal synaptic N-methyl-d-aspartate (NMDA) glutamate receptor function and expression, hippocampal NMDA receptor-dependent synaptic plasticity, and hippocampal-dependent memory function. Although sleep is essential, the signals linking sleep to hippocampal function are not known. One potential signal is growth hormone. Growth hormone is released during sleep, and its release is suppressed during sleep deprivation. If growth hormone links sleep to hippocampal function, then restoration of growth hormone during sleep deprivation should prevent adverse consequences of sleep loss. To test this hypothesis, we examined rat hippocampus for spontaneous excitatory synaptic currents in CA1 pyramidal neurons, long-term potentiation in area CA1, and NMDA receptor subunit proteins in synaptic membranes. Three days of sleep deprivation caused a significant reduction in NMDA receptor-mediated synaptic currents compared with control treatments. When rats were injected with growth hormone once per day during sleep deprivation, the loss of NMDA receptor-mediated synaptic currents was prevented. Growth hormone injections also prevented the impairment of long-term potentiation that normally follows sleep deprivation. In addition, sleep deprivation led to a selective loss of NMDA receptor 2B (NR2B) from hippocampal synaptic membranes, but normal NR2B expression was restored by growth hormone injection. Our results identify growth hormone as a critical mediator linking sleep to normal synaptic function of the hippocampus. PMID:20237303

  10. Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle.

    Directory of Open Access Journals (Sweden)

    Wilfredo Blanco

    2015-05-01

    Full Text Available Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS followed by a rebound during rapid-eye-movement sleep (REM. The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes

  11. Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle.

    Science.gov (United States)

    Blanco, Wilfredo; Pereira, Catia M; Cota, Vinicius R; Souza, Annie C; Rennó-Costa, César; Santos, Sharlene; Dias, Gabriella; Guerreiro, Ana M G; Tort, Adriano B L; Neto, Adrião D; Ribeiro, Sidarta

    2015-05-01

    Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic

  12. The effects of eszopiclone on sleep spindles and memory consolidation in schizophrenia: a randomized placebo-controlled trial.

    Science.gov (United States)

    Wamsley, Erin J; Shinn, Ann K; Tucker, Matthew A; Ono, Kim E; McKinley, Sophia K; Ely, Alice V; Goff, Donald C; Stickgold, Robert; Manoach, Dara S

    2013-09-01

    In schizophrenia there is a dramatic reduction of sleep spindles that predicts deficient sleep-dependent memory consolidation. Eszopiclone (Lunesta), a non-benzodiazepine hypnotic, acts on γ-aminobutyric acid (GABA) neurons in the thalamic reticular nucleus where spindles are generated. We investigated whether eszopiclone could increase spindles and thereby improve memory consolidation in schizophrenia. In a double-blind design, patients were randomly assigned to receive either placebo or 3 mg of eszopiclone. Patients completed Baseline and Treatment visits, each consisting of two consecutive nights of polysomnography. On the second night of each visit, patients were trained on the motor sequence task (MST) at bedtime and tested the following morning. Academic research center. Twenty-one chronic, medicated schizophrenia outpatients. We compared the effects of two nights of eszopiclone vs. placebo on stage 2 sleep spindles and overnight changes in MST performance. Eszopiclone increased the number and density of spindles over baseline levels significantly more than placebo, but did not significantly enhance overnight MST improvement. In the combined eszopiclone and placebo groups, spindle number and density predicted overnight MST improvement. Eszopiclone significantly increased sleep spindles, which correlated with overnight motor sequence task improvement. These findings provide partial support for the hypothesis that the spindle deficit in schizophrenia impairs sleep-dependent memory consolidation and may be ameliorated by eszopiclone. Larger samples may be needed to detect a significant effect on memory. Given the general role of sleep spindles in cognition, they offer a promising novel potential target for treating cognitive deficits in schizophrenia.

  13. Association between the DTNBP1 gene and intelligence: a case-control study in young patients with schizophrenia and related disorders and unaffected siblings

    Directory of Open Access Journals (Sweden)

    Tanck Michael W

    2007-04-01

    Full Text Available Abstract Background The dystrobrevin-binding protein 1 (DTNBP1 gene is a susceptibility gene for schizophrenia. There is growing evidence that DTNPB1 contributes to intelligence and cognition. In this study, we investigated association between single nucleotide polymorphisms (SNPs in the DTNBP1 gene and intellectual functioning in patients with a first episode of schizophrenia or related psychotic disorder (first-episode psychosis, FEP, their healthy siblings, and unrelated controls. Methods From all subjects IQ measurements were obtained (verbal IQ [VIQ], performance IQ [PIQ], and full scale IQ [FSIQ]. Seven SNPs in the DTNBP1 gene were genotyped using single base primer extension and analyzed by matrix-assisted laser deionization mass spectrometry (MALDI-TOF. Results Mean VIQ, PIQ, and FSIQ scores differed significantly (p Conclusion Although preliminary, our results provide evidence for association between the DTNBP1 gene and intelligence in patients with FEP and their unaffected siblings. Genetic variation in the DTNBP1 gene may increase schizophrenia susceptibility by affecting intellectual functioning.

  14. The effect of mirtazapine augmentation of clozapine in the treatment of negative symptoms of schizophrenia: a double-blind, placebo-controlled study.

    Science.gov (United States)

    Zoccali, Rocco; Muscatello, Maria Rosaria; Cedro, Clemente; Neri, Pietro; La Torre, Diletta; Spina, Edoardo; Di Rosa, Antonio Enrico; Meduri, Mario

    2004-03-01

    The development of therapeutic strategies to effectively treat negative symptoms remains one of the primary goals in the treatment of schizophrenia. Mirtazapine is the first of a new class of dual action compounds, the noradrenergic and specific serotonergic antidepressants (NaSSa), whose activity is related to the enhancement of noradrenergic and serotonergic transmission by a presynaptic alpha2 antagonism and postsynaptic 5-HT2 and 5-HT3 antagonism, respectively. This study was a 8-week double-blind, randomized, placebo-controlled trial of 30 mg adjunctive mirtazapine to clozapine therapy in 24 patients with DSM-IV schizophrenia. The main finding at the end of the trial was a significant reduction on the Scale for the Assessment of Negative Symptoms (SANS) total scores in the mirtazapine group compared to placebo (P<0.01) with a significant improvement on the SANS subscales avolition/apathy and anhedonia/asociality. The Brief Psychiatric Rating Scale total score at week 8 showed superiority of mirtazapine over placebo. These findings suggest a potential role for mirtazapine as an augmentation strategy in the treatment of negative symptoms of schizophrenia.

  15. A double-blind, placebo-controlled, randomized study evaluating the effect of paliperidone extended-release tablets on sleep architecture in patients with schizophrenia.

    Science.gov (United States)

    Luthringer, Remy; Staner, Luc; Noel, Nadine; Muzet, Muriel; Gassmann-Mayer, Cristiana; Talluri, Krishna; Cleton, Adriaan; Eerdekens, Marielle; Battisti, Wendy P; Palumbo, Joseph M

    2007-09-01

    The effects of paliperidone extended-release on sleep architecture in patients with schizophrenia-related insomnia were evaluated in this multicenter, double-blind, randomized, placebo-controlled study. Patients received paliperidone extended-release 9 mg/day or matching placebo during the 14-day double-blind phase. Sleep architecture and sleep continuity were evaluated using polysomnograms. Subjective sleep measures were evaluated daily using the Leeds Sleep Evaluation Questionnaire. Efficacy and safety were also assessed. Thirty-six patients (17 on paliperidone extended-release, 19 on placebo; mean age 32.2 years) completed the study. Paliperidone extended-release treatment vs. placebo resulted in clinically and statistically significant differences in sleep measurements from baseline to endpoint including a reduction in: persistent sleep latency (41 min), sleep onset latency (35 min), number of awakenings after sleep onset (7), time awake in bed (50 min), and stage 1 sleep duration (12 min); prolongation in: total sleep time (53 min), sleep period time (42 min), stage 2 sleep duration (51 min), and rapid eye movement sleep duration (18 min); and an increase in sleep efficiency index (11%). Paliperidone extended-release, compared with placebo, did not exacerbate daytime somnolence and improved symptoms of schizophrenia. Paliperidone extended-release was well tolerated and improved sleep architecture and sleep continuity in patients diagnosed with schizophrenia and concomitant insomnia.

  16. Rethinking schizophrenia in the context of normal neurodevelopment

    Science.gov (United States)

    Catts, Vibeke S.; Fung, Samantha J.; Long, Leonora E.; Joshi, Dipesh; Vercammen, Ans; Allen, Katherine M.; Fillman, Stu G.; Rothmond, Debora A.; Sinclair, Duncan; Tiwari, Yash; Tsai, Shan-Yuan; Weickert, Thomas W.; Shannon Weickert, Cynthia

    2013-01-01

    The schizophrenia brain is differentiated from the normal brain by subtle changes, with significant overlap in measures between normal and disease states. For the past 25 years, schizophrenia has increasingly been considered a neurodevelopmental disorder. This frame of reference challenges biological researchers to consider how pathological changes identified in adult brain tissue can be accounted for by aberrant developmental processes occurring during fetal, childhood, or adolescent periods. To place schizophrenia neuropathology in a neurodevelopmental context requires solid, scrutinized evidence of changes occurring during normal development of the human brain, particularly in the cortex; however, too often data on normative developmental change are selectively referenced. This paper focuses on the development of the prefrontal cortex and charts major molecular, cellular, and behavioral events on a similar time line. We first consider the time at which human cognitive abilities such as selective attention, working memory, and inhibitory control mature, emphasizing that attainment of full adult potential is a process requiring decades. We review the timing of neurogenesis, neuronal migration, white matter changes (myelination), and synapse development. We consider how molecular changes in neurotransmitter signaling pathways are altered throughout life and how they may be concomitant with cellular and cognitive changes. We end with a consideration of how the response to drugs of abuse changes with age. We conclude that the concepts around the timing of cortical neuronal migration, interneuron maturation, and synaptic regression in humans may need revision and include greater emphasis on the protracted and dynamic changes occurring in adolescence. Updating our current understanding of post-natal neurodevelopment should aid researchers in interpreting gray matter changes and derailed neurodevelopmental processes that could underlie emergence of psychosis. PMID

  17. Rethinking Schizophrenia in the Context of Normal Neurodevelopment

    Directory of Open Access Journals (Sweden)

    Vibeke Sorensen Catts

    2013-05-01

    Full Text Available The schizophrenia brain is differentiated from the normal brain by subtle changes, with significant overlap in measures between normal and disease states. For the past 25 years, schizophrenia has increasingly been considered a neurodevelopmental disorder. This frame of reference challenges biological researchers to consider how pathological changes identified in adult brain tissue can be accounted for by aberrant developmental processes occurring during fetal, childhood or adolescent periods. To place schizophrenia neuropathology in a neurodevelopmental context requires solid, scrutinized evidence of changes occurring during normal development of the human brain, particularly in the cortex; however, too often data on normative developmental change are selectively referenced. This paper focuses on the development of the prefrontal cortex and charts major molecular, cellular and behavioral events on a similar time line. We first consider the time at which human cognitive abilities such as selective attention, working memory and inhibitory control mature, emphasizing that attainment of full adult potential is a process requiring decades. We review the timing of neurogenesis, neuronal migration, white matter changes (myelination, and synapse development. We consider how molecular changes in neurotransmitter signaling pathways are altered throughout life and how they may be concomitant with cellular and cognitive changes. We end with a consideration of how the response to drugs of abuse changes with age. We conclude that the concepts around the timing of cortical neuronal migration, interneuron maturation and synaptic regression in humans may need revision and include greater emphasis on the protracted and dynamic changes occurring in adolescence. Updating our current understanding of post-natal neurodevelopment should aid researchers in interpreting grey matter changes and derailed neurodevelopmental processes that could underlie emergence of

  18. Randomized, Double-Blind, Placebo-Controlled Study of Encenicline, an α7 Nicotinic Acetylcholine Receptor Agonist, as a Treatment for Cognitive Impairment in Schizophrenia.

    Science.gov (United States)

    Keefe, Richard S E; Meltzer, Herbert A; Dgetluck, Nancy; Gawryl, Maria; Koenig, Gerhard; Moebius, Hans J; Lombardo, Ilise; Hilt, Dana C

    2015-12-01

    Encenicline is a novel, selective α7 nicotinic acetylcholine receptor agonist in development for treating cognitive impairment in schizophrenia and Alzheimer's disease. A phase 2, double-blind, randomized, placebo-controlled, parallel-design, multinational study was conducted. Patients with schizophrenia on chronic stable atypical antipsychotics were randomized to encenicline 0.27 or 0.9 mg once daily or placebo for 12 weeks. The primary efficacy end point was the Overall Cognition Index (OCI) score from the CogState computerized battery. Secondary end points include MATRICS Consensus Cognitive Battery (MCCB) (in US patients), the Schizophrenia Cognition Rating Scale (SCoRS) total score, SCoRS global rating, and Positive and Negative Syndrome Scale (PANSS) total and subscale and cognition factor scores. Of 319 randomized patients, 317 were included in the safety population, and 307 were included in the intent-to-treat population. Notable trends in improvement were demonstrated across all cognition scales. For the OCI score, the LS mean difference for encenicline 0.27 mg vs placebo was significant (Cohen's d=0.257; P=0.034). Mean SCoRS total scores decreased showing improvement in function over time, and the difference was significant for encenicline 0.9 mg vs placebo (P=0.011). Furthermore, the difference between encenicline 0.9 mg and placebo was significant for the PANSS Cognition Impairment Domain (P=0.0098, Cohen's d=0.40) and for the PANSS Negative scale (P=0.028, Cohen's d=0.33). Treatment-emergent adverse events were reported at similar frequencies across all treatment groups (39.0% with placebo, 23.4% with encenicline 0.27 mg, and 33.3% with encenicline 0.9 mg). Overall, encenicline was generally well tolerated and demonstrated clinically meaningful improvements in cognition and function in patients with schizophrenia.

  19. Study protocol: a randomised controlled trial of cognitive remediation for a national cohort of forensic mental health patients with schizophrenia or schizoaffective disorder.

    Science.gov (United States)

    O'Reilly, Ken; Donohoe, Gary; O'Sullivan, Danny; Coyle, Ciaran; Mullaney, Ronan; O'Connell, Paul; Maddock, Catherine; Nulty, Andrea; O'Flynn, Padraic; O'Connell, Carina; Kennedy, Harry G

    2016-01-13

    Evidence is accumulating that cognitive remediation therapy (CRT) is an effective intervention for patients with schizophrenia or schizoaffective disorder. To date there has been no randomised controlled trial (RCT) cohort study of cognitive remediation within a forensic hospital. The goal of this study is to examine the effectiveness of a trial of cognitive remediation for forensic mental health patients with schizophrenia or schizoaffective disorder. An estimated sixty patients will be enrolled in the study. Participants will be randomised to one of two conditions: CRT with treatment as usual (TAU), or TAU. CRT will consist of 42 individual sessions and 14 group sessions. The primary outcome measure for this study is change in cognitive functioning using the MATRICS Consensus Cognitive Battery (MCCB). Secondary outcomes include change in social and occupational functioning, disorganised symptoms, negative symptoms, violence, participation in psychosocial treatment and recovery. In addition to these effectiveness measures, we will examine patient satisfaction. Cognitive difficulties experienced by schizophrenia spectrum patients are associated with general functioning, ability to benefit from psychosocial interventions and quality of life. Research into the treatment of cognitive difficulties within a forensic setting is therefore an important priority. The results of the proposed study will help answer the question whether cognitive remediation improves functional outcomes in forensic mental health patients with schizophrenia or schizoaffective disorder. Forensic mental health patients are detained for the dual purpose of receiving treatment and for public protection. There can be conflict between these two roles perhaps causing forensic services to have an increased length of stay compared to general psychiatric admissions. Ultimately a focus on emphasising cognition and general functioning over symptoms may decrease tension between the core responsibilities of

  20. Intranasal desmopressin as an adjunct to risperidone for negative symptoms of schizophrenia: a randomized, double-blind, placebo-controlled, clinical trial.

    Science.gov (United States)

    Hosseini, Seyed Mohammad Reza; Farokhnia, Mehdi; Rezaei, Farzin; Gougol, Amirhossein; Yekehtaz, Habibeh; Iranpour, Negar; Salehi, Bahman; Tabrizi, Mina; Tajdini, Masih; Ghaleiha, Ali; Akhondzadeh, Shahin

    2014-06-01

    Considering the role of neurohypophyseal peptides in normal development and function of higher cortical processes along with their proven abnormalities in schizophrenic patients, these pathways have recently attracted greater attention as treatment targets for schizophrenia. Desmopressin (DDAVP) is a synthetic analog of vasopressin. This study aimed to evaluate the efficacy and safety of DDAVP nasal spray as an adjunct to risperidone in improving negative symptoms of schizophrenia. In this randomized double-blind placebo-controlled clinical trial, forty patients aged 18-50 years with a DSM IV-TR diagnosis of chronic schizophrenia and a minimum score of 60 on positive and negative syndrome scale (PANSS) were equally randomized to receive DDAVP nasal spray (20mcg/day) or placebo in addition to risperidone for 8 weeks. Patients were partially stabilized and treated with a stable dose of risperidone (5 or 6mg/day) for at least four weeks prior to entry. Participants were rated by PANSS every two weeks and decrease in the PANSS negative subscale score was considered as our primary outcome. By the study endpoint, DDAVP-treated patients showed significantly greater improvement in the negative symptoms (P=0.001) as well as the PANSS total and general psychopathology subscale scores (P=0.005 and P=0.003; respectively) compared to the placebo group. Treatment group was the strongest predictor of changes in negative symptoms (β=-0.48, t=-3.67, P=001). No serious adverse event or fluid/electrolyte imbalance was reported in this trial. In conclusion, DDAVP nasal spray showed to be an effective and safe medication for improving negative symptoms in patients with chronic schizophrenia. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  1. Raloxifene as an Adjunctive Treatment for Postmenopausal Women With Schizophrenia: A 24-Week Double-Blind, Randomized, Parallel, Placebo-Controlled Trial.

    Science.gov (United States)

    Usall, Judith; Huerta-Ramos, Elena; Labad, Javier; Cobo, Jesús; Núñez, Christian; Creus, Marta; Parés, Gemma García; Cuadras, Daniel; Franco, José; Miquel, Eva; Reyes, Julio César; Roca, Mercedes

    2016-03-01

    The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator, appears to act similarly to estrogens on dopamine and serotonin brain systems. One previous trial by our team found that raloxifene was useful to improve negative, positive, and general psychopathological symptoms, without having the negative side effects of estrogens. In this study, we assess the utility of raloxifene in treating negative and other psychotic symptoms in postmenopausal women with schizophrenia exhibiting prominent negative symptoms. This was a 24-week, randomized, parallel, double-blind, placebo-controlled study. Patients were recruited from the inpatient and outpatient departments of Parc Sanitari Sant Joan de Déu, Hospital Universitari Institut Pere Mata, and Corporació Sanitària Parc Taulí. Seventy postmenopausal women with schizophrenia (DSM-IV) were randomized to either adjunctive raloxifene (38 women) or adjunctive placebo (32 women). Psychopathological symptoms were assessed at baseline and at weeks 4, 12, and 24 with the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). The addition of raloxifene (60 mg/d) to regular antipsychotic treatment significantly reduced negative (P = .027), general (P = .003), and total symptomatology (P = .005) measured with the PANSS during the 24-week trial, as compared to women receiving placebo. Also Alogia SANSS subscale improved more in the raloxifene (P = .048) than the placebo group. In conclusion, raloxifene improved negative and general psychopathological symptoms, compared with antipsychotic medication alone, in postmenopausal women with schizophrenia. These data replicate our previous results with a larger sample and a longer follow-up. NCT01573637. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For

  2. Episodic foresight and schizophrenia.

    Science.gov (United States)

    Lyons, Amanda D; Henry, Julie D; Rendell, Peter G; Robinson, Gail; Suddendorf, Thomas

    2016-06-01

    People with schizophrenia have difficulty engaging in specific future-directed thoughts and behaviours, such as generating phenomenological characteristics of future events (a component of episodic foresight), and executing directed preparatory behaviours (a component of prospective memory). However, it remains unclear whether they also exhibit difficulties using episodic foresight to appropriately guide future-directed behaviours. People with schizophrenia and non-clinical controls were administered a behavioural measure that met strict criteria for assessing episodic foresight. In keeping with our focus on the functional application of foresight, this measure required participants to identify a problem, self-generate a resolution, and execute the appropriate future-directed intention. Relative to controls, people with schizophrenia were less likely to spontaneously acquire items that would later allow a problem to be solved, and were also less likely to subsequently use these items to solve the problems. There was no interaction between group and task, indicating that these two components of foresight were disrupted to an equivalent degree. In the clinical (but not the control) group, item acquisition and item use were correlated with general cognitive capacity. No significant associations with clinical variables emerged. The capacity to apply episodic foresight in a functionally adaptive way is disrupted in schizophrenia and may at least partially reflect broader cognitive dysfunction. Future work is now needed to clarify the implications of these difficulties in everyday life, as well as how these difficulties might be remediated. People with schizophrenia have known difficulties with episodic foresight, and it now appears that those difficulties extend to the performance of foresightful preparatory behaviours. Because preparatory behaviours are central to routine and adaptive planning, difficulties with episodic foresight may contribute to or be a result of

  3. The RNA-binding protein, ZC3H14, is required for proper poly(A) tail length control, expression of synaptic proteins, and brain function in mice.

