Neuropathological diagnostic accuracy.

NARCIS (Netherlands)

Murphy, M.; Loosemore, A.; Ferrer, I.; Wesseling, P.; Wilkins, P.R.; Bell, B.A.

2002-01-01

This study investigated variations in neuropathological diagnosis when histopathological slides are evaluated with access to all information pertinent to a case, compared with evaluation of H & E stained slides with only limited clinical information. The aim of the study is to evaluate the role of

Hippocampal volume as an index of Alzheimer neuropathology: findings from the Nun Study.

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Gosche, K M; Mortimer, J A; Smith, C D; Markesbery, W R; Snowdon, D A

2002-05-28

To determine whether hippocampal volume is a sensitive and specific indicator of Alzheimer neuropathology, regardless of the presence or absence of cognitive and memory impairment. Postmortem MRI scans were obtained for the first 56 participants of the Nun Study who were scanned. The area under receiver operating characteristic curves, sensitivity, specificity, and positive and negative predictive values were used to assess the diagnostic accuracy of hippocampal volume in predicting fulfillment of Alzheimer neuropathologic criteria and differences in Braak staging. Hippocampal volume predicted fulfillment of neuropathologic criteria for AD for all 56 participants (p < 0.001): 24 sisters who were demented (p = 0.036); 32 sisters who remained nondemented (p < 0.001), 8 sisters who remained nondemented but had memory impairment (p < 0.001), and 24 sisters who were intact with regard to memory and cognition at the final examination prior to death (p = 0.003). In individuals who remained nondemented, hippocampal volume was a better indicator of AD neuropathology than a delayed memory measure. Among nondemented sisters, Braak stages III and VI were distinguishable from Braak stages II or lower (p = 0.001). Among cognitively intact individuals, those in Braak stage II could be distinguished from those in stage I or less (p = 0.025). Volumetric measures of the hippocampus may be useful in identifying nondemented individuals who satisfy neuropathologic criteria for AD as well as pathologic stages of AD that may be present decades before initial clinical expression.

Severe neonatal epileptic encephalopathy and KCNQ2 mutation: neuropathological substrate?

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Charlotte eDalen Meurs-Van Der Schoor

2014-12-01

Full Text Available Background:Neonatal convulsions are clinical manifestations in a heterogeneous group of disorders with different etiology and outcome. They are attributed to several genetic causes. Methods:We describe a patient with intractable neonatal seizures who died from respiratory compromise during a status epilepticus. Results:This case report provides EEG, MRI, genetic analysis and neuropathological data. Genetic analysis revealed a de novo heterozygous missense mutation in the KCNQ2 gene, which encodes a subunit of a voltage-gated potassium channel. KCNQ2 gene mutation is associated with intractable neonatal seizures. EEG, MRI data as well as mutation analysis have been described in other KCNQ2 cases. Postmortem neuropathologic investigation revealed mild malformation of cortical development with increased heterotopic neurons in the deep white matter compared to an age-matched control subject. The new finding of this study is the combination of a KCNQ2 mutation and the cortical abnormalities. Conclusions:KCNQ2 mutations should be considered in neonates with refractory epilepsy of unknown cause. The mild cortical malformation is an important new finding, though it remains unknown whether these cortical abnormalities are due to the KCNQ2 mutation or are secondary to the refractory seizures.

Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury

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Ojo, Joseph O.; Greenberg, M. Banks; Leary, Paige; Mouzon, Benoit; Bachmeier, Corbin; Mullan, Michael; Diamond, David M.; Crawford, Fiona

2014-01-01

Co-morbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) has become the signature disorder for returning combat veterans. The clinical heterogeneity and overlapping symptomatology of mTBI and PTSD underscore the need to develop a preclinical model that will enable the characterization of unique and overlapping features and allow discrimination between both disorders. This study details the development and implementation of a novel experimental paradigm for PTSD and combined PTSD-mTBI. The PTSD paradigm involved exposure to a danger-related predator odor under repeated restraint over a 21 day period and a physical trauma (inescapable footshock). We administered this paradigm alone, or in combination with a previously established mTBI model. We report outcomes of behavioral, pathological and biochemical profiles at an acute timepoint. PTSD animals demonstrated recall of traumatic memories, anxiety and an impaired social behavior. In both mTBI and combination groups there was a pattern of disinhibitory like behavior. mTBI abrogated both contextual fear and impairments in social behavior seen in PTSD animals. No major impairment in spatial memory was observed in any group. Examination of neuroendocrine and neuroimmune responses in plasma revealed a trend toward increase in corticosterone in PTSD and combination groups, and an apparent increase in Th1 and Th17 proinflammatory cytokine(s) in the PTSD only and mTBI only groups respectively. In the brain there were no gross neuropathological changes in any groups. We observed that mTBI on a background of repeated trauma exposure resulted in an augmentation of axonal injury and inflammatory markers, neurofilament L and ICAM-1 respectively. Our observations thus far suggest that this novel stress-trauma-related paradigm may be a useful model for investigating further the overlapping and distinct spatio-temporal and behavioral/biochemical relationship between mTBI and PTSD experienced by combat

Pain processing in dementia and its relation to neuropathology

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Scherder, E.J.A.; Sergeant, J.A.; Swaab, D.F.

2003-01-01

Most clinical studies of pain in dementia have focused on assessment procedures that are sensitive to pain in "demented" or "cognitively impaired" elderly patients. The neuropathology of dementia has not played a major part in pain assessment. In this review, the neuropathological effects of

The importance of brain banks for molecular neuropathological research: The New South Wales Tissue Resource Centre experience.

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Dedova, Irina; Harding, Antony; Sheedy, Donna; Garrick, Therese; Sundqvist, Nina; Hunt, Clare; Gillies, Juliette; Harper, Clive G

2009-01-01

New developments in molecular neuropathology have evoked increased demands for postmortem human brain tissue. The New South Wales Tissue Resource Centre (TRC) at The University of Sydney has grown from a small tissue collection into one of the leading international brain banking facilities, which operates with best practice and quality control protocols. The focus of this tissue collection is on schizophrenia and allied disorders, alcohol use disorders and controls. This review highlights changes in TRC operational procedures dictated by modern neuroscience, and provides examples of applications of modern molecular techniques to study the neuropathogenesis of many different brain disorders.

The neuropathology of hereditary congenital facial palsy vs Mobius syndrome.

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Verzijl, H.T.F.M.; Zwaag, B. van der; Lammens, M.M.Y.; Donkelaar, H.J. ten; Padberg, G.W.A.M.

2005-01-01

OBJECTIVE: To characterize the neuropathology of hereditary congenital facial palsy. METHODS: The authors compared brainstem pathology of three members of one family with autosomal dominant congenital facial palsy to that in three age-matched controls. The neuropathologic findings of the familial

Cell Type-Specific Contributions to the TSC Neuropathology

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2017-08-01

AWARD NUMBER: W81XWH-16-1-0415 TITLE: Cell Type-Specific Contributions to the TSC Neuropathology PRINCIPAL INVESTIGATOR: Gabriella D’Arcangelo...AND SUBTITLE Cell Type-Specific Contributions to the TSC Neuropathology 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0415 5c. PROGRAM...how heterozygous and homozygous Tsc2 mutations affect the development of mutant excitatory neurons as well as other surrounding brain cells , in vivo

Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings

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Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W.; Sisodiya, Sanjay M.

2015-01-01

Aims Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. Methods We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Results Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P epilepsy history and investigations. Conclusion Our findings support the contribution of examination of the whole fixed brain in SUDEP, with high rates of detection of relevant pathology. Availability of full clinical epilepsy‐related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. PMID:26300477

The future of neuropathology in childhood.

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Rorke, L B

2000-11-01

The current state of knowledge of pediatric neuropathology is based upon a rich historical heritage dating back many centuries and representing the genius of many people, although, relatively speaking, little specific attention was paid to the unique issues relating to infants and children. Aside from descriptions of morphological features of disease (including tumors), advances in understanding basic pathogenetic mechanisms have flowered only in the recent past. Most exciting has been the progress in molecular biology and genetics, which has yielded a phenomenal bank of information in a short time, uncovering details of genes involved in development of the nervous system and specifically associated with various types of tumors. The future of pediatric neuropathology requires partnership with molecular geneticists whose studies hold promise of defining morphology.

Neuropathologic features in the hippocampus and cerebellum of three older men with fragile X syndrome

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Greco Claudia M

2011-02-01

Full Text Available Abstract Background Fragile X syndrome (FXS is the most common inherited form of intellectual disability, and is the most common single-gene disorder known to be associated with autism. Despite recent advances in functional neuroimaging and our understanding of the molecular pathogenesis, only limited neuropathologic information on FXS is available. Methods Neuropathologic examinations were performed on post-mortem brain tissue from three older men (aged 57, 64 and 78 years who had received a clinical or genetic diagnosis of FXS. In each case, physical and cognitive features were typical of FXS, and one man was also diagnosed with autism. Guided by reports of clinical and neuroimaging abnormalities of the limbic system and cerebellum of individuals with FXS, the current analysis focused on neuropathologic features present in the hippocampus and the cerebellar vermis. Results Histologic and immunologic staining revealed abnormalities in both the hippocampus and cerebellar vermis. Focal thickening of hippocampal CA1 and irregularities in the appearance of the dentate gyrus were identified. All lobules of the cerebellar vermis and the lateral cortex of the posterior lobe of the cerebellum had decreased numbers of Purkinje cells, which were occasionally misplaced, and often lacked proper orientation. There were mild, albeit excessive, undulations of the internal granular cell layer, with patchy foliar white matter axonal and astrocytic abnormalities. Quantitative analysis documented panfoliar atrophy of both the anterior and posterior lobes of the vermis, with preferential atrophy of the posterior lobule (VI to VII compared with age-matched normal controls. Conclusions Significant morphologic changes in the hippocampus and cerebellum in three adult men with FXS were identified. This pattern of pathologic features supports the idea that primary defects in neuronal migration, neurogenesis and aging may underlie the neuropathology reported in FXS.

Neuropathologic features in the hippocampus and cerebellum of three older men with fragile X syndrome

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2011-01-01

Background Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, and is the most common single-gene disorder known to be associated with autism. Despite recent advances in functional neuroimaging and our understanding of the molecular pathogenesis, only limited neuropathologic information on FXS is available. Methods Neuropathologic examinations were performed on post-mortem brain tissue from three older men (aged 57, 64 and 78 years) who had received a clinical or genetic diagnosis of FXS. In each case, physical and cognitive features were typical of FXS, and one man was also diagnosed with autism. Guided by reports of clinical and neuroimaging abnormalities of the limbic system and cerebellum of individuals with FXS, the current analysis focused on neuropathologic features present in the hippocampus and the cerebellar vermis. Results Histologic and immunologic staining revealed abnormalities in both the hippocampus and cerebellar vermis. Focal thickening of hippocampal CA1 and irregularities in the appearance of the dentate gyrus were identified. All lobules of the cerebellar vermis and the lateral cortex of the posterior lobe of the cerebellum had decreased numbers of Purkinje cells, which were occasionally misplaced, and often lacked proper orientation. There were mild, albeit excessive, undulations of the internal granular cell layer, with patchy foliar white matter axonal and astrocytic abnormalities. Quantitative analysis documented panfoliar atrophy of both the anterior and posterior lobes of the vermis, with preferential atrophy of the posterior lobule (VI to VII) compared with age-matched normal controls. Conclusions Significant morphologic changes in the hippocampus and cerebellum in three adult men with FXS were identified. This pattern of pathologic features supports the idea that primary defects in neuronal migration, neurogenesis and aging may underlie the neuropathology reported in FXS. PMID:21303513

MicroRNA Implications across Neurodevelopment and Neuropathology

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Sabata Martino

2009-01-01

Full Text Available MicroRNAs (miRNAs have rapidly emerged as biologically important mediators of posttranscriptional and epigenetic regulation in both plants and animals. miRNAs function through a variety of mechanisms including mRNA degradation and translational repression; additionally, miRNAs may guide gene expression by serving as transcription factors. miRNAs are highly expressed in human brain. Tissue and cell type-specific enrichments of certain miRNAs within the nervous system argue for a biological significance during neurodevelopmental stages. On the other hand, a large number of studies have reported links between alterations of miRNA homeostasis and pathologic conditions such as cancer, heart diseases, and neurodegeneration. Thus, profiles of distinct or aberrant miRNA signatures have most recently surged as one of the most fascinating interests in current biology. Here, the most recent insights into the involvement of miRNAs in the biology of the nervous system and the occurrence of neuropathological disorders are reviewed and discussed.

A quantitative study of the neuropathology of 32 sporadic and familial cases of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP).

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Armstrong, R A; Carter, D; Cairns, N J

2012-02-01

To further characterize the neuropathology of the heterogeneous molecular disorder frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). We quantified the neuronal cytoplasmic inclusions, glial inclusions, neuronal intranuclear inclusions, dystrophic neurites, surviving neurones, abnormally enlarged neurones, and vacuoles in regions of the frontal and temporal lobe using a phosphorylation-independent TDP-43 antibody in 32 cases of FTLD-TDP comprising sporadic and familial cases, with associated pathology such as hippocampal sclerosis (HS) or Alzheimer's disease (AD), and four neuropathological subtypes using TDP-43 immunohistochemistry. Analysis of variance (anova) was used to compare differences between the various groups of cases. These data from FTLD-TDP cases demonstrate quantitative differences in pathological features between: (i) regions of the frontal and temporal lobe; (ii) upper and lower cortex; (iii) sporadic and progranulin (GRN) mutation cases; (iv) cases with and without AD or HS; and (v) between assigned subtypes. The data confirm that the dentate gyrus is a major site of neuropathology in FTLD-TDP and that most laminae of the cerebral cortex are affected. GRN mutation cases are quantitatively different from sporadic cases, while cases with associated HS and AD have increased densities of dystrophic neurites and abnormally enlarged neurones respectively. There is little correlation between the subjective assessment of subtypes and the more objective quantitative data. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

The history of attention deficit hyperactivity disorder

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Reichl, Susanne; Lange, Katharina M.; Tucha, Lara; Tucha, Oliver

2010-01-01

The contemporary concept of attention deficit hyperactivity disorder (ADHD) as defined in the DSM-IV-TR (American Psychiatric Association 2000) is relatively new. Excessive hyperactive, inattentive, and impulsive children have been described in the literature since the nineteenth century. Some of the early depictions and etiological theories of hyperactivity were similar to current descriptions of ADHD. Detailed studies of the behavior of hyperactive children and increasing knowledge of brain function have changed the concepts of the fundamental behavioral and neuropathological deficits underlying the disorder. This article presents an overview of the conceptual history of modern-day ADHD. PMID:21258430

Neuropathological Alterations in Alzheimer Disease

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Serrano-Pozo, Alberto; Frosch, Matthew P.; Masliah, Eliezer; Hyman, Bradley T.

2011-01-01

The neuropathological hallmarks of Alzheimer disease (AD) include “positive” lesions such as amyloid plaques and cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and “negative” lesions such as neuronal and synaptic loss. Despite their inherently cross-sectional nature, postmortem studies have enabled the staging of the progression of both amyloid and tangle pathologies, and, consequently, the development of diagnostic criteria that are now used worldwide. In addition, clinicopathological correlation studies have been crucial to generate hypotheses about the pathophysiology of the disease, by establishing that there is a continuum between “normal” aging and AD dementia, and that the amyloid plaque build-up occurs primarily before the onset of cognitive deficits, while neurofibrillary tangles, neuron loss, and particularly synaptic loss, parallel the progression of cognitive decline. Importantly, these cross-sectional neuropathological data have been largely validated by longitudinal in vivo studies using modern imaging biomarkers such as amyloid PET and volumetric MRI. PMID:22229116

Neuropathological characteristics of the brain in two patients with SLC19A3 mutations related to the biotin-thiamine-responsive basal ganglia disease

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Maciej Pronicki

2017-06-01

Full Text Available Biotin-thiamine-responsive basal ganglia disease is a severe form of a rare neurogenetic disorder caused by pathogenic molecular variants in the thiamine transporter gene. Nowadays, a potentially effective treatment is known, therefore the early diagnosis is mandatory. The aim of the paper was to assess the contribution of neuropathological and magnetic resonance imaging (MRI studies to a proper diagnosis. We present the brain study of two Polish patients with SLC19A3 mutations, including (1 an infant with an intriguing “walnut” appearance of the brain autopsied many years before the discovery of the SLC19A3 defect, and (2 a one-year-old patient with clinical features of Leigh syndrome. In patient 2, biotin/thiamine responsiveness was not tested at the time of diagnosis and causal treatment started with one-year delay. The central nervous system lesions found in the patients displayed almost clearly a specific pattern for SLC19A3 defect, as previously proposed in diagnostic criteria. Our study presents a detailed description of neuropathological and MRI findings of both patients. We confirm that the autopsy and/or MRI of the brain is sufficient to qualify a patient with an unknown neuropathological disorder directly for SLC19A3 mutations testing and a prompt trial of specific treatment.

Healthy ageing in the Nun Study: definition and neuropathologic correlates.

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Tyas, Suzanne L; Snowdon, David A; Desrosiers, Mark F; Riley, Kathryn P; Markesbery, William R

2007-11-01

Although the concept of healthy ageing has stimulated considerable interest, no generally accepted definition has been developed nor has its biological basis been determined. To develop a definition of healthy ageing and investigate its association with longevity and neuropathology. Analyses were based on cognitive, physical, and post-mortem assessments from 1991 to 1998 in the Nun Study, a longitudinal study of ageing in participants 75+ years at baseline. We defined three mutually exclusive levels of healthy ageing (excellent, very good, and good) based on measures of global cognitive function, short-term memory, basic and instrumental activities of daily living, and self-rated function. Mortality analyses were based on 636 participants; neuropathologic analyses were restricted to 221 who had died and were autopsied. Only 11% of those meeting criteria for the excellent level of healthy ageing at baseline subsequently died, compared with 24% for the very good, 39% for the good, and 60% for the remaining participants. Survival curves showed significantly greater longevity with higher levels of healthy ageing. The risk of not attaining healthy ageing, adjusted for age, increased two-fold in participants with brain infarcts alone, six-fold in those with Alzheimer neuropathology alone, and more than thirteen-fold in those with both brain infarcts and Alzheimer neuropathology. The biological validity of our definition of healthy ageing is supported by its strong association with mortality and longevity. Avoiding Alzheimer and stroke neuropathology is critical to the maintenance of healthy ageing, and the presence of both pathologies dramatically decreases the likelihood of healthy ageing.

A Mutual Self- and Informant-Report of Cognitive Complaint Correlates with Neuropathological Outcomes in Mild Cognitive Impairment.

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Katherine A Gifford

Full Text Available This study examines whether different sources of cognitive complaint (i.e., self and informant predict Alzheimer's disease (AD neuropathology in elders with mild cognitive impairment (MCI.Data were drawn from the National Alzheimer's Coordinating Center Uniform and Neuropathology Datasets (observational studies for participants with a clinical diagnosis of MCI and postmortem examination (n = 1843, 74±8 years, 52% female. Cognitive complaint (0.9±0.5 years prior to autopsy was classified into four mutually exclusive groups: no complaint, self-only, informant-only, or mutual (both self and informant complaint. Postmortem neuropathological outcomes included amyloid plaques and neurofibrillary tangles. Proportional odds regression related complaint to neuropathology, adjusting for age, sex, race, education, depressed mood, cognition, APOE4 status, and last clinical visit to death interval.Mutual complaint related to increased likelihood of meeting NIA/Reagan Institute (OR = 6.58, p = 0.004 and Consortium to Establish a Registry for Alzheimer's Disease criteria (OR = 5.82, p = 0.03, and increased neurofibrillary tangles (OR = 3.70, p = 0.03, neuritic plaques (OR = 3.52, p = 0.03, and diffuse plaques (OR = 4.35, p = 0.02. Informant-only and self-only complaint was not associated with any neuropathological outcome (all p-values>0.12.In MCI, mutual cognitive complaint relates to AD pathology whereas self-only or informant-only complaint shows no relation to pathology. Findings support cognitive complaint as a marker of unhealthy brain aging and highlight the importance of obtaining informant corroboration to increase confidence of underlying pathological processes.

Relation of genomic variants for Alzheimer disease dementia to common neuropathologies.

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Farfel, Jose M; Yu, Lei; Buchman, Aron S; Schneider, Julie A; De Jager, Philip L; Bennett, David A

2016-08-02

To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies. © 2016 American Academy of Neurology.

Linking Essential Tremor to the Cerebellum: Neuropathological Evidence.

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Louis, Elan D

2016-06-01

A fundamental question about essential tremor (ET) is whether its associated pathological changes and disease mechanisms are linkable to a specific brain region. To that end, recent tissue-based studies have made significant strides in elucidating changes in the ET brain. Emerging from these studies is increasing neuropathological evidence linking ET to the cerebellum. These studies have systematically identified a broad range of structural, degenerative changes in the ET cerebellum, spanning across all Purkinje cell compartments. These include the dendritic compartment (where there is an increase in number of Purkinje cell dendritic swellings, a pruning of the dendritic arbor, and a reduction in spine density), the cell body (where, aside from reductions in Purkinje cell linear density in some studies, there is an increase in the number of heterotopic Purkinje cell soma), and the axonal compartment (where a plethora of changes in axonal morphology have been observed, including an increase in the number of thickened axonal profiles, torpedoes, axonal recurrent collaterals, axonal branching, and terminal axonal sprouting). Additional changes, possibly due to secondary remodeling, have been observed in neighboring neuronal populations. These include a hypertrophy of basket cell axonal processes and changes in the distribution of climbing fiber-Purkinje cell synapses. These changes all distinguish ET from normal control brains. Initial studies further indicate that the profile (i.e., constellation) of these changes may separate ET from other diseases of the cerebellum, thereby serving as a disease signature. With the discovery of these changes, a new model of ET has arisen, which posits that it may be a neurodegenerative disorder centered in the cerebellar cortex. These newly emerging neuropathological studies pave the way for anatomically focused, hypothesis-driven, molecular mechanistic studies of disease pathogenesis.

Ischemic perinatal brain damage. Neuropathologic and CT correlations

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Crisi, G; Mauri, C; Canossi, G; Della Giustina, E

1986-01-01

The term ''hypoxic-ischemic encephalopathy'' covers a large part of neonatal neuropathology including the various forms of intracerebral haemorrhage. In the present work the term is confined to ischemic brain edema and actual infarction, be it diffuse or focal. Eighteen newborns with CT evidence of ischemic brain lesions and infarctual necrosis were selected. Emphasis is placed on current data on neuropathology of ischemic brain edema and its CT appearance. Particular entities such as periventricular leukomalacia and multicystic encephalopathy are discussed. Relationship between CT and temporal profile of cerebral damage is emphasized in order to predict the structural sequelae and the longterm prognosis. 31 refs.

Neuropathology in mice expressing mouse alpha-synuclein.

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Claus Rieker

Full Text Available α-Synuclein (αSN in human is tightly linked both neuropathologically and genetically to Parkinson's disease (PD and related disorders. Disease-causing properties in vivo of the wildtype mouse ortholog (mαSN, which carries a threonine at position 53 like the A53T human mutant version that is genetically linked to PD, were never reported. To this end we generated mouse lines that express mαSN in central neurons at levels reaching up to six-fold compared to endogenous mαSN. Unlike transgenic mice expressing human wildtype or mutant forms of αSN, these mαSN transgenic mice showed pronounced ubiquitin immunopathology in spinal cord and brainstem. Isoelectric separation of mαSN species revealed multiple isoforms including two Ser129-phosphorylated species in the most severely affected brain regions. Neuronal Ser129-phosphorylated αSN occurred in granular and small fibrillar aggregates and pathological staining patterns in neurites occasionally revealed a striking ladder of small alternating segments staining either for Ser129-phosphorylated αSN or ubiquitin but not both. Axonal degeneration in long white matter tracts of the spinal cord, with breakdown of myelin sheaths and degeneration of neuromuscular junctions with loss of integrity of the presynaptic neurofilament network in mαSN transgenic mice, was similar to what we have reported for mice expressing human αSN wildtype or mutant forms. In hippocampal neurons, the mαSN protein accumulated and was phosphorylated but these neurons showed no ubiquitin immunopathology. In contrast to the early-onset motor abnormalities and muscle weakness observed in mice expressing human αSN, mαSN transgenic mice displayed only end-stage phenotypic alterations that manifested alongside with neuropathology. Altogether these findings show that increased levels of wildtype mαSN does not induce early-onset behavior changes, but drives end-stage pathophysiological changes in murine neurons that are

Updating neuropathology and neuropharmacology of monoaminergic systems.

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Ramsay, Rona R; De Deurwaerdère, Philippe; Di Giovanni, Giuseppe

2016-07-01

This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc. © 2016 The British Pharmacological Society.

Altered lysosome distribution is an early neuropathological event in neurological forms of Gaucher disease.

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Zigdon, Hila; Meshcheriakova, Anna; Farfel-Becker, Tamar; Volpert, Giora; Sabanay, Helena; Futerman, Anthony H

2017-03-01

In the lysosomal storage disorder Gaucher disease (GD), glucosylceramide (GlcCer) accumulates due to the defective activity of glucocerebrosidase. A subset of GD patients develops neuropathology. We now show mislocalization of Limp2-positive puncta and a large reduction in the number of Lamp1-positive puncta, which are associated with impaired tubulin. These changes occur at an early stage in animal models of GD, prior to development of overt symptoms and considerably earlier than neuronal loss. Altered lysosomal localization and cytoskeleton disruption precede the neuroinflammatory pathways, axonal dystrophy and neuronal loss previously characterized in neuronal forms of GD. © 2017 Federation of European Biochemical Societies.

Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia Aging Studies.

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White, Lon R; Edland, Steven D; Hemmy, Laura S; Montine, Kathleen S; Zarow, Chris; Sonnen, Joshua A; Uyehara-Lock, Jane H; Gelber, Rebecca P; Ross, G Webster; Petrovitch, Helen; Masaki, Kamal H; Lim, Kelvin O; Launer, Lenore J; Montine, Thomas J

2016-03-15

To examine frequencies and relationships of 5 common neuropathologic abnormalities identified at autopsy with late-life cognitive impairment and dementia in 2 different autopsy panels. The Nun Study (NS) and the Honolulu-Asia Aging Study (HAAS) are population-based investigations of brain aging that included repeated cognitive assessments and comprehensive brain autopsies. The neuropathologic abnormalities assessed were Alzheimer disease (AD) neuropathologic changes, neocortical Lewy bodies (LBs), hippocampal sclerosis, microinfarcts, and low brain weight. Associations with screening tests for cognitive impairment were examined. Neuropathologic abnormalities occurred at levels ranging from 9.7% to 43%, and were independently associated with cognitive impairment in both studies. Neocortical LBs and AD changes were more frequent among the predominantly Caucasian NS women, while microinfarcts were more common in the Japanese American HAAS men. Comorbidity was usual and very strongly associated with cognitive impairment. Apparent cognitive resilience (no cognitive impairment despite Braak stage V) was strongly associated with minimal or no comorbid abnormalities, with fewer neocortical AD lesions, and weakly with longer interval between final testing and autopsy. Total burden of comorbid neuropathologic abnormalities, rather than any single lesion type, was the most relevant determinant of cognitive impairment in both cohorts, often despite clinical diagnosis of only AD. These findings emphasize challenges to dementia pathogenesis and intervention research and to accurate diagnoses during life. © 2016 American Academy of Neurology.

Frontotemporal dementia with severe thalamic involvement : a clinical and neuropathological study

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Radanovic Márcia

2003-01-01

Full Text Available Frontotemporal dementia (FTD is the third-leading cause of cortical dementia after Alzheimer's disease and Lewy body dementia, and is characterized by a dementia where behavioral disturbances are prominent and appear early in the course of the disease. We report the case of a 58 year-old man affected by dementia with behavioral disturbances, in addition to rigid-hypokinetic and a lower motor neuron syndrome that were present at later stages of the illness. Neuroimaging studies showed frontotemporal atrophy. Neuropathological studies revealed intense thalamic neuronal loss and astrocytic gliosis, as well as moderate frontotemporal neuronal loss, astrocytosis and spongiform degeneration. Thalamic degeneration has previously been described among the wide group of neuropathological features of FTD. The aim of the present study is to show the clinical and neuropathological aspects of thalamic degeneration in FTD, along with its role in behavioral disturbances, a common finding in this condition.

The neuropathology of sport.

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McKee, Ann C; Daneshvar, Daniel H; Alvarez, Victor E; Stein, Thor D

2014-01-01

The benefits of regular exercise, physical fitness and sports participation on cardiovascular and brain health are undeniable. Physical activity reduces the risk for cardiovascular disease, type 2 diabetes, hypertension, obesity, and stroke, and produces beneficial effects on cholesterol levels, antioxidant systems, inflammation, and vascular function. Exercise also enhances psychological health, reduces age-related loss of brain volume, improves cognition, reduces the risk of developing dementia, and impedes neurodegeneration. Nonetheless, the play of sports is associated with risks, including a risk for mild TBI (mTBI) and, rarely, catastrophic traumatic injury and death. There is also growing awareness that repetitive mTBIs, such as concussion and subconcussion, can occasionally produce persistent cognitive, behavioral, and psychiatric problems as well as lead to the development of a neurodegeneration, chronic traumatic encephalopathy (CTE). In this review, we summarize the beneficial aspects of sports participation on psychological, emotional, physical and cognitive health, and specifically analyze some of the less common adverse neuropathological outcomes, including concussion, second-impact syndrome, juvenile head trauma syndrome, catastrophic sudden death, and CTE. CTE is a latent neurodegeneration clinically associated with behavioral changes, executive dysfunction and cognitive impairments, and pathologically characterized by frontal and temporal lobe atrophy, neuronal and axonal loss, and abnormal deposits of paired helical filament (PHF)-tau and 43 kDa TAR deoxyribonucleic acid (DNA)-binding protein (TDP-43). CTE often occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including motor neuron disease (CTE-MND). Although the incidence and prevalence of CTE are not known, CTE has been reported most frequently in American football players and boxers. Other sports associated with CTE include ice hockey, professional

Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias.

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Gary W Beecham

2014-09-01

Full Text Available Alzheimer's disease (AD and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study and analysis of known genetic risk loci for AD dementia using neuropathologic data from 4,914 brain autopsies. Neuropathologic data were used to define clinico-pathologic AD dementia or controls, assess core neuropathologic features of AD (neuritic plaques, NPs; neurofibrillary tangles, NFTs, and evaluate commonly co-morbid neuropathologic changes: cerebral amyloid angiopathy (CAA, Lewy body disease (LBD, hippocampal sclerosis of the elderly (HS, and vascular brain injury (VBI. Genome-wide significance was observed for clinico-pathologic AD dementia, NPs, NFTs, CAA, and LBD with a number of variants in and around the apolipoprotein E gene (APOE. GalNAc transferase 7 (GALNT7, ATP-Binding Cassette, Sub-Family G (WHITE, Member 1 (ABCG1, and an intergenic region on chromosome 9 were associated with NP score; and Potassium Large Conductance Calcium-Activated Channel, Subfamily M, Beta Member 2 (KCNMB2 was strongly associated with HS. Twelve of the 21 non-APOE genetic risk loci for clinically-defined AD dementia were confirmed in our clinico-pathologic sample: CR1, BIN1, CLU, MS4A6A, PICALM, ABCA7, CD33, PTK2B, SORL1, MEF2C, ZCWPW1, and CASS4 with 9 of these 12 loci showing larger odds ratio in the clinico-pathologic sample. Correlation of effect sizes for risk of AD dementia with effect size for NFTs or NPs showed positive correlation, while those for risk of VBI showed a moderate negative correlation. The other co-morbid neuropathologic features showed only nominal association with the known AD loci. Our results discovered new genetic associations with specific neuropathologic features and aligned known genetic risk for AD dementia with specific neuropathologic changes in the largest brain autopsy study of AD and related

GENE-07. MOLECULAR NEUROPATHOLOGY 2.0 - INCREASING DIAGNOSTIC ACCURACY IN PEDIATRIC NEUROONCOLOGY

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Sturm, Dominik; Jones, David T.W.; Capper, David; Sahm, Felix; von Deimling, Andreas; Rutkoswki, Stefan; Warmuth-Metz, Monika; Bison, Brigitte; Gessi, Marco; Pietsch, Torsten; Pfister, Stefan M.

2017-01-01

Abstract The classification of central nervous system (CNS) tumors into clinically and biologically distinct entities and subgroups is challenging. Children and adolescents can be affected by >100 histological variants with very variable outcomes, some of which are exceedingly rare. The current WHO classification has introduced a number of novel molecular markers to aid routine neuropathological diagnostics, and DNA methylation profiling is emerging as a powerful tool to distinguish CNS tumor classes. The Molecular Neuropathology 2.0 study aims to integrate genome wide (epi-)genetic diagnostics with reference neuropathological assessment for all newly-diagnosed pediatric brain tumors in Germany. To date, >350 patients have been enrolled. A molecular diagnosis is established by epigenetic tumor classification through DNA methylation profiling and targeted panel sequencing of >130 genes to detect diagnostically and/or therapeutically useful DNA mutations, structural alterations, and fusion events. Results are aligned with the reference neuropathological diagnosis, and discrepant findings are discussed in a multi-disciplinary tumor board including reference neuroradiological evaluation. Ten FFPE sections as input material are sufficient to establish a molecular diagnosis in >95% of tumors. Alignment with reference pathology results in four broad categories: a) concordant classification (~77%), b) discrepant classification resolvable by tumor board discussion and/or additional data (~5%), c) discrepant classification without currently available options to resolve (~8%), and d) cases currently unclassifiable by molecular diagnostics (~10%). Discrepancies are enriched in certain histopathological entities, such as histological high grade gliomas with a molecularly low grade profile. Gene panel sequencing reveals predisposing germline events in ~10% of patients. Genome wide (epi-)genetic analyses add a valuable layer of information to routine neuropathological

African ancestry protects against Alzheimer's disease-related neuropathology.

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Schlesinger, D; Grinberg, L T; Alba, J G; Naslavsky, M S; Licinio, L; Farfel, J M; Suemoto, C K; de Lucena Ferretti, R E; Leite, R E P; de Andrade, M P; dos Santos, A C F; Brentani, H; Pasqualucci, C A; Nitrini, R; Jacob-Filho, W; Zatz, M

2013-01-01

Previous studies in dementia epidemiology have reported higher Alzheimer's disease rates in African-Americans when compared with White Americans. To determine whether genetically determined African ancestry is associated with neuropathological changes commonly associated with dementia, we analyzed a population-based brain bank in the highly admixed city of São Paulo, Brazil. African ancestry was estimated through the use of previously described ancestry-informative markers. Risk of presence of neuritic plaques, neurofibrillary tangles, small vessel disease, brain infarcts and Lewy bodies in subjects with significant African ancestry versus those without was determined. Results were adjusted for multiple environmental risk factors, demographic variables and apolipoprotein E genotype. African ancestry was inversely correlated with neuritic plaques (P=0.03). Subjects with significant African ancestry (n=112, 55.4%) showed lower prevalence of neuritic plaques in the univariate analysis (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.55-0.95, P=0.01) and when adjusted for age, sex, APOE genotype and environmental risk factors (OR 0.43, 95% CI 0.21-0.89, P=0.02). There were no significant differences for the presence of other neuropathological alterations. We show for the first time, using genetically determined ancestry, that African ancestry may be highly protective of Alzheimer's disease neuropathology, functioning through either genetic variants or unknown environmental factors. Epidemiological studies correlating African-American race/ethnicity with increased Alzheimer's disease rates should not be interpreted as surrogates of genetic ancestry or considered to represent African-derived populations from the developing nations such as Brazil.

Delayed recall, hippocampal volume and Alzheimer neuropathology: findings from the Nun Study.

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Mortimer, J A; Gosche, K M; Riley, K P; Markesbery, W R; Snowdon, D A

2004-02-10

To examine the associations of hippocampal volume and the severity of neurofibrillary lesions determined at autopsy with delayed verbal recall performance evaluated an average of 1 year prior to death. Hippocampal volumes were computed using postmortem brain MRI from the first 56 scanned participants of the Nun Study. Quantitative neuropathologic studies included lesion counts, Braak staging, and determination of whether neuropathologic criteria for Alzheimer disease (AD) were met. Multiple regression was used to assess the association of hippocampal volume and neuropathologic lesions with the number of words (out of 10) recalled on the Consortium to Establish a Registry for Alzheimer's Disease Delayed Word Recall Test administered an average of 1 year prior to death. When entered separately, hippocampal volume, Braak stage, and the mean neurofibrillary tangle counts in the CA-1 region of the hippocampus and the subiculum were strongly associated with the number of words recalled after a delay, adjusting for age and education. When hippocampal volume was entered together with each neuropathologic index, only hippocampal volume retained a significant association with the delayed recall measure. The association between hippocampal volume and the number of words recalled was present in both demented and nondemented individuals as well as in those with and without substantial AD neurofibrillary pathology. The association of neurofibrillary tangles with delayed verbal recall may reflect associated hippocampal atrophy.

Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap

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Gandal, Michael J; Haney, Jillian R; Parikshak, Neelroop N

2018-01-01

-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation...

Fluoxetine Ameliorates Behavioral and Neuropathological Deficits in a Transgenic Model Mouse of α-synucleinopathy

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Ubhi, Kiren; Inglis, Chandra; Mante, Michael; Patrick, Christina; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; May, Verena; Winkler, Juergen; Masliah, Eliezer

2013-01-01

The term α-synucleinopathies refers to a group of age-related neurological disorders including Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) that display an abnormal accumulation of alpha-synuclein (α-syn). In contrast to the neuronal α-syn accumulation observed in PD and DLB, MSA is characterized by a widespread oligodendrocytic α-syn accumulation. Transgenic mice expressing human α-syn under the oligodendrocyte-specific myelin basic protein promoter (MBP1-hαsyn tg mice) model many of the behavioral and neuropathological alterations observed in MSA. Fluoxetine, a selective serotonin reuptake inhibitor, has been shown to be protective in toxin-induced models of PD, however its effects in an in vivo transgenic model of α-synucleinopathy remain unclear. In this context, this study examined the effect of fluoxetine in the MBP1-hαsyn tg mice, a model of MSA. Fluoxetine adminstration ameliorated motor deficits in the MBP1-hαsyn tg mice, with a concomitant decrease in neurodegenerative pathology in the basal ganglia, neocortex and hippocampus. Fluoxetine adminstration also increased levels of the neurotrophic factors, GDNF (glial-derived neurotrophic factor) and BDNF (brain-derived neurotrophic factor) in the MBP1-hαsyn tg mice compared to vehicle-treated tg mice. This fluoxetine-induced increase in GDNF and BDNF protein levels was accompanied by activation of the ERK signaling pathway. The effects of fluoxetine adminstration on myelin and serotonin markers were also examined. Collectively these results indicate that fluoxetine may represent a novel therapeutic intervention for MSA and other neurodegenerative disorders. PMID:22281106

The Neurobiology and Genetics of Impulse Control Disorders: Relationships to Drug Addictions

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Brewer, Judson A.; Potenza, Marc N.

2008-01-01

Impulse control disorders (ICDs), including pathological gambling, trichotillomania, kleptomania and others, have been conceptualized to lie along an impulsive-compulsive spectrum. Recent data have suggested that these disorders may be considered addictions. Here we review the genetic and neuropathological bases of the impulse control disorders and consider the disorders within these non-mutually exclusive frameworks. PMID:17719013

Dopamine and oxytocin interactions underlying behaviors: potential contributions to behavioral disorders.

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Baskerville, Tracey A; Douglas, Alison J

2010-06-01

Dopamine is an important neuromodulator that exerts widespread effects on the central nervous system (CNS) function. Disruption in dopaminergic neurotransmission can have profound effects on mood and behavior and as such is known to be implicated in various neuropsychiatric behavioral disorders including autism and depression. The subsequent effects on other neurocircuitries due to dysregulated dopamine function have yet to be fully explored. Due to the marked social deficits observed in psychiatric patients, the neuropeptide, oxytocin is emerging as one particular neural substrate that may be influenced by the altered dopamine levels subserving neuropathologic-related behavioral diseases. Oxytocin has a substantial role in social attachment, affiliation and sexual behavior. More recently, it has emerged that disturbances in peripheral and central oxytocin levels have been detected in some patients with dopamine-dependent disorders. Thus, oxytocin is proposed to be a key neural substrate that interacts with central dopamine systems. In addition to psychosocial improvement, oxytocin has recently been implicated in mediating mesolimbic dopamine pathways during drug addiction and withdrawal. This bi-directional role of dopamine has also been implicated during some components of sexual behavior. This review will discuss evidence for the existence dopamine/oxytocin positive interaction in social behavioral paradigms and associated disorders such as sexual dysfunction, autism, addiction, anorexia/bulimia, and depression. Preliminary findings suggest that whilst further rigorous testing has to be conducted to establish a dopamine/oxytocin link in human disorders, animal models seem to indicate the existence of broad and integrated brain circuits where dopamine and oxytocin interactions at least in part mediate socio-affiliative behaviors. A profound disruption to these pathways is likely to underpin associated behavioral disorders. Central oxytocin pathways may serve as a

Impact of Cytokines and Chemokines on Alzheimer's Disease Neuropathological Hallmarks.

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Domingues, Catarina; da Cruz E Silva, Odete A B; Henriques, Ana Gabriela

2017-01-01

Alzheimer's disease (AD) is the most common neurodegenerative disorder, neuropathologically characterized by aggregates of β-amyloid peptides, which deposit as senile plaques, and of TAU protein, which forms neurofibrillary tangles. It is now widely accepted that neuroinflammation is implicated in AD pathogenesis. Indeed, inflammatory mediators, such as cytokines and chemokines (chemotactic cytokines) can impact on the Alzheimer´s amyloid precursor protein by affecting its expression levels and amyloidogenic processing and/or β -amyloid aggregation. Additionally, cytokines and chemokines can influence kinases' activities, leading to abnormal TAU phosphorylation. To date there is no cure for AD, but several therapeutic strategies have been directed to prevent neuroinflammation. Anti-inflammatory, but also anti-amyloidogenic compounds, such as flavonoids were shown to favourably modulate some pathological events associated with neurodegeneration. This review focuses on the role of cytokines and chemokines in AD-associated pathologies, and summarizes the potential anti-inflammatory therapeutic approaches aimed at preventing or slowing down disease progression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fluoxetine ameliorates behavioral and neuropathological deficits in a transgenic model mouse of α-synucleinopathy.

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Ubhi, Kiren; Inglis, Chandra; Mante, Michael; Patrick, Christina; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; May, Verena; Winkler, Juergen; Masliah, Eliezer

2012-04-01

The term α-synucleinopathies refers to a group of age-related neurological disorders including Parkinson's disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) that display an abnormal accumulation of alpha-synuclein (α-syn). In contrast to the neuronal α-syn accumulation observed in PD and DLB, MSA is characterized by a widespread oligodendrocytic α-syn accumulation. Transgenic mice expressing human α-syn under the oligodendrocyte-specific myelin basic protein promoter (MBP1-hαsyn tg mice) model many of the behavioral and neuropathological alterations observed in MSA. Fluoxetine, a selective serotonin reuptake inhibitor, has been shown to be protective in toxin-induced models of PD, however its effects in an in vivo transgenic model of α-synucleinopathy remain unclear. In this context, this study examined the effect of fluoxetine in the MBP1-hαsyn tg mice, a model of MSA. Fluoxetine administration ameliorated motor deficits in the MBP1-hαsyn tg mice, with a concomitant decrease in neurodegenerative pathology in the basal ganglia, neocortex and hippocampus. Fluoxetine administration also increased levels of the neurotrophic factors, GDNF (glial-derived neurotrophic factor) and BDNF (brain-derived neurotrophic factor) in the MBP1-hαsyn tg mice compared to vehicle-treated tg mice. This fluoxetine-induced increase in GDNF and BDNF protein levels was accompanied by activation of the ERK signaling pathway. The effects of fluoxetine administration on myelin and serotonin markers were also examined. Collectively these results indicate that fluoxetine may represent a novel therapeutic intervention for MSA and other neurodegenerative disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9

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Loy Clement T

2008-08-01

Full Text Available Abstract Background Frontotemporal lobar degeneration (FTLD represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD and motor neuron disease (MND. The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND. Methods Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing. Results Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree. Conclusion Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease

Tau, APP, NCT and BACE1 in lymphocytes through cognitively normal ageing and neuropathology

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MARISOL HERRERA-RIVERO

2013-01-01

Full Text Available Although Alzheimer's disease is a brain disorder, a number of peripheral alterations have been found in these patients; however, little is known about how the key genes involved in the pathophysiology express in peripheral cells such as lymphocytes during normal compared to neuropathological ageing. We analysed the expression of tau, of the amyloid precursor protein, of nicastrin and of the β-site APP cleaving enzyme genes by RT-PCR in lymphocytes from a small group of late-onset Alzheimer's disease patients, from aged patients suffering from neuropsychological conditions different from Alzheimer's and from cognitively healthy subjects divided in four groups by age. We also investigated correlations between gene expression and levels of blood pressure, glucose, total cholesterol and triglycerides as risk factors for Alzheimer's. Results show no tau expression in lymphocytes, a lack of detection of nicastrin expression in Alzheimer's patients and correlations between the medical conditions studied and gene expression in lymphocytes. We believe nicastrin gene expression in lymphocytes should be considered of interest for further analyses in a wider population to investigate whether it might represent a potential biomarker to differentiate Alzheimer's from other neuropsychological disorders.

Cerebral Dysfunctions Related to Perinatal Organic Damage: Clinical-Neuropathologic Correlations.

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Towbin, Abraham

1978-01-01

Recent neuropathology studies identify hypoxia as the main cause of perinatal cerebral damage. Cerebral lesions present at birth, with transition to chronic scar lesions, are correlated to mental retardation, cerebral palsy, epilepsy, and minimal brain dysfunction. Gestation age and severity of hypoxic exposure essentially determine the cerebral…

Neuropathological biomarker candidates in brain tumors: key issues for translational efficiency.

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Hainfellner, J A; Heinzl, H

2010-01-01

Brain tumors comprise a large spectrum of rare malignancies in children and adults that are often associated with severe neurological symptoms and fatal outcome. Neuropathological tumor typing provides both prognostic and predictive tissue information which is the basis for optimal postoperative patient management and therapy. Molecular biomarkers may extend and refine prognostic and predictive information in a brain tumor case, providing more individualized and optimized treatment options. In the recent past a few neuropathological brain tumor biomarkers have translated smoothly into clinical use whereas many candidates show protracted translation. We investigated the causes of protracted translation of candidate brain tumor biomarkers. Considering the research environment from personal, social and systemic perspectives we identified eight determinants of translational success: methodology, funding, statistics, organization, phases of research, cooperation, self-reflection, and scientific progeny. Smoothly translating biomarkers are associated with low degrees of translational complexity whereas biomarkers with protracted translation are associated with high degrees. Key issues for translational efficiency of neuropathological brain tumor biomarker research seem to be related to (i) the strict orientation to the mission of medical research, that is the improval of medical practice as primordial purpose of research, (ii) definition of research priorities according to clinical needs, and (iii) absorption of translational complexities by means of operatively beneficial standards. To this end, concrete actions should comprise adequate scientific education of young investigators, and shaping of integrative diagnostics and therapy research both on the local level and the level of influential international brain tumor research platforms.

TREM2 Overexpression has No Improvement on Neuropathology and Cognitive Impairment in Aging APPswe/PS1dE9 Mice.

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Jiang, Teng; Wan, Yu; Zhang, Ying-Dong; Zhou, Jun-Shan; Gao, Qing; Zhu, Xi-Chen; Shi, Jian-Quan; Lu, Huan; Tan, Lan; Yu, Jin-Tai

2017-03-01

Previously, we showed that overexpression of triggering receptor expressed on myeloid cells 2 (TREM2), a microglia-specific immune receptor, in the brain of a middle-aged (7 months old) APPswe/PS1dE9 mice could ameliorate Alzheimer's disease (AD)-related neuropathology by enhancement of microglial amyloid-β (Aβ) phagocytosis. Since AD is an age-related neurodegenerative disorder, it is critical to assess the efficacy of TREM2 overexpression in aging animals with an advanced disease stage. In vivo, we employed a lentiviral strategy to overexpress TREM2 in the brain of aging (18 months old) APPswe/PS1dE9 mice, and observed its efficacy on AD-related neuropathology and cognitive functions. Afterwards, we directly isolated microglia from middle-aged and aging APPswe/PS1dE9 mice and determined effects of TREM2 overexpression on microglial Aβ phagocytosis and Aβ-binding receptors expression in vitro. In aging APPswe/PS1dE9 mice, TREM2 overexpression has no beneficial effect on AD-related neuropathology and spatial cognitive functions. Of note, in vitro experiments showed a significant reduction of Aβ phagocytosis in microglia from aging APPswe/PS1dE9 mice, possibly attributing to the declined expression of Aβ-binding receptors. Meanwhile, this phagocytic deficit in microglia from aging APPswe/PS1dE9 mice cannot be rescued by TREM2 overexpression. Taken together, our study shows that TREM2 overexpression fails to provide neuroprotection in aging APPswe/PS1dE9 mice, possibly attributing to deficits in microglial Aβ phagocytosis at the late-stage of disease progression. These findings indicate that TREM2-mediated protection in AD is at least partially dependent on the reservation of microglial phagocytic functions, emphasizing the importance of early therapeutic interventions for this devastating disease.

Early life linguistic ability, late life cognitive function, and neuropathology: findings from the Nun Study.

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Riley, Kathryn P; Snowdon, David A; Desrosiers, Mark F; Markesbery, William R

2005-03-01

The relationships between early life variables, cognitive function, and neuropathology were examined in participants in the Nun Study who were between the ages of 75 and 95. Our early life variable was idea density, which is a measure of linguistic ability, derived from autobiographies written at a mean age of 22 years. Six discrete categories of cognitive function, including mild cognitive impairments, were evaluated, using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. Neuropathologic data included Braak staging, neurofibrillary tangle and senile plaque counts, brain weight, degree of cerebral atrophy, severity of atherosclerosis, and the presence of brain infarcts. Early-life idea density was significantly related to the categories of late-life cognitive function, including mild cognitive impairments: low idea density was associated with greater impairment. Low idea density also was significantly associated with lower brain weight, higher degree of cerebral atrophy, more severe neurofibrillary pathology, and the likelihood of meeting neuropathologic criteria for Alzheimer's disease.