    Science.gov (United States)

    Rha, Jennifer; Jones, Stephanie K; Fidler, Jonathan; Banerjee, Ayan; Leung, Sara W; Morris, Kevin J; Wong, Jennifer C; Inglis, George Andrew S; Shapiro, Lindsey; Deng, Qiudong; Cutler, Alicia A; Hanif, Adam M; Pardue, Machelle T; Schaffer, Ashleigh; Seyfried, Nicholas T; Moberg, Kenneth H; Bassell, Gary J; Escayg, Andrew; García, Paul S; Corbett, Anita H

    2017-10-01

    A number of mutations in genes that encode ubiquitously expressed RNA-binding proteins cause tissue specific disease. Many of these diseases are neurological in nature revealing critical roles for this class of proteins in the brain. We recently identified mutations in a gene that encodes a ubiquitously expressed polyadenosine RNA-binding protein, ZC3H14 (Zinc finger CysCysCysHis domain-containing protein 14), that cause a nonsyndromic, autosomal recessive form of intellectual disability. This finding reveals the molecular basis for disease and provides evidence that ZC3H14 is essential for proper brain function. To investigate the role of ZC3H14 in the mammalian brain, we generated a mouse in which the first common exon of the ZC3H14 gene, exon 13 is removed (Zc3h14Δex13/Δex13) leading to a truncated ZC3H14 protein. We report here that, as in the patients, Zc3h14 is not essential in mice. Utilizing these Zc3h14Δex13/Δex13mice, we provide the first in vivo functional characterization of ZC3H14 as a regulator of RNA poly(A) tail length. The Zc3h14Δex13/Δex13 mice show enlarged lateral ventricles in the brain as well as impaired working memory. Proteomic analysis comparing the hippocampi of Zc3h14+/+ and Zc3h14Δex13/Δex13 mice reveals dysregulation of several pathways that are important for proper brain function and thus sheds light onto which pathways are most affected by the loss of ZC3H14. Among the proteins increased in the hippocampi of Zc3h14Δex13/Δex13 mice compared to control are key synaptic proteins including CaMK2a. This newly generated mouse serves as a tool to study the function of ZC3H14 in vivo. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Impaired perception of negative emotional prosody in schizophrenia

    NARCIS (Netherlands)

    Pijnenborg, G.H M; Withaar, F.K.; van den Bosch, R.J; Brouwer, W.H.

    This paper aims to report on the perception of emotional prosody, in schizophrenia and to discuss its relationship with perfomance on neurocognitive measures. It consists of a comparison of 20 clinically stable schizophrenia patients with 20 healthy, controls. Schizophrenia patients were impaired in

  5. Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task

    Science.gov (United States)

    Suridjan, Ivonne; Rusjan, Pablo; Addington, Jean; Wilson, Alan A.; Houle, Sylvain; Mizrahi, Romina

    2013-01-01

    Background The dopamine (DA) D2 receptors exist in 2 states: a high-affinity state (D2high) that is linked to second messenger systems, responsible for functional effects, exhibits high affinity for agonists (e.g., DA), and a low-affinity state that is functionally inert exhibits lower affinity for agonists. The DA D3 receptor subtype exhibits high agonist affinity, whereas the existence of the multiple affinity states is controversial. Preclinical studies in animal models of psychosis have shown a selective increase of D2high as the common factor in psychosis, and the D3 receptor has been suggested to be involved in the pathophysiology of schizophrenia. Methods We studied D2high and D3 in people at clinical high risk (CHR) for schizophrenia and in antipsychotic-naive patients with schizophrenia using the novel positron emission tomography radiotracer, [11C]-(+)-PHNO. The binding potential nondisplaceable (BPND) was examined in the regions of interest (ROI; caudate, putamen, ventral striatum, globus pallidus, substantia nigra and thalamus) using an ROI and a voxel-wise approach while participants performed a cognitive task. Results We recruited 12 CHR individuals and 13 antipsychotic-naive patients with schizophrenia-spectrum disorder, whom we compared with 12 age- and sex-matched healthy controls. The BPND between patients and controls did not differ in any of the ROIs, consistent with the voxel-wise analysis. Correlations between the BPND in D3-rich regions and psychopathology warrant further investigation. Limitations In the absence of resting-state (baseline) BPND data, or following a depletion paradigm (i.e., α-methyl partyrosine), it is not possible to ascertain whether the lack of difference among the groups is owing to different levels of baseline DA or to release during the cognitive task. Conclusion To our knowledge, the present study represents the first effort to measure the D2 and D3 receptors under a cognitive challenge in individuals putative

  6. Schizophrenia: genetics, prevention and rehabilitation.

    Science.gov (United States)

    Olgiati, Paolo; Mandelli, Laura; Lorenzi, Cristina; Marino, Elena; Adele, Pirovano; Ferrari, Barbara; De Ronchi, Diana; Serretti, Alessandro

    2009-06-01

    Genetic factors are largely implicated in predisposing to schizophrenia. Environmental factors contribute to the onset of the disorder in individuals at increased genetic risk. Cognitive deficits have emerged as endophenotypes and potential therapeutic targets for schizophrenia because of their association with functional outcome. The aims of this review were to analyse the joint effect of genetic and environmental (G×E) factors on liability to schizophrenia and to investigate relationships between genes and cognitive endophenotypes focusing on practical applications for prevention and rehabilitation. Medline search of relevant studies published between 1990 and 2008. In schizophrenia, examples of G×E interaction include the catechol-O-methyl transferase (COMT) (Val158Met) polymorphism, which was found to moderate the onset of psychotic manifestations in response to stress and to increase the risk for psychosis related to cannabis use, and neurodevelopmental genes such as AKT1 (serine-threonine kinase), brain-derived neurotrophic factor (BDNF), DTNBP1 (dysbindin) and GRM3 (metabotropic glutamate receptor 3), which were associated with development of schizophrenia in adulthood after exposure to perinatal obstetric complications. Neurocognitive deficits are recognised as core features of schizophrenia that facilitate the onset of the disorder and have a great impact on functional outcome. Neurocognitive deficits are also endophenotypes that have been linked to a variety of genes [COMT, neuregulin (NRG1), BDNF, Disrupted-In-Schizophrenia 1 (DISC1) and dysbindin] conferring susceptibility to schizophrenia. Recently, it has emerged that cognitive improvement during rehabilitation therapy was under control of COMT (Val158Met) polymorphism. This review could indicate a pivotal role of psychiatric genetics in prevention and rehabilitation of schizophrenic psychoses.

  7. Electroconvulsive Therapy Added to Non-Clozapine Antipsychotic Medication for Treatment Resistant Schizophrenia: Meta-Analysis of Randomized Controlled Trials.

    Directory of Open Access Journals (Sweden)

    Wei Zheng

    Full Text Available This meta-analysis of randomized controlled trials (RCTs examined the efficacy and safety of the combination of electroconvulsive therapy (ECT and antipsychotic medication (except for clozapine versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS. Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD, risk ratio (RR ±95% confidence intervals (CIs, number needed to treat (NNT, and number needed to harm (NNH were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1 symptomatic improvement at last-observation endpoint with an SMD of -0.67 (p<0.00001; I(2 = 62%, separating the two groups as early as weeks 1-2 with an SMD of -0.58 (p<0.00001; I(2 = 0%; (2 study-defined response (RR = 1.48, p<0.0001 with an NNT of 6 (CI = 4-9 and remission rate (RR = 2.18, p = 0.0002 with an NNT of 8 (CI = 6-16; (3 PANSS positive and general symptom sub-scores at endpoint with a WMD between -3.48 to -1.32 (P = 0.01 to 0.009. Subgroup analyses were conducted comparing double blind/rater-masked vs. open RCTs, those with and without randomization details, and high quality (Jadad≥adadup analyses were Jadad<3 studies. The ECT-antipsychotic combination caused more headache (p = 0.02 with an NNH of 6 (CI = 4-11 and memory impairment (p = 0.001 with an NNH of 3 (CI = 2-5. The use of ECT to augment antipsychotic treatment (clozapine excepted can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache.

  8. Assessing brain structural associations with working memory related brain patterns in schizophrenia and healthy controls using linked independent component analysis

    Directory of Open Access Journals (Sweden)

    Christine Lycke Brandt

    2015-01-01

    Full Text Available Schizophrenia (SZ is a psychotic disorder with significant cognitive dysfunction. Abnormal brain activation during cognitive processing has been reported, both in task-positive and task-negative networks. Further, structural cortical and subcortical brain abnormalities have been documented, but little is known about how task-related brain activation is associated with brain anatomy in SZ compared to healthy controls (HC. Utilizing linked independent component analysis (LICA, a data-driven multimodal analysis approach, we investigated structure–function associations in a large sample of SZ (n = 96 and HC (n = 142. We tested for associations between task-positive (fronto-parietal and task-negative (default-mode brain networks derived from fMRI activation during an n-back working memory task, and brain structural measures of surface area, cortical thickness, and gray matter volume, and to what extent these associations differed in SZ compared to HC. A significant association (p < .05, corrected for multiple comparisons was found between a component reflecting the task-positive fronto-parietal network and another component reflecting cortical thickness in fronto-temporal brain regions in SZ, indicating increased activation with increased thickness. Other structure–function associations across, between and within groups were generally moderate and significant at a nominal p-level only, with more numerous and stronger associations in SZ compared to HC. These results indicate a complex pattern of moderate associations between brain activation during cognitive processing and brain morphometry, and extend previous findings of fronto-temporal brain abnormalities in SZ by suggesting a coupling between cortical thickness of these brain regions and working memory-related brain activation.

  9. Placebo-controlled trial of atomoxetine for weight reduction in people with schizophrenia treated with clozapine or olanzapine.

    Science.gov (United States)

    Ball, M Patricia; Warren, Kimberly R; Feldman, Stephanie; McMahon, Robert P; Kelly, Deanna L; Buchanan, Robert W

    2011-04-01

    In recent years, several pharmacological and psychosocial interventions have examined ways to prevent or treat weight gain in people receiving second-generation antipsychotics. While there has been some success, in general, results have not been compelling. Atomoxetine is a selective norepinepherine reuptake inhibitor found to be associated with appetite suppression. Therefore, we examined whether atomoxetine may be of benefit for those who have gained weight on either clozapine or olanzapine. The study was a double-blind, placebo-controlled trial. All participants received the same psychosocial platform: a structured support and exercise group. People with schizophrenia or schizoaffective disorder, on olanzapine or clozapine, who had gained at least 7% of their pre-clozapine or pre-olanzapine weight were eligible for a 24-week, randomized, parallel group, double-blind comparison of adjunctive atomoxetine or placebo. Thirty-seven participants (20 atomoxetine, 17 placebo) were randomized and 26 participants (14 atomoxetine, 12 placebo; 70.2%) completed the study. There were no significant group differences in baseline BMI (atomoxetine: 34.5±4.9; placebo: 35.7±7.0) or weight (atomoxetine: 102.2±15.7 kg; placebo: 104.3±17.5 kg). Both treatment groups showed modest, not significant, trends in weight loss, averaging about 2 kg. Gender or baseline antipsychotic treatment did not modify treatment effects on weight. Secondary outcomes included neuropsychological assessments, symptom assessments (BPRS, SANS) and safety assessments. Of these, only the group difference in Gordon distractibility test scores was statistically significant and favored treatment with atomoxetine. Atomoxetine is not effective for weight loss in this population, but both olanzapine and clozapine participants can lose weight with structured group support and exercise.

  10. The Role of Proteases in Hippocampal Synaptic Plasticity: Putting Together Small Pieces of a Complex Puzzle.

    Science.gov (United States)

    Salazar, Ivan L; Caldeira, Margarida V; Curcio, Michele; Duarte, Carlos B

    2016-02-01

    Long-term synaptic plasticity in the hippocampus is thought to underlie the formation of certain forms of memory, including spatial memory. The early phase of long-term synaptic potentiation and synaptic depression depends on post-translational modifications of synaptic proteins, while protein synthesis is also required for the late-phase of both forms of synaptic plasticity (L-LTP and L-LTD). Numerous pieces of evidence show a role for different types of proteases in synaptic plasticity, further increasing the diversity of mechanisms involved in the regulation of the intracellular and extracellular protein content. The cleavage of extracellular proteins is coupled to changes in postsynaptic intracellular mechanisms, and additional alterations in this compartment result from the protease-mediated targeting of intracellular proteins. Both mechanisms contribute to initiate signaling cascades that drive downstream pathways coupled to synaptic plasticity. In this review we summarize the evidence pointing to a role for extracellular and intracellular proteases, with distinct specificities, in synaptic plasticity. Where in the cells the proteases are located, and how they are regulated is also discussed. The combined actions of proteases and translation mechanisms contribute to a tight control of the synaptic proteome relevant for long-term synaptic potentiation and synaptic depression in the hippocampus. Additional studies are required to elucidate the mechanisms whereby these changes in the synaptic proteome are related with plasticity phenomena.

  11. Relapse prevention in first-episode schizophrenia--maintenance vs intermittent drug treatment with prodrome-based early intervention: results of a randomized controlled trial within the German Research Network on Schizophrenia.

    Science.gov (United States)

    Gaebel, Wolfgang; Riesbeck, Mathias; Wölwer, Wolfgang; Klimke, Ansgar; Eickhoff, Matthias; von Wilmsdorff, Martina; Lemke, Matthias; Heuser, Isabella; Maier, Wolfgang; Huff, Wolfgang; Schmitt, Andrea; Sauer, Heinrich; Riedel, Michael; Klingberg, Stefan; Köpcke, Wolfgang; Ohmann, Christian; Möller, Hans-Jürgen

    2011-02-01

    After acute treatment of the first illness episode in schizophrenia, antipsychotic maintenance treatment is recommended for at least 1 year. Evidence for the optimal subsequent treatment is still scarce. Targeted intermittent treatment was found to be less effective than continuous treatment at preventing relapse in multiple episode patients; however, a post hoc analysis of our own data from a previous study suggested comparable efficacy of the 2 treatment approaches in first-episode patients. The current study was therefore designed to compare prospectively the relapse preventive efficacy of further maintenance treatment and targeted intermittent treatment in patients with ICD-10-diagnosed first-episode schizophrenia. A randomized controlled trial was conducted within the German Research Network on Schizophrenia. Entry screening took place between November 2000 and May 2004. After 1 year of antipsychotic maintenance treatment, stable first-episode patients were randomly assigned to 12 months of further maintenance treatment or stepwise drug discontinuation and targeted intermittent treatment. In case of prodromal symptoms of an impending relapse, patients in both groups received early drug intervention, guided by a decision algorithm. The primary outcome measure was relapse (increase in the Positive and Negative Syndrome Scale positive score > 10, Clinical Global Impressions-Change score ≥ 6, and decrease in Global Assessment of Functioning score > 20 between 2 visits). Of 96 first-episode patients, only 44 were eligible for the assigned treatment (maintenance treatment, n = 23; intermittent treatment, n = 21). The rates of relapse (19% vs 0%; P = .04) and deterioration (up to 57% vs 4%; P maintenance treatment group, but quality-of-life scores were comparable. Intermittent treatment patients received a significantly lower amount of antipsychotics (in haloperidol equivalents; P Maintenance treatment is more effective than targeted intermittent treatment in

  12. Childhood adversity and cognitive function in schizophrenia spectrum disorders and healthy controls: evidence for an association between neglect and social cognition.

    Science.gov (United States)

    Kilian, S; Asmal, L; Chiliza, B; Olivier, M R; Phahladira, L; Scheffler, F; Seedat, S; Marder, S R; Green, M F; Emsley, R

    2017-12-22

    Childhood adversity is associated with cognitive impairments in schizophrenia. However, findings to date are inconsistent and little is known about the relationship between social cognition and childhood trauma. We investigated the relationship between childhood abuse and neglect and cognitive function in patients with a first-episode of schizophrenia or schizophreniform disorder (n = 56) and matched healthy controls (n = 52). To the best of our knowledge, this is the first study assessing this relationship in patients and controls exposed to similarly high levels of trauma. Pearson correlational coefficients were used to assess correlations between Childhood Trauma Questionnaire abuse and neglect scores and cognition. For the MCCB domains displaying significant (p childhood neglect remained a significant predictor of impairment in social cognition in both patients and controls. Neglect was also a significant predictor of poorer verbal learning in patients and of attention/vigilance in controls. However, childhood abuse did not significantly predict cognitive impairments in either patients or controls. These findings are cross sectional and do not infer causality. Nonetheless, they indicate that associations between one type of childhood adversity (i.e. neglect) and social cognition are present and are not illness-specific.

  13. Bridging Levels of Understanding in Schizophrenia Through Computational Modeling

    Science.gov (United States)

    Anticevic, Alan; Murray, John D.; Barch, Deanna M.

    2015-01-01

    Schizophrenia is an illness with a remarkably complex symptom presentation that has thus far been out of reach of neuroscientific explanation. This presents a fundamental problem for developing better treatments that target specific symptoms or root causes. One promising path forward is the incorporation of computational neuroscience, which provides a way to formalize experimental observations and, in turn, make theoretical predictions for subsequent studies. We review three complementary approaches: (a) biophysically based models developed to test cellular-level and synaptic hypotheses, (b) connectionist models that give insight into large-scale neural-system-level disturbances in schizophrenia, and (c) models that provide a formalism for observations of complex behavioral deficits, such as negative symptoms. We argue that harnessing all of these modeling approaches represents a productive approach for better understanding schizophrenia. We discuss how blending these approaches can allow the field to progress toward a more comprehensive understanding of schizophrenia and its treatment. PMID:25960938

  14. Cannabis and schizophrenia.

    Science.gov (United States)

    McLoughlin, Benjamin C; Pushpa-Rajah, Jonathan A; Gillies, Donna; Rathbone, John; Variend, Hannele; Kalakouti, Eliana; Kyprianou, Katerina

    2014-10-14

    Schizophrenia is a mental illness causing disordered beliefs, ideas and sensations. Many people with schizophrenia smoke cannabis, and it is unclear why a large proportion do so and if the effects are harmful or beneficial. It is also unclear what the best method is to allow people with schizophrenia to alter their cannabis intake. To assess the effects of specific psychological treatments for cannabis reduction in people with schizophrenia.To assess the effects of antipsychotics for cannabis reduction in people with schizophrenia.To assess the effects of cannabinoids (cannabis related chemical compounds derived from cannabis or manufactured) for symptom reduction in people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register, 12 August 2013, which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE, PUBMED and PsycINFO.We searched all references of articles selected for inclusion for further relevant trials. We contacted the first author of included studies for unpublished trials or data. We included all randomised controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed:1) treatments to reduce cannabis use in people with schizophrenia;2) the effects of cannabinoids on people with schizophrenia. We independently inspected citations, selected papers and then re-inspected the studies if there were discrepancies, and extracted data. For dichotomous data we calculated risk ratios (RR) and for continuous data, we calculated mean differences (MD), both with 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. We excluded data if loss to follow-up was greater than 50%. We assessed risk of bias for included studies and used GRADE to rate the quality of the evidence. We identified eight randomised trials, involving 530 participants, which met our selection criteria.For the cannabis reduction studies no one treatment showed superiority for reduction

  15. CNVs conferring risk of autism or schizophrenia affect cognition in controls

    DEFF Research Database (Denmark)

    Stefansson, Hreinn; Meyer-Lindenberg, Andreas; Steinberg, Stacy

    2014-01-01

    to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion...

  16. Synaptic electronics: materials, devices and applications.

    Science.gov (United States)

    Kuzum, Duygu; Yu, Shimeng; Wong, H-S Philip

    2013-09-27

    In this paper, the recent progress of synaptic electronics is reviewed. The basics of biological synaptic plasticity and learning are described. The material properties and electrical switching characteristics of a variety of synaptic devices are discussed, with a focus on the use of synaptic devices for neuromorphic or brain-inspired computing. Performance metrics desirable for large-scale implementations of synaptic devices are illustrated. A review of recent work on targeted computing applications with synaptic devices is presented.

  17. Neurocognitive functioning and cannabis use in schizophrenia.

    Science.gov (United States)

    Segev, Aviv; Lev-Ran, Shaul

    2012-01-01

    Cannabis is the most prevalent illicit substance used among schizophrenia patients. The effects of cannabis are mediated through the endocannabinoid system, which is a major regulator of neurotransmission and may be disturbed in schizophrenia. Though cognitive impairment in schizophrenia is well established, the effects of cannabis on cognition in schizophrenia patients are still unclear. This paper reviews 19 studies that examine the cognitive effects of cannabis on schizophrenia by comparing cognitive functioning of cannabis-using and non-using schizophrenia patients across a vast range of domains (memory, attention and processing speed, executive functions, visuospatial, psychomotor and language). Of the studies included in the review, 11 reported better cognitive functions among cannabis-using schizophrenia patients compared to non-users, 5 found minimal or no difference between the groups and 3 found poorer cognitive functions among cannabis-using schizophrenia patients compared to non-users. The inconsistencies in the studies reviewed may stem from significant methodological variance between the studies regarding patient selection, adequate controls, cognitive measures used, measures of cannabis use, additional drugs used, and clinical aspects of schizophrenia. These methodological issues are discussed, as well as possible explanations for the results presented and suggestions for future research in this field.

  18. Discrimination within Recognition Memory in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Scott R. Sponheim

    2013-06-01

    Full Text Available Episodic memory is one of the most affected cognitive domains in schizophrenia. First-degree biological relatives of individuals with schizophrenia also have been found to exhibit a similar, but milder, episodic memory deficit. Unlike most studies that focus on the percent of previously presented items recognized, the current investigation sought to further elucidate the nature of memory dysfunction associated with schizophrenia by examining the discrimination of old and new material during recognition (measured by d' to consider false recognition of new items. Using the Recurring Figures Test and the California Verbal Learning Test (CVLT, we studied a sample of schizophrenia probands and the first-degree biological relatives of patients with schizophrenia, as well as probands with bipolar disorder and first-degree biological relatives to assess the specificity of recognition memory dysfunction to schizophrenia. The schizophrenia sample had poorer recognition discrimination in both nonverbal and verbal modalities; no such deficits were identified in first-degree biological relatives or bipolar disorder probands. Discrimination in schizophrenia and bipolar probands failed to benefit from the geometric structure in the designs in the manner that controls did on the nonverbal test. Females performed better than males in recognition of geometric designs. Episodic memory dysfunction in schizophrenia is present for a variety of stimulus domains and reflects poor use of item content to increase discrimination of old and new items.

  19. GABAA Receptor-Mediated Bidirectional Control of Synaptic Activity, Intracellular Ca2+, Cerebral Blood Flow, and Oxygen Consumption in Mouse Somatosensory Cortex In Vivo

    DEFF Research Database (Denmark)

    Jessen, Sanne Barsballe; Brazhe, Alexey; Lind, Barbara Lykke

    2015-01-01

    of GABA is incompletely understood. Here we performed in vivo studies in mice to investigate how THIP (which tonically activates extrasynaptic GABAARs) and Zolpidem (a positive allosteric modulator of synaptic GABAARs) impact stimulation-induced ΔCBF, ΔCMRO2, local field potentials (LFPs), and fluorescent......Neural activity regulates local increases in cerebral blood flow (ΔCBF) and the cortical metabolic rate of oxygen (ΔCMRO2) that constitutes the basis of BOLD functional neuroimaging signals. Glutamate signaling plays a key role in brain vascular and metabolic control; however, the modulatory effect...

  20. Graph metrics of structural brain networks in individuals with schizophrenia and healthy controls : Group differences, relationships with intelligence, and genetics

    NARCIS (Netherlands)

    Yeo, Ronald A.; Ryman, Sephira G.; Van Den Heuvel, Martijn P.; De Reus, Marcel A.; Jung, Rex E.; Pommy, Jessica; Mayer, Andrew R.; Ehrlich, Stefan; Schulz, S. Charles; Morrow, Eric M.; Manoach, Dara; Ho, Beng Choon; Sponheim, Scott R.; Calhoun, Vince D.

    2016-01-01

    Objectives: One of the most prominent features of schizophrenia is relatively lower general cognitive ability (GCA). An emerging approach to understanding the roots of variation in GCA relies on network properties of the brain. In this multi-center study, we determined global characteristics of

  1. Physical Exercise Keeps the Brain Connected : Biking Increases White Matter Integrity in Patients With Schizophrenia and Healthy Controls

    NARCIS (Netherlands)

    Svatkova, Alena; Mandl, Rene C. W.|info:eu-repo/dai/nl/304814172; Scheewe, Thomas W.; Cahn, Wiepke|info:eu-repo/dai/nl/250566370; Kahn, Rene S.|info:eu-repo/dai/nl/073778532; Pol, Hilleke E. Hulshoff|info:eu-repo/dai/nl/142348228

    It has been shown that learning a new skill leads to structural changes in the brain. However, it is unclear whether it is the acquisition or continuous practicing of the skill that causes this effect and whether brain connectivity of patients with schizophrenia can benefit from such practice. We

  2. Family intervention for schizophrenia

    Science.gov (United States)

    Pharoah, Fiona; Mari, Jair; Rathbone, John; Wong, Winson

    2014-01-01

    Background People with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of emotions. Forms of psychosocial intervention, designed to reduce these levels of expressed emotions within families, are now widely used. Objectives To estimate the effects of family psychosocial interventions in community settings for people with schizophrenia or schizophrenia-like conditions compared with standard care. Search strategy We updated previous searches by searching the Cochrane Schizophrenia Group Trials Register (September 2008). Selection criteria We selected randomised or quasi-randomised studies focusing primarily on families of people with schizophrenia or schizoaffective disorder that compared community-orientated family-based psychosocial intervention with standard care. Data collection and analysis We independently extracted data and calculated fixed-effect relative risk (RR), the 95% confidence intervals (CI) for binary data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). Main results This 2009-10 update adds 21 additional studies, with a total of 53 randomised controlled trials included. Family intervention may decrease the frequency of relapse (n = 2981, 32 RCTs, RR 0.55 CI 0.5 to 0.6, NNT 7 CI 6 to 8), although some small but negative studies might not have been identified by the search. Family intervention may also reduce hospital admission (n = 481, 8 RCTs, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13) and encourage compliance with medication (n = 695, 10 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 6 CI 5 to 9) but it does not obviously affect the tendency of individuals/families to leave care (n = 733, 10 RCTs, RR 0.74 CI 0.5 to 1.0). Family intervention also seems to improve general social impairment and the levels of

  3. Do common genotypes of FK506 binding protein 5 (FKBP5) moderate the effects of childhood maltreatment on cognition in schizophrenia and healthy controls?

    Science.gov (United States)

    Green, Melissa J; Raudino, Alessandra; Cairns, Murray J; Wu, Jingqin; Tooney, Paul A; Scott, Rodney J; Carr, Vaughan J

    2015-11-01

    Common variants of the FK506 binding protein 5 (FKBP5) gene are implicated in psychotic and other disorders, via their role in regulating glucocorticoid receptor (GR) receptor sensitivity and effects on the broader function of the HPA system in response to stress. In this study, the effects of four FKBP5 polymorphisms (rs1360780, rs9470080, rs4713902, rs9394309) on IQ and eight other cognitive domains were examined in the context of exposure to childhood maltreatment in 444 cases with schizophrenia and 292 healthy controls (from a total sample of 617 cases and 659 controls obtained from the Australian Schizophrenia Research Bank; ASRB). Participants subjected to any kind of maltreatment (including physical, emotional, or sexual abuse or physical or emotional neglect) in childhood were classified as 'exposed'; cognitive functioning was measured with Repeatable Battery for the Assessment of Neuropsychological Status, the Controlled Oral Word Association Test, and IQ was estimated with the Weschler Test of Adult Reading. Hierarchical regressions were used to test the main effects of genotype and childhood maltreatment, and their additive interactive effects, on cognitive function. For rs1360870, there were significant main effects of genotype and childhood maltreatment, and a significant interaction of genotype with childhood trauma affecting attention in both schizophrenia and healthy participants (C-homozygotes in both groups showed worse attention in the context of maltreatment); in SZ, this SNP also affected global neuropsychological function regardless of exposure to childhood trauma, with T-homozygotes showing worse cognition than other genotypes. The mechanisms of trauma-dependent effects of FKBP5 following early life trauma deserve further exploration in healthy and psychotic samples, in the context of epigenetic effects and perhaps epistasis with other genes. Study of these processes may be particularly informative in subgroups exposed to various other forms

  4. Effectiveness of self-management training in community residents with chronic schizophrenia: a single-blind randomized controlled trial in Shanghai, China.

    Science.gov (United States)

    Zhou, Bin; Zhang, Pu; Gu, Yiwei

    2014-04-01

    Evaluate the effectiveness of self-management training in community-dwelling adults with schizophrenia. A total of 201 individuals with chronic schizophrenia (mean duration of illness of 17.4 years) were recruited and randomized into the self-management intervention group (n=103) and treatment-as-usual control group (n=98). The self-management training involved weekly group sessions for 6 months in which basic self-management skills were discussed and modelled followed by monthly group booster sessions for 24 months in which a community health worker reviewed patients' self-management checklist journals. Two psychiatrists who were blind to group assignment evaluated the symptoms and social functioning of participants at baseline and 6 months and 30 months after enrollment using the Brief Psychiatric Rating Scale (BPRS), Social Disability Screening Schedule (SDSS), and Morningside Rehabilitation Status Scale (MRSS). A total of 194 individuals (99 from the intervention group and 95 from the control group) completed the 2.5-year follow-up. Intention-to-treat analysis with the last observation carried forward method was used for analysis. Compared to the control group, the intervention group had lower mean scores in the BPRS, SDSS and MRSS at both follow-up points. The scores in the intervention group continued to improve during the maintenance phase of the treatment from 6 months to 30 months after enrollment. Self-management training is an effective method to improve symptoms and social functioning among individuals with chronic schizophrenia living in the community. After six months of weekly training in self-management skills, monthly booster sessions reviewing patients' daily checklist of illness-related symptoms events are sufficient to maintain the beneficial effects of the training. Further study of the long-term cost-effectiveness of this method is needed.

  5. Neuregulin-1 genotypes and eye movements in schizophrenia

    DEFF Research Database (Denmark)

    Haraldsson, H.M.; Ettinger, U.; Magnusdottir, B.B.

    2010-01-01

    Neuregulin-1 (NRG-1) is a putative susceptibility gene for schizophrenia but the neurocognitive processes that may involve NRG-1 in schizophrenia are unknown. Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are promising endophenotypes, which may be associated with brain...... dysfunctions underlying the pathophysiology of schizophrenia. The aim of this study was to investigate the associations of NRG-1 genotypes with AS and SPEM in schizophrenia patients and healthy controls. Patients (N = 113) and controls (N = 106) were genotyped for two NRG-1 single nucleotide polymorphisms...... findings of impaired AS and SPEM performance in schizophrenia patients (all P

  6. Prevalence of comorbid anxiety disorders in schizophrenia

    Directory of Open Access Journals (Sweden)

    Chandra Kiran

    2016-01-01

    Full Text Available Background: Diagnostic and treatment hierarchical reductionisms have resulted in an oversight of anxiety syndromes in schizophrenia. Aim: The aim of this study was to find the prevalence of different anxiety disorders in schizophrenia patients. Materials and Methods: The study was conducted on inpatients of a tertiary care psychiatric hospital using a prospective, purposive sampling technique. The study consisted of 93 schizophrenia patients and a similar number of normal controls. The schizophrenia patients and controls were evaluated for psychopathology and the presence of anxiety disorder. Results: The prevalence of anxiety disorder was significantly higher in schizophrenia patients (45.16% compared to controls (16.12%. Further, the prevalence of panic disorder, social anxiety disorder, and obsessive-compulsive disorder (OCD was significantly higher in schizophrenia patients. No significant correlation was observed between anxiety disorder scores and psychopathology scores. Conclusions: The prevalence of comorbid anxiety disorders (panic disorder, social anxiety disorder, and OCD in schizophrenia is significantly higher in the general population. The onset of anxiety disorder commonly precedes the onset of schizophrenia.

  7. Seroprevalence of anti-Toxoplasma gondii and anti-Borrelia species antibodies in patients with schizophrenia: a case-control study from western Turkey.

    Science.gov (United States)

    Cevizci, Sibel; Celik, Merve; Akcali, Alper; Oyekcin, Demet Gulec; Sahin, Ozlem Oztürk; Bakar, Coskun

    2015-06-01

    We examined IgG antibody seroprevalence and risk factors for anti-Toxoplasma gondii and anti-Borrelia sp. in schizophrenic patients. This case-control study included 30 schizophrenic patients and 60 healthy individuals. Serological analyses were identified by using ELISA technique. In the case group the Toxoplasma seropositivity was 33.3% and Borrelia seropositivity was 13.3%, while in the control group the Toxoplasma positivity was 21.7% and Borrelia seropositivity was 15.0%. There was no significant difference with regard to seroprevalence between the groups (P = 0.232; P = 0.832, respectively). There was statistically significant difference between case and control groups related to hand and kitchen utensil hygiene after dealing with raw meat (P = 0.001). Our data showed the rate of Toxoplasma antibodies was higher in the case group, while the rate of Borrelia antibodies was higher in the control group. In both groups the high rates of seropositivity for Toxoplasma gondii and Borrelia sp. is thought to be due to neglect of personal hygiene. The present study also is the first to examine the association between Borrelia sp. and schizophrenia. Further studies are needed to determine whether there is an association between Borrelia sp. and schizophrenia or not.

  8. Early-onset schizophrenia

    OpenAIRE

    Hojka Gregorič Kumperščak

    2013-01-01

    Early-onset schizophrenia is defined as schizophrenia with onset before the age of 18 years. While schizophrenia is a very rare disorder in childhood, it becomes increasingly common during adolescence and peaks in early adulthood. Even though childhood and adolescent schizophrenia lie on a continuum with adult schizophrenia and show roughly the same clinical picture, they both have some developmental specifics. They display greater symptom variability making the ...

  9. Pannexin 1 Regulates Bidirectional Hippocampal Synaptic Plasticity in Adult Mice

    Directory of Open Access Journals (Sweden)

    Alvaro O. Ardiles

    2014-10-01

    Full Text Available The threshold for bidirectional modification of synaptic plasticity is known to be controlled by several factors, including the balance between protein phosphorylation and dephosphorylation, postsynaptic free Ca2+ concentration and NMDA receptor (NMDAR composition of GluN2 subunits. Pannexin 1 (Panx1, a member of the integral membrane protein family, has been shown to form non-selective channels and to regulate the induction of synaptic plasticity as well as hippocampal-dependent learning. Although Panx1 channels have been suggested to play a role in excitatory long-term potentiation (LTP, it remains unknown whether these channels also modulate long-term depression (LTD or the balance between both types of synaptic plasticity. To study how Panx1 contributes to excitatory synaptic efficacy, we examined the age-dependent effects of eliminating or blocking Panx1 channels on excitatory synaptic plasticity within the CA1 region of the mouse hippocampus. By using different protocols to induce bidirectional synaptic plasticity, Panx1 channel blockade or lack of Panx1 were found to enhance LTP, whereas both conditions precluded the induction of LTD in adults, but not in young animals. These findings suggest that Panx1 channels restrain the sliding threshold for the induction of synaptic plasticity and underlying brain mechanisms of learning and memory.

  10. Pannexin 1 regulates bidirectional hippocampal synaptic plasticity in adult mice.

    Science.gov (United States)

    Ardiles, Alvaro O; Flores-Muñoz, Carolina; Toro-Ayala, Gabriela; Cárdenas, Ana M; Palacios, Adrian G; Muñoz, Pablo; Fuenzalida, Marco; Sáez, Juan C; Martínez, Agustín D

    2014-01-01

    The threshold for bidirectional modification of synaptic plasticity is known to be controlled by several factors, including the balance between protein phosphorylation and dephosphorylation, postsynaptic free Ca(2+) concentration and NMDA receptor (NMDAR) composition of GluN2 subunits. Pannexin 1 (Panx1), a member of the integral membrane protein family, has been shown to form non-selective channels and to regulate the induction of synaptic plasticity as well as hippocampal-dependent learning. Although Panx1 channels have been suggested to play a role in excitatory long-term potentiation (LTP), it remains unknown whether these channels also modulate long-term depression (LTD) or the balance between both types of synaptic plasticity. To study how Panx1 contributes to excitatory synaptic efficacy, we examined the age-dependent effects of eliminating or blocking Panx1 channels on excitatory synaptic plasticity within the CA1 region of the mouse hippocampus. By using different protocols to induce bidirectional synaptic plasticity, Panx1 channel blockade or lack of Panx1 were found to enhance LTP, whereas both conditions precluded the induction of LTD in adults, but not in young animals. These findings suggest that Panx1 channels restrain the sliding threshold for the induction of synaptic plasticity and underlying brain mechanisms of learning and memory.

  11. Large recurrent microdeletions associated with schizophrenia

    DEFF Research Database (Denmark)

    Stefansson, H.; Rujescu, D.; Cichon, S.

    2008-01-01

    Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account...... and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33......,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses...

  12. A Calcium-Dependent Plasticity Rule for HCN Channels Maintains Activity Homeostasis and Stable Synaptic Learning

    Science.gov (United States)

    Honnuraiah, Suraj; Narayanan, Rishikesh

    2013-01-01

    for experimentally observed plasticity in HCN channels accompanying synaptic plasticity in hippocampal neurons, and uncover potential links between HCN-channel plasticity and calcium influx, dynamic gain control and stable synaptic learning. PMID:23390543

  13. Efficacy of a family intervention program for prevention of hospitalization in patients with schizophrenia. A naturalistic multicenter controlled and randomized study in Spain.

    Science.gov (United States)

    Mayoral, Fermín; Berrozpe, Adela; de la Higuera, Jesús; Martinez-Jambrina, Juan José; de Dios Luna, Juan; Torres-Gonzalez, Francisco

    2015-01-01

    According to most relevant guidelines, family psycho-educational interventions are considered to be one the most effective psychosocial treatments for people with schizophrenia. The main outcome measure in controlled and randomized studies has been prevention of relapses and admissions, and encouragement of compliance, although some questions remain about its applicability and results in clinical practice. The aim of study was to evaluate the efficacy and implementation of a single family psychoeducational intervention in 'real' conditions for people diagnosed with schizophrenia. A total of 88 families were randomized in two groups. The family intervention group received a 12 months psychoeducational treatment, and the other group followed normal standard treatment. Assessments were made at baseline, at 12 and at 18 months. The main outcome measure was hospitalization, and secondary outcome measures were clinical condition (BPRS-E) and social disability (DAS-II). A total of 71 patients finished the study (34 family intervention group and 37 control group). Patients who received family intervention reduced the risk of hospitalization by 40% (P = .4018; 95%CI: 0.1833-0.6204). Symptomatology improved significantly at 12 months (P = .4018; 95%CI: 0.1833-0.6204), but not at 18 months (P = .4018; 95%CI: 0.1833-0.6204). Social disability was significantly reduced in the family intervention group at 12 months and 18 months. Family psychoeducational intervention reduces hospitalization risk and improves clinical condition and social functioning of people with schizophrenia. Copyright © 2013 SEP y SEPB. Published by Elsevier España. All rights reserved.

  14. Unrestricted synaptic growth in spinster-a late endosomal protein implicated in TGF-beta-mediated synaptic growth regulation.

    Science.gov (United States)

    Sweeney, Sean T; Davis, Graeme W

    2002-10-24

    In a genetic screen for genes that control synapse development, we have identified spinster (spin), which encodes a multipass transmembrane protein. spin mutant synapses reveal a 200% increase in bouton number and a deficit in presynaptic release. We demonstrate that spin is expressed in both nerve and muscle and is required both pre- and postsynaptically for normal synaptic growth. We have localized Spin to a late endosomal compartment and present evidence for altered endosomal/lysosomal function in spin. We also present evidence that synaptic overgrowth in spin is caused by enhanced/misregulated TGF-beta signaling. TGF-beta receptor mutants show dose-dependent suppression of synaptic overgrowth in spin. Furthermore, mutations in Dad, an inhibitory Smad, cause synapse overgrowth. We present a model for synaptic growth control with implications for the etiology of lysosomal storage and neurodegenerative disease.