Trends in the Molecular Pathogenesis and Clinical Therapeutics of Common Neurodegenerative Disorders

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Sibongile R. Sibambo

2009-06-01

Full Text Available The term neurodegenerative disorders, encompasses a variety of underlying conditions, sporadic and/or familial and are characterized by the persistent loss of neuronal subtypes. These disorders can disrupt molecular pathways, synapses, neuronal subpopulations and local circuits in specific brain regions, as well as higher-order neural networks. Abnormal network activities may result in a vicious cycle, further impairing the integrity and functions of neurons and synapses, for example, through aberrant excitation or inhibition. The most common neurodegenerative disorders are Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis and Huntington’s disease. The molecular features of these disorders have been extensively researched and various unique neurotherapeutic interventions have been developed. However, there is an enormous coercion to integrate the existing knowledge in order to intensify the reliability with which neurodegenerative disorders can be diagnosed and treated. The objective of this review article is therefore to assimilate these disorders’ in terms of their neuropathology, neurogenetics, etiology, trends in pharmacological treatment, clinical management, and the use of innovative neurotherapeutic interventions.

Interactive social neuroscience to study autism spectrum disorder.

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Rolison, Max J; Naples, Adam J; McPartland, James C

2015-03-01

Individuals with autism spectrum disorder (ASD) demonstrate difficulty with social interactions and relationships, but the neural mechanisms underlying these difficulties remain largely unknown. While social difficulties in ASD are most apparent in the context of interactions with other people, most neuroscience research investigating ASD have provided limited insight into the complex dynamics of these interactions. The development of novel, innovative "interactive social neuroscience" methods to study the brain in contexts with two interacting humans is a necessary advance for ASD research. Studies applying an interactive neuroscience approach to study two brains engaging with one another have revealed significant differences in neural processes during interaction compared to observation in brain regions that are implicated in the neuropathology of ASD. Interactive social neuroscience methods are crucial in clarifying the mechanisms underlying the social and communication deficits that characterize ASD.

Neuroimaging Endophenotypes in Autism Spectrum Disorder

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Mahajan, Rajneesh; Mostofsky, Stewart H.

2015-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has a strong genetic basis, and is heterogeneous in its etiopathogenesis and clinical presentation. Neuroimaging studies, in concert with neuropathological and clinical research, have been instrumental in delineating trajectories of development in children with ASD. Structural neuroimaging has revealed ASD to be a disorder with general and regional brain enlargement, especially in the frontotemporal cortices, while functional neuroimaging studies have highlighted diminished connectivity, especially between frontal-posterior regions. The diverse and specific neuroimaging findings may represent potential neuroendophenotypes, and may offer opportunities to further understand the etiopathogenesis of ASD, predict treatment response and lead to the development of new therapies. PMID:26234701

Neuropathological assessment and validation of mouse models for Alzheimer's disease: applying NIA-AA guidelines

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C. Dirk Keene

2016-06-01

Full Text Available Dozens of transgenic mouse models, generally based on mutations associated with familial Alzheimer's disease (AD, have been developed, in part, for preclinical testing of candidate AD therapies. However, none of these models has successfully predicted the clinical efficacy of drugs for treating AD patients. Therefore, development of more translationally relevant AD mouse models remains a critical unmet need in the field. A concept not previously implemented in AD preclinical drug testing is the use of mouse lines that have been validated for neuropathological features of human AD. Current thinking suggests that amyloid plaque and neurofibrillary tangle deposition is an essential component for accurate modeling of AD. Therefore, the AD translational paradigm would require pathologic Aβ and tau deposition, a disease-relevant distribution of plaques and tangles, and a pattern of disease progression of Aβ and tau isoforms similar to the neuropathological features found in the brains of AD patients. Additional parameters useful to evaluate parallels between AD and animal models would include 1 cerebrospinal fluid (CSF AD biomarker changes with reduced Aβ and increased phospho-tau/tau; 2 structural and functional neuroimaging patterns including MRI hippocampal atrophy, fluorodeoxyglucose (FDG, and amyloid/tau PET alterations in activity and/or patterns of pathologic peptide deposition and distribution; and 3 cognitive impairment with emphasis on spatial learning and memory to distinguish presymptomatic and symptomatic mice at specific ages. A validated AD mouse model for drug testing would likely show tau-related neurofibrillary degeneration following Aβ deposition and demonstrate changes in pathology, CSF analysis, and neuroimaging that mirror human AD. Development of the ideal model would revolutionize the ability to establish the translational value of AD mouse models and serve as a platform for discussions about national phenotyping guidelines

Professor Camillo Negro's Neuropathological Films.

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Chiò, Adriano; Gianetto, Claudia; Dagna, Stella

2016-01-01

Camillo Negro, Professor in Neurology at the University of Torino, was a pioneer of scientific film. From 1906 to 1908, with the help of his assistant Giuseppe Roasenda and in collaboration with Roberto Omegna, one of the most experienced cinematographers in Italy, he filmed some of his patients for scientific and educational purposes. During the war years, he continued his scientific film project at the Military Hospital in Torino, filming shell-shocked soldiers. In autumn 2011, the Museo Nazionale del Cinema, in partnership with the Faculty of Neurosciences of the University of Torino, presented a new critical edition of the neuropathological films directed by Negro. The Museum's collection also includes 16 mm footage probably filmed in 1930 by Doctor Fedele Negro, Camillo's son. One of these films is devoted to celebrating the effects of the so-called "Bulgarian cure" on Parkinson's disease.

Congenital Hypothalamic "Hamartoblastoma" Versus "Hamartoma": Suggestions for Neuropathologic Terminology Emanating From a Mid-gestational Autopsy Case of Pallister-Hall Syndrome.

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Dunham, C; McFadden, D; Dahlgren, L; Butler, B; Hamilton, S; McKinnon, M

2018-01-01

Pallister-Hall syndrome (PHS) is a rare malformative disorder that is due to truncating functional repressor mutations in GLI3. Since the seminal publication in 1980, hypothalamic tumors have been recognized to be a cardinal feature of PHS. In their original description of the neuropathologic features of PHS, Clarren et al. coined the term "hamartoblastoma" to characterize what they deemed to be a dual malformative and neoplastic mass of the hypothalamus. In subsequent published cases/series of PHS, the term "hamartoma" was often substituted for hamartoblastoma given what appeared to be a benign natural history of this lesion. Additional confusion in the literature has ensued since most hypothalamic hamartomas (HH) encountered on the clinical neuropathology service are "isolated" in nature (ie, no other congenital malformations) and present in a very different and stereotypical fashion with gelastic seizures and/or precocious puberty. While genomic investigations of isolated HH have begun to uncover a mutational profile of these cases, GLI3 mutations have only been recognized in a small subset of isolated HH. Herein, we describe the autopsy findings from a 21-week gestational age fetus with features of PHS. Moreover, we provide a detailed description of the hypothalamic tumor affecting this fetus and propose a novel subclassification of HH, distinguishing syndromic from isolated forms based upon the presence or absence of neocortical-like areas.

Core neuropathological abnormalities in progranulin-deficient mice are penetrant on multiple genetic backgrounds.

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Petkau, T L; Hill, A; Leavitt, B R

2016-02-19

Loss-of-function mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal lobar degeneration (FTLD). A high degree of heterogeneity in the age-of-onset, duration of disease, and clinical presentation of FTLD, even among families carrying the same GRN mutation, suggests that additional modifying genes may be important to pathogenesis. Progranulin-knockout mice display subtle behavioral abnormalities and progressive neuropathological changes, as well as altered dendritic morphology and synaptic deficits in the hippocampus. In this study we evaluated multiple neuropathological endpoints in aged progranulin knockout mice and their wild-type littermates on two different genetic backgrounds: C57Bl/6 and 129/SvImJ. We find that in most brain regions, both strains are susceptible to progranulin-mediated neuropathological phenotypes, including astrogliosis, microgliosis, and highly accelerated deposition of the aging pigment lipofuscin. Neuroinflammation due to progranulin deficiency is exaggerated in the B6 strain and present, but less pronounced, in the 129 strain. Differences between the strains in hippocampal neuron counts and neuronal morphology suggest a complex role for progranulin in the hippocampus. We conclude that core progranulin-mediated neurodegenerative phenotypes are penetrant on multiple inbred mouse strains, but that genetic background modulates progranulin's role in neuroinflammation and hippocampal biology. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Alzheimer neuropathology without frontotemporal lobar degeneration hallmarks (TAR DNA-binding protein 43 inclusions) in missense progranulin mutation Cys139Arg.

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Redaelli, Veronica; Rossi, Giacomina; Maderna, Emanuela; Kovacs, Gabor G; Piccoli, Elena; Caroppo, Paola; Cacciatore, Francesca; Spinello, Sonia; Grisoli, Marina; Sozzi, Giuliano; Salmaggi, Andrea; Tagliavini, Fabrizio; Giaccone, Giorgio

2018-01-01

Null mutations in progranulin gene (GRN) reduce the progranulin production resulting in haploinsufficiency and are tightly associated with tau-negative frontotemporal lobar degeneration with TAR DNA-binding protein 43-positive inclusions (FTLD-TDP). Missense mutations of GRN were also identified, but their effects are not completely clear, in particular unanswered is the question of what neuropathology they elicit, also considering that their occurrence has been reported in patients with typical clinical features of Alzheimer disease. They describe two fraternal twins carrying the missense GRN Cys139Arg mutation affected by late-onset dementia and we report the neuropathological study of one of them. Both patients were examined by neuroimaging, neuropsychological assessment and genetic analysis of GRN and other genes associated with dementia. The brain of one was obtained at autopsy and examined neuropathologically. One sister presented clinical and MRI features leading to the diagnosis of Alzheimer disease. The other underwent autopsy and the brain showed neuropathological hallmarks of Alzheimer disease with abundant Aβ-amyloid deposition and Braak stage V of neurofibrillary pathology, in the absence of the hallmark lesions of FTLD-TDP. Their findings may contribute to better clarify the role of progranulin in neurodegenerative diseases indicating that some GRN mutations, in particular missense ones, may act as strong risk factor for Alzheimer disease rather than induce FTLD-TDP. © 2016 International Society of Neuropathology.

A retrospective study of the neuropathology and diagnosis of naturally occurring feline infectious peritonitis.

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Rissi, Daniel R

2018-05-01

Feline infectious peritonitis (FIP) is one of the most important viral diseases of cats worldwide. Our study describes the neuropathology and the diagnostic features of 26 cases of FIP in domestic cats. The average age of affected individuals was 11.8 mo, and there was no sex or breed predisposition. Clinical neurologic signs were noted in 22 cases, and rabies was clinically suspected in 11 cases. Twenty cats had lesions in multiple organs, and 6 cats had lesions only in the brain. Gross neuropathologic changes occurred in 15 cases and consisted of hydrocephalus (10 cases), cerebellar herniation through the foramen magnum (6 cases), cerebral swelling with flattening of gyri (2 cases), and accumulation of fibrin within ventricles (2 cases) or leptomeninges (1 case). Histologically, 3 main distinct distributions of neuropathologic changes were observed, namely periventricular encephalitis (12 cases), rhombencephalitis (8 cases), and diffuse leptomeningitis with superficial encephalitis (6 cases). Fresh tissue samples were submitted for fluorescent antibody testing (FAT) after autopsy in 17 cases, and positive results were found in only 7 cases. Immunohistochemistry (IHC) for feline coronavirus confirmed the diagnosis in all 26 cases. IHC appears to be a more sensitive and reliable test for confirmation of FIP than is FAT.

Bipolar Affective Disorder and Migraine

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Birk Engmann

2012-01-01

Full Text Available This paper consists of a case history and an overview of the relationship, aetiology, and treatment of comorbid bipolar disorder migraine patients. A MEDLINE literature search was used. Terms for the search were bipolar disorder bipolar depression, mania, migraine, mood stabilizer. Bipolar disorder and migraine cooccur at a relatively high rate. Bipolar II patients seem to have a higher risk of comorbid migraine than bipolar I patients have. The literature on the common roots of migraine and bipolar disorder, including both genetic and neuropathological approaches, is broadly discussed. Moreover, bipolar disorder and migraine are often combined with a variety of other affective disorders, and, furthermore, behavioural factors also play a role in the origin and course of the diseases. Approach to treatment options is also difficult. Several papers point out possible remedies, for example, valproate, topiramate, which acts on both diseases, but no first-choice treatments have been agreed upon yet.

Scanning electron microscopy of the neuropathology of murine cerebral malaria

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Brenneis Christian

2006-11-01

Full Text Available Abstract Background The mechanisms leading to death and functional impairments due to cerebral malaria (CM are yet not fully understood. Most of the knowledge about the pathomechanisms of CM originates from studies in animal models. Though extensive histopathological studies of the murine brain during CM are existing, alterations have not been visualized by scanning electron microscopy (SEM so far. The present study investigates the neuropathological features of murine CM by applying SEM. Methods C57BL/6J mice were infected with Plasmodium berghei ANKA blood stages. When typical symptoms of CM developed perfused brains were processed for SEM or light microscopy, respectively. Results Ultrastructural hallmarks were disruption of vessel walls, parenchymal haemorrhage, leukocyte sequestration to the endothelium, and diapedesis of macrophages and lymphocytes into the Virchow-Robin space. Villous appearance of observed lymphocytes were indicative of activated state. Cerebral oedema was evidenced by enlargement of perivascular spaces. Conclusion The results of the present study corroborate the current understanding of CM pathophysiology, further support the prominent role of the local immune system in the neuropathology of CM and might expose new perspectives for further interventional studies.

Resistance to Alzheimer Disease Neuropathologic Changes and Apparent Cognitive Resilience in the Nun and Honolulu-Asia Aging Studies.

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Latimer, Caitlin S; Keene, C Dirk; Flanagan, Margaret E; Hemmy, Laura S; Lim, Kelvin O; White, Lon R; Montine, Kathleen S; Montine, Thomas J

2017-06-01

Two population-based studies key to advancing knowledge of brain aging are the Honolulu-Asia Aging Study (HAAS) and the Nun Study. Harmonization of their neuropathologic data allows cross comparison, with findings common to both studies likely generalizable, while distinct observations may point to aging brain changes that are dependent on sex, ethnicity, environment, or lifestyle factors. Here, we expanded the neuropathologic evaluation of these 2 studies using revised NIA-Alzheimer's Association guidelines and compared directly the neuropathologic features of resistance and apparent cognitive resilience. There were significant differences in prevalence of Alzheimer disease neuropathologic change, small vessel vascular brain injury, and Lewy body disease between these 2 studies, suggesting that sex, ethnicity, and lifestyle factors may significantly influence resistance to developing brain injury with age. In contrast, hippocampal sclerosis prevalence was very similar, but skewed to poorer cognitive performance, suggesting that hippocampal sclerosis could act sequentially with other diseases to impair cognitive function. Strikingly, despite these observed differences, the proportion of individuals resistant to all 4 diseases of brain or displaying apparent cognitive resilience was virtually identical between HAAS and Nun Study participants. Future in vivo validation of these results awaits comprehensive biomarkers of these 4 brain diseases. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

The aging brain and neurodegenerative disorders

International Nuclear Information System (INIS)

Braffman, B.H.; Trojanowski, J.Q.; Atlas, S.W.

1991-01-01

Both the aging brain and neurodegenerative disorders are characterized by a lack of vital endurance of affected neurons resulting in their premature death. Neuronal shrinkage or atrophy and death are normal and inevitable aspects of normal or successful aging; this is unexpected, excessive, and premature in neurodegenerative disorders. These histologic changes result in the neuroimaging findings of focal and/or diffuse atrophy with consequent enlargement of cerebrospinal fluid (CSF) spaces. The aging brain and neurodegenerative disorders share other magnetic resonance (MR) changes, i.e., markedly hypointense extrapyramidal nuclei and hyperintense white matter foci. The sequelae of senescent vascular changes result in additional characteristic features of the aging brain. This paper presents the MR and neuropathologic manifestations of both the normal aging brain and the brain affected by neurodegenerative disorders

4D flow mri post-processing strategies for neuropathologies

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Schrauben, Eric Mathew

4D flow MRI allows for the measurement of a dynamic 3D velocity vector field. Blood flow velocities in large vascular territories can be qualitatively visualized with the added benefit of quantitative probing. Within cranial pathologies theorized to have vascular-based contributions or effects, 4D flow MRI provides a unique platform for comprehensive assessment of hemodynamic parameters. Targeted blood flow derived measurements, such as flow rate, pulsatility, retrograde flow, or wall shear stress may provide insight into the onset or characterization of more complex neuropathologies. Therefore, the thorough assessment of each parameter within the context of a given disease has important medical implications. Not surprisingly, the last decade has seen rapid growth in the use of 4D flow MRI. Data acquisition sequences are available to researchers on all major scanner platforms. However, the use has been limited mostly to small research trials. One major reason that has hindered the more widespread use and application in larger clinical trials is the complexity of the post-processing tasks and the lack of adequate tools for these tasks. Post-processing of 4D flow MRI must be semi-automated, fast, user-independent, robust, and reliably consistent for use in a clinical setting, within large patient studies, or across a multicenter trial. Development of proper post-processing methods coupled with systematic investigation in normal and patient populations pushes 4D flow MRI closer to clinical realization while elucidating potential underlying neuropathological origins. Within this framework, the work in this thesis assesses venous flow reproducibility and internal consistency in a healthy population. A preliminary analysis of venous flow parameters in healthy controls and multiple sclerosis patients is performed in a large study employing 4D flow MRI. These studies are performed in the context of the chronic cerebrospinal venous insufficiency hypothesis. Additionally, a

Neuropathological findings processed by artificial neural networks (ANNs) can perfectly distinguish Alzheimer's patients from controls in the Nun Study.

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Grossi, Enzo; Buscema, Massimo P; Snowdon, David; Antuono, Piero

2007-06-21

Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this study is to discover the hidden and non-linear associations among AD pathognomonic brain lesions and the clinical diagnosis of AD in participants in the Nun Study through Artificial Neural Networks (ANNs) analysis The analyses were based on 26 clinically- and pathologically-confirmed AD cases and 36 controls who had normal cognitive function. The inputs used for the analyses were just NFT and neuritic plaques counts in neocortex and hippocampus, for which, despite substantial differences in mean lesions counts between AD cases and controls, there was a substantial overlap in the range of lesion counts. By taking into account the above four neuropathological features, the overall predictive capability of ANNs in sorting out AD cases from normal controls reached 100%. The corresponding accuracy obtained with Linear Discriminant Analysis was 92.30%. These results were consistently obtained in ten independent experiments. The same experiments were carried out with ANNs on a subgroup of 13 non severe AD patients and on the same 36 controls. The results obtained in terms of prediction accuracy with ANNs were exactly the same. Input relevance analysis confirmed the relative dominance of NFT in neocortex in discriminating between AD patients and controls and indicated the lesser importance played by NP in the hippocampus. The results of this study

EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy

NARCIS (Netherlands)

Byrne, Susan; Jansen, Lara; U-King-Im, Jean-Marie; Siddiqui, Ata; Lidov, Hart G. W.; Bodi, Istvan; Smith, Luke; Mein, Rachael; Cullup, Thomas; Dionisi-Vici, Carlo; Al-Gazali, Lihadh; Al-Owain, Mohammed; Bruwer, Zandre; Al Thihli, Khalid; El-Garhy, Rana; Flanigan, Kevin M.; Manickam, Kandamurugu; Zmuda, Erik; Banks, Wesley; Gershoni-Baruch, Ruth; Mandel, Hanna; Dagan, Efrat; Raas-Rothschild, Annick; Barash, Hila; Filloux, Francis; Creel, Donnell; Harris, Michael; Hamosh, Ada; Kölker, Stefan; Ebrahimi-Fakhari, Darius; Hoffmann, Georg F.; Manchester, David; Boyer, Philip J.; Manzur, Adnan Y.; Lourenco, Charles Marques; Pilz, Daniela T.; Kamath, Arveen; Prabhakar, Prab; Rao, Vamshi K.; Rogers, R. Curtis; Ryan, Monique M.; Brown, Natasha J.; McLean, Catriona A.; Said, Edith; Schara, Ulrike; Stein, Anja; Sewry, Caroline; Travan, Laura; Wijburg, Frits A.; Zenker, Martin; Mohammed, Shehla; Fanto, Manolis; Gautel, Mathias; Jungbluth, Heinz

2016-01-01

Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in

Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease with Cerebellar Atrophy: A Report of a Father and Son.

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Latimer, Caitlin S; Flanagan, Margaret E; Cimino, Patrick J; Jayadev, Suman; Davis, Marie; Hoffer, Zachary S; Montine, Thomas J; Gonzalez-Cuyar, Luis F; Bird, Thomas D; Keene, C Dirk

2017-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a trinucleotide (CAG) repeat expansion in huntingtin (HTT) on chromosome 4. Anticipation can cause longer repeat expansions in children of HD patients. Juvenile Huntington's disease (JHD), defined as HD arising before age 20, accounts for 5-10% of HD cases, with cases arising in the first decade accounting for approximately 1%. Clinically, JHD differs from the predominately choreiform adult onset Huntington's disease (AOHD) with variable presentations, including symptoms such as myoclonus, seizures, Parkinsonism, and cognitive decline. The neuropathologic changes of AOHD are well characterized, but there are fewer reports that describe the neuropathology of JHD. Here we report a case of a six-year-old boy with paternally-inherited JHD caused by 169 CAG trinucleotide repeats who presented at age four with developmental delay, dysarthria, and seizures before dying at age 6. The boy's clinical presentation and neuropathological findings are directly compared to those of his father, who presented with AOHD and 54 repeats. A full autopsy was performed for the JHD case and a brain-only autopsy was performed for the AOHD case. Histochemically- and immunohistochemically-stained slides were prepared from formalin-fixed, paraffin-embedded tissue sections. Both cases had neuropathology corresponding to Vonsattel grade 3. The boy also had cerebellar atrophy with huntingtin-positive inclusions in the cerebellum, findings not present in the father. Autopsies of father and son provide a unique opportunity to compare and contrast the neuropathologic findings of juvenile and adult onset HD while also providing the first immunohistochemical evidence of cerebellar involvement in JHD. Additionally this is the first known report to include findings from peripheral tissue in a case of JHD.

Neuropathologic Studies of the Baltimore Longitudinal Study of Aging (BLSA)

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O’Brien, Richard J.; Resnick, Susan M.; Zonderman, Alan B.; Ferrucci, Luigi; Crain, Barbara J.; Pletnikova, Olga; Rudow, Gay; Iacono, Diego; Riudavets, Miguel A.; Driscoll, Ira; Price, Donald L.; Martin, Lee J.; Troncoso, Juan C.

2010-01-01

The Baltimore Longitudinal Study of Aging (BLSA) was established in 1958 and is one the oldest prospective studies of aging in the USA and the world. The BLSA is supported by the National Institute of Aging (NIA) and its mission is to learn what happens to people as they get old and how to sort out changes due to aging and from those due to disease or other causes. In 1986, an autopsy program combined with comprehensive neurologic and cognitive evaluations was established in collaboration with the Johns Hopkins University Alzheimer’s Disease Research Center (ADRC). Since then, 211 subjects have undergone autopsy. Here we review the key clinical neuropathological correlations from this autopsy series. The focus is on the morphological and biochemical changes that occur in normal aging, and the early neuropathological changes of neurodegenerative diseases, especially Alzheimer’s disease (AD). We highlight the combined clinical, pathologic, morphometric, and biochemical evidence of asymptomatic AD, a state characterized by normal clinical evaluations in subjects with abundant AD pathology. We conclude that in some individuals, successful cognitive aging results from compensatory mechanisms that occur at the neuronal level (i.e., neuronal hypertrophy and synaptic plasticity) whereas a failure of compensation may culminate in disease. PMID:19661626

Neuropathological findings processed by artificial neural networks (ANNs can perfectly distinguish Alzheimer's patients from controls in the Nun Study

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Snowdon David

2007-06-01

Full Text Available Abstract Background Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this study is to discover the hidden and non-linear associations among AD pathognomonic brain lesions and the clinical diagnosis of AD in participants in the Nun Study through Artificial Neural Networks (ANNs analysis Methods The analyses were based on 26 clinically- and pathologically-confirmed AD cases and 36 controls who had normal cognitive function. The inputs used for the analyses were just NFT and neuritic plaques counts in neocortex and hippocampus, for which, despite substantial differences in mean lesions counts between AD cases and controls, there was a substantial overlap in the range of lesion counts. Results By taking into account the above four neuropathological features, the overall predictive capability of ANNs in sorting out AD cases from normal controls reached 100%. The corresponding accuracy obtained with Linear Discriminant Analysis was 92.30%. These results were consistently obtained in ten independent experiments. The same experiments were carried out with ANNs on a subgroup of 13 non severe AD patients and on the same 36 controls. The results obtained in terms of prediction accuracy with ANNs were exactly the same. Input relevance analysis confirmed the relative dominance of NFT in neocortex in discriminating between AD patients and controls and indicated the lesser importance

Clinical and neuropathological features of ALS/FTD with TIA1 mutations.

Science.gov (United States)

Hirsch-Reinshagen, Veronica; Pottier, Cyril; Nicholson, Alexandra M; Baker, Matt; Hsiung, Ging-Yuek R; Krieger, Charles; Sengdy, Pheth; Boylan, Kevin B; Dickson, Dennis W; Mesulam, Marsel; Weintraub, Sandra; Bigio, Eileen; Zinman, Lorne; Keith, Julia; Rogaeva, Ekaterina; Zivkovic, Sasha A; Lacomis, David; Taylor, J Paul; Rademakers, Rosa; Mackenzie, Ian R A

2017-12-07

Mutations in the stress granule protein T-cell restricted intracellular antigen 1 (TIA1) were recently shown to cause amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD). Here, we provide detailed clinical and neuropathological descriptions of nine cases with TIA1 mutations, together with comparisons to sporadic ALS (sALS) and ALS due to repeat expansions in C9orf72 (C9orf72+). All nine patients with confirmed mutations in TIA1 were female. The clinical phenotype was heterogeneous with a range in the age at onset from late twenties to the eighth decade (mean = 60 years) and disease duration from one to 6 years (mean = 3 years). Initial presentation was either focal weakness or language impairment. All affected individuals received a final diagnosis of ALS with or without FTD. No psychosis or parkinsonism was described. Neuropathological examination on five patients found typical features of ALS and frontotemporal lobar degeneration (FTLD-TDP, type B) with anatomically widespread TDP-43 proteinopathy. In contrast to C9orf72+ cases, caudate atrophy and hippocampal sclerosis were not prominent. Detailed evaluation of the pyramidal motor system found a similar degree of neurodegeneration and TDP-43 pathology as in sALS and C9orf72+ cases; however, cases with TIA1 mutations had increased numbers of lower motor neurons containing round eosinophilic and Lewy body-like inclusions on HE stain and round compact cytoplasmic inclusions with TDP-43 immunohistochemistry. Immunohistochemistry and immunofluorescence failed to demonstrate any labeling of inclusions with antibodies against TIA1. In summary, our TIA1 mutation carriers developed ALS with or without FTD, with a wide range in age at onset, but without other neurological or psychiatric features. The neuropathology was characterized by widespread TDP-43 pathology, but a more restricted pattern of neurodegeneration than C9orf72+ cases. Increased numbers of round eosinophilic and Lewy

A Clinical, Neuropathological and Genetic Study of Homozygous A467T POLG-Related Mitochondrial Disease.

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Sanjeev Rajakulendran

Full Text Available Mutations in the nuclear gene POLG (encoding the catalytic subunit of DNA polymerase gamma are an important cause of mitochondrial disease. The most common POLG mutation, A467T, appears to exhibit considerable phenotypic heterogeneity. The mechanism by which this single genetic defect results in such clinical diversity remains unclear. In this study we evaluate the clinical, neuropathological and mitochondrial genetic features of four unrelated patients with homozygous A467T mutations. One patient presented with the severe and lethal Alpers-Huttenlocher syndrome, which was confirmed on neuropathology, and was found to have a depletion of mitochondrial DNA (mtDNA. Of the remaining three patients, one presented with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS, one with a phenotype in the Myoclonic Epilepsy, Myopathy and Sensory Ataxia (MEMSA spectrum and one with Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO. All three had secondary accumulation of multiple mtDNA deletions. Complete sequence analysis of muscle mtDNA using the MitoChip resequencing chip in all four cases demonstrated significant variation in mtDNA, including a pathogenic MT-ND5 mutation in one patient. These data highlight the variable and overlapping clinical and neuropathological phenotypes and downstream molecular defects caused by the A467T mutation, which may result from factors such as the mtDNA genetic background, nuclear genetic modifiers and environmental stressors.

Sleep disorders in children with traumatic brain injury: a case of serious neglect.

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Stores, Gregory; Stores, Rachel

2013-09-01

The aim of this study was to review the basic aspects of sleep disturbance in children with traumatic brain injury (TBI). A search was performed on reports of sleep disturbances in children who had suffered TBI. Adults with TBI were also considered to anticipate the nature and significance of such disturbances in younger patients. Types of reported sleep disturbance were noted and their possible aetiology and management considered. Sleep disturbance has consistently been associated with TBI but the literature suggests that this aspect of patient care is often inadequately considered and there has been little research on the subject, especially in relation to children. Excessive daytime sleepiness is often mentioned, less so insomnia and parasomnias, but there is little information about the specific sleep disorders underlying these problems. Sleep disorders with potentially important developmental consequences have been neglected in the care of children with TBI. Screening for sleep problems should be routine and followed, if indicated, by a detailed diagnosis of the child's underlying specific sleep disorder, the possible aetiology of which includes neuropathology and potential medical, psychological, or psychiatric comorbidities. Appropriate assessments and modern treatment options are now well defined although generally underutilized. Further well-designed research is needed for which guidelines are available. © 2013 Mac Keith Press.

HANSENS DISEASE : STUDY OF CLINICAL, NEUROPATHOLOGICAL, NEUROPHYSIOLOGICAL PATTERN OF LEPROUS NEUROPATHY

OpenAIRE

Vijay Kumar; Ajay Kumar

2015-01-01

A need still exists to determine the clinical and neurophysiological characteristics of leprosy neuropathy at distinct times of the disease by different methods that measure the various nerve fiber functions. A prospective clinical study was performed 100 patients of clinically proven Hansen’s will take in study and given diagnosis is made by dermatologist and neurologist. For Study of Clinical, Neuropathological , Neurophysiological Pattern of leprous neuropathy and r...

[Genetic and neuroendocrine aspects in autism spectrum disorder].

Science.gov (United States)

Oviedo, Norma; Manuel-Apolinar, Leticia; de la Chesnaye, Elsa; Guerra-Araiza, Christian

The autism spectrum disorder (ASD) was described in 1943 and is defined as a developmental disorder that affects social interaction and communication. It is usually identified in early stages of development from 18 months of age. Currently, autism is considered a neurological disorder with a spectrum covering cases of different degrees, which is associated with genetic factors, not genetic and environmental. Among the genetic factors, various syndromes have been described that are associated with this disorder. Also, the neurobiology of autism has been studied at the genetic, neurophysiological, neurochemical and neuropathological levels. Neuroimaging techniques have shown multiple structural abnormalities in these patients. There have also been changes in the serotonergic, GABAergic, catecholaminergic and cholinergic systems related to this disorder. This paper presents an update of the information presented in the genetic and neuroendocrine aspects of autism spectrum disorder. Copyright © 2014 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations.

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Barua, Neil U; Gill, Steven S; Love, Seth

2014-03-01

Convection-enhanced delivery (CED) describes a direct method of drug delivery to the brain through intraparenchymal microcatheters. By establishing a pressure gradient at the tip of the infusion catheter in order to exploit bulk flow through the interstitial spaces of the brain, CED offers a number of advantages over conventional drug delivery methods-bypass of the blood-brain barrier, targeted distribution through large brain volumes and minimization of systemic side effects. Despite showing early promise, CED is yet to fulfill its potential as a mainstream strategy for the treatment of neurological disease. Substantial research effort has been dedicated to optimize the technology for CED and identify the parameters, which govern successful drug distribution. It seems likely that successful clinical translation of CED will depend on suitable catheter technology being used in combination with drugs with optimal physicochemical characteristics, and on neuropathological analysis in appropriate preclinical models. In this review, we consider the factors most likely to influence the success or failure of CED, and review its application to the treatment of high-grade glioma, Parkinson's disease (PD) and Alzheimer's disease (AD). © 2013 International Society of Neuropathology.

Anterior temporal white matter lesions in myotonic dystrophy with intellectual impairment: an MRI and neuropathological study

International Nuclear Information System (INIS)

Ogata, A.; Tashiro, K.; Terae, S.; Fujita, M.

1998-01-01

We studied 12 patients with myotonic dystrophy using MRI and the Mini-mental state examination (MMSE), to see it specific MRI findings were associated with intellectual impairment. We also compared them with the neuropathological findings in an autopsy case of MD with intellectual impairment. Mild intellectual impairment was found in 8 of the 12 patients. On T 2-weighted and proton density-weighted images, high-intensity areas were seen in cerebral white matter in 10 of the 12 patients. In seven of these, anterior temporal white-matter lesions (ATWML) were found; all seven had mild intellectual impairment (MMSE 22-26), whereas none of the four patients with normal mentation had ATWML. In only one of the eight patients with intellectual impairment were white-matter lesions not found. Pathological findings were severe loss and disordered arrangement of myelin sheaths and axons in addition to heterotopic neurons within anterior temporal white matter. Bilateral ATWML might be a factor for intellectual impairment in MD. The retrospective pathological study raised the possibility that the ATWML are compatible with focal dysplasia of white matter. (orig.)

Patient with rapidly evolving neurological disease with neuropathological lesions of Creutzfeldt-Jakob disease, Lewy body dementia, chronic subcortical vascular encephalopathy and meningothelial meningioma.

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Vita, Maria Gabriella; Tiple, Dorina; Bizzarro, Alessandra; Ladogana, Anna; Colaizzo, Elisa; Capellari, Sabina; Rossi, Marcello; Parchi, Piero; Masullo, Carlo; Pocchiari, Maurizio

2017-04-01

We report a case of rapidly evolving neurological disease in a patient with neuropathological lesions of Creutzfeldt-Jakob disease (CJD), Lewy body dementia (LBD), chronic subcortical vascular encephalopathy and meningothelial meningioma. The coexistence of severe multiple pathologies in a single patient strengthens the need to perform accurate clinical differential diagnoses in rapidly progressive dementias. © 2016 Japanese Society of Neuropathology.

Leptomeninges-Derived Induced Pluripotent Stem Cells and Directly Converted Neurons From Autopsy Cases With Varying Neuropathologic Backgrounds.

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Rose, Shannon E; Frankowski, Harald; Knupp, Allison; Berry, Bonnie J; Martinez, Refugio; Dinh, Stephanie Q; Bruner, Lauren T; Willis, Sherry L; Crane, Paul K; Larson, Eric B; Grabowski, Thomas; Darvas, Martin; Keene, C Dirk; Young, Jessica E

2018-05-01

Patient-specific stem cell technology from skin and other biopsy sources has transformed in vitro models of neurodegenerative disease, permitting interrogation of the effects of complex human genetics on neurotoxicity. However, the neuropathologic changes that underlie cognitive and behavioral phenotypes can only be determined at autopsy. To better correlate the biology of derived neurons with age-related and neurodegenerative changes, we generated leptomeningeal cell lines from well-characterized research subjects that have undergone comprehensive postmortem neuropathologic examinations. In a series of proof of principle experiments, we reprogrammed autopsy leptomeningeal cell lines to human-induced pluripotent stem cells (hiPSCs) and differentiated these into neurons. We show that leptomeningeal-derived hiPSC lines can be generated from fresh and frozen leptomeninges, are pluripotent, and retain the karyotype of the starting cell population. Additionally, neurons differentiated from these hiPSCs are functional and produce measurable Alzheimer disease-relevant analytes (Aβ and Tau). Finally, we used direct conversion protocols to transdifferentiate leptomeningeal cells to neurons. These resources allow the generation of in vitro models to test mechanistic hypotheses as well as diagnostic and therapeutic strategies in association with neuropathology, clinical and cognitive data, and biomarker studies, aiding in the study of late-onset Alzheimer disease and other age-related neurodegenerative diseases.

Pitfalls in the use of whole slide imaging for the diagnosis of central nervous system tumors: A pilot study in surgical neuropathology

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Melike Pekmezci

2016-01-01

Full Text Available Background: Whole slide imaging (WSI finds increasingly higher value in everyday surgical pathology in addition to its well-established use for educational and research purposes. However, its diagnostic utility, especially in subspecialty settings such as neuropathology, is not fully validated. Neuropathology practice is unique with smaller overall tissue size and frequent need for high-power evaluation. In addition, tumor grade is an integral part of the initial diagnosis. The purpose of this study is to assess the feasibility of primary pathology diagnosis of surgical neuropathology specimens using WSI. Materials and Methods: We reviewed consecutive surgical neuropathology cases diagnosed in our institution during a 2-month period and identified a single diagnostic slide, which was scanned at 40× magnification. Two neuropathologists who were blinded to the original diagnoses reviewed the whole slide image and rendered a diagnosis including tumor grade when applicable. They reviewed the single diagnostic slide after a wash-out period. Intra- and inter-observer discrepancies, as well as reasons for discrepancies, were evaluated. Results: The concordance rates were 94.9% and 88% for two neuropathologists. Two critical issues leading to discrepancies were identified: (1 identification of mitoses and (2 recognition of nuclear details. Conclusions: Given the current study is exclusively for surgical neuropathology cases, an all-encompassing conclusion about the utility of WSI for diagnostic purposes may not be available. Nevertheless, pathologists should be aware of the potential pitfalls due to identification of mitotic figures and nuclear details. We recommend independent validation for each subspecialty of pathology to identify subspecialty-specific concerns, so they can be properly addressed.

Reduced Number of Pigmented Neurons in the Substantia Nigra of Dystonia Patients? Findings from Extensive Neuropathologic, Immunohistochemistry, and Quantitative Analyses

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Diego Iacono

2015-05-01

Full Text Available Background: Dystonias (Dys represent the third most common movement disorder after essential tremor (ET and Parkinson's disease (PD. While some pathogenetic mechanisms and genetic causes of Dys have been identified, little is known about their neuropathologic features. Previous neuropathologic studies have reported generically defined neuronal loss in various cerebral regions of Dys brains, mostly in the basal ganglia (BG, and specifically in the substantia nigra (SN. Enlarged pigmented neurons in the SN of Dys patients with and without specific genetic mutations (e.g., GAG deletions in DYT1 dystonia have also been described. Whether or not Dys brains are associated with decreased numbers or other morphometric changes of specific neuronal types is unknown and has never been addressed with quantitative methodologies. Methods: Quantitative immunohistochemistry protocols were used to estimate neuronal counts and volumes of nigral pigmented neurons in 13 SN of Dys patients and 13 SN of age‐matched control subjects (C. Results: We observed a significant reduction (∼20% of pigmented neurons in the SN of Dys compared to C (p<0.01. Neither significant volumetric changes nor evident neurodegenerative signs were observed in the remaining pool of nigral pigmented neurons in Dys brains. These novel quantitative findings were confirmed after exclusion of possible co‐occurring SN pathologies including Lewy pathology, tau‐neurofibrillary tangles, β‐amyloid deposits, ubiquitin (ubiq, and phosphorylated‐TAR DNA‐binding protein 43 (pTDP43‐positive inclusions. Discussion: A reduced number of nigral pigmented neurons in the absence of evident neurodegenerative signs in Dys brains could indicate previously unconsidered pathogenetic mechanisms of Dys such as neurodevelopmental defects in the SN.

Under-recognition and under-treatment of DSM-IV classified mood and anxiety disorders among disability claimants

NARCIS (Netherlands)

Cornelius, Lammert; van der Klink, Jac J. L.; Brouwer, Sandra; Groothoff, Johan W.

2014-01-01

Purpose: This study aimed to examine under-recognition, under-treatment and severity of under-treated DSM-IV mood and anxiety disorders among disability claimants. Methods: In a representative sample of Dutch disability claimants (n = 346), registry codes certified according to the International

Reducing GBA2 Activity Ameliorates Neuropathology in Niemann-Pick Type C Mice.

Directory of Open Access Journals (Sweden)

André R A Marques

Full Text Available The enzyme glucocerebrosidase (GBA hydrolyses glucosylceramide (GlcCer in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as major genetic risk factor for Parkinsonism. Disturbed metabolism of GlcCer may therefore play a role in neuropathology. Besides lysosomal GBA, cells also contain a non-lysosomal glucosylceramidase (GBA2. Given that the two β-glucosidases share substrates, we speculated that over-activity of GBA2 during severe GBA impairment might influence neuropathology. This hypothesis was studied in Niemann-Pick type C (Npc1-/- mice showing secondary deficiency in GBA in various tissues. Here we report that GBA2 activity is indeed increased in the brain of Npc1-/- mice. We found that GBA2 is particularly abundant in Purkinje cells (PCs, one of the most affected neuronal populations in NPC disease. Inhibiting GBA2 in Npc1-/- mice with a brain-permeable low nanomolar inhibitor significantly improved motor coordination and extended lifespan in the absence of correction in cholesterol and ganglioside abnormalities. This trend was recapitulated, although not to full extent, by introducing a genetic loss of GBA2 in Npc1-/- mice. Our findings point to GBA2 activity as therapeutic target in NPC.

The neuropathology of morality: Germany 1930-1960.

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Schirmann, Felix

2014-01-01

This article analyzes brain scientists' attempts to trace morality in the brain in Germany from 1930 to 1960. The debate around Karl Kleist's localization of the Gemeinschafts-Ich [community-I] in the 1930s is depicted in order to illustrate the central arguments for and against localizations of morality. The focus of this article is on the period 1936-1960 in which experts put forth specific ideas on morality's cerebral underpinnings that mirror the larger theoretical shift from strict localization doctrine to a more holistic understanding of the brain. As a result of this shift, experts avoided exact localizations of morality. Instead, they posited correlations between brain areas and morality. The analysis illustrates the dependence of neuropathological research on morality on general theories of brain functioning and marks a first contribution to the history of the neuroscience of morality for the time after 1930.

Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway

OpenAIRE

Lahiri, Debomoy K.; Sokol, Deborah K.; Erickson, Craig; Ray, Balmiki; Ho, Chang Y.; Maloney, Bryan

2013-01-01

Autism is a neurodevelopmental disorder marked by social skills and communication deficits and interfering repetitive behavior. Intellectual disability often accompanies autism. In addition to behavioral deficits, autism is characterized by neuropathology and brain overgrowth. Increased intracranial volume often accompanies this brain growth. We have found that the Alzheimer’s disease (AD) associated amyloid-β precursor protein (APP), especially its neuroprotective processing product, secrete...

"Boomerang Neuropathology" of Late-Onset Alzheimer's Disease is Shrouded in Harmful "BDDS": Breathing, Diet, Drinking, and Sleep During Aging.

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Daulatzai, Mak Adam

2015-07-01

Brain damage begins years before substantial neurodegeneration and Alzheimer's dementia. Crucial fundamental activities of life are breathing, eating, drinking, and sleeping. When these pivotal functions are maligned over a prolonged period, they impart escalating dyshomeostasis. The latter may lead to disastrous consequences including cognitive dysfunction and Alzheimer's disease (AD). The current theme here is that multiple pathophysiological derangements are promoted over a prolonged period by the very fundamental activities of life-when "rendered unhealthy." They may converge on several regulating/modulating factors (e.g., mitochondrial energy production, oxidative stress, innate immunity, and vascular function) and promote insidious neuropathology that culminates in cognitive decline in the aged. This is of course associated with the accumulation of amyloid beta and phosphorylated tau in the brain. Epidemiological, biomarker, and neuroimaging studies have provided significant copious evidence on the presence of indolent prodromal AD neuropathology many years prior to symptomatic onset. Progressive oxidative damage to specific gene promoters may result in gene silencing. A mechanistic link may possibly exist between epigenomic state, DNA damage, and chronically unhealthy/dysfunctional body systems. This paper, therefore, addresses and delineates the deleterious pathophysiological impact triggered by dysfunctional breathing, harmful diet, excess of alcohol consumption, and sleep deprivation; indeed, their impact may alter epigenetic state. It is mandatory, therefore, to abrogate cognitive decline and attenuate AD pathology through adoption of a healthy lifestyle, in conjunction with combination therapy with known moderators of cognitive decline. This strategy may thwart multiple concurrent and synergistic pathologies, including epigenetic dysfunction. A multi-factorial therapeutic intervention is required to overcome wide ranging neuropathology and multi

Disordered APP metabolism and neurovasculature in trauma and aging: Combined risks for chronic neurodegenerative disorders.

Science.gov (United States)

Ikonomovic, Milos D; Mi, Zhiping; Abrahamson, Eric E

2017-03-01

Traumatic brain injury (TBI), advanced age, and cerebral vascular disease are factors conferring increased risk for late onset Alzheimer's disease (AD). These conditions are also related pathologically through multiple interacting mechanisms. The hallmark pathology of AD consists of pathological aggregates of amyloid-β (Aβ) peptides and tau proteins. These molecules are also involved in neuropathology of several other chronic neurodegenerative diseases, and are under intense investigation in the aftermath of TBI as potential contributors to the risk for developing AD and chronic traumatic encephalopathy (CTE). The pathology of TBI is complex and dependent on injury severity, age-at-injury, and length of time between injury and neuropathological evaluation. In addition, the mechanisms influencing pathology and recovery after TBI likely involve genetic/epigenetic factors as well as additional disorders or comorbid states related to age and central and peripheral vascular health. In this regard, dysfunction of the aging neurovascular system could be an important link between TBI and chronic neurodegenerative diseases, either as a precipitating event or related to accumulation of AD-like pathology which is amplified in the context of aging. Thus with advanced age and vascular dysfunction, TBI can trigger self-propagating cycles of neuronal injury, pathological protein aggregation, and synaptic loss resulting in chronic neurodegenerative disease. In this review we discuss evidence supporting TBI and aging as dual, interacting risk factors for AD, and the role of Aβ and cerebral vascular dysfunction in this relationship. Evidence is discussed that Aβ is involved in cyto- and synapto-toxicity after severe TBI, and that its chronic effects are potentiated by aging and impaired cerebral vascular function. From a therapeutic perspective, we emphasize that in the fields of TBI- and aging-related neurodegeneration protective strategies should include preservation of

Functional evaluations of genes disrupted in patients with Tourette’s Disorder

Directory of Open Access Journals (Sweden)

Nawei eSun

2016-02-01

Full Text Available Tourette Disorder (TD is a highly heritable neurodevelopmental disorder with complex genetic architecture and unclear neuropathology. Disruptions of particular genes have been identified in subsets of TD patients. However, none of the findings has been replicated, probably due to the complex and heterogeneous genetic architecture of TD that involves both common and rare variants. To understand the etiology of TD, functional analyses are required to characterize the molecular and cellular consequences caused by mutations in candidate genes. Such molecular and cellular alterations may converge into common biological pathways underlying the heterogeneous genetic etiology of TD patients. Herein, we review specific genes implicated in TD etiology, discuss the functions of these genes in the mammalian central nervous system and the corresponding behavioral anomalies exhibited in animal models and, importantly, review functional analyses that can be performed to evaluate the role(s that the genetic disruptions might play in TD. Specifically, the functional assays include novel cell culture systems, genome editing techniques, bioinformatics approaches, transcriptomic analyses and genetically modified animal models applied or developed to study genes associated with TD or with other neurodevelopmental and neuropsychiatric disorders. By describing methods used to study diseases with genetic architecture similar to TD, we hope to develop a systematic framework for investigating the etiology of TD and related disorders.

Clinical and Neurobiological Relevance of Current Animal Models of Autism Spectrum Disorders

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Kim, Ki Chan; Gonzales, Edson Luck; Lázaro, María T.; Choi, Chang Soon; Bahn, Geon Ho; Yoo, Hee Jeong; Shin, Chan Young

2016-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to assess and test diverse risk factors of ASD, both genetic and environmental, and measure their contribution to the manifestation of autistic symptoms. At a broader scale, rodent models have helped consolidate molecular pathways and unify the neurophysiological mechanisms underlying each one of the various etiologies. This approach will potentially enable the stratification of ASD into clinical, molecular, and neurophenotypic subgroups, further proving their translational utility. It is henceforth paramount to establish a common ground of mechanistic theories from complementing results in preclinical research. In this review, we cluster the ASD animal models into lesion and genetic models and further classify them based on the corresponding environmental, epigenetic and genetic factors. Finally, we summarize the symptoms and neuropathological highlights for each model and make critical comparisons that elucidate their clinical and neurobiological relevance. PMID:27133257

Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain.

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Yang, Weili; Wang, Guohao; Wang, Chuan-En; Guo, Xiangyu; Yin, Peng; Gao, Jinquan; Tu, Zhuchi; Wang, Zhengbo; Wu, Jing; Hu, Xintian; Li, Shihua; Li, Xiao-Jiang

2015-05-27

Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2-3, 7-8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD. Copyright © 2015 the authors 0270-6474/15/358345-14$15.00/0.

Lipid raft disarrangement as a result of neuropathological progresses: a novel strategy for early diagnosis?

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Marin, R; Rojo, J A; Fabelo, N; Fernandez, C E; Diaz, M

2013-08-15

Lipid rafts are the preferential site of numerous membrane signaling proteins which are involved in neuronal functioning and survival. These proteins are organized in multiprotein complexes, or signalosomes, in close contact with lipid classes particularly represented in lipid rafts (i.e. cholesterol, sphingolipids and saturated fatty acids), which may contribute to physiological responses leading to neuroprotection. Increasing evidence indicates that alteration of lipid composition in raft structures as a consequence of neuropathologies, such as Alzheimer's disease (AD) and Parkinson's disease (PD), causes a dramatic increase in lipid raft order. These phenomena may correlate with perturbation of signalosome activities, likely contributing to neurodegenerative progression. Interestingly, significant disruption of stable raft microenvironments has been already observed in the first stages of either AD or PD, suggesting that these alterations may represent early events in the neuropathological development. In this regard, the search for biochemical markers, such as specific metabolic products altered in the brain at the first steps of the disease, presently represents an important challenge for early diagnostic strategies. Alterations of these biomarkers may be reflected in either plasma or cerebrospinal fluid, thus representing a potential strategy to predict an accurate diagnosis. We propose that pathologically-linked lipid raft markers may be interesting candidates to be explored at this level, although it has not been studied so far to what extent alteration of different signalosome components may be reflected in peripheral fluids. In this mini-review, we will discuss on relevant aspects of lipid rafts that contribute to the modulation of neuropathological events related to AD and PD. An interesting hypothesis is that anomalies on raft biomarkers measured at peripheral fluids might mirror the lipid raft pathology observed in early stages of AD and PD. Copyright

Pneumomediastinum on Multidetector CT: The Radiologic Signs and Underlying Disorders

Energy Technology Data Exchange (ETDEWEB)

Oh, Soo Jin; Kim, Young Tong [Soonchunhyang University Chunan Hospital, Cheonan (Korea, Republic of)

2011-02-15

We can see the typical signs of pneumomediastinum on chest radiography and we can also see them on the multiplanar reformatted (MPR) image of multidetector CT (MDCT). MDCT can help to understand the anatomical feature of these signs and differentiate pneumomediastinum from pneumothorax, pneumopericardium and the Mach band effect. MDCT shows the peribronchovascular air, which reveals the Macklin effect, and it can also evaluate the underlying disorders that cause pneumomediastinum. The purpose of this pictorial essay is to inform physicians about the mechanism and anatomical features of pneumomediastinum, and to help them understand the imaging findings and underlying disorders of pneumomediastinum as seen on MDCT

Effect of Common Neuropathologies on Progression of Late Life Cognitive Impairment

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Yu, Lei; Boyle, Patricia A.; Leurgans, Sue; Schneider, Julie A.; Kryscio, Richard J.; Wilson, Robert S.; Bennett, David A.