  15. BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia

    Directory of Open Access Journals (Sweden)

    Zhengrong Zhang

    2017-09-01

    Full Text Available Schizophrenia is a chronic psychiatric disorder with a lifetime prevalence of about 1% in the general population. Recent studies have shown that Neuregulin-1 (Nrg1 is a candidate gene for schizophrenia. At least 15 alternative splicing of NRG1 isoforms all contain an extracellular epidermal growth factor (EGF-like domain, which is sufficient for Nrg1 biological activity including the formation of myelin sheaths and the regulation of synaptic plasticity. It is known that Nrg1 can be cleaved by β-secretase (BACE1 and the resulting N-terminal fragment (Nrg1-ntf binds to receptor tyrosine kinase ErbB4, which activates Nrg1/ErbB4 signaling. While changes in Nrg1 expression levels in schizophrenia still remain controversial, understanding the BACE1-cleaved Nrg1-ntf and Nrg1/ErbB4 signaling in schizophrenia neuropathogenesis is essential and important. In this review paper, we included three major parts: (1 Nrg1 structure and cleavage pattern by BACE1; (2 BACE1-dependent Nrg1 cleavage associated with schizophrenia in human studies; and (3 Animal studies of Nrg1 and BACE1 mutations with behavioral observations. Our review will provide a better understanding of Nrg1 in schizophrenia and a potential strategy for using BACE1 cleavage of Nrg1 as a unique biomarker for diagnosis, as well as a new therapeutic target, of schizophrenia.

  16. Molecular Recognition within Synaptic Scaffolds

    DEFF Research Database (Denmark)

    Erlendsson, Simon

    domains, responsible for tethering their respective synaptic protein ligands. Therefore, understanding the specificity and binding mechanisms of PDZ domain proteins is essential to understand regulation of synaptic plasticity. PICK1 is a PDZ domain-containing scaffolding protein predominantly expressed...... and characterized in the postsynaptic neurons, where it is involved in regulating processes underlying LTP and LTD. However, PICK1 has also been found to interact with a wide range of other regulatory proteins, receptors and transporters, which implicates PICK1 in several processes important for proper synaptic...

  17. Deconvolution of Voltage Sensor Time Series and Electro-diffusion Modeling Reveal the Role of Spine Geometry in Controlling Synaptic Strength.

    Science.gov (United States)

    Cartailler, Jerome; Kwon, Taekyung; Yuste, Rafael; Holcman, David

    2018-02-05

    Most synaptic excitatory connections are made on dendritic spines. But how the voltage in spines is modulated by its geometry remains unclear. To investigate the electrical properties of spines, we combine voltage imaging data with electro-diffusion modeling. We first present a temporal deconvolution procedure for the genetically encoded voltage sensor expressed in hippocampal cultured neurons and then use electro-diffusion theory to compute the electric field and the current-voltage conversion. We extract a range for the neck resistances of 〈R〉=100±35MΩ. When a significant current is injected in a spine, the neck resistance can be inversely proportional to its radius, but not to the radius square, as predicted by Ohm's law. We conclude that the postsynaptic voltage cannot only be modulated by changing the number of receptors, but also by the spine geometry. Thus, spine morphology could be a key component in determining synaptic transduction and plasticity. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Cerebellar Synaptic Plasticity and the Credit Assignment Problem.

    Science.gov (United States)

    Jörntell, Henrik

    2016-04-01

    The mechanism by which a learnt synaptic weight change can contribute to learning or adaptation of brain function is a type of credit assignment problem, which is a key issue for many parts of the brain. In the cerebellum, detailed knowledge not only of the local circuitry connectivity but also of the topography of different sources of afferent/external information makes this problem particularly tractable. In addition, multiple forms of synaptic plasticity and their general rules of induction have been identified. In this review, we will discuss the possible roles of synaptic and cellular plasticity at specific locations in contributing to behavioral changes. Focus will be on the parts of the cerebellum that are devoted to limb control, which constitute a large proportion of the cortex and where the knowledge of the external connectivity is particularly well known. From this perspective, a number of sites of synaptic plasticity appear to primarily have the function of balancing the overall level of activity in the cerebellar circuitry, whereas the locations at which synaptic plasticity leads to functional changes in terms of limb control are more limited. Specifically, the postsynaptic forms of long-term potentiation (LTP) and long-term depression (LTD) at the parallel fiber synapses made on interneurons and Purkinje cells, respectively, are the types of plasticity that mediate the widest associative capacity and the tightest link between the synaptic change and the external functions that are to be controlled.

  19. Synaptic Scaling in Combination with many Generic Plasticity Mechanisms Stabilizes Circuit Connectivity

    Directory of Open Access Journals (Sweden)

    Christian eTetzlaff

    2011-11-01

    Full Text Available Synaptic scaling is a slow process that modifies synapses, keeping the firing rate of neural circuits in specific regimes. Together with other processes, such as conventional synaptic plasticity in the form of long term depression and potentiation, this changes the synaptic patterns in a network, ensuring diverse, functionally relevant, stable and input-dependent connectivity. How synaptic patterns are generated and stabilized, however, is largely unknown. Here we formally describe and analyze synaptic scaling based on results from experimental studies and demonstrate that the combination of different conventional plasticity mechanisms and synaptic scaling provides a powerful general framework for regulating network connectivity. In addition, we design several simple models, which reproduce experimentally observed synaptic distributions as well as the observed synaptic modifications during sustained activity changes. These models predict that the combination of plasticity with scaling generates globally stable, input-controlled synaptic patterns, also in recurrent networks. Thus, in combination with other forms of plasticity, synaptic scaling can robustly yield neuronal circuits with high synaptic diversity, which potentially allows in a more robust way for the dynamic storage of complex activation patterns. This mechanism is even more pronounced when considering networks with a realistic degree of inhibition. This, could be the basis for the learning of structured behavior even in initially random networks.

  20. Isolation of Synaptosomes, Synaptic Plasma Membranes, and Synaptic Junctional Complexes.

    Science.gov (United States)

    Michaelis, Mary L; Jiang, Lei; Michaelis, Elias K

    2017-01-01

    Isolation of synaptic nerve terminals or synaptosomes provides an opportunity to study the process of neurotransmission at many levels and with a variety of approaches. For example, structural features of the synaptic terminals and the organelles within them, such as synaptic vesicles and mitochondria, have been elucidated with electron microscopy. The postsynaptic membranes are joined to the presynaptic "active zone" of transmitter release through cell adhesion molecules and remain attached throughout the isolation of synaptosomes. These "post synaptic densities" or "PSDs" contain the receptors for the transmitters released from the nerve terminals and can easily be seen with electron microscopy. Biochemical and cell biological studies with synaptosomes have revealed which proteins and lipids are most actively involved in synaptic release of neurotransmitters. The functional properties of the nerve terminals, such as responses to depolarization and the uptake or release of signaling molecules, have also been characterized through the use of fluorescent dyes, tagged transmitters, and transporter substrates. In addition, isolated synaptosomes can serve as the starting material for the isolation of relatively pure synaptic plasma membranes (SPMs) that are devoid of organelles from the internal environment of the nerve terminal, such as mitochondria and synaptic vesicles. The isolated SPMs can reseal and form vesicular structures in which transport of ions such as sodium and calcium, as well as solutes such as neurotransmitters can be studied. The PSDs also remain associated with the presynaptic membranes during isolation of SPM fractions, making it possible to isolate the synaptic junctional complexes (SJCs) devoid of the rest of the plasma membranes of the nerve terminals and postsynaptic membrane components. Isolated SJCs can be used to identify the proteins that constitute this highly specialized region of neurons. In this chapter, we describe the steps involved

  1. Association Study of CHRNA7 Promoter Variants with Sensory and Sensorimotor Gating in Schizophrenia Patients and Healthy Controls

    DEFF Research Database (Denmark)

    Bertelsen, Birgitte; Oranje, Bob; Melchior, Linea

    2015-01-01

    Schizophrenia is a severe psychiatric disorder with a core component of impaired cognitive function still remaining as one of the greatest challenges in the pharmacological treatment of the disorder. The CHRNA7 gene, encoding the subunit of the human α7 nicotinic acetylcholine receptor (α7nAChR),...... and startle magnitude, indicating that cholinergic neurotransmission involving the α7nAChR could be involved in sensory registration processes.......Schizophrenia is a severe psychiatric disorder with a core component of impaired cognitive function still remaining as one of the greatest challenges in the pharmacological treatment of the disorder. The CHRNA7 gene, encoding the subunit of the human α7 nicotinic acetylcholine receptor (α7n...

  2. Synaptic Mitochondrial Pathology in Alzheimer's Disease

    Science.gov (United States)

    Du, Heng; Guo, Lan

    2012-01-01

    Abstract Significance: Synaptic degeneration, an early pathological feature in Alzheimer's disease (AD), is closely correlated to impaired cognitive function and memory loss. Recent studies suggest that involvement of amyloid-beta peptide (Aβ) in synaptic mitochondrial alteration underlies these synaptic lesions. Thus, to understand the Aβ-associated synaptic mitochondrial perturbations would fortify our understanding of synaptic stress in the pathogenesis of AD. Recent Advances: Increasing evidence suggests that synaptic mitochondrial dysfunction is strongly associated with synaptic failure in many neurodegenerative diseases including AD. Based on recent findings in human AD subjects, AD animal models, and AD cellular models, synaptic mitochondria undergo multiple malfunctions including Aβ accumulation, increased oxidative stress, decreased respiration, and compromised calcium handling capacity, all of which occur earlier than changes seen in nonsynaptic mitochondria before predominant AD pathology. Of note, the impact of Aβ on mitochondrial motility and dynamics exacerbates synaptic mitochondrial alterations. Critical Issues: Synaptic mitochondria demonstrate early deficits in AD; in combination with the role that synaptic mitochondria play in sustaining synaptic functions, deficits in synaptic mitochondria may be a key factor involved in an early synaptic pathology in AD. Future Directions: The importance of synaptic mitochondria in supporting synapses and the high vulnerability of synaptic mitochondria to Aβ make them a promising target of new therapeutic strategy for AD. Antioxid. Redox Signal. 16, 1467–1475. PMID:21942330

  3. Add-on mirtazapine enhances antipsychotic effect of first generation antipsychotics in schizophrenia: a double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Joffe, Grigori; Terevnikov, Viatcheslav; Joffe, Marina; Stenberg, Jan-Henry; Burkin, Mark; Tiihonen, Jari

    2009-03-01

    Mirtazapine, an antidepressant with a broad spectrum of receptor affinity may, if combined with first generation antipsyhotics (FGAs), improve clinical profile of the FGAs. However, potentiation of the antipsychotic effect by mirtazapine has not been reported thus far. We explored the efficacy of adjunctive mirtazapine on symptoms of schizophrenia in patients having an insufficient response to different FGAs. Schizophrenia-diagnosed patients with a prolonged disease and a history of a poor response to numerous antipsychotics, who were at least moderately ill despite their FGAs treatment, received add-on mirtazapine (n=20) or placebo (n=19) in a 6-week double-blind randomized controlled trial (RCT). The analysis was made on a Modified Intent-to-Treat (MITT) basis with Last Observations Carried Forward (LOCF). Mirtazapine outranged placebo on almost all measures. The clear-cut clinical relevance of this finding was demonstrated by a large effect size of 1.00 (95% CI 0.23-1.67, p=0.003) on the total Positive and Negative Syndrome Scale (PANSS) scores (the primary outcome). The PANSS positive subscale scores decreased by 17.2% with mirtazapine vs. 1.6% with placebo (p<0.001), and the PANSS negative subscale scores by 12% and 3% (p<0.001), correspondingly. This is the first RCT reporting a robust additive antipsychotic effect of an adjunctive antidepressant. Mirtazapine-FGAs combination appears to be a safe, well-tolerated and efficacious treatment option in this challenging population. These findings are important due to the current re-emerging attention to FGAs. The focus of further studies should be expanded to include combinations with or switching to novel antipsychotics, different subpopulations of patients with schizophrenia, finding of optimal doses, and comparison with clozapine.

  4. Cardiometabolic risks of blonanserin and perospirone in the management of schizophrenia: a systematic review and meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Taro Kishi

    Full Text Available BACKGROUND: The present study aimed to evaluate cardiometabolic risks [weight gain, blood lipid levels (total cholesterol and triglycerides, blood glucose levels, hemoglobin A1c (HbA1c levels, and corrected QT interval (QTc prolongation] associated with the use of blonanserin and perospirone versus other antipsychotics in the management of patients with schizophrenia. METHOD: We conducted a systematic review and meta-analysis of patient data from randomized controlled trials comparing blonanserin or perospirone with other antipsychotics. RESULTS: In total, 4 blonanserin studies (n = 1080 were identified [vs. risperidone (2 studies, n = 508; vs. haloperidol (2 studies, n = 572]. Blonanserin produced less weight gain compared with risperidone (weighted mean difference = -0.86, 95% confidence intervals = -1.36 to -0.36, p = 0.0008; 2 studies, 480 patients. However, no significant differences were observed in blood lipid, glucose, and HbA1c levels or QTc prolongation between blonanserin and risperidone or haloperidol. For perospirone studies, 5 studies [562 adult patients with schizophrenia randomized to perospirone (n = 256, olanzapine (n = 20, quetiapine (n = 28, risperidone (n = 53, aripiprazole (n = 49, haloperidol (n = 75, or mosapramine (n = 81] were identified. Perospirone did not differ from other antipsychotics with regard to weight gain and total cholesterol levels. CONCLUSIONS: Our results suggest that blonanserin is associated with a lower of weight gain compared with other antipsychotics. Because the number of studies was small, additional controlled clinical trials with larger number of patients are indicated.

  5. Cardiometabolic risks of blonanserin and perospirone in the management of schizophrenia: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Kishi, Taro; Matsuda, Yuki; Iwata, Nakao

    2014-01-01

    The present study aimed to evaluate cardiometabolic risks [weight gain, blood lipid levels (total cholesterol and triglycerides), blood glucose levels, hemoglobin A1c (HbA1c) levels, and corrected QT interval (QTc) prolongation] associated with the use of blonanserin and perospirone versus other antipsychotics in the management of patients with schizophrenia. We conducted a systematic review and meta-analysis of patient data from randomized controlled trials comparing blonanserin or perospirone with other antipsychotics. In total, 4 blonanserin studies (n = 1080) were identified [vs. risperidone (2 studies, n = 508); vs. haloperidol (2 studies, n = 572)]. Blonanserin produced less weight gain compared with risperidone (weighted mean difference = -0.86, 95% confidence intervals = -1.36 to -0.36, p = 0.0008; 2 studies, 480 patients). However, no significant differences were observed in blood lipid, glucose, and HbA1c levels or QTc prolongation between blonanserin and risperidone or haloperidol. For perospirone studies, 5 studies [562 adult patients with schizophrenia randomized to perospirone (n = 256), olanzapine (n = 20), quetiapine (n = 28), risperidone (n = 53), aripiprazole (n = 49), haloperidol (n = 75), or mosapramine (n = 81)] were identified. Perospirone did not differ from other antipsychotics with regard to weight gain and total cholesterol levels. Our results suggest that blonanserin is associated with a lower of weight gain compared with other antipsychotics. Because the number of studies was small, additional controlled clinical trials with larger number of patients are indicated.

  6. Synaptic devices based on purely electronic memristors

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Ruobing [Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China); Institute of Materials Science, School of Materials Science and Engineering, Shanghai University, Shanghai 200072 (China); Li, Jun; Zhuge, Fei, E-mail: zhugefei@nimte.ac.cn, E-mail: h-cao@nimte.ac.cn; Zhu, Liqiang; Liang, Lingyan; Zhang, Hongliang; Gao, Junhua; Cao, Hongtao, E-mail: zhugefei@nimte.ac.cn, E-mail: h-cao@nimte.ac.cn; Fu, Bing; Li, Kang [Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China)

    2016-01-04

    Memristive devices have been widely employed to emulate biological synaptic behavior. In these cases, the memristive switching generally originates from electrical field induced ion migration or Joule heating induced phase change. In this letter, the Ti/ZnO/Pt structure was found to show memristive switching ascribed to a carrier trapping/detrapping of the trap sites (e.g., oxygen vacancies or zinc interstitials) in ZnO. The carrier trapping/detrapping level can be controllably adjusted by regulating the current compliance level or voltage amplitude. Multi-level conductance states can, therefore, be realized in such memristive device. The spike-timing-dependent plasticity, an important Hebbian learning rule, has been implemented in this type of synaptic device. Compared with filamentary-type memristive devices, purely electronic memristors have potential to reduce their energy consumption and work more stably and reliably, since no structural distortion occurs.

  7. Parental psychiatric hospitalisation and offspring schizophrenia

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Mortensen, Erik L; Reinisch, June M

    2009-01-01

    The risk of schizophrenia has been linked with a family history of schizophrenia and less strongly with other psychiatric disorders in family members. Using data from the Copenhagen Perinatal Cohort and from the Danish Psychiatric Case Register, we studied the relationship between offspring risk...... of schizophrenia and a range of psychotic and non-psychotic psychiatric diagnoses in parents. Psychiatric admission data after 1969 were available for 7047 cohort members born between 1959 and 1961, and for 7006 mothers and 6993 fathers. Univariate analysis showed that neurosis, alcohol and substance dependence...... in both parents were associated with elevated risk of offspring schizophrenia; in addition, maternal schizophrenia, affective disorder and personality disorder were associated with elevated risk. Controlling for parental age, parental social status, and parental psychiatric co-diagnosis, offspring risk...

  8. Vergence eye movements in patients with schizophrenia.

    Science.gov (United States)

    Bolding, Mark S; Lahti, Adrienne C; White, David; Moore, Claire; Gurler, Demet; Gawne, Timothy J; Gamlin, Paul D

    2014-09-01

    Previous studies have shown that smooth pursuit eye movements are impaired in patients with schizophrenia. However, under normal viewing conditions, targets move not only in the frontoparallel plane but also in depth, and tracking them requires both smooth pursuit and vergence eye movements. Although previous studies in humans and non-human primates suggest that these two eye movement subsystems are relatively independent of one another, to our knowledge, there have been no prior studies of vergence tracking behavior in patients with schizophrenia. Therefore, we have investigated these eye movements in patients with schizophrenia and in healthy controls. We found that patients with schizophrenia exhibited substantially lower gains compared to healthy controls during vergence tracking at all tested speeds (e.g. 0.25 Hz vergence tracking mean gain of 0.59 vs. 0.86). Further, consistent with previous reports, patients with schizophrenia exhibited significantly lower gains than healthy controls during smooth pursuit at higher target speeds (e.g. 0.5 Hz smooth pursuit mean gain of 0.64 vs. 0.73). In addition, there was a modest (r≈0.5), but significant, correlation between smooth pursuit and vergence tracking performance in patients with schizophrenia. Our observations clearly demonstrate substantial vergence tracking deficits in patients with schizophrenia. In these patients, deficits for smooth pursuit and vergence tracking are partially correlated suggesting overlap in the central control of smooth pursuit and vergence eye movements. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Personality dimensions in schizophrenia: A family study.

    Science.gov (United States)

    Goghari, Vina M

    2017-05-01

    Studies have demonstrated that personality traits differ in schizophrenia patients and family members compared to controls, suggesting familial risk. This study evaluated personality traits in a family study of schizophrenia, as well as the relationship between personality traits and symptoms and social functioning in schizophrenia patients. Thirty-two schizophrenia patients, 28 adult non-psychotic relatives, and 27 community controls completed the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ). Schizophrenia patients differed on many dimensions of the DAPP-BQ compared to controls and/or relatives: affective lability, anxiousness, callousness, conduct problems, cognitive dysregulation, identity problem, intimacy, insecure attachment, low affiliation, narcissism, oppositionality, restricted expression, self-harm, submissiveness, and suspiciousness. No differences were found between relatives and controls. Furthermore, in schizophrenia patients, associations were found between personality and particularly general symptoms, as well as social functioning. Personality traits can be conceptualized as an extended phenotype in schizophrenia patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  10. Dermatoglyphics in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Fereshteh Shakibaei

    2011-01-01

    Full Text Available Background: There are controversial evidences on the association between fingerprint traits and schizophrenia. We compared fingerprint traits of patients with schizophrenia and normal individuals in Iranian population. Methods: Finger tip dermal ridge of 290 patients with schizophrenia and 290 normal subjects were studied for four dermal traits. Data was analyzed with Pearson correlation and student′s tests. Results: Finger print patterns and secondary creases were not significantly different between the two groups (p > 0.05. Although mean ridge counts of left and right index fingers of the case group were greater than the control group (p < 0.05, these differences were not significant in females. Conclusions: Probably the left index ridge counts and fluctuating asymmetry in schizophrenic patients are different from those of the normal population. This difference may serve as a diagnostic biological marker for screening people susceptible to schizophrenia. Further studies are needed to determine predictive value of fingerprint trait as a biomarker for the schizophrenia.

  11. Imbalanced kynurenine pathway in schizophrenia.

    Science.gov (United States)

    Kegel, Magdalena E; Bhat, Maria; Skogh, Elisabeth; Samuelsson, Martin; Lundberg, Kristina; Dahl, Marja-Liisa; Sellgren, Carl; Schwieler, Lilly; Engberg, Göran; Schuppe-Koistinen, Ina; Erhardt, Sophie

    2014-01-01

    Several studies suggest a role for kynurenic acid (KYNA) in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN). Here we investigate the levels of QUIN in cerebrospinal fluid (CSF) of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22) and those of controls (n = 26) were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36). CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls (P = 0.027). In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.

  12. Imbalanced Kynurenine Pathway in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Magdalena E. Kegel

    2014-01-01

    Full Text Available Several studies suggest a role for kynurenic acid (KYNA in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN. Here we investigate the levels of QUIN in cerebrospinal fluid (CSF of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22 and those of controls (n = 26 were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36. CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls ( P = 0.027. In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.

  13. The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: a randomized, double-blind, placebo-controlled, multicentre study.

    Science.gov (United States)

    Garcia, Esther; Robert, Marta; Peris, Francesc; Nakamura, Hiroshi; Sato, Noriko; Terazawa, Yoshikatsu

    2009-01-01

    Blonanserin is a novel atypical antipsychotic agent with potent dopamine D(2) and serotonin 5-HT(2) antagonist properties. It may potentially have a lower incidence of adverse events than other antipsychotic agents. To determine the efficacy and safety of three doses of blonanserin compared with placebo and haloperidol in patients with acute-phase schizophrenia. This was a 6-week, randomized, double-blind, placebo- and haloperidol-controlled, international, multicentre study. Patients with an acute exacerbation of their schizophrenia, with a Positive and Negative Syndrome Scale (PANSS) score >/=70 and a Clinical Global Impression - Severity of Illness (CGI-S) score >/=4 ('moderately ill') [with no decrease >/=20% or >/=1 point, respectively, during the wash-out period] were randomized into one of five treatment groups (blonanserin 2.5, 5 or 10 mg, haloperidol 10 mg or placebo once daily). Patients were assessed weekly for clinical efficacy, adverse events, extrapyramidal symptoms (EPS) and drug compliance, and were assessed biweekly for other safety variables. All 307 randomized patients received at least one dose of study medication and 228 (74.3%) completed the study. The mean reduction in PANSS total score at week 6 was significantly greater with all active treatments compared with placebo (-12.58; p blonanserin 10 mg was significantly superior to blonanserin 2.5 mg (-30.18 vs -20.6; p blonanserin 5 mg (-27.19) and haloperidol 10 mg (-28.16) were not. All active treatments showed greater efficacy against the positive symptoms of schizophrenia, and blonanserin (5 and 10 mg) was more effective against the negative symptoms than haloperidol. Blonanserin was well tolerated at all doses and there was no evidence of clinically important weight gain, orthostatic hypotension, corrected QT interval prolongation or clinically relevant changes in laboratory test results. Haloperidol caused persistent elevation in prolactin levels, but this was not seen with any dose of

  14. Synaptic Plasticity, Metaplasticity and Depression.

    Science.gov (United States)

    Vose, Linnea R; Stanton, Patric K

    2017-01-01

    The development of a persistent depressive affective state has for some time been thought to result from persistent alterations in neurotransmitter-mediated synaptic transmission. While the identity of those transmitters has changed over the years, the literature has lacked mechanistic connections between the neurophysiological mechanisms they regulate, and how these mechanisms alter neuronal function, and, hence, affective homeostasis. This review will examine recent work that suggests that both long-term activity-dependent changes in synaptic strength ("plasticity"), and shifting set points for the ease of induction of future long-term changes ("metaplasticity"), may be critical to establishing and reversing a depressive behavioral state. Activitydependent long-term synaptic plasticity involves both strengthening and weakening of synaptic connections associated with a dizzying array of neurochemical alterations that include synaptic insertion and removal of a number of subtypes of AMPA, NMDA and metabotropic glutamate receptors, changes in presynaptic glutamate release, and structural changes in dendritic spines. Cellular mechanisms of metaplasticity are far less well understood. Here, we will review the growing evidence that long-term synaptic changes in glutamatergic transmission, in brain regions that regulate mood, are key determinants of affective homeostasis and therapeutic targets with immense potential for drug development.

  15. Methamphetamine enhances the development of schizophrenia in first-degree relatives of patients with schizophrenia.

    Science.gov (United States)

    Li, Huabing; Lu, Qiong; Xiao, Enhua; Li, Qiuyun; He, Zhong; Mei, Xilong

    2014-02-01

    Although there is some evidence that methamphetamine (MA) abuse may play a causative role in the development of schizophrenia, studies directly linking these 2 are rare. In our study, the effect of MA abuse on the development of schizophrenia was investigated in 15 MA abusers who are offspring of patients with schizophrenia and 15 siblings of MA abusers without a history of drug abuse. Cognitive deficits and resting-state brain function were evaluated in all participants. Correlations between cognitive deficits and schizophrenia development were investigated. Significantly more cognitive impairments were observed in MA abusers, compared with their siblings without a history of drug use. Significant abnormalities in regional homogeneity (ReHo) signals were observed in resting brain in MA abusers. Decreased ReHo was found to be distributed over the bilateral cingulate gyrus, right Brodmann area 24, and bilateral anterior cingulate cortex. Seven MA abusers were diagnosed with schizophrenia, while 1 control sibling was diagnosed with schizophrenia during the 5-year follow-up. The cognitive scores correlated with the development of schizophrenia in MA abusers. Our study provides direct evidence for the causative role of MA use in the etiology of schizophrenia and highlights the role of MA-induced brain abnormalities in cognitive deficiency and development of schizophrenia.

  16. DERMATOGLYPHIC PATTERNS IN SCHIZOPHRENIA

    Directory of Open Access Journals (Sweden)

    Uday N

    2016-01-01

    Full Text Available Dermatoglyphic is the scientific study of epidermal ridges and their configuration on the palmar region of hand and the fingers and plantar region of sole and toes. Dermatoglyphic pattern, such as Whorls, Arches, Loops and atd angle have been hypothesized to be indirect measure for early abnormal development process that can lead later psychiatric disorder such as schizophrenia. Under the genetic background of dermatoglyphic patterns and schizophrenia, the study was undertaken to determine the correlation between them. The present study include 63 male and 46 female of schizophrenic patient diagnosed at Institute of Psychiatry and Human Behaviour(IPHB Hospital, Goa were compared with control group accordingly. The patterns seen on hand and fingers were calculated and compared with the frequency of finger print patterns in control group. It was observed that there is increased frequency of arches and decrease frequency of whorls in control males and females which was significant difference, where as in female schizophrenics there is decrease frequency of radial loop compared to male schizophrenics and significant difference observed in atd angle of right and left hand between female control and female schizophrenics.

  17. Management of treatment resistant schizophrenia

    African Journals Online (AJOL)

    Adele

    Abstract. Whilst gains have been made in recent years in the pharmacological treatment of schizophrenia, a number of patients still have residual symptoms and disabilities, or simply do not show response to antipsychotic medications. For such 'treatment resistant' patients, there is little by way of randomised controlled data ...

  18. Abnormal visuomotor processing in schizophrenia

    Directory of Open Access Journals (Sweden)

    Siân E. Robson

    2016-01-01

    Full Text Available Subtle disturbances of visual and motor function are known features of schizophrenia and can greatly impact quality of life; however, few studies investigate these abnormalities using simple visuomotor stimuli. In healthy people, electrophysiological data show that beta band oscillations in sensorimotor cortex decrease during movement execution (event-related beta desynchronisation (ERBD, then increase above baseline for a short time after the movement (post-movement beta rebound (PMBR; whilst in visual cortex, gamma oscillations are increased throughout stimulus presentation. In this study, we used a self-paced visuomotor paradigm and magnetoencephalography (MEG to contrast these responses in patients with schizophrenia and control volunteers. We found significant reductions in the peak-to-peak change in amplitude from ERBD to PMBR in schizophrenia compared with controls. This effect was strongest in patients who made fewer movements, whereas beta was not modulated by movement in controls. There was no significant difference in the amplitude of visual gamma between patients and controls. These data demonstrate that clear abnormalities in basic sensorimotor processing in schizophrenia can be observed using a very simple MEG paradigm.

  19. Differences in omega-3 and omega-6 polyunsaturated fatty acid consumption in people at ultra-high risk of psychosis, first-episode schizophrenia, and in healthy controls.

    Science.gov (United States)

    Pawełczyk, Tomasz; Trafalska, Elżbieta; Pawełczyk, Agnieszka; Kotlicka-Antczak, Magdalena

    2017-12-01

    Supplementation with omega-3 PUFA showed efficacy in reducing the risk of transition into psychosis in UHR individuals. It is uncertain whether dietary patterns can be partly responsible for n-3 deficiencies observed in susceptible participants before the diagnosis of schizophrenia. The study was designed to assess differences in omega-3 and omega-6 PUFA consumption in healthy controls (HC), UHR participants and FES patients as well as to verify the hypothesis that dietary changes in PUFA consumption are present before active psychosis develops, that is, in UHR individuals. Dietary habits during the previous year were assessed in 34 patients at UHR of psychosis, 33 patients diagnosed with FES and 33 HC participants using a validated Food-Frequency Questionnaire and the Polish Food Composition Tables. Significant differences in omega-3 and omega-6 PUFA intake were observed between study groups. UHR and FES groups reported significantly higher consumption of omega-6 PUFA in comparison with HC. FES patients also reported a higher consumption of alpha-linolenic acid (omega-3) in comparison with HC. No significant differences were seen in consumption of long-chain marine PUFA. Differences in omega-6 and omega-3 PUFA consumption exist before development of psychotic symptoms, fulfilling the criteria of schizophrenia. © 2015 Wiley Publishing Asia Pty Ltd.

  20. Who "jumps to conclusions"? A comprehensive assessment of probabilistic reasoning in psychosis following traumatic brain injury (PFTBI), and comparison with TBI, schizophrenia, and nonclinical controls.

    Science.gov (United States)

    Batty, Rachel A; Francis, Andrew; Thomas, Neil; Hopwood, Malcolm; Ponsford, Jennie; Rossell, Susan L

    2016-01-01

    The "jumping to conclusions" (JTC) bias has received significant attention in the schizophrenia and delusion literature as an important aspect of cognition characterising psychosis. The JTC bias has not been explored in psychosis following traumatic brain injury (PFTBI). JTC was investigated in 10 patients with PFTBI using the beads task (ratios 85:15 and 60:40). Probabilistic predictions, draws-to-decision, self-rated decision confidence, and JTC bias were recorded. Responses from 10 patients with traumatic brain injury (TBI), 23 patients with schizophrenia, and 23 nonclinical controls were compared. Relationships were explored between draws-to-decision and current intelligence quotient, affective state, executive function, delusions (severity and type), and illness chronicity (duration). Groups were comparable on JTC measures. Delusion severity and type were not related to draws-to-decision for either trial. In the entire sample, executive function (reduced mental flexibility) was significantly related to more draws-to-decision on the 60:40 ratio trial. We found no evidence for an elevated JTC bias in patients with PFTBI or TBI alone. The influence of executive dysfunction should be considered by future studies using the beads tasks in patient populations. These findings need to be replicated in larger PFTBI and TBI samples.

  1. Language lateralization in schizophrenia

    NARCIS (Netherlands)

    Sommer, I.E.C.

    2004-01-01

    Schizophrenia is a severe chronic psychiatric illness that affects approximately 1-2% of the populations worldwide. Schizophrenia is characterized by episodes of psychosis, in which patients experience hallucinations (false perceptions) and delusions (false beliefs). Apart from the psychotic

  2. The etiology of schizophrenia

    National Research Council Canada - National Science Library

    Gejman, Pablo V; Sanders, Alan R

    2012-01-01

    Research conducted in recent years represents a new dawn of knowledge for the risk factors of schizophrenia, and genome-wide approaches have revolutionized the field of genetic mapping of schizophrenia...

  3. Schizophrenia - Multiple Languages

    Science.gov (United States)

    ... MP3 Schizophrenia (An Introduction) - English MP4 Schizophrenia (An Introduction) - español (Spanish) MP4 Healthy Roads Media Characters not displaying correctly on this page? See language display issues . Return to the MedlinePlus Health Information ...

  4. Animal Assisted Therapy (AAT) Program As a Useful Adjunct to Conventional Psychosocial Rehabilitation for Patients with Schizophrenia: Results of a Small-scale Randomized Controlled Trial.

    Science.gov (United States)

    Calvo, Paula; Fortuny, Joan R; Guzmán, Sergio; Macías, Cristina; Bowen, Jonathan; García, María L; Orejas, Olivia; Molins, Ferran; Tvarijonaviciute, Asta; Cerón, José J; Bulbena, Antoni; Fatjó, Jaume

    2016-01-01

    Currently, one of the main objectives of human-animal interaction research is to demonstrate the benefits of animal assisted therapy (AAT) for specific profiles of patients or participants. The aim of this study is to assess the effect of an AAT program as an adjunct to a conventional 6-month psychosocial rehabilitation program for people with schizophrenia. Our hypothesis is that the inclusion of AAT into psychosocial rehabilitation would contribute positively to the impact of the overall program on symptomology and quality of life, and that AAT would be a positive experience for patients. To test these hypotheses, we compared pre-program with post-program scores for the Positive and Negative Syndrome Scale (PANSS) and the EuroQoL-5 dimensions questionnaire (EuroQol-5D), pre-session with post-session salivary cortisol and alpha-amylase for the last four AAT sessions, and adherence rates between different elements of the program. We conducted a randomized, controlled study in a psychiatric care center in Spain. Twenty-two institutionalized patients with chronic schizophrenia completed the 6-month rehabilitation program, which included individual psychotherapy, group therapy, a functional program (intended to improve daily functioning), a community program (intended to facilitate community reintegration) and a family program. Each member of the control group (n = 8) participated in one activity from a range of therapeutic activities that were part of the functional program. In place of this functional program activity, the AAT-treatment group (n = 14) participated in twice-weekly 1-h sessions of AAT. All participants received the same weekly total number of hours of rehabilitation. At the end of the program, both groups (control and AAT-treatment) showed significant improvements in positive and overall symptomatology, as measured with PANSS, but only the AAT-treatment group showed a significant improvement in negative symptomatology. Adherence to the AAT

  5. Animal assisted therapy (AAT program as a useful adjunct to conventional psychosocial rehabilitation for patients with schizophrenia: results of a small-scale randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Paula eCalvo

    2016-05-01

    Full Text Available Currently, one of the main objectives of human-animal interaction research is to demonstrate the benefits of animal-assisted therapy (AAT for specific profiles of patients or participants.The aim of this study is to assess the effect of an AAT program as an adjunct to a conventional 6-month psychosocial rehabilitation program for people with schizophrenia. Our hypothesis is that the inclusion of AAT into psychosocial rehabilitation would contribute positively to the impact of the overall program on symptomology and quality of life, and that AAT would be a positive experience for patients. To test these hypotheses, we compared pre-program with post-program scores for the Positive and Negative Syndrome Scale (PANSS and the EuroQoL-5 dimensions questionnaire (EuroQol-5D, pre-session with post-session salivary cortisol and alpha-amylase for the last four AAT sessions, and adherence rates between different elements of the program.We conducted a randomized, controlled study in a psychiatric care center in Spain. Twenty-two institutionalized patients with chronic schizophrenia completed the 6-month rehabilitation program, which included individual psychotherapy, group therapy, a functional program (intended to improve daily functioning, a community program (intended to facilitate community reintegration and a family program. Each member of the control group (n=8 participated in one activity from a range of therapeutic activities that were part of the functional program. In place of this functional program activity, the AAT-treatment group (n=14 participated in twice-weekly 1-hour sessions of AAT. All participants received the same weekly total number of hours of rehabilitation. At the end of the program, both groups (control and AAT-treatment showed significant improvements in positive and overall symptomatology, as measured with PANSS, but only the AAT-treatment group showed a significant improvement in negative symptomatology. Adherence to the AAT

  6. Dysregulated Expression of Neuregulin-1 by Cortical Pyramidal Neurons Disrupts Synaptic Plasticity

    Directory of Open Access Journals (Sweden)

    Amit Agarwal

    2014-08-01

    Full Text Available Neuregulin-1 (NRG1 gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions. Loss of NRG1 from cortical projection neurons resulted in increased inhibitory neurotransmission, reduced synaptic plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain (CRD-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered steady-state levels of synaptic plasticity-related proteins, and impaired sensorimotor gating. We conclude that an “optimal” level of NRG1 signaling balances excitatory and inhibitory neurotransmission in the cortex. Our data provide a potential pathomechanism for impaired synaptic plasticity and suggest that human NRG1 risk haplotypes exert a gain-of-function effect.

  7. Special Report: Schizophrenia.

    Science.gov (United States)

    Mosher, Loren R.; Feinsilver, David

    The review and analysis of the current status of knowledge about schizophrenia and its treatment begins with a brief review of some statistics on mental health, the National Institute of Mental Health's grants program in schizophrenia, an NIMH-sponsored international conference on Schizophrenia - the Implications of Research Findings for Treatment…

  8. Overview of Childhood Schizophrenia.

    Science.gov (United States)

    Bryan, Betsy

    Childhood schizophrenia is a rare but serious disorder with complex symptoms that affect children and their families. Childhood schizophrenia was once the term applied for all childhood psychoses, including autism and mood disorders, but more recently researchers have distinguished childhood schizophrenia from other disorders. There are differing…

  9. Dreaming and Schizophrenia.

    Science.gov (United States)

    Stickney, Jeffrey L.

    Parallels between dream states and schizophrenia suggest that the study of dreams may offer some information about schizophrenia. A major theoretical assumption of the research on dreaming and schizophrenia is that, in schizophrenics, the dream state intrudes on the awake state creating a dreamlike symptomatology. This theory, called the REM…

  10. Changes in verbal learning and memory in schizophrenia and non-psychotic controls in midlife: A nine-year follow-up in the Northern Finland Birth Cohort study 1966.

    Science.gov (United States)

    Rannikko, Irina; Haapea, Marianne; Miettunen, Jouko; Veijola, Juha; Murray, Graham K; Barnett, Jennifer H; Husa, Anja P; Jones, Peter B; Isohanni, Matti; Jääskeläinen, Erika

    2015-08-30

    Findings on longitudinal change of cognitive performance in schizophrenia are extremely variable in the case of verbal learning and memory, and it is still unclear which dimensions of verbal learning and memory exhibit possible deterioration over the long-term. Our aim was to compare the change in verbal learning and memory in individuals with schizophrenia 10-20 years after the illness onset and healthy controls during a nine-year follow-up in a general population sample. Our sample included 41 schizophrenia spectrum subjects and 73 controls from the Northern Finland Birth Cohort study 1966. The California Verbal Learning Test (CVLT) was used to estimate the degree of change in verbal learning and memory during a nine-year follow-up from age 34-years to 43- years. Both cases and controls deteriorated. There was statistically significant decline in two out of 20 CVLT items among cases and in 13 out of 20 CVLT items among controls. With the exception of two variables, the decline in verbal learning and memory over nine years was not significantly larger in cases. We conclude that during midlife verbal learning and memory in schizophrenia mostly declines in a normative fashion with aging at the same rate as the general population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Benzodiazepines for schizophrenia.