2015-01-01

Brain pathologies of Alzheimer’s, cerebrovascular and Lewy body diseases are common in old age, but the relationship of these pathologies with progression from normal cognitive function to the various stages of cognitive impairment is unknown. In this study, we fit latent Markov models from longitudinal cognitive data to empirically derive three latent stages corresponding to no impairment, mild impairment, and moderate impairment; then, we examined the associations of common neuropathologies with the rates of transition among these stages. Cognitive and neuropathological data were available from 653 autopsied participants in two ongoing cohort studies of aging who were cognitively healthy at baseline (mean baseline age 79.1 years) and had longitudinal cognitive data. On average, participants in these analyses developed mild impairment 5 years after enrollment, progressed to moderate impairment after an additional 3.4 years, and stayed impaired for 2.8 years until death. AD and chronic macroscopic infarcts were associated with a higher risk of progression to mild impairment and subsequently to moderate impairment. By contrast, Lewy bodies were associated only with progression from mild to moderate impairment. The 5-year probability of progression to mild or moderate impairment was 20% for persons without any of these three pathologies, 38% for AD only, 51% for AD and macroscopic infarcts, and 56% for AD, infarcts and Lewy bodies. Thus, the presence of AD pathology alone nearly doubles the risk of developing cognitive impairment in late life, and the presence of multiple pathologies further increases this risk over multiple years prior to death. PMID:25976345

Interhemispheric Cortical Inhibition Is Reduced in Young Adults With Developmental Coordination Disorder

OpenAIRE

Jason L. He; Ian Fuelscher; Peter G. Enticott; Wei-peng Teo; Pamela Barhoun; Christian Hyde

2018-01-01

IntroductionWhile the etiology of developmental coordination disorder (DCD) is yet to be established, brain-behavior modeling provides a cogent argument that neuropathology may subserve the motor difficulties typical of DCD. We argue that a number of the core behavioral features of the DCD profile (such as poor surround inhibition, compromised motor inhibition, and the presence of mirror movements) are consistent with difficulties regulating inhibition within the primary motor cortex (M1). Th...

A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force

Science.gov (United States)

Sajatovic, Martha; Strejilevich, Sergio A; Gildengers, Ariel G; Dols, Annemiek; Al Jurdi, Rayan K; Forester, Brent P; Kessing, Lars Vedel; Beyer, John; Manes, Facundo; Rej, Soham; Rosa, Adriane R; Schouws, Sigfried NTM; Tsai, Shang-Ying; Young, Robert C; Shulman, Kenneth I

2015-01-01

Objectives In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older-Age Bipolar Disorder (OABD). Methods This task force report addresses the unique aspects of OABD including epidemiology and clinical features, neuropathology and biomarkers, physical health, cognition, and care approaches. Results The report describes an expert consensus summary on OABD that is intended to advance the care of patients, and shed light on issues of relevance to BD research across the lifespan. Although there is still a dearth of research and health efforts focused on older adults with BD, emerging data has brought some answers, innovative questions, and novel perspectives related to the notion of late onset, medical comorbidity, and the vexing issue of cognitive impairment and decline. Conclusions Improving our understanding of the biological, clinical, and social underpinnings relevant to OABD is an indispensable step in building a complete map of BD across the lifespan. PMID:26384588

Next-Generation Sequencing in Neuropathologic Diagnosis of Infections of the Nervous System (Open Access)

Science.gov (United States)

2016-06-13

nervous system ABSTRACT Objective: To determine the feasibility of next-generation sequencing (NGS) microbiome ap- proaches in the diagnosis of infectious...V, van Doorn HR, Nghia HD, et al. Identification of a new cyclovirus in cerebrospinal fluid of patients with acute central nervous system infections...Kumar, et al. system Next-generation sequencing in neuropathologic diagnosis of infections of the nervous This information is current as of June 13

Structural brain abnormalities in autism : neuroimaging and neuropathology studies

NARCIS (Netherlands)

Palmen, Saskia Johanna Maria Christina

2005-01-01

JUSTIFY Autism is currently viewed as a largely genetically determined neurodevelopmental disorder. Over the last decades, an increasing number of studies have been performed, trying to establish the underlying biological causes of autism. However, its exact etiology still remains unclear. In this

Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

Science.gov (United States)

2017-01-01

The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD) hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates), persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment. PMID:28567415

Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

Directory of Open Access Journals (Sweden)

Nguyen Quoc Vuong Tran

2017-01-01

Full Text Available The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD and attention deficit hyperactivity disorder (ADHD, calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates, persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment.

The Neuropathology of Chronic Traumatic Encephalopathy

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McKee, Ann C.; Stein, Thor D.; Kiernan, Patrick T.; Alvarez, Victor E.

2015-01-01

Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43 kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. PMID:25904048

Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature

Science.gov (United States)

Nelson, Peter T.; Alafuzoff, Irina; Bigio, Eileen H.; Bouras, Constantin; Braak, Heiko; Cairns, Nigel J.; Castellani, Rudolph J.; Crain, Barbara J.; Davies, Peter; Del Tredici, Kelly; Duyckaerts, Charles; Frosch, Matthew P.; Haroutunian, Vahram; Hof, Patrick R.; Hulette, Christine M.; Hyman, Bradley T.; Iwatsubo, Takeshi; Jellinger, Kurt A.; Jicha, Gregory A.; Kövari, Enikö; Kukull, Walter A.; Leverenz, James B.; Love, Seth; Mackenzie, Ian R.; Mann, David M.; Masliah, Eliezer; McKee, Ann C.; Montine, Thomas J.; Morris, John C.; Schneider, Julie A.; Sonnen, Joshua A.; Thal, Dietmar R.; Trojanowski, John Q.; Troncoso, Juan C.; Wisniewski, Thomas; Woltjer, Randall L.; Beach, Thomas G.

2013-01-01

Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. β-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of Aβ plaques and neurofibrillary tangles. Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles. PMID:22487856

Under-diagnosis of mood disorders in Canada.

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Pelletier, L; O'Donnell, S; Dykxhoorn, J; McRae, L; Patten, S B

2017-08-01

Under-diagnosis of mood disorders occurs worldwide. In this study, we characterized and compared Canadians with symptoms compatible with a mood disorder by diagnosis status; and described the associated health impacts, use of health services and perceived need for care. Respondents to the 2012 Canadian Community Health Survey - Mental Health, a nationally representative sample of Canadians age ≥15 years were assessed for symptoms compatible with mood disorders based on a Canadian adaptation of the World Health Organization Composite International Diagnostic Interview (n = 23 504). Descriptive and multivariate regression analyses were performed. In 2012, an estimated 5.4% (1.5 million) Canadians aged 15 years and older reported symptoms compatible with a mood disorder, of which only half reported having been professionally diagnosed. The undiagnosed individuals were more likely to be younger (mean age: 36.2 v. 41.8), to be single (49.5 v. 32.7%), to have less than a post-secondary graduation (49.8 v. 41.1%) and to have no physical co-morbidities (56.4 v. 35.7%), and less likely to be part of the two lower income quintiles (49.6 v. 62.7%) compared with those with a previous diagnosis. Upon controlling for all socio-demographic and health characteristics, the associations with age and marital status disappeared. While those with a previous diagnosis reported significantly greater health impacts and were more likely to have consulted a health professional for their emotional and mental health problems in the previous 12 months compared with those undiagnosed (79.4 v. 31.0%), about a third of both groups reported that their health care needs were only partially met or not met at all. Mood disorders are prevalent and can profoundly impact the life of those affected, however, their diagnosis remains suboptimal and health care use falls short of apparent needs. Improvements in mental health literacy, help-seeking behaviours and diagnosis are needed. In light of the

Tooth loss, dementia and neuropathology in the Nun study.

Science.gov (United States)

Stein, Pamela Sparks; Desrosiers, Mark; Donegan, Sara Jean; Yepes, Juan F; Kryscio, Richard J

2007-10-01

Numerous studies have linked dementia to the subsequent deterioration of oral health. Few investigators, however, have examined oral disease as a potential risk factor in the development of dementia. The authors conducted a study to investigate a potential association between a history of oral disease and the development of dementia. Longitudinal dental records supplemented data collected from 10 annual cognitive assessments of 144 Milwaukee participants in the Nun Study, a longitudinal study of aging and Alzheimer disease, who were 75 to 98 years old. Neuropathologic findings at autopsy were available for 118 participants who died. A low number of teeth increased the risk of higher prevalence and incidence of dementia. Participants with the fewest teeth had the highest risk of prevalence and incidence of dementia. Edentulism or very few (one to nine) teeth may be predictors of dementia late in life.

Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

Science.gov (United States)

VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

2016-01-01

People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

Pisotriquetral joint disorders: an under-recognized cause of ulnar side wrist pain

Energy Technology Data Exchange (ETDEWEB)

Moraux, A. [Hopital Roger Salengro, Service d' Imagerie Musculo-Squelettique, Centre de Consultation de l' Appareil Locomoteur, CHRU Lille (France); Imagerie Medicale Jacquemars Gielee, Lille (France); Lefebvre, G.; Pansini, V.; Aucourt, J.; Vandenbussche, L.; Cotten, A. [Hopital Roger Salengro, Service d' Imagerie Musculo-Squelettique, Centre de Consultation de l' Appareil Locomoteur, CHRU Lille (France); Demondion, X. [Hopital Roger Salengro, Service d' Imagerie Musculo-Squelettique, Centre de Consultation de l' Appareil Locomoteur, CHRU Lille (France); Pole Recherche Faculte de Medecine de Lille, Laboratoire d' Anatomie, Lille (France)

2014-06-15

Pisotriquetral joint disorders are often under-recognized in routine clinical practice. They nevertheless represent a significant cause of ulnar side wrist pain. The aim of this article is to present the main disorders of this joint and discuss the different imaging modalities that can be useful for its assessment. (orig.)

Schizophrenia and bipolar disorder: The road from similarities and clinical heterogeneity to neurobiological types.

Science.gov (United States)

Dacquino, Claudia; De Rossi, Pietro; Spalletta, Gianfranco

2015-09-20

Although diagnosis is a central issue in medical care, in psychiatry its value is still controversial. The function of diagnosis is to indicate treatments and to help clinicians take better care of patients. The fundamental role of diagnosis is to predict outcome and prognosis. To date serious concern persists regarding the clinical utility and predictive validity of the diagnosis system in psychiatry, which is at the most syndromal. Schizophrenia and bipolar disorder, which nosologists consider two distinct disorders, are the most discussed psychiatric illnesses. Recent findings in different fields of psychiatric research, such as neuroimaging, neuropathology, neuroimmunology, neuropsychology and genetics, have led to other conceptualizations. Individuals with schizophrenia or bipolar disorder vary greatly with regard to symptoms, illness course, treatment response, cognitive and functional impairment and biological correlates. In fact, it is possible to find heterogeneous correlates even within the same syndrome, i.e., from one stage of the disorder to another. Thus, it is possible to identify different subsyndromes, which share some clinical and neurobiological characteristics. The main goal of modern psychiatry is to ovethrow these barriers and to obtain a better understanding of the biological profiles underlying heterogeneous clinical features and thus reduce the variance and lead to a homogeneous definition. The translational research model, which connects the basic neuroscience research field with clinical experience in psychiatry, aims to investigate different neurobiological features of syndromes and of the shared neurobiological features between two syndromes. In fact, this approach should help us to better understand the neurobiological pathways underlying clinical entities, and even to distinguish different, more homogeneous, diagnostic subtypes. Copyright © 2015 Elsevier B.V. All rights reserved.

The urea cycle disorders.

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Helman, Guy; Pacheco-Colón, Ileana; Gropman, Andrea L

2014-07-01

The urea cycle is the primary nitrogen-disposal pathway in humans. It requires the coordinated function of six enzymes and two mitochondrial transporters to catalyze the conversion of a molecule of ammonia, the α-nitrogen of aspartate, and bicarbonate into urea. Whereas ammonia is toxic, urea is relatively inert, soluble in water, and readily excreted by the kidney in the urine. Accumulation of ammonia and other toxic intermediates of the cycle lead to predominantly neurologic sequelae. The disorders may present at any age from the neonatal period to adulthood, with the more severely affected patients presenting earlier in life. Patients are at risk for metabolic decompensation throughout life, often triggered by illness, fasting, surgery and postoperative states, peripartum, stress, and increased exogenous protein load. Here the authors address neurologic presentations of ornithine transcarbamylase deficiency in detail, the most common of the urea cycle disorders, neuropathology, neurophysiology, and our studies in neuroimaging. Special attention to late-onset presentations is given. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence.

LENUS (Irish Health Repository)

Murphy, S

2012-02-01

BACKGROUND: Cognitive impairment and dementia has been reported in autosomal dominant hereditary spastic paraparesis (HSP) linked to the SPG4 locus. There has only been one postmortem examination described; not all accept that progressive cognitive decline is a feature of this disorder. OBJECTIVE: A family with SPG4-HSP known to have a deletion of exon 17 in the spastin gene (SPG4delEx17) was cognitively assessed over a 7-year period. The index family member died and a postmortem examination was performed. METHODS: Thirteen family members older than 40 years were clinically and cognitively assessed using the Cambridge Cognitive Assessment over a 7-year period. The presence of SPG4delEx17 was assessed; a neuropathologic examination of the brain of the index family member was performed. RESULTS: Cognitive decline occurred in 6 of the 13 family members and in all 4 older than 60 years. Two genetic deletions were identified: SPG4delEx17 in 12 of the 13 family members and a deletion of SPG6 (SPG6del) in 5. Eight individuals had the SPG4delEx17 deletion only; 4 had evidence of progressive cognitive impairment. Four family members had both SPG4delEx17 and SPG6del; 2 of these had cognitive impairment. One family member with the SPG6del alone had neither HSP nor cognitive impairment. The index case with both deletions died with dementia; the brain showed widespread ubiquitin positivity within the neocortex and white matter. CONCLUSION: Cognitive decline and dementia is a feature of SPG4-HSP due to a deletion of exon 17 of the spastin gene.

Intraoperative neuropathology of glioma recurrence: cell detection and classification

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Abas, Fazly S.; Gokozan, Hamza N.; Goksel, Behiye; Otero, Jose J.; Gurcan, Metin N.

2016-03-01

Intraoperative neuropathology of glioma recurrence represents significant visual challenges to pathologists as they carry significant clinical implications. For example, rendering a diagnosis of recurrent glioma can help the surgeon decide to perform more aggressive resection if surgically appropriate. In addition, the success of recent clinical trials for intraoperative administration of therapies, such as inoculation with oncolytic viruses, may suggest that refinement of the intraoperative diagnosis during neurosurgery is an emerging need for pathologists. Typically, these diagnoses require rapid/STAT processing lasting only 20-30 minutes after receipt from neurosurgery. In this relatively short time frame, only dyes, such as hematoxylin and eosin (H and E), can be implemented. The visual challenge lies in the fact that these patients have undergone chemotherapy and radiation, both of which induce cytological atypia in astrocytes, and pathologists are unable to implement helpful biomarkers in their diagnoses. Therefore, there is a need to help pathologists differentiate between astrocytes that are cytologically atypical due to treatment versus infiltrating, recurrent, neoplastic astrocytes. This study focuses on classification of neoplastic versus non-neoplastic astrocytes with the long term goal of providing a better neuropathological computer-aided consultation via classification of cells into reactive gliosis versus recurrent glioma. We present a method to detect cells in H and E stained digitized slides of intraoperative cytologic preparations. The method uses a combination of the `value' component of the HSV color space and `b*' component of the CIE L*a*b* color space to create an enhanced image that suppresses the background while revealing cells on an image. A composite image is formed based on the morphological closing of the hue-luminance combined image. Geometrical and textural features extracted from Discrete Wavelet Frames and combined to classify

Progression of regional neuropathology in Alzheimer disease and normal elderly: findings from the Nun study.

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Wolf, D S; Gearing, M; Snowdon, D A; Mori, H; Markesbery, W R; Mirra, S S

1999-01-01

Although diffuse plaques in the neocortex may represent an early stage in the evolution of neuritic plaques, plaques in the striatum and cerebellum retain their predominantly diffuse nature in Alzheimer disease (AD), regardless of disease duration. We had the opportunity to explore the progression of these regional features by using autopsy brain specimens from 15 cognitively normal and five AD subjects, all Catholic sisters enrolled in the Nun Study, a longitudinal study on aging and AD. Neuropathologic changes were assessed in the temporal cortex, striatum, and cerebellum without knowledge of clinical status. We found diffuse plaques in the striatum in six (40%) and cerebellar plaques in none of the brains from the non-demented subjects. Striatal plaques were present in all five and cerebellar plaques in four of the five AD cases. In the 20 cases overall, the presence of striatal plaques generally paralleled the occurrence of neuritic plaques in neocortex and correlated with lower scores on several neuropsychologic tests assessing memory. Our findings suggest that striatal diffuse plaques occur relatively early in the progression of AD pathology and coincide with neocortical pathology and cognitive changes. Thus, it is unlikely that temporal factors alone account for regional differences in progression of AD neuropathology.

A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force.

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Sajatovic, Martha; Strejilevich, Sergio A; Gildengers, Ariel G; Dols, Annemiek; Al Jurdi, Rayan K; Forester, Brent P; Kessing, Lars Vedel; Beyer, John; Manes, Facundo; Rej, Soham; Rosa, Adriane R; Schouws, Sigfried Ntm; Tsai, Shang-Ying; Young, Robert C; Shulman, Kenneth I

2015-11-01

In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older-Age Bipolar Disorder (OABD). This task force report addresses the unique aspects of OABD including epidemiology and clinical features, neuropathology and biomarkers, physical health, cognition, and care approaches. The report describes an expert consensus summary on OABD that is intended to advance the care of patients, and shed light on issues of relevance to BD research across the lifespan. Although there is still a dearth of research and health efforts focused on older adults with BD, emerging data have brought some answers, innovative questions, and novel perspectives related to the notion of late onset, medical comorbidity, and the vexing issue of cognitive impairment and decline. Improving our understanding of the biological, clinical, and social underpinnings relevant to OABD is an indispensable step in building a complete map of BD across the lifespan. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetic dissection of a cell-autonomous neurodegenerative disorder: lessons learned from mouse models of Niemann-Pick disease type C

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Manuel E. Lopez

2013-09-01

Full Text Available Understanding neurodegenerative disease progression and its treatment requires the systematic characterization and manipulation of relevant cell types and molecular pathways. The neurodegenerative lysosomal storage disorder Niemann-Pick disease type C (NPC is highly amenable to genetic approaches that allow exploration of the disease biology at the organismal, cellular and molecular level. Although NPC is a rare disease, genetic analysis of the associated neuropathology promises to provide insight into the logic of disease neural circuitry, selective neuron vulnerability and neural-glial interactions. The ability to control the disorder cell-autonomously and in naturally occurring spontaneous animal models that recapitulate many aspects of the human disease allows for an unparalleled dissection of the disease neurobiology in vivo. Here, we review progress in mouse-model-based studies of NPC disease, specifically focusing on the subtype that is caused by a deficiency in NPC1, a sterol-binding late endosomal membrane protein involved in lipid trafficking. We also discuss recent findings and future directions in NPC disease research that are pertinent to understanding the cellular and molecular mechanisms underlying neurodegeneration in general.

Neuropathologic features of the hippocampus and amygdala in cats with familial spontaneous epilepsy.

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Yu, Yoshihiko; Hasegawa, Daisuke; Hamamoto, Yuji; Mizoguchi, Shunta; Kuwabara, Takayuki; Fujiwara-Igarashi, Aki; Tsuboi, Masaya; Chambers, James Ken; Fujita, Michio; Uchida, Kazuyuki

2018-03-01

OBJECTIVE To investigate epilepsy-related neuropathologic changes in cats of a familial spontaneous epileptic strain (ie, familial spontaneous epileptic cats [FSECs]). ANIMALS 6 FSECs, 9 age-matched unrelated healthy control cats, and 2 nonaffected (without clinical seizures)dams and 1 nonaffected sire of FSECs. PROCEDURES Immunohistochemical analyses were used to evaluate hippocampal sclerosis, amygdaloid sclerosis, mossy fiber sprouting, and granule cell pathological changes. Values were compared between FSECs and control cats. RESULTS Significantly fewer neurons without gliosis were detected in the third subregion of the cornu ammonis (CA) of the dorsal and ventral aspects of the hippocampus as well as the central nucleus of the amygdala in FSECs versus control cats. Gliosis without neuronal loss was also observed in the CA4 subregion of the ventral aspect of the hippocampus. No changes in mossy fiber sprouting and granule cell pathological changes were detected. Moreover, similar changes were observed in the dams and sire without clinical seizures, although to a lesser extent. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that the lower numbers of neurons in the CA3 subregion of the hippocampus and the central nucleus of the amygdala were endophenotypes of familial spontaneous epilepsy in cats. In contrast to results of other veterinary medicine reports, severe epilepsy-related neuropathologic changes (eg, hippocampal sclerosis, amygdaloid sclerosis, mossy fiber sprouting, and granule cell pathological changes) were not detected in FSECs. Despite the use of a small number of cats with infrequent seizures, these findings contributed new insights on the pathophysiologic mechanisms of genetic-related epilepsy in cats.

The Effect of Vascular Neuropathology on Late-life Cognition: Results from the SMART Project.

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Kryscio, R J; Abner, E L; Nelson, P T; Bennett, D; Schneider, J; Yu, L; Hemmy, L S; Lim, K O; Masaki, K; Cairns, N; Xiong, C; Woltjer, R; Dodge, H H; Tyas, S; Fardo, D W; Lou, W; Wan, L; Schmitt, F A

2016-06-01

Cerebral vascular pathology may contribute to cognitive decline experienced by some elderly near death. Given evidence for mixed neuropathologies in advanced age, preventing or reducing cerebrovascular burden in late life may be beneficial. To correlate measures of cerebral vascular pathology with cognitive trajectories. Observational study. A cohort of 2,274 individuals who came to autopsy at a mean age of 89.3 years and 82 percent of whom had at least two cognitive assessments within the last six years of life was compiled from six centers conducting longitudinal studies. For each cognitive domain: immediate and delayed memory, language, and naming, three trajectories were examined: good, intermediate, and poor cognition. The probability of a participant belonging to each trajectory was associated with measures of cerebral vascular pathology after adjustment for demographics, APOE, and Alzheimer neuropathology. A large proportion of the cohort (72-94%) experienced good or intermediate cognition in the four domains examined. The presence of arteriolosclerosis and the presence of lacunar infarcts doubled the odds of belonging to the poor cognitive trajectory for language when compared to the good trajectory. The presence of lacunar infarcts increased the odds of an intermediate or poor trajectory for immediate and delayed recall while the presence of large artery infarcts increased the odds of poor trajectories for all four cognitive domains examined. Microinfarcts and cerebral amyloid angiopathy had little effect on the trajectories. Indicators of cerebral vascular pathology act differently on late life cognition.

Neuropathology of the recessive A673V APP mutation: Alzheimer disease with distinctive features.

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Giaccone, Giorgio; Morbin, Michela; Moda, Fabio; Botta, Mario; Mazzoleni, Giulia; Uggetti, Andrea; Catania, Marcella; Moro, Maria Luisa; Redaelli, Veronica; Spagnoli, Alberto; Rossi, Roberta Simona; Salmona, Mario; Di Fede, Giuseppe; Tagliavini, Fabrizio

2010-12-01

Mutations of three different genes, encoding β-amyloid precursor protein (APP), presenilin 1 and presenilin 2 are associated with familial Alzheimer's disease (AD). Recently, the APP mutation A673V has been identified that stands out from all the genetic defects previously reported in these three genes, since it causes the disease only in the homozygous state (Di Fede et al. in Science 323:1473-1477, 2009). We here provide the detailed neuropathological picture of the proband of this family, who was homozygous for the APP A673V mutation and recently came to death. The brain has been studied by histological and immunohistochemical techniques, at the optical and ultrastructural levels. Cerebral Aβ accumulation and tau pathology were severe and extensive. Peculiar features were the configuration of the Aβ deposits that were of large size, mostly perivascular and exhibited a close correspondence between the pattern elicited by amyloid stainings and the labeling obtained with immunoreagents specific for Aβ40 or Aβ42. Moreover, Aβ deposition spared the neostriatum while deeply affecting the cerebellum, and therefore was not in compliance with the hierarchical topographical sequence of involvement documented in sporadic AD. Therefore, the neuropathological picture of familial AD caused by the APP recessive mutation A673V presents distinctive characteristics compared to sporadic AD or familial AD inherited as a dominant trait. Main peculiar features are the morphology, structural properties and composition of the Aβ deposits as well as their topographic distribution in the brain.