    Science.gov (United States)

    Dold, Markus; Li, Chunbo; Tardy, Magdolna; Khorsand, Vesal; Gillies, Donna; Leucht, Stefan

    2012-11-14

    Because of the high number of people with schizophrenia not responding adequately to monotherapy with antipsychotic agents, the evidence regarding the efficacy and safety of additional medication was examined in a number of clinical trials. One approach to this research question was the use of benzodiazepines, as monotherapy as well as in combination with antipsychotics. To determine the efficacy, acceptability, and tolerability of benzodiazepines in people with schizophrenia and schizophrenia-like psychoses. In February 2011, we updated the literature search of the previous version of this systematic review (last search March 2005). We searched the trial register of the Cochrane Schizophrenia Group (containing methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings). Additionally, we inspected references of all identified studies for further relevant studies and contacted authors of relevant publications in order to obtain missing data from existing trials. We applied no language restrictions. We included all randomised controlled trials comparing benzodiazepines (as monotherapy or as adjunctive agent) with antipsychotic drugs or placebo for the pharmacological management of schizophrenia and/or schizophrenia-like psychoses. Review authors (MD and CL) analysed independently the new references of the update-search referring to the inclusion criteria. MD and CL extracted all data from the included trials. For dichotomous outcomes we calculated risk ratios (RR) and their 95% confidence intervals (CI). We analysed continuous data by using mean differences (MD) and their 95% CI. We assessed each pre-selected outcome from the included trials with the risk of bias tool. The 2011 update search yielded three further randomised controlled trials. The review currently includes 34 studies with 2657 participants. Most

  12. Synaptic determinants of Rett syndrome

    Directory of Open Access Journals (Sweden)

    Elena M B Boggio

    2010-08-01

    Full Text Available There is mounting evidence showing that the structural and molecular organization of synaptic connections are affected both in human patients and in animal models of neurological and psychiatric diseases. As a consequence of these experimental observations, it has been introduced the concept of synapsopathies, a notion describing brain disorders of synaptic function and plasticity. A close correlation between neurological diseases and synaptic abnormalities is especially relevant for those syndromes including also mental retardation in their symptomatology, such as Rett Syndrome (RS. RS (MIM312750 is an X-linked dominant neurological disorder that is caused, in the majority of cases by mutations in methyl-CpG-binding protein 2 (MeCP2. This review will focus on the current knowledge of the synaptic alterations produced by mutations of the gene MeCP2 in mouse models of RS and will highlight prospects experimental therapies currently in use. Different experimental approaches have revealed that RS could be the consequence of an impairment in the homeostasis of synaptic transmission in specific brain regions. Indeed, several forms of experience-induced neuronal plasticity are impaired in the absence of MeCP2. Based on the results presented in this review, it is reasonable to propose that understanding how the brain is affected by diseases such as RS is at reach. This effort will bring us closer to identify the neurobiological bases of human cognition.

  13. Social cognition in patients with schizophrenia, their unaffected first degree relatives and healthy controls. Comparison between groups and analysis of associated clinical and sociodemographic variables.

    Science.gov (United States)

    Rodríguez Sosa, Juana Teresa; Gil Santiago, Hiurma; Trujillo Cubas, Angel; Winter Navarro, Marta; León Pérez, Petra; Guerra Cazorla, Luz Marina; Martín Jiménez, José María

    2013-01-01

    To evaluate and compare the social cognition in patients with schizophrenia, healthy first-degree relatives and controls, by studying the relationship between social cognition and nonsocial cognition, psychopathology, and other clinical and sociodemographic variables. The total sample was comprised of patients diagnosed with paranoid schizophrenia (N = 29), healthy first-degree relatives (N = 21) and controls (N = 28). All groups were assessed with an ad hoc questionnaire and a Social Cognition Scale, which assessed the domains: emotional processing, social perception and attributional style in a Spanish population. The patient group was also assessed with the Scale for the Positive and Negative Syndrome Scale and the Mini-mental state examination. Statistical analyses were performed with SPSS version 15.0. Patients scored significantly worse in all domains of social cognition assessed, compared with controls, and mastery attributional style, compared with relatives. The type of psychopathology correlated negatively and statistically significantly with different domains of social cognition: negative symptoms with emotional processing and attributional style, and positive symptoms with social perception. Basic cognition scores correlated positively and statistically significantly with the domains social perception and attributional style. Social cognition has become an interesting object of study, especially in how it relates to non-social cognition, psychopathology and global functioning of patients, bringing new elements to be considered in the early detection, comprehensive treatment and psychosocial rehabilitation of patients. Its conceptualization as trait variable, the consideration of the existence of a continuum between patients and relatives are plausible hypotheses that require further research. Copyright © 2012 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

  14. Delayed early proprioceptive information processing in schizophrenia

    DEFF Research Database (Denmark)

    Arnfred, Sidse M; Hemmingsen, RP; Parnas, Josef

    2006-01-01

    It was first suggested that disordered proprioception was a core feature of schizophrenia by Sandor Rado in 1953. Using a recently designed proprioceptive event-related potential paradigm based on a change of load, we studied 12 unmedicated male out-patients with schizophrenia and 24 controls....... In the patients, the early contralateral parietal activity was delayed and later central activity had increased amplitude, but gating was unaffected. The results could be understood within the "deficiency of corollary discharge" model of schizophrenia but not within the "filtering" theory. Further studies...

  15. A Multilevel Functional Study of aSNAP25At-Risk Variant for Bipolar Disorder and Schizophrenia.

    Science.gov (United States)

    Houenou, Josselin; Boisgontier, Jennifer; Henrion, Annabelle; d'Albis, Marc-Antoine; Dumaine, Anne; Linke, Julia; Wessa, Michèle; Daban, Claire; Hamdani, Nora; Delavest, Marine; Llorca, Pierre-Michel; Lançon, Christophe; Schürhoff, Franck; Szöke, Andrei; Le Corvoisier, Philippe; Barau, Caroline; Poupon, Cyril; Etain, Bruno; Leboyer, Marion; Jamain, Stéphane

    2017-10-25

    The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant in SNAP25 , rs6039769 , that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combined in vitro and in vivo approaches in humans to understand the functional impact of the at-risk allele. Thus, we showed in vitro that the rs6039769 C allele was sufficient to increase the SNAP25 transcription level. In a postmortem expression analysis of 33 individuals affected with schizophrenia and 30 unaffected control subjects, we showed that the SNAP25b / SNAP25a ratio was increased in schizophrenic patients carrying the rs6039769 at-risk allele. Last, using genetics imaging in a cohort of 71 subjects, we showed that male risk carriers had an increased amygdala-ventromedial prefrontal cortex functional connectivity and a larger amygdala than non-risk carriers. The latter association has been replicated in an independent cohort of 121 independent subjects. Altogether, results from these multilevel functional studies are bringing strong evidence for the functional consequences of this allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal-limbic network, which therefore may increase the vulnerability to both early-onset bipolar disorder and schizophrenia. SIGNIFICANCE STATEMENT Functional characterization of disease-associated variants is a key challenge in understanding neuropsychiatric disorders and will open an avenue in the development of personalized treatments. Recent studies have accumulated evidence that the SNARE complex, and more specifically

  16. An interactive sports video game as an intervention for rehabilitation of community-living patients with schizophrenia: A controlled, single-blind, crossover study

    OpenAIRE

    Shimizu, Nobuko; UMEMURA, Tomohiro; Matsunaga, Masahiro; Hirai, Takayoshi

    2017-01-01

    Hypofrontality is a state of decreased cerebral blood flow in the prefrontal cortex during executive function performance; it is commonly observed in patients with schizophrenia. Cognitive dysfunction, as well as the psychological symptoms of schizophrenia, influences the ability of patients to reintegrate into society. The current study investigated the effects of an interactive sports video game (IVG; Nintendo Wii™ Sports Resort) on frontal lobe function of patients with schizophrenia. A sa...

  17. EXECUTIVE FUNCTIONING IN SCHIZOPHRENIA

    Directory of Open Access Journals (Sweden)

    Gricel eOrellana

    2013-06-01

    Full Text Available The executive function (EF is a set of abilities, which allows us to invoke voluntary control of our behavioral responses. These functions enable human beings to develop and carry out plans, make up analogies, obey social rules, solve problems, adapt to unexpected circumstances, do many tasks simultaneously and locate episodes in time and place. EF includes divided attention and sustained attention, working memory, set-shifting, flexibility, planning and the regulation of goal directed behavior and can be defined as a brain function underlying the human faculty to act or think not only in reaction to external events but also in relation with internal goals and states. EF is mostly associated with dorsolateral prefrontal cortex (PFC. Besides EF, PFC is involved in self-regulation of behavior, i.e. the ability to regulate behavior according to internal goals and constraints, particularly in less structured situations. Self-regulation of behavior is subtended by ventral medial /orbital PFC. Impairment of EF is one of the most commonly observed deficits in schizophrenia through the various disease stages. Impairment in tasks measuring conceptualization, planning, cognitive flexibility, verbal fluency, ability to solve complex problems and working memory occur in schizophrenia. Disorders detected by executive tests are consistent with evidence from functional neuroimaging, which have shown PFC dysfunction in patients while performing these kinds of tasks. Schizophrenics also exhibit deficit in odor identifying, decision-making and self-regulation of behavior suggesting dysfunction of the orbital PFC. However, impairment in executive tests is explained by dysfunction of prefronto-striato-thalamic, prefronto-parietal and prefronto-temporal neural networks mainly. Disorders in executive functions may be considered central facts with respect to schizophrenia and it has been suggested that negative symptoms may be explained by that executive dysfunction.

  18. A synaptic trek to autism.

    Science.gov (United States)

    Bourgeron, Thomas

    2009-04-01

    Autism spectrum disorders (ASD) are diagnosed on the basis of three behavioral features namely deficits in social communication, absence or delay in language, and stereotypy. The susceptibility genes to ASD remain largely unknown, but two major pathways are emerging. Mutations in TSC1/TSC2, NF1, or PTEN activate the mTOR/PI3K pathway and lead to syndromic ASD with tuberous sclerosis, neurofibromatosis, or macrocephaly. Mutations in NLGN3/4, SHANK3, or NRXN1 alter synaptic function and lead to mental retardation, typical autism, or Asperger syndrome. The mTOR/PI3K pathway is associated with abnormal cellular/synaptic growth rate, whereas the NRXN-NLGN-SHANK pathway is associated with synaptogenesis and imbalance between excitatory and inhibitory currents. Taken together, these data strongly suggest that abnormal synaptic homeostasis represent a risk factor to ASD.

  19. Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

    Directory of Open Access Journals (Sweden)

    Christoph Straub

    2016-07-01

    Full Text Available Synaptic communication between neurons requires the precise localization of neurotransmitter receptors to the correct synapse type. Kainate-type glutamate receptors restrict synaptic localization that is determined by the afferent presynaptic connection. The mechanisms that govern this input-specific synaptic localization remain unclear. Here, we examine how subunit composition and specific subunit domains contribute to synaptic localization of kainate receptors. The cytoplasmic domain of the GluK2 low-affinity subunit stabilizes kainate receptors at synapses. In contrast, the extracellular domain of the GluK4/5 high-affinity subunit synergistically controls the synaptic specificity of kainate receptors through interaction with C1q-like proteins. Thus, the input-specific synaptic localization of the native kainate receptor complex involves two mechanisms that underlie specificity and stabilization of the receptor at synapses.

  20. Alignment and theory of mind in schizophrenia.

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    Stewart, Suzanne L K; Corcoran, Rhiannon; Drake, Richard J

    2008-09-01

    We predicted that participants with schizophrenia would be able to successfully "align" during conversation in the context of impaired theory of mind. Alignment is a process by which interlocutors' representations of the conversational situation converge; and it may, in part, explain how people with schizophrenia can often participate successfully in dialogue despite experiencing impaired mentalising. Fifty-nine people with schizophrenia and 38 healthy adults completed a standardised, empirical conversational alignment task with a mentalising component and a measure of current IQ. The patients also completed two independent theory of mind tests. We used ANCOVAs to compare the groups' performances. The participants with schizophrenia and the healthy participants demonstrated equivalent alignment skills even though the schizophrenia participants displayed clear theory of mind difficulties. Symptom subtype analyses found no differences between subtype groups in alignment, but healthy controls and remitted patients performed significantly better on the mentalising component than the paranoia group. These results are consistent with the schizophrenia participants having intact alignment skills alongside mentalising impairments. We propose that this explains why people with schizophrenia can often participate successfully in conversation but have difficulties with more complex dialogues, with resolving misunderstandings, and with untangling ambiguities during conversation.

  1. Synaptic Effects of Electric Fields

    Science.gov (United States)

    Rahman, Asif

    Learning and sensory processing in the brain relies on the effective transmission of information across synapses. The strength and efficacy of synaptic transmission is modifiable through training and can be modulated with noninvasive electrical brain stimulation. Transcranial electrical stimulation (TES), specifically, induces weak intensity and spatially diffuse electric fields in the brain. Despite being weak, electric fields modulate spiking probability and the efficacy of synaptic transmission. These effects critically depend on the direction of the electric field relative to the orientation of the neuron and on the level of endogenous synaptic activity. TES has been used to modulate a wide range of neuropsychiatric indications, for various rehabilitation applications, and cognitive performance in diverse tasks. How can a weak and diffuse electric field, which simultaneously polarizes neurons across the brain, have precise changes in brain function? Designing therapies to maximize desired outcomes and minimize undesired effects presents a challenging problem. A series of experiments and computational models are used to define the anatomical and functional factors leading to specificity of TES. Anatomical specificity derives from guiding current to targeted brain structures and taking advantage of the direction-sensitivity of neurons with respect to the electric field. Functional specificity originates from preferential modulation of neuronal networks that are already active. Diffuse electric fields may recruit connected brain networks involved in a training task and promote plasticity along active synaptic pathways. In vitro, electric fields boost endogenous synaptic plasticity and raise the ceiling for synaptic learning with repeated stimulation sessions. Synapses undergoing strong plasticity are preferentially modulated over weak synapses. Therefore, active circuits that are involved in a task could be more susceptible to stimulation than inactive circuits

  2. Weaving a Net of Neurobiological Mechanisms in Schizophrenia and Unraveling the Underlying Pathophysiology.

    Science.gov (United States)

    Bitanihirwe, Byron K Y; Mauney, Sarah A; Woo, Tsung-Ung W

    2016-10-15

    Perineuronal nets (PNNs) are enigmatic structures composed of extracellular matrix molecules that encapsulate the soma, dendrites, and axon segments of neurons in a lattice-like fashion. Although most PNNs condense around parvalbumin-expressing gamma-aminobutyric acidergic interneurons, some glutamatergic pyramidal cells in the brain are also surrounded by PNNs. Experimental findings suggest pivotal roles of PNNs in the regulation of synaptic formation and function. Also, an increasing body of evidence links PNN abnormalities to schizophrenia. The number of PNNs progressively increases during postnatal development until plateauing around the period of late adolescence and early adulthood, which temporally coincides with the age of onset of schizophrenia. Given the established role of PNNs in modulating developmental plasticity, the PNN represents a possible candidate for altering the onset and progression of schizophrenia. Similarly, the reported function of PNNs in regulating the trafficking of glutamate receptors places them in a critical position to modulate synaptic pathology, considered a cardinal feature of schizophrenia. We discuss the physiologic role of PNNs in neural function, synaptic assembly, and plasticity as well as how they interface with circuit/system mechanisms of cognition. An integrated understanding of these neurobiological processes should provide a better basis to elucidate how PNN abnormalities influence brain function and contribute to the pathogenesis of neurodevelopmental disorders such as schizophrenia. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Effects of exercise training with traditional dancing on functional capacity and quality of life in patients with schizophrenia: a randomized controlled study.

    Science.gov (United States)

    Kaltsatou, A; Kouidi, E; Fountoulakis, K; Sipka, C; Theochari, V; Kandylis, D; Deligiannis, A

    2015-09-01

    To examine the effects of an eight-month exercise training programme with Greek traditional dancing on functional capacity and quality of life in patients with schizophrenia. Randomized controlled trial. Sports Medicine Laboratory. A total of 31 patients, aged 59.9 ± 14.1 years. They were randomly assigned either to a Greek traditional dancing programme (Group A) or to a sedentary control group (Group B). A functional capacity assessment was performed at baseline and the end of the study. Global Assessment of Functioning Scale and Positive and Negative Syndrome Scale were also used. Quality of life was examined using the Quality of Life and Satisfaction questionnaire. After the eight months, Group A increased walking distance in the 6-minute walk test (328.4 ± 35.9 vs. 238.0 ± 47.6 m), sit-to-stand test (19.1 ± 1.8 vs. 25.1 ± 1.4 seconds), Berg Balance Scale score (53.1 ± 2.1 vs. 43.2 ± 6.7), lower limbs maximal isometric force (77.7 ± 25.7 vs. 51.0 ± 29.8 lb), Positive and Negative Syndrome Scale total score (77.0 ± 23.1 vs. 82.0 ± 24.4), Global Assessment of Functioning Scale total score (51.3 ± 15.5 vs. 47.7 ± 13.3) and Quality of Life total score (34.9 ± 5.2 vs. 28 ± 4.5), compared with Group B. Our results demonstrate that Greek traditional dances improve functional capacity and quality of life in patients with schizophrenia. © The Author(s) 2014.

  4. Token economy for schizophrenia.

    Science.gov (United States)

    McMonagle, T; Sultana, A

    2000-01-01

    A token economy is a behavioural therapy technique in which the desired change is achieved by means of tokens administered for the performance of predefined behaviours according to a program. Though token economy programmes were widespread in the 1970s they became largely restricted to wards where long-stay patients from institutions are prepared for transfer into the community and were particularly aimed at changing negative symptoms of schizophrenia - poor motivation, poor attention and social withdrawal. To review the effects of token economies for people with schizophrenia, or other serious or chronic mental illnesses, compared with standard care. Electronic searches of Biological Abstracts (1985-1999), CINAHL (1982-1998), The Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register of Trials (February 1999), EMBASE (1980-1999) and PsycLIT (1987-1998) were supplemented with reference searches, personal contact with trial authors and hand searches. Randomised studies comparing a token economy regime (one in which change is achieved by means of use of non-monetary, non-consumable tokens) to standard care for those with schizophrenia or any other similar chronic or serious mental illness. Studies were reliably selected, quality rated and data extracted. For dichotomous data relative risk (RR) with 95% confidence intervals (CI) was estimated. Where possible, the number needed to treat statistic (NNT) was also calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality. Only three randomised controlled trials could be included in the analyses (total n=110). There were no usable data on target or non-target behaviour. One small study favoured the token economy approach for the outcome 'change in mental state' on the SANS-CV with improvement in negative symptoms at three months (n=40

  5. The genetic validation of heterogeneity in schizophrenia

    Directory of Open Access Journals (Sweden)

    Moritani Makiko

    2011-10-01

    Full Text Available Abstract Introduction Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To overcome this state of uncertainty, the SZGene database has been established by including all published case-control genetic association studies appearing in peer-reviewed journals. In the current study, we aimed to determine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our case-control samples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of seven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative diagnostic manual, the DSM-IV. Methods Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven top-ranked variants (p Results No statistically significant deviation between cases and controls was observed in the genetic risk-index derived from all seven variants on the top-ranked polymorphisms. In fact, the average risk-index score in the schizophrenia group (6.5+/-1.57 was slightly lower than among controls (6.6+/-1.39. Conclusion The current work illustrates the difficulty in identifying universal and definitive risk-conferring polymorphisms for schizophrenia. Our employed number of samples was small, so we can not preclude the possibility that some or all of these variants are minor risk factors for schizophrenia in the Japanese population. It is also important to aggregate the updated positive variants in the SZGene database when the replication work is conducted.

  6. Personality traits in established schizophrenia: aspects of usability and differences between patients and controls using the Swedish universities Scales of Personality.

    Science.gov (United States)

    Fagerberg, Tomas; Söderman, Erik; Gustavsson, J Petter; Agartz, Ingrid; Jönsson, Erik G

    2016-08-01

    Personality is considered as an important aspect that can affect symptoms and social function in persons with schizophrenia. The personality questionnaire Swedish universities Scales of Personality (SSP) has not previously been used in psychotic disorder. To investigate if SSP has a similar internal consistency and factor structure in a psychosis population as among healthy controls and if patients with psychotic disorders differ from non-psychotic individuals in their responses to the SSP. Patients with psychotic disorders (n = 107) and healthy controls (n = 119) completed SSP. SSP scores were analyzed for internal consistency and case-control differences by Cronbach's alfa and multiple analysis of covariance, respectively. Internal consistencies among patients were overall similar to that of controls. The patients scored significantly higher in seven (Somatic trait anxiety, Psychic trait anxiety, Stress susceptibility, Lack of assertiveness, Detachment, Embitterment, Mistrust) and lower in three (Physical trait aggression, Verbal trait aggression, Adventure seeking) of the 13 scales of the inventory. In three scales (Impulsiveness, Social desirability and Trait irritability) there was no significant difference between the scoring of patients and healthy controls. The reliability estimates suggest that SSP can be used by patients with psychotic disorders in stable remission. Patients score higher on neuroticism-related scales and lower on aggression-related scales than controls, which is in accordance with earlier studies where other personality inventories were used.

  7. Longitudinal Changes in Total Brain Volume in Schizophrenia: Relation to Symptom Severity, Cognition and Antipsychotic Medication

    NARCIS (Netherlands)

    Veijola, J.; Guo, J.Y.; Moilanen, J.S.; Jaaskelainen, E.; Miettunen, J.; Kyllonen, M.; Haapea, M.; Huhtaniska, S.; Alaraisanen, A.; Maki, P.; Kiviniemi, V.; Nikkinen, J.; Starck, T.; Remes, J.J.; Tanskanen, P.; Tervonen, O.; Wink, A.M.; Kehagia, A.; Suckling, J.; Kobayashi, H.; Barnett, J.H.; Barnes, A.; Koponen, H.J.; Jones, P.B.; Isohanni, M.; Murray, G.K.