Neuropathological changes in brain cortex and hippocampus in a rat model of Alzheimer's disease.

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Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Rahbar Rooshandel, Nahid; Omidzahir, Shila

2011-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and Beta amyloid (ABeta) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 muL of ABeta (1-40) into the hippocampal fissure. In the present study, ABeta (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. ABeta injection CA1 caused ABeta deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group.

Reorganization of circuits underlying cerebellar modulation of prefrontal cortical dopamine in mouse models of autism spectrum disorder.

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Rogers, Tiffany D; Dickson, Price E; McKimm, Eric; Heck, Detlef H; Goldowitz, Dan; Blaha, Charles D; Mittleman, Guy

2013-08-01

Imaging, clinical, and pre-clinical studies have provided ample evidence for a cerebellar involvement in cognitive brain function including cognitive brain disorders, such as autism and schizophrenia. We previously reported that cerebellar activity modulates dopamine release in the mouse medial prefrontal cortex (mPFC) via two distinct pathways: (1) cerebellum to mPFC via dopaminergic projections from the ventral tegmental area (VTA) and (2) cerebellum to mPFC via glutamatergic projections from the mediodorsal and ventrolateral thalamus (ThN md and vl). The present study compared functional adaptations of cerebello-cortical circuitry following developmental cerebellar pathology in a mouse model of developmental loss of Purkinje cells (Lurcher) and a mouse model of fragile X syndrome (Fmr1 KO mice). Fixed potential amperometry was used to measure mPFC dopamine release in response to cerebellar electrical stimulation. Mutant mice of both strains showed an attenuation in cerebellar-evoked mPFC dopamine release compared to respective wildtype mice. This was accompanied by a functional reorganization of the VTA and thalamic pathways mediating cerebellar modulation of mPFC dopamine release. Inactivation of the VTA pathway by intra-VTA lidocaine or kynurenate infusions decreased dopamine release by 50 % in wildtype and 20-30 % in mutant mice of both strains. Intra-ThN vl infusions of either drug decreased dopamine release by 15 % in wildtype and 40 % in mutant mice of both strains, while dopamine release remained relatively unchanged following intra-ThN md drug infusions. These results indicate a shift in strength towards the thalamic vl projection, away from the VTA. Thus, cerebellar neuropathologies associated with autism spectrum disorders may cause a reduction in cerebellar modulation of mPFC dopamine release that is related to a reorganization of the mediating neuronal pathways.

Strain-specific viral distribution and neuropathology of feline immunodeficiency virus.

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Miller, Craig; Bielefeldt-Ohmann, Helle; MacMillan, Martha; Huitron-Resendiz, Salvador; Henriksen, Steven; Elder, John; VandeWoude, Susan

2011-10-15

Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic cats, and is the causative agent of feline AIDS. Similar to human immunodeficiency virus (HIV), the pathogenesis of FIV involves infection of lymphocytes and macrophages, and results in chronic progressive immune system collapse and death. Neuropathologic correlates of FIV infection have not yet been elucidated, and may be relevant to understanding HIV-associated neurologic disease (neuroAIDS). As in HIV, FIV strains have been shown to express differential tendencies towards development of clinical neuroAIDS. To interrogate viral genetic determinants that might contribute to neuropathogenicity, cats were exposed to two well-characterized FIV strains with divergent clinical phenotypes and a chimeric strain as follows: FIV(PPR) (PPR, relatively apathogenic but associated with neurologic manifestations), FIV(C36) (C36, immunopathogenic but without associated neurologic disease), and Pcenv (a chimeric virus consisting of a PPR backbone with substituted C36 env region). A sham inoculum control group was also included. Peripheral nerve conduction velocity, CNS imaging studies, viral loads and hematologic analysis were performed over a 12 month period. At termination of the study (350 days post-inoculation), brain sections were obtained from four anatomic locations known to be involved in human and primate lentiviral neuroAIDS. Histological and immunohistochemical evaluation with seven markers of inflammation revealed that Pcenv infection resulted in mild inflammation of the CNS, microglial activation, neuronal degeneration and apoptosis, while C36 and PPR strains induced minimal neuropathologic changes. Conduction velocity aberrations were noted peripherally in all three groups at 63 weeks post-infection. Pcenv viral load in this study was intermediate to the parental strains (C36 demonstrating the highest viral load and PPR the lowest). These results collectively suggest that (i) 3' C36

The Sleep Disorder in Anti-lgLON5 Disease.

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Gaig, Carles; Iranzo, Alex; Santamaria, Joan; Graus, Francesc

2018-05-23

To review the clinical and polysomnographic features of the sleep disorder occurring in the recently described anti-IgLON5 disease. The hallmark of the disease is the presence of antibodies against IgLON5, a neural cell adhesion molecule of unknown function. The disease presents a robust HLA association, and the neuropathological examination shows a novel neuronal tauopathy with predominant hypothalamic and brainstem involvement. Most patients (> 80%) present sleep-related vocalizations with movements and behaviors and sleep-disordered breathing. Polysomnographic studies show (1) a complex NREM sleep parasomnia at sleep initiation characterized by undifferentiated NREM or poorly structured N2 sleep with sleep-talking or mumbling, and simple or finalistic movements followed by normal periods of N3 or N2 NREM sleep, (2) REM sleep behavior disorder (RBD), and (3) obstructive sleep apnea with stridor. The last two features appear mainly in periods where NREM sleep normalizes. Identification of the anti-IgLON5 sleep disorder is important to suspect the disease. The combination of abnormal NREM sleep initiation, followed by normal periods of NREM sleep and RBD, represents a novel parasomnia.

Early behavioral changes and quantitative analysis of neuropathological features in murine prion disease

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Borner, Roseane; Bento-Torres, João; Souza, Diego RV; Sadala, Danyelle B; Trevia, Nonata; Farias, José Augusto; Lins, Nara; Passos, Aline; Quintairos, Amanda; Diniz, José Antônio; Perry, Victor Hugh; Vasconcelos, Pedro Fernando; Cunningham, Colm

2011-01-01

Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression. PMID:21862877

Self-Referential Thinking, Suicide, and Function of the Cortical Midline Structures and Striatum in Mood Disorders: Possible Implications for Treatment Studies of Mindfulness-Based Interventions for Bipolar Depression

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William R. Marchand

2012-01-01

Full Text Available Bipolar depression is often refractory to treatment and is frequently associated with anxiety symptoms and elevated suicide risk. There is a great need for adjunctive psychotherapeutic interventions. Treatments with effectiveness for depressive and anxiety symptoms as well as suicide-related thoughts and behaviors would be particularly beneficial. Mindfulness-based interventions hold promise, and studies of these approaches for bipolar disorder are warranted. The aim of this paper is to provide a conceptual background for such studies by reviewing key findings from diverse lines of investigation. Results of that review indicate that cortical midline structures (CMS appear to link abnormal self-referential thinking to emotional dysregulation in mood disorders. Furthermore, CMS and striatal dysfunction may play a role in the neuropathology underlying suicide-related thoughts and behaviors. Thus, combining studies of mindfulness interventions targeting abnormal self-referential thinking with functional imaging of CMS and striatal function may help delineate the neurobiological mechanisms of action of these treatments.

Identification of genes associated with dissociation of cognitive performance and neuropathological burden: Multistep analysis of genetic, epigenetic, and transcriptional data.

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Charles C White

2017-04-01

Full Text Available The molecular underpinnings of the dissociation of cognitive performance and neuropathological burden are poorly understood, and there are currently no known genetic or epigenetic determinants of the dissociation."Residual cognition" was quantified by regressing out the effects of cerebral pathologies and demographic characteristics on global cognitive performance proximate to death. To identify genes influencing residual cognition, we leveraged neuropathological, genetic, epigenetic, and transcriptional data available for deceased participants of the Religious Orders Study (n = 492 and the Rush Memory and Aging Project (n = 487. Given that our sample size was underpowered to detect genome-wide significance, we applied a multistep approach to identify genes influencing residual cognition, based on our prior observation that independent genetic and epigenetic risk factors can converge on the same locus. In the first step (n = 979, we performed a genome-wide association study with a predefined suggestive p < 10-5, and nine independent loci met this threshold in eight distinct chromosomal regions. Three of the six genes within 100 kb of the lead SNP are expressed in the dorsolateral prefrontal cortex (DLPFC: UNC5C, ENC1, and TMEM106B. In the second step, in the subset of participants with DLPFC DNA methylation data (n = 648, we found that residual cognition was related to differential DNA methylation of UNC5C and ENC1 (false discovery rate < 0.05. In the third step, in the subset of participants with DLPFC RNA sequencing data (n = 469, brain transcription levels of UNC5C and ENC1 were evaluated for their association with residual cognition: RNA levels of both UNC5C (estimated effect = -0.40, 95% CI -0.69 to -0.10, p = 0.0089 and ENC1 (estimated effect = 0.0064, 95% CI 0.0033 to 0.0096, p = 5.7 × 10-5 were associated with residual cognition. In secondary analyses, we explored the mechanism of these associations and found that ENC1 may be related to

Heme Oxygenase-1 Activity as a Correlate to Exercise-Mediated Amelioration of Cognitive Decline and Neuropathological Alterations in an Aging Rat Model of Dementia

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Andrea Kurucz

2018-01-01

Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder with cognitive impairment. Physical exercise has long been proven to be beneficial in the disorder. The present study was designed to examine the effect of voluntary exercise on spatial memory, imaging, and pathological abnormalities. Particular focus has been given to the role of heme oxygenase-1 (HO-1—an important cellular cytoprotectant in preserving mental acuity—using an aging rat model of dementia. Male and female Wistar rats were segregated into six groups—namely, (i aged sedentary (control females (ASF, n=8; (ii aged sedentary (control males (ASM, n=8; (iii aged running females (ARF, n=8; (iv aged running males (ARM, n=8; (v young control females (YCF, n=8; and (vi young control males (YCM, n=8. Rats in the ARF and ARM groups had free access to a standardized inbuilt running wheel during the 3-month evaluation period. Spatial memory was investigated using the Morris Water Test, imaging and pathological alterations were assessed using positron emission tomography (PET imaging and histopathological examinations (H&E, Congo red staining, respectively, and HO-1 enzyme activity assays were also conducted. The outcomes suggest that voluntary physical exercise mitigates impaired spatial memory and neuropathological changes exhibited by the aging sedentary group, via elevated HO-1 activity, contributing to the antioxidant capacity in the aging brain.

A model of disordered zone formation in Cu3Au under cascade-producing irradiation

International Nuclear Information System (INIS)

Kapinos, V.G.; Bacon, D.J.

1995-01-01

A model to describe the disordering of ordered Cu 3 Au under irradiation is proposed. For the thermal spike phase of a displacement cascade, the processes of heat evolution and conduction in the cascade region are modelled by solving the thermal conduction equation by a discretization method for a medium that can melt and solidify under appropriate conditions. The model considers disordering to result from cascade core melting, with the final disordered zone corresponding to the largest molten zone achieved. The initial conditions for this treatment are obtained by simulation of cascades by the MARLOWE code. The contrast of disordered zones imaged in a superlattice dark-field reflection and projected on the plane parallel to the surface of a thin foil was calculated. The average size of images from hundreds of cascades created by incident Cu + ions were calculated for different ion energies and compared with experimental transmission electron microscopy data. The model is in reasonable quantitative agreement with the experimentally observed trends. (author)

Neuropathological findings in entorhinal cortex of subjects aged 50 years or older and their correlation with dementia in a sample from Southern Brazil

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Edson Rodrigues Neto

Full Text Available ABSTRACT Introduction: The aims of this study were to survey neurodegenerative changes detected by abnormal protein deposits in the Entorhinal Cortex (EC of subjects aged 50 years or older and to correlate these findings with suspected dementia, as detected by the IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly . Methods: Fourteen brains were submitted to the immunohistochemistry technique for different proteins (beta-amyloid, tau, -synuclein and phospho-TDP-43 and data obtained compared with IQCODE scores. Results: Fifty-seven percent of the individuals exhibited IQCODE results compatible with dementia, being classified into the demented group (DG: 87.5% of patients had neuropathological findings corresponding to Alzheimer's-like brain pathology (ALBP. Of the patients in the non-demented group (NDG, 16.7% met neuropathological criteria for ALBP. All individuals in the DG showed deposits of more than one kind of protein in the EC. The most common association was hyperphosphorylated tau and beta-amyloid protein (87.5%. Discussion: Most individuals with dementia had neuropathological findings of ALBP, as did one individual with no signs of dementia, characterizing a preclinical stage. The results of this study suggest that deposits of a single type of anomalous protein are normal findings in an aging brain, while more than one kind of protein or the combined presence of anomalous protein deposits indicate the presence of dementia.

Esophageal lichen planus: A rare and under-recognized disorder

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Md Nadeem Parvez

2016-01-01

Full Text Available Lichen planus (LP is a chronic idiopathic disorder involving the skin and mucosal surfaces. Although oral mucosal involvement is common, esophageal LP (ELP is uncommon and also under-reported. Here, we present a case of ELP who was symptomatic with dysphagia for a year, but was untreated. Increasing awareness of this condition can help identify more cases and increase our understanding of this uncommon but interesting condition.

Reduced thalamic and pontine connectivity in Kleine-Levin syndrome

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Maria eEngström

2014-04-01

Full Text Available The Kleine-Levin syndrome is a rare sleep disorder, characterized by exceptionally long sleep episodes. The neuropathology of the syndrome is unknown and treatment is often inadequate. The aim of the study was to improve understanding of the underlying neuropathology, related to cerebral networks, in Kleine-Levin syndrome during sleep episodes. One patient with Kleine-Levin syndrome and congenital nystagmus, was investigated by resting state functional Magnetic Resonance Imaging during both asymptomatic and hypersomnic periods. Fourteen healthy subjects were also investigated as control samples. Functional connectivity was assessed from seed regions of interest in the thalamus and the dorsal pons. Thalamic connectivity was normal in the asymptomatic patient whereas the connectivity between the brain stem, including dorsal pons, and the thalamus was diminished during hypersomnia. These results suggest that the patient’s nystagmus and hypersomnia might have their pathological origin in adjacent dorsal pontine regions. This finding provides additional knowledge of the cerebral networks involved in the neuropathology of this disabling disorder. Furthermore, these findings regarding a rare syndrome have broad implications and results could be of interest to researchers and clinicians in the whole field of sleep medicine.

Neuroanatomy and neuropathology associated with Korsakoff's syndrome.

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Kril, Jillian J; Harper, Clive G

2012-06-01

Although the neuropathology of Korsakoff's syndrome (KS) was first described well over a century ago and the characteristic brain pathology does not pose a diagnostic challenge to pathologists, there is still controversy over the neuroanatomical substrate of the distinctive memory impairment in these patients. Cohort studies of KS suggest a central role for the mammillary bodies and mediodorsal thalamus, and quantitative studies suggest additional damage to the anterior thalamus is required. Rare cases of KS caused by pathologies other than those of nutritional origin provide support for the role of the anterior thalamus and mammillary bodies. Taken together the evidence to date shows that damage to the thalamus and hypothalamus is required, in particular the anterior thalamic nucleus and the medial mammillary nucleus of the hypothalamus. As these nuclei form part of wider memory circuits, damage to the inter-connecting white matter tracts can also result in a similar deficit as direct damage to the nuclei. Although these nuclei and their connections appear to be the primary site of damage, input from other brain regions within the circuits, such as the frontal cortex and hippocampus, or more distant regions, including the cerebellum and amygdala, may have a modulatory role on memory function. Further studies to confirm the precise site(s) and extend of brain damage necessary for the memory impairment of KS are required.

Neuropathological Changes in Brain Cortex and Hippocampus in a Rat Model of Alzheimer’s Disease

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Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Roosh, Nahid Rahbar; Omidzahir, Shila

2011-01-01

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Methods: Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and β-amyloid (Aβ) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 µL of Aβ (1-40) into the hippocampal fissure. Results: In the present study, Aβ (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. Aβ injection CA1 caused Aβ deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. Conclusion: We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group. PMID:21725500

Molecular Neuropathology of Astrocytes and Oligodendrocytes in Alcohol Use Disorders

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José J. Miguel-Hidalgo

2018-03-01

Full Text Available Postmortem studies reveal structural and molecular alterations of astrocytes and oligodendrocytes in both the gray and white matter (GM and WM of the prefrontal cortex (PFC in human subjects with chronic alcohol abuse or dependence. These glial cellular changes appear to parallel and may largely explain structural and functional alterations detected using neuroimaging techniques in subjects with alcohol use disorders (AUDs. Moreover, due to the crucial roles of astrocytes and oligodendrocytes in neurotransmission and signal conduction, these cells are very likely major players in the molecular mechanisms underpinning alcoholism-related connectivity disturbances between the PFC and relevant interconnecting brain regions. The glia-mediated etiology of alcohol-related brain damage is likely multifactorial since metabolic, hormonal, hepatic and hemodynamic factors as well as direct actions of ethanol or its metabolites have the potential to disrupt distinct aspects of glial neurobiology. Studies in animal models of alcoholism and postmortem human brains have identified astrocyte markers altered in response to significant exposures to ethanol or during alcohol withdrawal, such as gap-junction proteins, glutamate transporters or enzymes related to glutamate and gamma-aminobutyric acid (GABA metabolism. Changes in these proteins and their regulatory pathways would not only cause GM neuronal dysfunction, but also disturbances in the ability of WM axons to convey impulses. In addition, alcoholism alters the expression of astrocyte and myelin proteins and of oligodendrocyte transcription factors important for the maintenance and plasticity of myelin sheaths in WM and GM. These changes are concomitant with epigenetic DNA and histone modifications as well as alterations in regulatory microRNAs (miRNAs that likely cause profound disturbances of gene expression and protein translation. Knowledge is also available about interactions between astrocytes and

An order in Lewy body disorders: Retrograde degeneration in hyperbranching axons as a fundamental structural template accounting for focal/multifocal Lewy body disease.

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Uchihara, Toshiki

2017-04-01

Initial clinical recognition of "paralysis agitans" by James Parkinson was expanded by Jean-Martin Charcot, who recognized additional clinical findings of his own, such as slowness (distinct from paralysis), rigidity (distinct from spasticity) and characteristic countenance. Charcot assembled these findings under the umbrella of "Parkinson disease (PD)". This purely clinical concept was so prescient and penetrating that subsequent neuropathological and biochemical evidences were ordered along this axis to establish the nigra-central trinity of PD (dopamine depletion, nigral lesion with Lewy bodies: LBs). Although dramatic efficacy of levodopa boosted an enthusiasm for this nigra-centralism, extranigral lesions were identified, especially after identification of alpha-synuclein (αS) as a major constituent of LBs. Frequent αS lesions in the lower brainstem with their presumed upward spread were coupled with the self-propagating property of αS molecule, as a molecular template, to constitute the prion-Braak hypothesis. This hybrid concept might expectedly explain clinical, structural and biochemical features of PD/dementia with Lewy bodies (DLB) as if they were stereotypic. In spite of this ordered explanation, recent studies have demonstrated unexpectedly that αS lesions in the human brain, as well as their corresponding clinical manifestations, are much more disordered. Even with such a chaos of LB disorders, affected neuronal groups are uniformly characterized by hyperbranching axons, which may facilitate distal-dominant degeneration and retrograde progression of LB-related degeneration along axons as a fundamental structural order to template LB disorders. This "structural template" hypothesis may explain why: (i) some selective groups are prone to develop Lewy pathology; (ii) their clinical manifestations (especially non-motor components) are vague and generalized without somatotopic accentuation; (iii) distal axons and terminals are preferentially affected

Hemodynamic and neuropathological analysis in rats with aluminum trichloride-induced Alzheimer's disease.

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Szu-Ming Chen

Full Text Available BACKGROUND AND AIMS: Hemodynamic normality is crucial to maintaining the integrity of cerebral vessels and, therefore, preserving the cognitive functions of Alzheimer's disease patients. This study investigates the implications of the hemodynamic changes and the neuropathological diversifications of AlCl3-induced AD. METHODS: The experimental animals were 8- to 12-wk-old male Wistar rats. The rats were randomly divided into 2 groups: a control group and a (+control group. Food intake, water intake, and weight changes were recorded daily for 22 wk. Synchronously, the regional cerebral blood flow (rCBF of the rats with AlCl3-induced AD were measured using magnetic resonance imaging (MRI. The hemorheological parameters were analyzed using a computerized auto-rotational rheometer. The brain tissue of the subjects was analyzed using immunohistological chemical (IHC staining to determine the beta-amyloid (Aβ levels. RESULTS: The results of hemodynamic analysis revealed that the whole blood viscosity (WBV, fibrinogen, plasma viscosity and RBC aggregation index (RAI in (+control were significantly higher than that of control group, while erythrocyte electrophoresis (EI of whole blood in (+control were significantly lower than that of control group. The results of acetylcholinesterase-RBC (AChE-RBCin the (+control group was significantly higher than that of the control group. The results also show that the reduction of rCBF in rats with AlCl3-induced AD was approximately 50% to 60% that of normal rats. IHC stain results show that significantly more Aβ plaques accumulated in the hippocampus and cortex of the (+control than in the control group. CONCLUSION: The results accentuate the importance of hemorheology and reinforce the specific association between hemodynamic and neuropathological changes in rats with AlCl3-induced AD. Hemorheological parameters, such as WBV and fibrinogen, and AChE-RBC were ultimately proven to be useful biomarkers of the

Neuropathological survey reveals underestimation of the prevalence of neuroinfectious diseases in cattle in Switzerland.

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Truchet, Laura; Walland, Julia; Wüthrich, Daniel; Boujon, Céline L; Posthaus, Horst; Bruggmann, Rémy; Schüpbach-Regula, Gertraud; Oevermann, Anna; Seuberlich, Torsten

2017-09-01

Neuroinfectious diseases in livestock represent a severe threat to animal health, but their prevalence is not well documented and the etiology of disease often remains unidentified. The aims of this study were to generate baseline data on the prevalence of neuroinfectious diseases in cattle in Switzerland by neuropathological survey, and to identify disease-associated pathogens. The survey was performed over a 1-year period using a representative number of brainstem samples (n=1816) from fallen cattle. In total, 4% (n=73) of the animals had significant lesions, the most frequent types of which were indicative of viral (n=27) and bacterial (n=31) etiologies. Follow-up diagnostics by immunohistochemistry, PCR protocols and next-generation sequencing identified infection with Listeria monocytogenes (n=6), ovine herpesvirus 2 (n=7), bovine astrovirus CH13 (n=2), bovine herpesvirus 6 (n=6), bovine retrovirus CH15 (n=2), posavirus 1 (n=2), and porcine astroviruses (n=2). A retrospective questionnaire-based investigation indicated that animals' owners observed clinical signs of neurological disease in about one-third of cases with lesions, which was estimated to correspond to approximately 85 cases per year in the adult fallen cattle population in Switzerland. This estimate stands in sharp contrast to the number of cases reported to the authorities and reveals a gap in disease surveillance. Systematic neuropathological examination and follow-up molecular testing of neurologically diseased cattle could significantly enhance the efficiency of disease detection for the purposes of estimating the prevalence of endemic diseases, identifying new or re-emerging pathogens, and providing "early warnings" of disease outbreaks. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuropathological and biochemical criteria to identify acquired Creutzfeldt-Jakob disease among presumed sporadic cases.

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Kobayashi, Atsushi; Parchi, Piero; Yamada, Masahito; Mohri, Shirou; Kitamoto, Tetsuyuki

2016-06-01

As an experimental model of acquired Creutzfeldt-Jakob disease (CJD), we performed transmission studies of sporadic CJD using knock-in mice expressing human prion protein (PrP). In this model, the inoculation of the sporadic CJD strain V2 into animals homozygous for methionine at polymorphic codon 129 (129 M/M) of the PRNP gene produced quite distinctive neuropathological and biochemical features, that is, widespread kuru plaques and intermediate type abnormal PrP (PrP(Sc) ). Interestingly, this distinctive combination of molecular and pathological features has been, to date, observed in acquired CJD but not in sporadic CJD. Assuming that these distinctive phenotypic traits are specific for acquired CJD, we revisited the literature and found two cases showing widespread kuru plaques despite the 129 M/M genotype, in a neurosurgeon and in a patient with a medical history of neurosurgery without dura mater grafting. By Western blot analysis of brain homogenates, we revealed the intermediate type of PrP(Sc) in both cases. Furthermore, transmission properties of brain extracts from these two cases were indistinguishable from those of a subgroup of dura mater graft-associated iatrogenic CJD caused by infection with the sporadic CJD strain V2. These data strongly suggest that the two atypical CJD cases, previously thought to represent sporadic CJD, very likely acquired the disease through exposure to prion-contaminated brain tissues. Thus, we propose that the distinctive combination of 129 M/M genotype, kuru plaques, and intermediate type PrP(Sc) , represents a reliable criterion for the identification of acquired CJD cases among presumed sporadic cases. © 2015 Japanese Society of Neuropathology.

Depression and Alzheimer's disease: is stress the initiating factor in a common neuropathological cascade?

DEFF Research Database (Denmark)

Aznar, Susana; Knudsen, Gitte M

2011-01-01

The existence of a high co-morbidity between Alzheimer's disease (AD) and depression has been known for a long time. More interesting though are recent studies indicating that depression and number of depressive episodes earlier in life is associated with increased risk of AD development....... This suggests the existence of common neuropathological mechanisms behind depression and AD. Here we propose that the brain changes associated with depressive episodes that compromise the brain's ability to cope with stress may constitute risk factors for development of AD. Furthermore, in individuals...... serotonergic and cholinergic system, hypothalamic-pituitary-adrenal axis and brain derived neurotrophic factor, and discussed in relation to AD....

Creutzfeldt-Jacob-disease: The computerized tomogram in relation to clinical, electroencephalographic and neuropathological findings

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Zieger, A.; Vonofakos, D.; Vitzthum, H.

1981-12-01

The computerized tomogram (CT) of a senile case of Creutzfeldt-Jacob disease with rapid progress, showed after an initially minor parietal dilatation of the gyri, a volume increase, predominantly on the right side, in the area of the cerebral convexity and a right-preponderant dilatation of the anterior horns. By neuropathologic examination indications for a passed cerebral oedema was found, covering the cortex atrophy, which previously had been detected by CT. Progression and local intensity of the atrophic signs in CT - in combination with clinical and electroencephalographic findings - suggest the existence of a Creutzfeldt-Jakob disease and permit its delineation against other atrophying processes.

Creutzfeldt-Jacob-disease: The computerized tomogram in relation to clinical, electroencephalographic and neuropathological findings

International Nuclear Information System (INIS)

Zieger, A.

1981-01-01

The computerized tomogram (CT) of a senile case of Creutzfeldt-Jakob disease with rapid progress, showed after an initially minor parietal dilatation of the gyri, a volume increase, predominantly on the right side, in the area of the cerebral convexity and a right-preponderant dilatation of the anterior horns. By neuropathologic examination indications for a passed cerebral oedema was found, covering the cortex atrophy, which previously had been detected by CT. Progression and local intensity of the atrophic signs in CT - in combination with clinical and electroencephalographic findings - let appear probable the existence of a Creutzfeldt-Jakob disease and permit its delineation against other atrophying processes. (orig./MG) [de

Neurological implications of urea cycle disorders

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Summar, M.; Leonard, J. V.

2013-01-01

Summary The urea cycle disorders constitute a group of rare congenital disorders caused by a deficiency of the enzymes or transport proteins required to remove ammonia from the body. Via a series of biochemical steps, nitrogen, the waste product of protein metabolism, is removed from the blood and converted into urea. A consequence of these disorders is hyperammonaemia, resulting in central nervous system dysfunction with mental status changes, brain oedema, seizures, coma, and potentially death. Both acute and chronic hyperammonaemia result in alterations of neurotransmitter systems. In acute hyperammonaemia, activation of the NMDA receptor leads to excitotoxic cell death, changes in energy metabolism and alterations in protein expression of the astrocyte that affect volume regulation and contribute to oedema. Neuropathological evaluation demonstrates alterations in the astrocyte morphology. Imaging studies, in particular 1H MRS, can reveal markers of impaired metabolism such as elevations of glutamine and reduction of myoinositol. In contrast, chronic hyperammonaemia leads to adaptive responses in the NMDA receptor and impairments in the glutamate–nitric oxide–cGMP pathway, leading to alterations in cognition and learning. Therapy of acute hyperammonaemia has relied on ammonia-lowering agents but in recent years there has been considerable interest in neuroprotective strategies. Recent studies have suggested restoration of learning abilities by pharmacological manipulation of brain cGMP with phosphodiesterase inhibitors. Thus, both strategies are intriguing areas for potential investigation in human urea cycle disorders. PMID:18038189

MM2-thalamic Creutzfeldt-Jakob disease: neuropathological, biochemical and transmission studies identify a distinctive prion strain.

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Moda, Fabio; Suardi, Silvia; Di Fede, Giuseppe; Indaco, Antonio; Limido, Lucia; Vimercati, Chiara; Ruggerone, Margherita; Campagnani, Ilaria; Langeveld, Jan; Terruzzi, Alessandro; Brambilla, Antonio; Zerbi, Pietro; Fociani, Paolo; Bishop, Matthew T; Will, Robert G; Manson, Jean C; Giaccone, Giorgio; Tagliavini, Fabrizio

2012-09-01

In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrP(Sc) ) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrP(Sc) and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrP(Sc) are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrP(Sc) . Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrP(Sc) , a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

Formulation of a medical food cocktail for Alzheimer's disease: beneficial effects on cognition and neuropathology in a mouse model of the disease.

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Anna Parachikova

2010-11-01

Full Text Available Dietary supplements have been extensively studied for their beneficial effects on cognition and AD neuropathology. The current study examines the effect of a medical food cocktail consisting of the dietary supplements curcumin, piperine, epigallocatechin gallate, α-lipoic acid, N-acetylcysteine, B vitamins, vitamin C, and folate on cognitive functioning and the AD hallmark features and amyloid-beta (Aβ in the Tg2576 mouse model of the disease.The study found that administering the medical food cocktail for 6 months improved cortical- and hippocampal- dependent learning in the transgenic mice, rendering their performance indistinguishable from non-transgenic controls. Coinciding with this improvement in learning and memory, we found that treatment resulted in decreased soluble Aβ, including Aβ oligomers, previously found to be linked to cognitive functioning.In conclusion, the current study demonstrates that combination diet consisting of natural dietary supplements improves cognitive functioning while decreasing AD neuropathology and may thus represent a safe, natural treatment for AD.

Rationalization of the Irrational Neuropathologic Basis of Hypothyroidism-Olfaction Disorders Paradox: Experimental Study.

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Aydin, Nazan; Ramazanoglu, Leyla; Onen, Mehmet Resid; Yilmaz, Ilhan; Aydin, Mehmet Dumlu; Altinkaynak, Konca; Calik, Muhammet; Kanat, Ayhan

2017-11-01

Hypothyroidism is defined as an underactive thyroid gland and one of the reasons for inadequate stimulation of thyroid is dysfunction of the hormone regulating brain centers. Olfaction disorders have been considered as a problem in hypothyroidism. It has been hypothesized that olfaction disorders reduce olfactory stimulation and diminished olfactory stimulus may trigger hypothyroidism. In this study, an examination was made of the thyroid hormone levels, histologic features of thyroid glands, and vagal nerve network degradation in an experimental animal model of olfactory bulbectomy (OBX). A total of 25 rats were divided into control (n = 5), SHAM (n = 5), and OBX (n = 15) groups and were followed up for 8 weeks. Thyroid hormone levels were measured before (1 time), during the experiment (1 time/month) and the animals were decapitated. The olfactory bulbs, dorsal motor nucleus of the vagal nerves, and thyroid gland sections were stained with hematoxylin-eosin and tunnel dye to determine OBX-related damage. Specimens were analyzed stereologically to evaluate neuron density of the vagal nucleus and hormone-filled total follicle volume (TFV) per cubic centimeter, and these were statistically compared with thyroid hormone levels. The mean degenerated neuron density of the vagal nucleus was 21 ± 8/mm 3 . TFV and triiodothyronine (T 3 )-thyroxine (T 4 ) levels were measured as TFV, (312 ± 91) × 10 6 μm 3 /cm 3 ; T 3 , 105 μg/dl; T 4 , 1.89 μg/dl in control (group I). Mean degenerated neuron density, 56 ± 12/mm 3 ; TFV, (284 ± 69) × 10 6 μm 3 /cm 3 ; T 3 , 103 μg/dl; T 4 , 1.85 μg/dl in SHAM (group II). Mean degenerated neuron density, 235 ± 64/mm 3 ; TFV, (193 ± 34) × 10 6 μm 3 /cm 3 ; T 3 , 86 μg/dl; T 4 , 1.37 μg/dl in the OBX group (group III). The TFV were significantly diminished because of apoptotic degradation in olfactory bulbs and thyroid gland with decreased T 3 - T 4 levels with increased thyroid-stimulating hormone levels in OBX

A Chronic Longitudinal Characterization of Neurobehavioral and Neuropathological Cognitive Impairment in a Mouse Model of Gulf War Agent Exposure

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Zakirova, Zuchra; Crynen, Gogce; Hassan, Samira; Abdullah, Laila; Horne, Lauren; Mathura, Venkatarajan; Crawford, Fiona; Ait-Ghezala, Ghania

2016-01-01

Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component that includes memory impairment as well as neurological and musculoskeletal deficits. Previous studies have shown that in the First Persian Gulf War conflict (1990–1991) exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and permethrin (PER), were key contributors to the etiology of GWI. For this study, we used our previously established mouse model of GW agent exposure (10 days PB+PER) and undertook an extensive lifelong neurobehavioral characterization of the mice from 11 days to 22.5 months post exposure in order to address the persistence and chronicity of effects suffered by the current GWI patient population, 24 years post-exposure. Mice were evaluated using a battery of neurobehavioral testing paradigms, including Open Field Test (OFT), Elevated Plus Maze (EPM), Three Chamber Testing, Radial Arm Water Maze (RAWM), and Barnes Maze (BM) Test. We also carried out neuropathological analyses at 22.5 months post exposure to GW agents after the final behavioral testing. Our results demonstrate that PB+PER exposed mice exhibit neurobehavioral deficits beginning at the 13 months post exposure time point and continuing trends through the 22.5 month post exposure time point. Furthermore, neuropathological changes, including an increase in GFAP staining in the cerebral cortices of exposed mice, were noted 22.5 months post exposure. Thus, the persistent neuroinflammation evident in our model presents a platform with which to identify novel biological pathways, correlating with emergent outcomes that may be amenable to therapeutic targeting. Furthermore, in this work we confirmed our previous findings that GW agent exposure causes neuropathological changes, and have presented novel data which demonstrate increased disinhibition, and lack of social preference in PB+PER exposed mice at 13 months after exposure. We also extended upon our previous work to

An under-diagnosed geriatric syndrome: sleep disorders among older adults.

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Tufan, Asli; Ilhan, Birkan; Bahat, Gulistan; Karan, Mehmet Akif

2017-06-01

Sleep disorders are commonly under-diagnosed in the geriatric population. We aimed to determine the prevalence of sleep problems among older adults admitted to the geriatrics out-patient clinic. Two hundred and three patients (136 female) older than 75 years of age were included in the study. Patients underwent comprehensive geriatric assessment, including identification of sleep problems using the Sleep Disturbance Scale, Rapid eye movement (REM) sleep behavior disorder (RBD) Single-Question Screen questionnaire (RBD1Q) and The Johns Hopkins Restless Leg Syndrome Severity Scale. Demographic and clinical data including age, sex, medications, comorbid diseases, body mass index and functional scores was noted. The mean age of the patients was 80.92±4.3 years. 35.5% of the patients had findings of REM-SBD and 32.5% of the patients had restless legs syndrome. Ninety-seven percent of the patients answered 'yes' to at least one of the sleep disturbance scale questions. There was no significant difference between male and female groups. We observed that sleep disorders were common among older adults. For this reason, the course and quality of sleep should be examined in all patients as a routine part of comprehensive geriatric assessment.

Review: Hippocampal sclerosis in epilepsy: a neuropathology review

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Thom, Maria

2014-01-01

Hippocampal sclerosis (HS) is a common pathology encountered in mesial temporal lobe epilepsy (MTLE) as well as other epilepsy syndromes and in both surgical and post-mortem practice. The 2013 International League Against Epilepsy (ILAE) classification segregates HS into typical (type 1) and atypical (type 2 and 3) groups, based on the histological patterns of subfield neuronal loss and gliosis. In addition, granule cell reorganization and alterations of interneuronal populations, neuropeptide fibre networks and mossy fibre sprouting are distinctive features of HS associated with epilepsies; they can be useful diagnostic aids to discriminate from other causes of HS, as well as highlighting potential mechanisms of hippocampal epileptogenesis. The cause of HS remains elusive and may be multifactorial; the contribution of febrile seizures, genetic susceptibility, inflammatory and neurodevelopmental factors are discussed. Post-mortem based research in HS, as an addition to studies on surgical samples, has the added advantage of enabling the study of the wider network changes associated with HS, the long-term effects of epilepsy on the pathology and associated comorbidities. It is likely that HS is heterogeneous in aspects of its cause, epileptogenetic mechanisms, network alterations and response to medical and surgical treatments. Future neuropathological studies will contribute to better recognition and understanding of these clinical and patho-aetiological subtypes of HS. PMID:24762203

Stimulation of Central A1 Adenosine Receptors Suppresses Seizure and Neuropathology in a Soman Nerve Agent Seizure Rat Model

Science.gov (United States)

2014-05-22

implantation site, Nissl stained , and then analyzed by a trained pathologist to verify the accuracy of cannulae placement and evaluate toxicity. The second...transcardial perfusion and fixation, the brains were sectioned and stained with Nissl . A trained pathologist then analyzed the sections and verified that CPA...proto- col was used for assessing neuropathology in the subsequent soman seizure experiments. Those brains were serial sec- tioned at 5 mm, stained

Development of psychotherapy as a method of mental disorders treatment at the Jagiellonian University and in Kraków before World War I.

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Dembińska, Edyta; Rutkowski, Krzysztof

2016-01-01

This article presents the origins of Polish psychotherapy with a special focus on psychotherapy development in Krakow and at the Jagiellonian University. The history of Krakow psychotherapy starts with the foundation of the Psychiatry and Neuropathology Clinic of the Jagiellonian University in 1905. Doctors working in the Department of psychotherapy developed their skills through contacts with the Zurich University Psychiatric Clinic Burgholzli. At the same time psychotherapy, and psychoanalysis in particular, were raising more and more interest in Poland. The most dynamic development of psychoanalysis reflected in the number of scientific publications, occurs in the years leading to the outbreak of War World I. This article presents brief portraits of the first Polish psychoanalysts ( Ludwik Jekels, Herman Nunberg, Ludwika Karpińska, Stefan Borowiecki, Jan Nelken, Kraol de Beaurain). Many of them worked in Psychiatry and Neuropathology Clinic of the Jagiellonian University. Their scientific achievements and contribution to the development of the international psychoanalytic movement are described, as well as relationships with leading psychoanalysts of this period (Freud, Jung). With the outbreak of World War I the research on and treatment of war neurosis was initiated in the Psychiatry and Neuropathology Clinic. Professor Piltz, the director of the clinic, together with his assistants (Borowiecki, de Beuarain, Artwiński) devised a unique in European psychiatry and highly efficient method of post-traumatic disorders treatment, in which psychotherapy was of key importance.

The Utility of Expert Diagnosis in Surgical Neuropathology: Analysis of Consultations Reviewed at 5 National Comprehensive Cancer Network Institutions.

Science.gov (United States)

Bruner, Janet M; Louis, David N; McLendon, Roger; Rosenblum, Marc K; Archambault, W Tad; Most, Susan; Tihan, Tarik

2017-03-01

The aim of this study was to characterize the type and degree of discrepancies between non-expert and expert diagnoses of CNS tumors to identify the value of consultations in surgical neuropathology. Neuropathology experts from 5 National Comprehensive Cancer Network (NCCN) member institutions participated in the review of 1281 consultations selected based on inclusion criteria. The consultation cases were re-reviewed at the NCCN headquarters to determine concordance with the original diagnoses. Among all consultations, 249 (19.4%) were submitted for expert diagnoses without final diagnoses from the submitting institution. Within the remaining 1032 patients, the serious/major discrepancy rate was 4.8%, and less serious and minor discrepancies were seen in 19.4% of the cases. The discrepancy rate was higher among patients who were referred to NCCN institutions for consultation compared to those who were referred for treatment only. The discrepancy rates, patient demographics, type of consultations and submitting institutions varied among participating NCCN institutions. Expert consultations identified a subset of cases with significant diagnostic discrepancies, and constituted the initial diagnoses in some cases. These data indicate that expert consultations in glial tumors and all types of pediatric CNS tumors can improve accurate diagnosis and enable appropriate management. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

A systems approach identifies networks and genes linking sleep and stress: implications for neuropsychiatric disorders.

Science.gov (United States)

Jiang, Peng; Scarpa, Joseph R; Fitzpatrick, Karrie; Losic, Bojan; Gao, Vance D; Hao, Ke; Summa, Keith C; Yang, He S; Zhang, Bin; Allada, Ravi; Vitaterna, Martha H; Turek, Fred W; Kasarskis, Andrew

2015-05-05

Sleep dysfunction and stress susceptibility are comorbid complex traits that often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multilevel organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J × A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type-specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests that the interplay among sleep, stress, and neuropathology emerges from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework for interrogating the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Visualizing the Comorbidity Burden in Children with Autism Spectrum Disorder Receiving Dental Treatment Under General Anesthesia.

Science.gov (United States)

Mathu-Muju, Kavita R; Li, Hsin-Fang; Nam, Lisa H; Bush, Heather M

2016-01-01

The purposes of this study were to: (1) describe the comorbidity burden in children with autism spectrum disorder (ASD) receiving dental treatment under general anesthesia (GA); and (2) characterize the complexity of these concurrent comorbidities. A retrospective chart review was completed of 303 children with ASD who received dental treatment under GA. All comorbidities, in addition to the primary diagnosis of ASD, were categorized using the International Classification of Diseases-10 codes. The interconnectedness of the comorbidities was graphically displayed using a network plot. Network indices (degree centrality, betweenness centrality, closeness centrality) were used to characterize the comorbidities that exhibited the highest connectedness to ASD. The network plot of medical diagnoses for children with ASD was highly complex, with multiple connected comorbidities. Developmental delay, speech delay, intellectual disability, and seizure disorders exhibited the highest connectedness to ASD. Children with autism spectrum disorder may have a significant comorbidity burden of closely related neurodevelopmental disorders. The medical history review should assess the severity of these concurrent disorders to evaluate a patient's potential ability to cooperate for dental treatment and to determine appropriate behavior guidance techniques to facilitate the delivery of dental care.

Neuronopathic lysosomal storage disorders: Approaches to treat the central nervous system.

Science.gov (United States)

Scarpa, Maurizio; Bellettato, Cinzia Maria; Lampe, Christina; Begley, David J

2015-03-01

Pharmacological research has always focused on developing new therapeutic strategies capable of modifying a disease's natural history and improving patients' quality of life. Despite recent advances within the fields of medicine and biology, some diseases still represent a major challenge for successful therapy. Neuronopathic lysosomal storage disorders, in particular, have high rates of morbidity and mortality and a devastating socio-economic effect. Many of the available therapies, such as enzyme replacement therapy, can reverse the natural history of the disease in peripheral organs but, unfortunately, are still unable to reach the central nervous system effectively because they cannot cross the blood-brain barrier that surrounds and protects the brain. Moreover, many lysosomal storage disorders are characterized by a number of blood-brain barrier dysfunctions, which may further contribute to disease neuropathology and accelerate neuronal cell death. These issues, and their context in the development of new therapeutic strategies, will be discussed in detail in this chapter. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brain imaging research in autism spectrum disorders: in search of neuropathology and health across the lifespan.

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Lainhart, Janet E

2015-03-01

Advances in brain imaging research in autism spectrum disorders (ASD) are rapidly occurring, and the amount of neuroimaging research has dramatically increased over the past 5 years. In this review, advances during the past 12 months and longitudinal studies are highlighted. Cross-sectional neuroimaging research provides evidence that the neural underpinnings of the behavioral signs of ASD involve not only dysfunctional integration of information across distributed brain networks but also basic dysfunction in primary cortices.Longitudinal studies of ASD show abnormally enlarged brain volumes and increased rates of brain growth during early childhood in only a small minority of ASD children. There is evidence of disordered development of white matter microstructure and amygdala growth, and at 2 years of age, network inefficiencies in posterior cerebral regions.From older childhood into adulthood, atypical age-variant and age-invariant changes in the trajectories of total and regional brain volumes and cortical thickness are apparent at the group level. There is evidence of abnormalities in posterior lobes and posterior brain networks during the first 2 years of life in ASD and, even in older children and adults, dysfunction in primary cortical areas.

Slower EEG alpha generation, synchronization and “flow”—possible biomarkers of cognitive impairment and neuropathology of minor stroke

OpenAIRE

Petrovic, Jelena; Milosevic, Vuk; Zivkovic, Miroslava; Stojanov, Dragan; Milojkovic, Olga; Kalauzi, Aleksandar; Saponjic, Jasna

2017-01-01

Background We investigated EEG rhythms, particularly alpha activity, and their relationship to post-stroke neuropathology and cognitive functions in the subacute and chronic stages of minor strokes. Methods We included 10 patients with right middle cerebral artery (MCA) ischemic strokes and 11 healthy controls. All the assessments of stroke patients were done both in the subacute and chronic stages. Neurological impairment was measured using the National Institute of Health Stroke Scale (NIHS...

MRI in sporadic Creutzfeldt-Jakob disease: Correlation with clinical and neuropathological data

International Nuclear Information System (INIS)

Urbach, H.; Solymosi, L.; Klisch, J.; Brechtelsbauer, D.; Wolf, H.K.; Gass, S.

1998-01-01

To ascertain whether increased grey matter signal intensity on T2-weighted images in patients with sporadic Creutzfeldt-Jakob disease (CJD) corresponds to the stage and severity of this disease, we correlated MRI findings in four of our own and previously reported patients with sporadic CJD with the clinical variants, neuropathological changes at autopsy, duration of the disease and survival time after MRI examination. Of 15 patients with the extrapyramidal type of CJD, 10 showed increased signal in the basal ganglia on T2-weighted images. One of seven patients with the Heidenhain variant had increased signal in the occipital cortex. Patients without increased grey matter signal intensity had a longer overall duration of CJD (P = 0.035). Although the interval between onset of neurological symptoms and MRI was not different, patients without increased grey matter signal also survived longer after MRI examination (P = 0.022). (orig.)

[Neurotransmission in developmental disorders].

Science.gov (United States)

Takeuchi, Yoshihiro

2008-11-01

Attention deficit/hyperactivity disorder (AD/HD) is a heterogeneous developmental disorder with an etiology that is not fully understood. AD/HD has been considered to occur due to a disturbance in cathecholaminergic neurotransmission, with particular emphasis on dopamine. The neurotransmission of dopamine in subcortical regions such as the basal ganglia and limbic areas is synaptic; on the other hand, dopamine neurotransmission in the frontal cortex is quite different, because there are very few dopamine transporters (DAT) in the frontal cortex that allow dopamine to diffuse away from the dopamine synapse ("volume transmission"). It is now clear that noradrenergic neurons play a key regulatory role in dopaminergic function in the frontal cortex. Furthermore, serotonergic neurons exert an inhibitory effect on midbrain dopamine cell bodies, and they have an influence on dopamine release in terminal regions. There is accumulating neurobiological evidence pointing toward a role of the serotonin system in AD/HD. The etiology of autism spectrum disorders (ASD) is still unclear, but information from genetics, neuropathology, brain imaging, and basic neuroscience has provided insights into the understanding of this developmental disorder. In addition to abnormal circuitry in specific limbic and neocortical areas of the cerebral cortex, impairments in brainstem, cerebellar, thalamic, and basal ganglia connections have been reported. Numerous studies have pointed to abnormalities in serotonin and glutamate neurotransmission. Three important aspects involved in the pathophysiology of ASD have been proposed. The first is cell migration, the second is unbalanced excitatory-inhibitory networks, and the third is synapse formation and pruning, the key factors being reelin, neurexin, and neuroligin. Serotonin is considered to play an important role in all of these aspects of the pathophysiology of ASD. Finally, I would like to emphasize that it is crucial in the field of child

Genetic neuropathology of obsessive psychiatric syndromes.

Science.gov (United States)

Jaffe, A E; Deep-Soboslay, A; Tao, R; Hauptman, D T; Kaye, W H; Arango, V; Weinberger, D R; Hyde, T M; Kleinman, J E

2014-09-02

Anorexia nervosa (AN), bulimia nervosa (BN) and obsessive-compulsive disorder (OCD) are complex psychiatric disorders with shared obsessive features, thought to arise from the interaction of multiple genes of small effect with environmental factors. Potential candidate genes for AN, BN and OCD have been identified through clinical association and neuroimaging studies; however, recent genome-wide association studies of eating disorders (ED) so far have failed to report significant findings. In addition, few, if any, studies have interrogated postmortem brain tissue for evidence of expression quantitative trait loci (eQTLs) associated with candidate genes, which has particular promise as an approach to elucidating molecular mechanisms of association. We therefore selected single-nucleotide polymorphisms (SNPs) based on candidate gene studies for AN, BN and OCD from the literature, and examined the association of these SNPs with gene expression across the lifespan in prefrontal cortex of a nonpsychiatric control cohort (N=268). Several risk-predisposing SNPs were significantly associated with gene expression among control subjects. We then measured gene expression in the prefrontal cortex of cases previously diagnosed with obsessive psychiatric disorders, for example, ED (N=15) and OCD/obsessive-compulsive personality disorder or tics (OCD/OCPD/Tic; N=16), and nonpsychiatric controls (N=102) and identified 6 and 286 genes that were differentially expressed between ED compared with controls and OCD cases compared with controls, respectively (false discovery rate (FDR) <5%). However, none of the clinical risk SNPs were among the eQTLs and none were significantly associated with gene expression within the broad obsessive cohort, suggesting larger sample sizes or other brain regions may be required to identify candidate molecular mechanisms of clinical association in postmortem brain data sets.

Olfactory identification deficits and associated response inhibition in obsessive-compulsive disorder: on the scent of the orbitofronto-striatal model.