    2014-01-01

    Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population

  8. Effects of a brief intervention for substance use on tobacco smoking and family relationship functioning in schizophrenia and related psychoses: a randomised controlled trial.

    Science.gov (United States)

    Tantirangsee, Nopporn; Assanangkornchai, Sawitri; Marsden, John

    2015-04-01

    Surveys indicate that substance use is prevalent in populations with schizophrenia. Family members may be able to support brief interventions (BI). We conducted a randomised controlled trial with 6-month follow-up among adult patients with schizophrenia and related psychoses who were referred to two hospitals in southern Thailand. Patients with psychosis were screened using the Alcohol Smoking and Substance Involvement Screening Test (ASSIST). 169 participants (all at moderate substance risk on the ASSIST) were randomised to receive simple advice (the clinics' treatment-as-usual, TAU condition), or single-session brief intervention (BI), or a single-session BI with family support (BI-FS). Given observed substance use, the primary outcome was the ASSIST tobacco smoking involvement score (SIS). Secondary outcomes were cigarettes smoked per day, change motivation (Taking Steps from the Stages of Change and Treatment Eagerness Scale), and DSM-IV Axis V Global Assessment of Relational Functioning (GARF). At follow-up, BI-FS participants reported a lower SIS (mean difference, -2.82, 95% confidence interval [CI] -4.84 to -0.81; Glass' effect size [Δ] = 0.57, 95% CI 0.19 to 0.95), smoked fewer cigarettes per day (mean difference -3.10, 95% CI -5.45 to -0.74; Δ = 0.56, 95% CI 0.18 to 0.94), had greater change motivation (mean difference 3.05, 95% CI 0.54 to 5.57; Δ = 0.41, 95% CI 0.03 to 0.79) and GARF (mean difference 6.75, 95% CI 1.57 to 11.93; Δ = 0.54, 95% CI 0.16 to 0.92). The BI-FS group also had better relational functioning in comparison to those receiving BI only (mean difference 5.44, 95% CI 0.20 to 10.67; Δ = 0.46, 95% CI 0.08 to 0.84). In schizophrenia and related psychoses, a brief intervention supported by a family member reduces smoking involvement, cigarette smoking intensity, and increases change motivation and relational functioning. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Ocular convergence deficits in schizophrenia

    Directory of Open Access Journals (Sweden)

    Mark S Bolding

    2012-10-01

    Full Text Available Individuals with schizophrenia have been reported to exhibit a higher prevalence of convergence insufficiency (CI than the normal adult population. The purpose of this study was to determine if individuals with schizophrenia exhibit clinical signs of CI and to determine if the Convergence Insufficiency Symptom Survey (CISS is an effective instrument for identifying CI in this population.Twenty participants with schizophrenia (SZ and 20 healthy controls (HC completed the study. The prevalence of CI (15% in the SZ group was slightly higher than reported norms, but the difference was not significant. The SZ group had significantly higher scores on the CISS than the HC group, but the CISS scores did not correlate with clinical measures of CI in individuals with SZ. The only exception was that SZ patients had a significantly reduced fusional reserve as determined by Sheard’s criteria. Further study is needed to determine why individuals with schizophrenia reported symptoms associated with CI even though clinical measures did not support this diagnosis.

  10. Reading Impairments in Schizophrenia Relate to Individual Differences in Phonological Processing and Oculomotor Control: Evidence from a Gaze-Contingent Moving Window Paradigm

    Science.gov (United States)

    Whitford, Veronica; O'Driscoll, Gillian A.; Pack, Christopher C.; Joober, Ridha; Malla, Ashok; Titone, Debra

    2013-01-01

    Language and oculomotor disturbances are 2 of the best replicated findings in schizophrenia. However, few studies have examined skilled reading in schizophrenia (e.g., Arnott, Sali, Copland, 2011; Hayes & O'Grady, 2003; Revheim et al., 2006; E. O. Roberts et al., 2012), and none have examined the contribution of cognitive and motor processes that…

  11. High educational performance is a distinctive feature of bipolar disorder : A study on cognition in bipolar disorder, schizophrenia patients, relatives and controls

    NARCIS (Netherlands)

    Vreeker, A.; Boks, M. P M; Abramovic, L.; Verkooijen, S.; Van Bergen, A. H.; Hillegers, M. H J; Spijker, A. T.; Hoencamp, E.; Regeer, E. J.; Riemersma-Van Der Lek, R. F.; Stevens, A. W M M; Schulte, P. F J; Vonk, R.; Hoekstra, R.; Van Beveren, N. J M; Kupka, R. W.; Brouwer, R. M.; Bearden, C. E.; MacCabe, J. H.; Ophoff, R. A.

    2016-01-01

    Background Schizophrenia is associated with lower intelligence and poor educational performance relative to the general population. This is, to a lesser degree, also found in first-degree relatives of schizophrenia patients. It is unclear whether bipolar disorder I (BD-I) patients and their

  12. High educational performance is a distinctive feature of bipolar disorder : a study on cognition in bipolar disorder, schizophrenia patients, relatives and controls

    NARCIS (Netherlands)

    Vreeker, A.; Boks, M. P. M.; Abramovic, L.; Verkooijen, S.; van Bergen, A. H.; Hillegers, M. H. J.; Spijker, A. T.; Hoencamp, E.; Regeer, E. J.; Riemersma-Van der Lek, R. F.; Stevens, A. W. M. M.; Schulte, P. F. J.; Vonk, R.; Hoekstra, R.; van Beveren, N. J. M.; Kupka, R. W.; Brouwer, R. M.; Bearden, C. E.; MacCabe, J. H.; Ophoff, R. A.

    Background. Schizophrenia is associated with lower intelligence and poor educational performance relative to the general population. This is, to a lesser degree, also found in first-degree relatives of schizophrenia patients. It is unclear whether bipolar disorder I (BD-I) patients and their

  13. Attribution bias and social anxiety in schizophrenia

    Directory of Open Access Journals (Sweden)

    Amelie M. Achim

    2016-06-01

    Full Text Available Studies on attribution biases in schizophrenia have produced mixed results, whereas such biases have been more consistently reported in people with anxiety disorders. Anxiety comorbidities are frequent in schizophrenia, in particular social anxiety disorder, which could influence their patterns of attribution biases. The objective of the present study was thus to determine if individuals with schizophrenia and a comorbid social anxiety disorder (SZ+ show distinct attribution biases as compared with individuals with schizophrenia without social anxiety (SZ− and healthy controls. Attribution biases were assessed with the Internal, Personal, and Situational Attributions Questionnaire in 41 individual with schizophrenia and 41 healthy controls. Results revealed the lack of the normal externalizing bias in SZ+, whereas SZ− did not significantly differ from healthy controls on this dimension. The personalizing bias was not influenced by social anxiety but was in contrast linked with delusions, with a greater personalizing bias in individuals with current delusions. Future studies on attribution biases in schizophrenia should carefully document symptom presentation, including social anxiety.

  14. A high-throughput model for investigating neuronal function and synaptic transmission in cultured neuronal networks.

    Science.gov (United States)

    Virdee, Jasmeet K; Saro, Gabriella; Fouillet, Antoine; Findlay, Jeremy; Ferreira, Filipa; Eversden, Sarah; O'Neill, Michael J; Wolak, Joanna; Ursu, Daniel

    2017-11-03

    Loss of synapses or alteration of synaptic activity is associated with cognitive impairment observed in a number of psychiatric and neurological disorders, such as schizophrenia and Alzheimer's disease. Therefore successful development of in vitro methods that can investigate synaptic function in a high-throughput format could be highly impactful for neuroscience drug discovery. We present here the development, characterisation and validation of a novel high-throughput in vitro model for assessing neuronal function and synaptic transmission in primary rodent neurons. The novelty of our approach resides in the combination of the electrical field stimulation (EFS) with data acquisition in spatially separated areas of an interconnected neuronal network. We integrated our methodology with state of the art drug discovery instrumentation (FLIPR Tetra) and used selective tool compounds to perform a systematic pharmacological validation of the model. We investigated pharmacological modulators targeting pre- and post-synaptic receptors (AMPA, NMDA, GABA-A, mGluR2/3 receptors and Nav, Cav voltage-gated ion channels) and demonstrated the ability of our model to discriminate and measure synaptic transmission in cultured neuronal networks. Application of the model described here as an unbiased phenotypic screening approach will help with our long term goals of discovering novel therapeutic strategies for treating neurological disorders.

  15. Ca2+ Dependence of Synaptic Vesicle Endocytosis.

    Science.gov (United States)

    Leitz, Jeremy; Kavalali, Ege T

    2016-10-01

    Ca(2+)-dependent synaptic vesicle recycling is essential for structural homeostasis of synapses and maintenance of neurotransmission. Although, the executive role of intrasynaptic Ca(2+) transients in synaptic vesicle exocytosis is well established, identifying the exact role of Ca(2+) in endocytosis has been difficult. In some studies, Ca(2+) has been suggested as an essential trigger required to initiate synaptic vesicle retrieval, whereas others manipulating synaptic Ca(2+) concentrations reported a modulatory role for Ca(2+) leading to inhibition or acceleration of endocytosis. Molecular studies of synaptic vesicle endocytosis, on the other hand, have consistently focused on the roles of Ca(2+)-calmodulin dependent phosphatase calcineurin and synaptic vesicle protein synaptotagmin as potential Ca(2+) sensors for endocytosis. Most studies probing the role of Ca(2+) in endocytosis have relied on measurements of synaptic vesicle retrieval after strong stimulation. Strong stimulation paradigms elicit fusion and retrieval of multiple synaptic vesicles and therefore can be affected by several factors besides the kinetics and duration of Ca(2+) signals that include the number of exocytosed vesicles and accumulation of released neurotransmitters thus altering fusion and retrieval processes indirectly via retrograde signaling. Studies monitoring single synaptic vesicle endocytosis may help resolve this conundrum as in these settings the impact of Ca(2+) on synaptic fusion probability can be uncoupled from its putative role on synaptic vesicle retrieval. Future experiments using these single vesicle approaches will help dissect the specific role(s) of Ca(2+) and its sensors in synaptic vesicle endocytosis. © The Author(s) 2015.

  16. Synaptic AMPA receptor plasticity and behavior

    NARCIS (Netherlands)

    Kessels, Helmut W.; Malinow, Roberto

    2009-01-01

    The ability to change behavior likely depends on the selective strengthening and weakening of brain synapses. The cellular models of synaptic plasticity, long-term potentiation (LTP) and depression (LTD) of synaptic strength, can be expressed by the synaptic insertion or removal of AMPA receptors

  17. Schizophrenia and processing of facial emotions : Sex matters

    NARCIS (Netherlands)

    Scholten, MRM; Aleman, A; Montagne, B; Kahn, RS

    2005-01-01

    The aim of this study was to examine sex differences in emotion processing in patients with schizophrenia and control subjects. To this end, 53 patients with schizophrenia (28 men and 25 women), and 42 controls (21 men and 21 women) were assessed with the use of a facial affect recognition morphing

  18. Dopamine serotonin stabilizer RP5063: A randomized, double-blind, placebo-controlled multicenter trial of safety and efficacy in exacerbation of schizophrenia or schizoaffective disorder.

    Science.gov (United States)

    Cantillon, Marc; Prakash, Arul; Alexander, Ajay; Ings, Robert; Sweitzer, Dennis; Bhat, Laxminarayan

    2017-11-01

    The study objectives were to evaluate the efficacy, safety, tolerability, and pharmacokinetics of RP5063 versus placebo. The study was conducted in adults with acute exacerbation of schizophrenia or schizoaffective disorder. This 28-day, multicenter, placebo-controlled, double-blind study randomized 234 subjects to RP5063 15, 30, or 50mg; aripiprazole; or placebo (3:3:3:1:2) once daily. The aripiprazole arm was included solely to show assay sensitivity and was not powered to show efficacy. The primary endpoint was change from baseline to Day 28/EOT (End-of-Treatment) in Positive and Negative Syndrome Scale (PANSS) total score; secondary endpoints included PANSS subscales, improvement ≥1 point on the Clinical Global Impressions-Severity (CGI-S), depression and cognition scales. The primary analysis of PANSS Total showed improvement by a mean (SE) of -20.23 (2.65), -15.42 (2.04), and -19.21 (2.39) in the RP5063 15, 30, and 50mg arms, versus -11.41 (3.45) in the placebo arm. The difference between treatment and placebo reached statistical significance for the 15mg (p=0.021) and 50mg (p=0.016) arms. Improvement with RP5063 was also seen for multiple secondary efficacy outcomes. Discontinuation for any reason was much lower for RP5063 (14%, 25%, 12%) versus placebo (26%) and aripiprazole (35%). The most common treatment-emergent adverse events (TEAE) in the RP5063 groups were insomnia and agitation. There were no significant changes in body weight, electrocardiogram, or incidence of orthostatic hypotension; there was a decrease in blood glucose, lipid profiles, and prolactin levels. In conclusion, the novel dopamine serotonin stabilizer, RP5063 is an efficacious and well-tolerated treatment for acute exacerbation of schizophrenia or schizoaffective disorder. Copyright © 2017. Published by Elsevier B.V.

  19. Puzzling Out Synaptic Vesicle 2 Family Members Functions

    Directory of Open Access Journals (Sweden)

    Odile Bartholome

    2017-05-01

    Full Text Available Synaptic vesicle proteins 2 (SV2 were discovered in the early 80s, but the clear demonstration that SV2A is the target of efficacious anti-epileptic drugs from the racetam family stimulated efforts to improve understanding of its role in the brain. Many functions have been suggested for SV2 proteins including ions or neurotransmitters transport or priming of SVs. Moreover, several recent studies highlighted the link between SV2 and different neuronal disorders such as epilepsy, Schizophrenia (SCZ, Alzheimer’s or Parkinson’s disease. In this review article, we will summarize our present knowledge on SV2A function(s and its potential role(s in the pathophysiology of various brain disorders.

  20. Experiential pleasure deficits in different stages of schizophrenia.

    Science.gov (United States)

    Li, Zhi; Lui, Simon S Y; Geng, Fu-Lei; Li, Ying; Li, Wen-Xiu; Wang, Chuan-Yue; Tan, Shu-Ping; Cheung, Eric F C; Kring, Ann M; Chan, Raymond C K

    2015-08-01

    Prior research has found dampened anticipatory pleasure but relatively intact consummatory pleasure in people with first-episode and more chronic schizophrenia, but no study has examined anticipatory and consummatory pleasure across the schizophrenia spectrum. To confirm the factor structure of the Chinese version of the Temporal Experience Pleasure Scale (TEPS), which measures four components of anhedonia, we recruited 364 people with schizophrenia for confirmatory factor analysis. To examine anhedonia in people across the schizophrenia spectrum, we recruited people with first-episode (n=76) and chronic schizophrenia (n=45), people with schizotypal traits (n=210), first-degree relatives (n=45) of people with schizophrenia and healthy controls. Deficit in abstract anticipatory pleasure appeared to be most severe in people with chronic schizophrenia, while dampened abstract consummatory pleasure was observed in people with schizotypal personality features and in people with chronic schizophrenia. In addition, both abstract anticipatory and abstract consummatory pleasure were negatively correlated with negative schizotypal personality features and schizophrenia symptoms. Our results suggest that deficits in anticipatory pleasure are present across the schizophrenia spectrum, particularly in the abstract domain. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Efficacy of Adjunctive Treatments Added to Olanzapine or Clozapine for Weight Control in Patients with Schizophrenia: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yun-Jung Choi

    2015-01-01

    Full Text Available Objectives. This study was conducted to review systematically adjunctive treatments for weight reduction in patients with schizophrenia and compare efficacies of clinical trials through meta-analysis, so as to provide effective clinical guideline regarding weight control for patients taking atypical antipsychotics. Methods. Candidate clinical trials were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, and PsycINFO. Fourteen randomized clinical trials were included for systematic review and meta-analysis from 132 potential trials. The Comprehensive Meta-Analysis version 2 was used for meta-analysis. Results. Difference in means and significances from meta-analyses regarding weight control by adjunctive treatments showed that topiramate, aripiprazole, or sibutramine was more effective than metformin or reboxetine. Psychiatric evaluations did not show statistically significant changes between treatment groups and placebo groups except topiramate adjunctive treatments. Adverse effects regarding adjunctive therapies were tolerable and showed statistically no significances compared to control groups. Conclusion. Though having several reports related to exacerbation of psychiatric symptoms, topiramate and aripiprazole are more efficacious than other medications in regard to weight reduction and less burden of critical adverse effects as well as being beneficial for clinical improvement.

  2. Working and strategic memory deficits in schizophrenia

    Science.gov (United States)

    Stone, M.; Gabrieli, J. D.; Stebbins, G. T.; Sullivan, E. V.

    1998-01-01

    Working memory and its contribution to performance on strategic memory tests in schizophrenia were studied. Patients (n = 18) and control participants (n = 15), all men, received tests of immediate memory (forward digit span), working memory (listening, computation, and backward digit span), and long-term strategic (free recall, temporal order, and self-ordered pointing) and nonstrategic (recognition) memory. Schizophrenia patients performed worse on all tests. Education, verbal intelligence, and immediate memory capacity did not account for deficits in working memory in schizophrenia patients. Reduced working memory capacity accounted for group differences in strategic memory but not in recognition memory. Working memory impairment may be central to the profile of impaired cognitive performance in schizophrenia and is consistent with hypothesized frontal lobe dysfunction associated with this disease. Additional medial-temporal dysfunction may account for the recognition memory deficit.

  3. Clinical effectiveness and cost-effectiveness of body psychotherapy in the treatment of negative symptoms of schizophrenia: a multicentre randomised controlled trial.

    Science.gov (United States)

    Priebe, Stefan; Savill, Mark; Wykes, Til; Bentall, Richard; Lauber, Christoph; Reininghaus, Ulrich; McCrone, Paul; Mosweu, Iris; Bremner, Stephen; Eldridge, Sandra; Röhricht, Frank

    2016-02-01

    The negative symptoms of schizophrenia significantly impact on quality of life and social functioning, and current treatment options are limited. In this study the clinical effectiveness and cost-effectiveness of group body psychotherapy as a treatment for negative symptoms were compared with an active control. A parallel-arm, multisite randomised controlled trial. Randomisation was conducted independently of the research team, using a 1 : 1 computer-generated sequence. Assessors and statisticians were blinded to treatment allocation. Analysis was conducted following the intention-to-treat principle. In the cost-effectiveness analysis, a health and social care perspective was adopted. age 18-65 years; diagnosis of schizophrenia with symptoms present at > 6 months; score of ≥ 18 on Positive and Negative Syndrome Scale (PANSS) negative symptoms subscale; no change in medication type in past 6 weeks; willingness to participate; ability to give informed consent; and community outpatient. inability to participate in the groups and insufficient command of English. Participants were recruited from NHS mental health community services in five different Trusts. All groups took place in local community spaces. Control intervention: a 10-week, 90-minute, 20-session group beginners' Pilates class, run by a qualified Pilates instructor. Treatment intervention: a 10-week, 90-minute, 20-session manualised group body psychotherapy group, run by a qualified dance movement psychotherapist. The primary outcome was the PANSS negative symptoms subscale score at end of treatment. Secondary outcomes included measures of psychopathology, functional, social, service use and treatment satisfaction outcomes, both at treatment end and at 6-month follow-up. A total of 275 participants were randomised (140 body psychotherapy group, 135 Pilates group). At the end of treatment, 264 participants were assessed (137 body psychotherapy group, 127 Pilates group). The adjusted difference in

  4. Neurocognitive deficits in schizophrenia are associated with alterations in blood levels of neurosteroids: a multiple regression analysis of findings from a double-blind, randomized, placebo-controlled, crossover trial with DHEA.

    Science.gov (United States)

    Ritsner, Michael S; Strous, Rael D

    2010-01-01

    While neurosteroids exert multiple effects in the central nervous system, their associations with neurocognitive deficits in schizophrenia are not yet fully understood. The purpose of this study was to identify the contribution of circulating levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), androstenedione, and cortisol to neurocognitive deficits through DHEA administration in schizophrenia. Data regarding cognitive function, symptom severity, daily doses, side effects of antipsychotic agents and blood levels of DHEA, DHEAS, androstenedione and cortisol were collected among 55 schizophrenia patients in a double-blind, randomized, placebo-controlled, crossover trial with DHEA at three intervals: upon study entry, after 6weeks of DHEA administration (200mg/d), and after 6weeks of a placebo period. Multiple regression analysis was applied for predicting sustained attention, memory, and executive function scores across three examinations controlling for clinical, treatment and background covariates. Findings indicated that circulating DHEAS and androstenedione levels are shown as positive predictors of cognitive functioning, while DHEA level as negative predictor. Overall, blood neurosteroid levels and their molar ratios accounted for 16.5% of the total variance in sustained attention, 8-13% in visual memory tasks, and about 12% in executive functions. In addition, effects of symptoms, illness duration, daily doses of antipsychotic agents, side effects, education, and age of onset accounted for variability in cognitive functioning in schizophrenia. The present study suggests that alterations in circulating levels of neurosteroids and their molar ratios may reflect pathophysiological processes, which, at least partially, underlie cognitive dysfunction in schizophrenia. Copyright 2009 Elsevier Ltd. All rights reserved.

  5. Dopamine, psychosis and schizophrenia

    DEFF Research Database (Denmark)

    Kesby, J P; Eyles, D W; McGrath, J J

    2018-01-01

    The stagnation in drug development for schizophrenia highlights the need for better translation between basic and clinical research. Understanding the neurobiology of schizophrenia presents substantial challenges but a key feature continues to be the involvement of subcortical dopaminergic...... dysfunction in those with psychotic symptoms. Our contemporary knowledge regarding dopamine dysfunction has clarified where and when dopaminergic alterations may present in schizophrenia. For example, clinical studies have shown patients with schizophrenia show increased presynaptic dopamine function...... in the associative striatum, rather than the limbic striatum as previously presumed. Furthermore, subjects deemed at high risk of developing schizophrenia show similar presynaptic dopamine abnormalities in the associative striatum. Thus, our view of subcortical dopamine function in schizophrenia continues to evolve...

  6. DNA Methylation in Schizophrenia.

    Science.gov (United States)

    Pries, Lotta-Katrin; Gülöksüz, Sinan; Kenis, Gunter

    2017-01-01

    Schizophrenia is a highly heritable psychiatric condition that displays a complex phenotype. A multitude of genetic susceptibility loci have now been identified, but these fail to explain the high heritability estimates of schizophrenia. In addition, epidemiologically relevant environmental risk factors for schizophrenia may lead to permanent changes in brain function. In conjunction with genetic liability, these environmental risk factors-likely through epigenetic mechanisms-may give rise to schizophrenia, a clinical syndrome characterized by florid psychotic symptoms and moderate to severe cognitive impairment. These pathophysiological features point to the involvement of epigenetic processes. Recently, a wave of studies examining aberrant DNA modifications in schizophrenia was published. This chapter aims to comprehensively review the current findings, from both candidate gene studies and genome-wide approaches, on DNA methylation changes in schizophrenia.

  7. Depression as a Glial-Based Synaptic Dysfunction

    Science.gov (United States)

    Rial, Daniel; Lemos, Cristina; Pinheiro, Helena; Duarte, Joana M.; Gonçalves, Francisco Q.; Real, Joana I.; Prediger, Rui D.; Gonçalves, Nélio; Gomes, Catarina A.; Canas, Paula M.; Agostinho, Paula; Cunha, Rodrigo A.

    2016-01-01

    Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processes occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia) tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the “quad-partite” synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increased microglia “activation” in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, brain-derived neurotrophic factor, BDNF) affect glia functioning, whereas antidepressant treatments (serotonin-selective reuptake inhibitors, SSRIs, electroshocks, deep brain stimulation) recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication—such as the purinergic neuromodulation system operated by adenosine 5′-triphosphate (ATP) and adenosine—emerge as promising candidates to “re-normalize” synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future

  8. Depression as a Glial-Based Synaptic Dysfunction

    Directory of Open Access Journals (Sweden)

    Daniel eRial

    2016-01-01

    Full Text Available Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processing occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the ‘quad-partite’ synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increase microglia ‘activation’ in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, BDNF affect glia functioning, whereas antidepressant treatments (SSRIs, electroshock, deep brain stimulation recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication - such as the purinergic neuromodulation system operated by ATP and adenosine - emerge as promising candidates to re-normalize synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future pharmacological tools to manage depression.

  9. Exercise-Induced Fatigue Impairs Bidirectional Corticostriatal Synaptic Plasticity.

    Science.gov (United States)

    Ma, Jing; Chen, Huimin; Liu, Xiaoli; Zhang, Lingtao; Qiao, Decai

    2018-01-01

    Exercise-induced fatigue (EF) is a ubiquitous phenomenon in sports competition and training. It can impair athletes' motor skill execution and cognition. Corticostriatal synaptic plasticity is considered to be the cellular mechanism of movement control and motor learning. However, the effect of EF on corticostriatal synaptic plasticity remains elusive. In the present study, using field excitatory postsynaptic potential recording, we found that the corticostriatal long-term potentiation (LTP) and long-term depression (LTD) were both impaired in EF mice. To further investigate the cellular mechanisms underlying the impaired synaptic plasticity in corticostriatal pathway, whole-cell patch clamp recordings were carried out on striatal medium spiny neurons (MSNs). MSNs in EF mice exhibited increased spontaneous excitatory postsynaptic current (sEPSC) frequency and decreased paired-pulse ratio (PPR), while with normal basic electrophysiological properties and normal sEPSC amplitude. Furthermore, the N-methyl-D-aspartate (NMDA)/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) ratio of MSNs was reduced in EF mice. These results suggest that the enhanced presynaptic glutamate (Glu) release and downregulated postsynaptic NMDA receptor function lead to the impaired corticostriatal plasticity in EF mice. Taken together, our findings for the first time show that the bidirectional corticostriatal synaptic plasticity is impaired after EF, and suggest that the aberrant corticostriatal synaptic plasticity may be involved in the production and/or maintenance of EF.

  10. Emotion recognition and theory of mind are related to gray matter volume of the prefrontal cortex in schizophrenia

    NARCIS (Netherlands)

    Maat, Arija; van Haren, Neeltje E M; Bartholomeusz, Cali F.; Kahn, René S.; Cahn, Wiepke

    2016-01-01

    Investigations of social cognition in schizophrenia have demonstrated consistent impairments compared to healthy controls. Functional imaging studies in schizophrenia patients and healthy controls have revealed that social cognitive processing depends critically on the amygdala and the prefrontal

  11. Language lateralization in schizophrenia

    OpenAIRE

    Sommer, I.E.C.

    2004-01-01

    Schizophrenia is a severe chronic psychiatric illness that affects approximately 1-2% of the populations worldwide. Schizophrenia is characterized by episodes of psychosis, in which patients experience hallucinations (false perceptions) and delusions (false beliefs). Apart from the psychotic episodes, patients frequently have negative symptoms: they become apathic, loose interest in hobbies and friends and lack energy. The cause of schizophrenia is not clear, though several theories have been...

  12. Dance therapy for schizophrenia.

    Science.gov (United States)

    Ren, Juanjuan; Xia, Jun

    2013-10-04

    Dance therapy or dance movement therapy (DMT) is defined as 'the psychotherapeutic use of movement as a process which furthers the emotional, social, cognitive, and physical integration of the individual'. It may be of value for people with developmental, medical, social, physical or psychological impairments. Dance therapy can be practiced in mental health rehabilitation units, nursing homes, day care centres and incorporated into disease prevention and health promotion programmes. To evaluate the effects of dance therapy for people with schizophrenia or schizophrenia-like illnesses compared with standard care and other interventions. We updated the original July 2007 search of the Cochrane Schizophrenia Group' register in July 2012. We also searched Chinese main medical databases. We included one randomised controlled trial (RCT) comparing dance therapy and related approaches with standard care or other psychosocial interventions for people with schizophrenia. We reliably selected, quality assessed and extracted data. For continuous outcomes, we calculated a mean difference (MD); for binary outcomes we calculated a fixed-effect risk ratio (RR) and their 95% confidence intervals (CI). We created a 'Summary of findings' table using the GRADE approach. We included one single blind study (total n = 45) of reasonable quality. It compared dance therapy plus routine care with routine care alone. Most people tolerated the treatment package but nearly 40% were lost in both groups by four months (1 RCT n = 45, RR 0.68 95% CI 0.31 to 1.51, low quality evidence). The Positive and Negative Syndrome Scale (PANSS) average endpoint total scores were similar in both groups (1 RCT n = 43, MD -0.50 95% CI -11.80 to 10.80, moderate quality evidence) as were the positive sub-scores (1 RCT n = 43, MD 2.50 CI -0.67 to 5.67, moderate quality evidence). At the end of treatment, significantly more people in the dance therapy group had a greater than 20% reduction in PANSS negative symptom

  13. Psychoeducation for schizophrenia

    Science.gov (United States)

    Xia, Jun; Merinder, Lars Bertil; Belgamwar, Madhvi R

    2014-01-01

    Background Schizophrenia can be a severe and chronic illness characterised by lack of insight and poor compliance with treatment. Psychoeducational approaches have been developed to increase patients’ knowledge of, and insight into, their illness and its treatment. It is supposed that this increased knowledge and insight will enable people with schizophrenia to cope in a more effective way with their illness, thereby improving prognosis. Objectives To assess the effects of psychoeducational interventions compared with standard levels of knowledge provision. Search methods We searched the Cochrane Schizophrenia Group Trials Register (February 2010). We updated this search November 2012 and added 27 new trials to the awaiting assessment section. Selection criteria All relevant randomised controlled trials focusing on psychoeducation for schizophrenia and/or related serious mental illnesses involving individuals or groups. We excluded quasi-randomised trials. Data collection and analysis At least two review authors extracted data independently from included papers. We contacted authors of trials for additional and missing data. We calculated risk ratios (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data. We used a fixed-effects model for heterogeneous dichotomous data. Where possible we also calculated the numbers needed to treat (NNT), as well as weighted means for continuous data. Main results This review includes a total of 5142 participants (mostly inpatients) from 44 trials conducted between 1988 and 2009 (median study duration ~ 12 weeks, risk of bias - moderate). We found that incidences of non-compliance were lower in the psychoeducation group in the short term (n = 1400, RR 0.52 CI 0.40 to 0.67, NNT 11 CI 9 to 16). This finding holds for the medium and long term. Relapse appeared to be lower in psychoeducation group (n = 1214, RR 0.70 CI 0.61 to 0.81, NNT 9 CI 7 to 14) and this also applied to readmission (n = 206, RR 0.71 CI 0.56 to 0

  14. Neurodevelopmental hypothesis of schizophrenia

    National Research Council Canada - National Science Library

    Owen, Michael J; O'Donovan, Michael C; Thapar, Anita; Craddock, Nicholas

    2011-01-01

    The neurodevelopmental hypothesis of schizophrenia provided a valuable framework that allowed a condition that usually presents with frank disorder in adolescence or early adulthood to be understood...

  15. The Danish schizophrenia registry

    DEFF Research Database (Denmark)

    Baandrup, Lone; Cerqueira, Charlotte; Haller, Lea

    2016-01-01

    Aim of database: To systematically monitor and improve the quality of treatment and care of patients with schizophrenia in Denmark. In addition, the database is accessible as a resource for research. Study population: Patients diagnosed with schizophrenia and receiving mental health care...... to the data for use in specific research projects by applying to the steering committee. Conclusion: The Danish Schizophrenia Registry represents a valuable source of informative data to monitor and improve the quality of care of patients with schizophrenia in Denmark. However, continuous resources and time...

  16. The Danish Schizophrenia Registry

    DEFF Research Database (Denmark)

    Baandrup, Lone; Cerqueira, Charlotte; Haller, Lea

    2016-01-01

    Aim of database: To systematically monitor and improve the quality of treatment and care of patients with schizophrenia in Denmark. In addition, the database is accessible as a resource for research. Study population: Patients diagnosed with schizophrenia and receiving mental health care...... to the data for use in specific research projects by applying to the steering committee. Conclusion: The Danish Schizophrenia Registry represents a valuable source of informative data to monitor and improve the quality of care of patients with schizophrenia in Denmark. However, continuous resources and time...

  17. Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity

    Science.gov (United States)

    Beckhauser, Thiago Fernando; Francis-Oliveira, José; De Pasquale, Roberto

    2016-01-01

    In the mammalian central nervous system, reactive oxygen species (ROS) generation is counterbalanced by antioxidant defenses. When large amounts of ROS accumulate, antioxidant mechanisms become overwhelmed and oxidative cellular stress may occur. Therefore, ROS are typically characterized as toxic molecules, oxidizing membrane lipids, changing the conformation of proteins, damaging nucleic acids, and causing deficits in synaptic plasticity. High ROS concentrations are associated with a decline in cognitive functions, as observed in some neurodegenerative disorders and age-dependent decay of neuroplasticity. Nevertheless, controlled ROS production provides the optimal redox state for the activation of transductional pathways involved in synaptic changes. Since ROS may regulate neuronal activity and elicit negative effects at the same time, the distinction between beneficial and deleterious consequences is unclear. In this regard, this review assesses current research and describes the main sources of ROS in neurons, specifying their involvement in synaptic plasticity and distinguishing between physiological and pathological processes implicated. PMID:27625575

  18. Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia.

    Science.gov (United States)

    Bossong, Matthijs G; Niesink, Raymond J M

    2010-11-01

    Cannabis use during adolescence increases the risk of developing psychotic disorders later in life. However, the neurobiological processes underlying this relationship are unknown. This review reports the results of a literature search comprising various neurobiological disciplines, ultimately converging into a model that might explain the neurobiology of cannabis-induced schizophrenia. The article briefly reviews current insights into brain development during adolescence. In particular, the role of the excitatory neurotransmitter glutamate in experience-dependent maturation of specific cortical circuitries is examined. The review also covers recent hypotheses regarding disturbances in strengthening and pruning of synaptic connections in the prefrontal cortex, and the link with latent psychotic disorders. In the present model, cannabis-induced schizophrenia is considered to be a distortion of normal late postnatal brain maturation. Distortion of glutamatergic transmission during critical periods may disturb prefrontal neurocircuitry in specific brain areas. Our model postulates that adolescent exposure to Δ9-tetrahydrocannabinol (THC), the primary psychoactive substance in cannabis, transiently disturbs physiological control of the endogenous cannabinoid system over glutamate and GABA release. As a result, THC may adversely affect adolescent experience-dependent maturation of neural circuitries within prefrontal cortical areas. Depending on dose, exact time window and duration of exposure, this may ultimately lead to the development of psychosis or schizophrenia. The proposed model provides testable hypotheses which can be addressed in future studies, including animal experiments, reanalysis of existing epidemiological data, and prospective epidemiological studies in which the role of the dose-time-effect relationship should be central. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Effectiveness of a community-based intervention for people with schizophrenia and their caregivers in India (COPSI): a randomised controlled trial

    Science.gov (United States)

    Chatterjee, Sudipto; Naik, Smita; John, Sujit; Dabholkar, Hamid; Balaji, Madhumitha; Koschorke, Mirja; Varghese, Mathew; Thara, Rangaswamy; Weiss, Helen A; Williams, Paul; McCrone, Paul; Patel, Vikram; Thornicroft, Graham

    2014-01-01

    Summary Background Observational evidence suggests that community-based services for people with schizophrenia can be successfully provided by community health workers, when supervised by specialists, in low-income and middle-income countries. We did the COmmunity care for People with Schizophrenia in India (COPSI) trial to compare the effectiveness of a collaborative community-based care intervention with standard facility-based care. Methods We did a multicentre, parallel-group, randomised controlled trial at three sites in India between Jan 1, 2009 and Dec 31, 2010. Patients aged 16–60 years with a primary diagnosis of schizophrenia according to the tenth edition of the International Classification of Diseases, Diagnostic Criteria for Research (ICD-10-DCR) were randomly assigned (2:1), via a computer-generated randomisation list with block sizes of three, six, or nine, to receive either collaborative community-based care plus facility-based care or facility-based care alone. Randomisation was stratified by study site. Outcome assessors were masked to group allocation. The primary outcome was a change in symptoms and disabilities over 12 months, as measured by the positive and negative syndrome scale (PANSS) and the Indian disability evaluation and assessment scale (IDEAS). Analysis was by modified intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 56877013. Findings 187 participants were randomised to the collaborative community-based care plus facility-based care group and 95 were randomised to the facility-based care alone group; 253 (90%) participants completed follow-up to month 12. At 12 months, total PANSS and IDEAS scores were lower in patients in the intervention group than in those in the control group (PANSS adjusted mean difference −3·75, 95% CI −7·92 to 0·42; p=0·08; IDEAS −0·95, −1·68 to −0·23; p=0·01). However, no difference was shown in the proportion of

  20. Influence of Polygenic Risk Scores on the Association Between Infections and Schizophrenia

    DEFF Research Database (Denmark)

    Benros, Michael E; Trabjerg, Betina; Meier, Sandra M

    2016-01-01

    BACKGROUND: Several studies have suggested an important role of infections in the etiology of schizophrenia; however, shared genetic liability toward infections and schizophrenia could influence the association. We therefore investigated the possible effect of polygenic risk scores (PRSs......) for schizophrenia on the association between infections and the risk of schizophrenia. METHODS: We conducted a nested case-control study on a Danish population-based sample born after 1981 comprising of 1692 cases diagnosed with schizophrenia between 1994 and 2008 and 1724 matched controls. All individuals were...... hospital contact with infection had occurred in 41% of the individuals with schizophrenia and increased the incidence rate ratio (IRR) of schizophrenia by 1.43 (95% confidence interval [CI] = 1.22-1.67). Adding PRS, which was robustly associated with schizophrenia (by an IRR of 1.46 [95% CI = 1...

  1. Altered Cortical Ensembles in Mouse Models of Schizophrenia.

    Science.gov (United States)

    Hamm, Jordan P; Peterka, Darcy S; Gogos, Joseph A; Yuste, Rafael

    2017-04-05

    In schizophrenia, brain-wide alterations have been identified at the molecular and cellular levels, yet how these phenomena affect cortical circuit activity remains unclear. We studied two mouse models of schizophrenia-relevant disease processes: chronic ketamine (KET) administration and Df(16)A +/- , modeling 22q11.2 microdeletions, a genetic variant highly penetrant for schizophrenia. Local field potential recordings in visual cortex confirmed gamma-band abnormalities similar to patient studies. Two-photon calcium imaging of local cortical populations revealed in both models a deficit in the reliability of neuronal coactivity patterns (ensembles), which was not a simple consequence of altered single-neuron activity. This effect was present in ongoing and sensory-evoked activity and was not replicated by acute ketamine administration or pharmacogenetic parvalbumin-interneuron suppression. These results are consistent with the hypothesis that schizophrenia is an "attractor" disease and demonstrate that degraded neuronal ensembles are a common consequence of diverse genetic, cellular, and synaptic alterations seen in chronic schizophrenia. Published by Elsevier Inc.

  2. Is there any role of latent toxoplasmosis in schizophrenia disease?

    Science.gov (United States)

    Karabulut, Nuran; Bilgiç, Serkan; Gürok, Mehmet Gürkan; Karaboğa, Fatih

    2015-09-01

    A large number of studies have hypothesized that Toxoplasma gondii is a potentially relevant etiological factor in some cases of schizophrenia. By contrast, some studies have disproved this association. The aim of this study was to investigate whether latent toxoplasmosis has any role in schizophrenia disease. Additionally, the association between T. gondii and subtypes of schizophrenia, and the impacts of toxoplasmosis on psychopathology were examined in the study. A total of 85 patients with schizophrenia and 60 healthy volunteers were included in this prospective study. Immunoglobulin G (IgG) antibody to T. gondii was examined by enzyme-linked immune-sorbent assay method. Seropositivity rates were 43.5% for the patients with schizophrenia and 43.3% for the healthy controls (odds ratio: 1.008, 95% confidence interval: 0.517-1.964, p = 0.981).There was no significant difference in T. gondii IgG positivity between the schizophrenia and control groups with respect to sex and age. The difference in seroprevalence of T. gondii IgG antibodies among the schizophrenia subtypes was not statistically significant (p = 0.934). No significant difference was found in Positive and Negative Syndrome Subscales between Toxoplasma-infected and Toxoplasma-free patients. In the study area with a high prevalence of T. gondii, no association between toxoplasmosis and schizophrenia was detected. These findings showed that toxoplasmosis has no role in the risk of schizophrenia disease. Copyright © 2015. Published by Elsevier Taiwan.

  3. In Sickness and in Health: Perineuronal Nets and Synaptic Plasticity in Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Harry Pantazopoulos

    2016-01-01

    Full Text Available Rapidly emerging evidence implicates perineuronal nets (PNNs and extracellular matrix (ECM molecules that compose or interact with PNNs, in the pathophysiology of several psychiatric disorders. Studies on schizophrenia, auti