Science.gov (United States)

Bersani, Giuseppe; Quartini, Adele; Ratti, Flavia; Pagliuca, Giulio; Gallo, Andrea

2013-11-30

Olfactory identification ability implicates the integrity of the orbitofrontal cortex (OFC). The fronto-striatal circuits including the OFC have been involved in the neuropathology of Obsessive Compulsive Disorder (OCD). However, only a few studies have examined olfactory function in patients with OCD. The Brief Smell Identification Test (B-SIT) and tests from the Cambridge Neuropsychological Automated Battery (CANTAB) were administered to 25 patients with OCD and to 21 healthy matched controls. OCD patients showed a significant impairment in olfactory identification ability as well as widely distributed cognitive deficits in visual memory, executive functions, attention, and response inhibition. The degree of behavioural impairment on motor impulsivity (prolonged response inhibition Stop-Signal Reaction Time) strongly correlated with the B-SIT score. Our study is the first to indicate a shared OFC pathological neural substrate underlying olfactory identification impairment, impulsivity, and OCD. Deficits in visual memory, executive functions and attention further indicate that regions outside of the orbitofronto-striatal loop may be involved in this disorder. Such results may help delineate the clinical complexity of OCD and support more targeted investigations and interventions. In this regard, research on the potential diagnostic utility of olfactory identification deficits in the assessment of OCD would certainly be useful. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Shared and unique mechanisms underlying binge eating disorder and addictive disorders

Science.gov (United States)

Schulte, Erica M.; Grilo, Carlos M.; Gearhardt, Ashley N.

2018-01-01

Scientific interest in “food addiction” is growing, but the topic remains controversial. One critique of “food addiction” is its high degree of phenotypic overlap with binge eating disorder (BED). In order to examine associations between problematic eating behaviors, such as binge eating and “food addiction,” we propose the need to move past examining similarities and differences in symptomology. Instead, focusing on relevant mechanisms may more effectively determine whether “food addiction” contributes to disordered eating behavior for some individuals. This paper reviews the evidence for mechanisms that are shared (i.e., reward dysfunction, impulsivity) and unique for addiction (i.e., withdrawal, tolerance) and eating disorder (i.e., dietary restraint, shape/weight concern) frameworks. This review will provide a guiding framework to outline future areas of research needed to evaluate the validity of the “food addiction” model and to understand its potential contribution to disordered eating. PMID:26879210

Degeneration of rapid eye movement sleep circuitry underlies rapid eye movement sleep behavior disorder.

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McKenna, Dillon; Peever, John

2017-05-01

During healthy rapid eye movement sleep, skeletal muscles are actively forced into a state of motor paralysis. However, in rapid eye movement sleep behavior disorder-a relatively common neurological disorder-this natural process is lost. A lack of motor paralysis (atonia) in rapid eye movement sleep behavior disorder allows individuals to actively move, which at times can be excessive and violent. At first glance this may sound harmless, but it is not because rapid eye movement sleep behavior disorder patients frequently injure themselves or the person they sleep with. It is hypothesized that the degeneration or dysfunction of the brain stem circuits that control rapid eye movement sleep paralysis is an underlying cause of rapid eye movement sleep behavior disorder. The link between brain stem degeneration and rapid eye movement sleep behavior disorder stems from the fact that rapid eye movement sleep behavior disorder precedes, in the majority (∼80%) of cases, the development of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, which are known to initially cause degeneration in the caudal brain stem structures where rapid eye movement sleep circuits are located. Furthermore, basic science and clinical evidence demonstrate that lesions within the rapid eye movement sleep circuits can induce rapid eye movement sleep-specific motor deficits that are virtually identical to those observed in rapid eye movement sleep behavior disorder. This review examines the evidence that rapid eye movement sleep behavior disorder is caused by synucleinopathic neurodegeneration of the core brain stem circuits that control healthy rapid eye movement sleep and concludes that rapid eye movement sleep behavior disorder is not a separate clinical entity from synucleinopathies but, rather, it is the earliest symptom of these disorders. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and

MRI in sporadic Creutzfeldt-Jakob disease: Correlation with clinical and neuropathological data

Energy Technology Data Exchange (ETDEWEB)

Urbach, H.; Solymosi, L. [Department of Neuroradiology, University of Wuerzburg (Germany); Klisch, J.; Brechtelsbauer, D. [Department of Neuroradiology, University of Bonn, Bonn (Germany); Wolf, H.K. [Department of Neuropathology, University of Bonn, Bonn (Germany); Gass, S. [Department of Neurology, University of Bonn, Bonn (Germany)

1998-02-01

To ascertain whether increased grey matter signal intensity on T2-weighted images in patients with sporadic Creutzfeldt-Jakob disease (CJD) corresponds to the stage and severity of this disease, we correlated MRI findings in four of our own and previously reported patients with sporadic CJD with the clinical variants, neuropathological changes at autopsy, duration of the disease and survival time after MRI examination. Of 15 patients with the extrapyramidal type of CJD, 10 showed increased signal in the basal ganglia on T2-weighted images. One of seven patients with the Heidenhain variant had increased signal in the occipital cortex. Patients without increased grey matter signal intensity had a longer overall duration of CJD (P = 0.035). Although the interval between onset of neurological symptoms and MRI was not different, patients without increased grey matter signal also survived longer after MRI examination (P = 0.022). (orig.) With 5 figs., 2 tabs., 23 refs.

Clinical Uses of Melatonin in Neurological Diseases and Mental and Behavioural Disorders.

Science.gov (United States)

Sanchez-Barcelo, Emilio J; Rueda, Noemi; Mediavilla, María D; Martinez-Cue, Carmen; Reiter, Russel J

2017-11-20

Melatonin is a molecule with numerous properties applicable to the treatment of neurological diseases. Among these properties are the following: potent scavenger of oxygen and nitrogen reactive species, anti-inflammatory features, immuno-enhancing nature, and modulation of circadian rhythmicity. Furthermore, low concentrations of melatonin are usually found in patients with neurological diseases and mental disorders. The positive results obtained in experimental models of diverse pathologies, including diseases of the nervous system (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, epilepsy, headaches, etc.) as well as mental and behavioural disordes (e.g., autism spectrum disorders, attention-deficit hyperactivity disorders, etc.), have served as a basis for the design of clinical trials to study melatonin's possible usefulness in human pathology, although the satisfactory results obtained from the laboratory "bench" are not always applicable to the patient's "bedside". In this article, we review those papers describing the results of the administration of melatonin to humans for various therapeutic purposes in the field of neuropathology. Clinical trials with strong methodologies and appropriate doses of melatonin are necessary to support or reject the usefulness of melatonin in neurological diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Depression and Alzheimer's disease: is stress the initiating factor in a common neuropathological cascade?

DEFF Research Database (Denmark)

Aznar, Susana; Knudsen, Gitte M

2011-01-01

. This suggests the existence of common neuropathological mechanisms behind depression and AD. Here we propose that the brain changes associated with depressive episodes that compromise the brain's ability to cope with stress may constitute risk factors for development of AD. Furthermore, in individuals......The existence of a high co-morbidity between Alzheimer's disease (AD) and depression has been known for a long time. More interesting though are recent studies indicating that depression and number of depressive episodes earlier in life is associated with increased risk of AD development...... with a genetic linkage to depression, there may be an increased vulnerability towards the initiation of a detrimental neurodegenerative cascade. The following review will deal with the various observations reported within the different neurobiological systems known to be involved and affected in depression, like...

The role of neurexins in schizophrenia and autistic spectrum disorder.

Science.gov (United States)

Reichelt, A C; Rodgers, R J; Clapcote, S J

2012-03-01

Schizophrenia and autistic spectrum disorder (ASD) are common, chronic mental conditions with both genetic and environmental components to their aetiology. The identification of genes influencing susceptibility to these disorders offers a rational route towards a clearer understanding of the neurobiology, and with this the prospect of treatment and prevention strategies tailored towards the remediation of the altered pathways. Copy number variants (CNVs) underlie many serious illnesses, including neurological and neurodevelopmental syndromes. Recent studies assessing copy number variation in ASD and schizophrenia have repeatedly observed heterozygous deletions eliminating exons of the neurexin-1α gene (but not the neurexin-1β gene) in patients with ASD and schizophrenia. The neurexins are synaptic adhesion proteins that are known to play a key role in synaptic formation and maintenance. The functional significance of the recurrent deletion is poorly understood, but the availability of mice with deletion of the promoter and first exon of neurexin-1α provides direct access to the biological effects of neurexin-1α disruption on phenotypes relevant to ASD and schizophrenia. We review the evidence for the role of neurexin-1α in schizophrenia and ASD, and consider how genetic disruption of neurexin-1α may underpin the neuropathology contributing to these distinct neurodevelopmental disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Demography and disorders of German Shepherd Dogs under primary veterinary care in the UK.

Science.gov (United States)

O'Neill, Dan G; Coulson, Noel R; Church, David B; Brodbelt, Dave C

2017-01-01

The German Shepherd Dog (GSD) has been widely used for a variety of working roles. However, concerns for the health and welfare of the GSD have been widely aired and there is evidence that breed numbers are now in decline in the UK. Accurate demographic and disorder data could assist with breeding and clinical prioritisation. The VetCompass TM Programme collects clinical data on dogs under primary veterinary care in the UK. This study included all VetCompass TM dogs under veterinary care during 2013. Demographic, mortality and clinical diagnosis data on GSDs were extracted and reported. GSDs dropped from 3.5% of the annual birth cohort in 2005 to 2.2% in 2013. The median longevity of GSDs was 10.3 years (IQR 8.0-12.1, range 0.2-17.0). The most common causes of death were musculoskeletal disorder (16.3%) and inability to stand (14.9%). The most prevalent disorders recorded were otitis externa ( n  = 131, 7.89, 95% CI: 6.64-9.29), osteoarthritis (92, 5.54%, 95% CI: 4.49-6.75), diarrhoea (87, 5.24%, 95% CI: 4.22-6.42), overweight/obesity (86, 5.18%, 95% CI: 4.16-6.36) and aggression (79, 4.76%, 95% CI: 3.79-5.90). This study identified that GSDs have been reducing in numbers in the UK in recent years. The most frequent disorders in GSDs were otitis externa, osteoarthritis, diarrhoea, overweight/obesity and aggression, whilst the most common causes of death were musculoskeletal disorders and inability to stand. Aggression was more prevalent in males than in females. These results may assist veterinarians to offer evidence-based advice at a breed level and help to identify priorities for GSD health that can improve the breed's health and welfare.

Development of antipsychotic medications with novel mechanisms of action based on computational modeling of hippocampal neuropathology.

Directory of Open Access Journals (Sweden)

Peter J Siekmeier

Full Text Available A large number of cellular level abnormalities have been identified in the hippocampus of schizophrenic subjects. Nonetheless, it remains uncertain how these pathologies interact at a system level to create clinical symptoms, and this has hindered the development of more effective antipsychotic medications. Using a 72-processor supercomputer, we created a tissue level hippocampal simulation, featuring multicompartmental neuron models with multiple ion channel subtypes and synaptic channels with realistic temporal dynamics. As an index of the schizophrenic phenotype, we used the specific inability of the model to attune to 40 Hz (gamma band stimulation, a well-characterized abnormality in schizophrenia. We examined several possible combinations of putatively schizophrenogenic cellular lesions by systematically varying model parameters representing NMDA channel function, dendritic spine density, and GABA system integrity, conducting 910 trials in total. Two discrete "clusters" of neuropathological changes were identified. The most robust was characterized by co-occurring modest reductions in NMDA system function (-30% and dendritic spine density (-30%. Another set of lesions had greater NMDA hypofunction along with low level GABA system dysregulation. To the schizophrenic model, we applied the effects of 1,500 virtual medications, which were implemented by varying five model parameters, independently, in a graded manner; the effects of known drugs were also applied. The simulation accurately distinguished agents that are known to lack clinical efficacy, and identified novel mechanisms (e.g., decrease in AMPA conductance decay time constant, increase in projection strength of calretinin-positive interneurons and combinations of mechanisms that could re-equilibrate model behavior. These findings shed light on the mechanistic links between schizophrenic neuropathology and the gamma band oscillatory abnormalities observed in the illness. As such, they

"Symptomatic" infection-associated acute encephalopathy in children with underlying neurological disorders.

Science.gov (United States)

Hirayama, Yoshimichi; Saito, Yoshiaki; Maegaki, Yoshihiro

2017-03-01

Development of infection-associated acute encephalopathy (AE) is precipitated by several factors, including viral agents, age, and genetic polymorphisms. In addition, children with prior underlying neurological disorders can also present with AE. We reviewed 55 children with AE who were referred to hospitals participating in the Status Epilepticus Study Group from 1988 to 2013. AE was classified into eight subtypes: acute encephalopathy with biphasic seizures and late reduced diffusion (AESD); hemiconvulsion-hemiplegia syndrome (HH); acute necrotizing encephalopathy; hemorrhagic shock and encephalopathy syndrome (HSES); clinically mild encephalitis/encephalopathy with a reversible splenial lesion; acute encephalitis with refractory, repetitive partial seizures; Reye-like syndrome; and unclassified. Of the 55 AE cases, 14 (25.4%) had underlying neurological disorders, including perinatal insults (n=6) and genetic syndrome and/or brain malformations (n=8). These preceding morbidities were relatively common in AESD (6/18, 33.3%), HH (3/9, 33.3%), and HSES (3/6, 50.0%). History of epilepsy or febrile seizures were frequent in HH cases (4/9, 44.4%), whereas they were rare in other AE subtypes. Among the AE subgroups, HH, HSES, and AESD frequently emerged in preceding etiologies with augmented neuronal excitability. These subgroups may have distinct pathomechanism from the "cytokine storm" mediated AEs during childhood. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Survival in the pre-senile dementia frontotemporal lobar degeneration with TDP-43 proteinopathy: effects of genetic, demographic and neuropathological variables

Directory of Open Access Journals (Sweden)

Richard A. Armstrong

2016-06-01

Full Text Available Factors associated with survival were studied in 84 neuropathologically documented cases of the pre-senile dementia frontotemporal dementia lobar degeneration (FTLD with transactive response (TAR DNA-binding protein of 43 kDa (TDP-43 proteinopathy (FTLD-TDP. Kaplan-Meier survival analysis estimated mean survival as 7.9 years (range: 1-19 years, SD = 4.64. Familial and sporadic cases exhibited similar survival, including progranulin (GRN gene mutation cases. No significant differences in survival were associated with sex, disease onset, Braak disease stage, or disease subtype, but higher survival was associated with lower post-mortem brain weight. Survival was significantly reduced in cases with associated motor neuron disease (FTLD-MND but increased with Alzheimer’s disease (AD or hippocampal sclerosis (HS co-morbidity. Cox regression analysis suggested that reduced survival was associated with increased densities of neuronal cytoplasmic inclusions (NCI while increased survival was associated with greater densities of enlarged neurons (EN in the frontal and temporal lobes. The data suggest that: (1 survival in FTLD-TDP is more prolonged than typical in pre-senile dementia but shorter than some clinical subtypes such as the semantic variant of primary progressive aphasia (svPPA, (2 MND co-morbidity predicts poor survival, and (3 NCI may develop early and EN later in the disease. The data have implications for both neuropathological characterization and subtyping of FTLD-TDP.

Parental age and the risk of obsessive compulsive disorder and Tourette syndrome / chronic tic disorder in a nationwide population-based sample.

Science.gov (United States)

Chudal, Roshan; Leivonen, Susanna; Rintala, Hanna; Hinkka-Yli-Salomäki, Susanna; Sourander, Andre

2017-12-01

Advancing paternal age has been associated with several neuropsychiatric disorders in children. However, there is limited understanding of this association with obsessive compulsive disorder (OCD) and Tourette syndrome/chronic tic disorder (TS/CT) with inconsistent findings. We examined the association between parental age and offspring OCD and TS/CT. This nested case-control study used the Finnish Hospital Discharge Register (FHDR) to identify 1358 individuals with OCD and 1195 with TS/CT, born from 1991 to 2009 and diagnosed by 2010. Each case was matched with four controls from the Finnish Population Register (FPR), without diagnoses of OCD, TS/CT or severe or profound mental retardation. Conditional logistic regression was used to examine the association between parental age and OCD, TS/CT. A trend of increasing odds was seen with advancing maternal age. In the final model, offspring of mothers aged 35-39 years had a 1.3-fold increased odd (OR = 1,31, 95% confidence interval (95% CI:1.03-1.66)) of OCD compared with maternal aged 25-29 years. Offspring of fathers younger than 20 years had increased odds of TS/CT in the unadjusted analysis (OR = 2.43, 95% CI: 1.27-4.56). The study limitations included using hospital diagnoses to identify cases, with limited diagnostic validity, and the possible over representation of moderate to severe cases. The lack of association between advancing paternal age and OCD is in contrast with schizophrenia, despite sharing demographic characteristics and possible shared neuropathology. Furthermore, these differences suggest different etiological pathways among TS/CT, autism spectrum disorder (ASD) and attention deficit/hyperactive disorder (ADHD), despite their frequently comorbid existence. Copyright © 2017 Elsevier B.V. All rights reserved.

Rates of Autism Spectrum Disorder Diagnosis Under the DSM-5 Criteria Compared to DSM-IV-TR Criteria in a Hospital-Based Clinic.

Science.gov (United States)

Hartley-McAndrew, Michelle; Mertz, Jana; Hoffman, Martin; Crawford, Donald

2016-04-01

We aimed to determine whether there was a decrease in the number of children diagnosed on the autism spectrum after the implementation of the new diagnostic criteria as outlined in the Diagnostic and Statistical Manual of Mental Health Disorders Fifth Edition published in May 2013. We reviewed 1552 charts of children evaluated at the Women and Children's Hospital of Buffalo, Autism Spectrum Disorders Clinic. A comparison was made of children diagnosed with autism spectrum disorder (autism, Asperger disorder, pervasive developmental disorder-not otherwise specified) from 2010 to May 2013 using the Diagnostic and Statistical Manual of Mental Health Disorders Fourth Edition, Text Revision criteria with children diagnosed from June 2013 through June 2015 under the Diagnostic and Statistical Manual of Mental Health Disorders Fifth Edition. Using χ(2) analysis, the 2013-2015 rate of autism spectrum disorder diagnosis (39%) was significantly lower (P disorder diagnosis was significantly lower under the recently implemented Diagnostic and Statistical Manual of Mental Health Disorders Fifth Edition criteria. Published by Elsevier Inc.

Individual differences in discriminatory fear learning under conditions of ambiguity: A vulnerability factor for anxiety disorders?

Directory of Open Access Journals (Sweden)

Inna eArnaudova

2013-05-01

Full Text Available Complex fear learning procedures might be better suited than the common differential fear conditioning paradigm for detecting individual differences related to vulnerability for anxiety disorders. Two such procedures are the blocking procedure and the protection-from-overshadowing procedure. Their comparison allows for the examination of discriminatory fear learning under conditions of ambiguity. The present study examined the role of individual differences in such discriminatory fear learning. We hypothesized that heightened trait anxiety would be related to a deficit in discriminatory fear learning. Participants gave US-expectancy ratings as an index for the threat value of individual CSs following blocking and protection-from-overshadowing training. The difference in threat value at test between the protected-from-overshadowing CS and the blocked CS was negatively correlated with scores on a self-report tension-stress scale that approximates facets of generalized anxiety disorder (DASS-S, but not with other individual difference variables. In addition, a behavioral test showed that only participants scoring high on the DASS-S avoided the protected-from-overshadowing CS. This observed deficit in discriminatory fear learning for participants with high levels of tension-stress might be an underlying mechanism for fear overgeneralization in diffuse anxiety disorders such as generalized anxiety disorder.

[Girls detained under civil and criminal law in juvenile detention centres; psychiatric disorders, trauma and psychosocial problems].

Science.gov (United States)

Hamerlynck, S M J J; Doreleijers, Th A H; Vermeiren, R R J M; Cohen-Kettenis, P T

2009-01-01

As from 2008, juveniles sentenced under civil law and juveniles sentenced under criminal law can no longer be assigned to the same juvenile detention centres. The reasoning runs as follows: the centres are unlikely to provide adequate treatment for the 'civil' group, and the 'criminal' group may exert a negative influence on the 'civil' group. Hitherto, there has been no research into the question of whether the problems and treatment requirements of girls in the two categories call for detention in the same detention centres or in different ones. The aim of this study is to investigate differences between the two groups of girls with regard to offence history, sociodemographic characteristics, contact with the social services, psychiatric disorders and trauma. Investigation of a representative sample of 211 female minors in three juvenile detention centres using standard instruments. results 82% of the girls were detained under civil law, 18% under criminal law. There were strong similarities between the groups. However, the 'criminal' group more often had a violent history of delinquency and a non-Dutch background, whereas the 'civil' group more often had a background of residential placements, oppositional-defiant disorder, suicidality and self-harm. Girls detained under civil and under criminal law differed in characteristics such as criminal record, but there were striking similarities in the girls' behavioural problems and psychiatric disorders. It is argued that assignment to a particular type of detention centre should depend on treatment requirements rather than on measures imposed by civil or criminal law.

Prevalence, Diagnosis, and Treatment Rates of Mood Disorders among Opioid Users under Criminal Justice Supervision.

Science.gov (United States)

Mbaba, Mary; Brown, Shan-Estelle; Wooditch, Alese; Kiss, Marissa; Murphy, Amy; Kumari, Suneeta; Taxman, Faye; Altice, Frederick; Lawson, William B; Springer, Sandra A

2018-01-15

Individuals involved in the criminal justice system have disproportionately high rates of psychiatric disorders when compared to the general U.S. If left untreated, the likelihood of subsequent arrest increases and risk for adverse health consequences is great, particularly among opioid users. To explore the prevalence, characteristics, and treatment of mood disorders among justice involved opioid-dependent populations. The current study enrolled 258 treatment-seeking opioid-dependent individuals under community-based criminal justice supervision (e.g., probation, parole) screened from the larger parent study, Project STRIDE, a seek/test/treat randomized control trial (RCT) examining HIV and opioid use treatment. During baseline, individuals were screened for depression using the Patient Health Questionnaire-9 (PHQ-9) and screened for bipolar disorder using the Mood Disorder Questionnaire (MDQ) tool. Overall, 78 (30%) participants screened positive for moderate to severe depression and 54 (21%) screened positive for bipolar disorder. Participants self-reported mood disorders at higher rates than they screened positive for these conditions. Participants screening positive for these conditions experienced significantly greater family, legal, and medical problems on the Addiction Severity Index-Lite (ASI-Lite) than those who did not screen positive. Incidence of a lifetime suicide attempt was found to be associated with a positive screen for both mood disorders. Prescribed psychotropic treatment utilization was similar among those who screened positive for depression or bipolar disorder with approximately 38% reporting taking medication. Findings suggest universal mood disorder screening to improve comprehensive psychiatric care and treatment of opioid-dependent justice-involved individuals.

Translational new approaches for investigating mood disorders in rodents and what they may reveal about the underlying neurobiology of major depressive disorder.

Science.gov (United States)

Robinson, Emma S J

2018-03-19

Mood disorders represent one of society's most costly and challenging health burdens. The drug treatments used today were initially discovered serendipitously in the 1950s. Animal models were then developed based on the ability of these drugs to alter specific behaviours. These models have played a major role in the development of the second generation of antidepressants. However, their use has been heavily criticized, particularly in relation to whether they recapitulate similar underlying biology to the psychiatric disorder they are proposed to represent. This article considers our work in the field of affective bias and the development of a translational research programme to try to develop and validate better animal models. We discuss whether the new data that have arisen from these studies support an alternative perspective on the underlying neurobiological processes that lead to major depressive disorder (MDD). Specifically, this article will consider whether a neuropsychological mechanism involving affective biases plays a causal role in the development of MDD and its associated emotional and behavioural symptoms. These animal studies also raise the possibility that neuropsychological mechanisms involving affective biases are a precursor to, rather than a consequence of, the neurotrophic changes linked to MDD.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'. © 2018 The Authors.

Functional connectivity in cortico-subcortical brain networks underlying reward processing in attention-deficit/hyperactivity disorder

NARCIS (Netherlands)

Oldehinkel, Marianne; Beckmann, Christian F.; Franke, Barbara; Hartman, Catharina A.; Hoekstra, Pieter J.; Oosterlaan, Jaap; Heslenfeld, Dirk; Buitelaar, Jan K.; Mennes, Maarten

2016-01-01

Background: Many patients with attention-deficit/hyperactivity disorder (ADHD) display aberrant reward-related behavior. Task-based fMRI studies have related atypical reward processing in ADHD to altered BOLD activity in regions underlying reward processing such as ventral striatum and orbitofrontal

Connectivity analysis is essential to understand neurological disorders

Directory of Open Access Journals (Sweden)

James Rowe

2010-09-01

Full Text Available Neurological and neuropsychiatric disorders are major causes of morbidity worldwide. A systems level analysis including functional and structural neuroimaging is particularly useful when the pathology leads to disorders of higher order cognitive functions in human patients. However, an analysis that is restricted to regional effects is impoverished and insensitive, compared to the analysis of distributed brain networks. We discuss the issues to consider when choosing an appropriate connectivity method, and compare the results from several different methods that are relevant to fMRI and PET data. These include psychophysiological interactions in general linear models, structural equation modeling, dynamic causal modeling and independent components analysis. The advantages of connectivity analysis are illustrated with a range of structural and neurodegenerative brain disorders. We illustrate the sensitivity of these methods to the presence or severity of disease and/or treatment, even where analyses of voxel-wise activations are insensitive. However, functional and structural connectivity methods should be seen as complementary to, not a substitute for, other imaging and behavioral approaches. The functional relevance of changes in connectivity, to motor or cognitive performance, are considered alongside the complex relationship between structural and functional changes with neuropathology. Finally some of the problems associated with connectivity analysis are discussed. We suggest that the analysis of brain connectivity is an essential complement to the analysis of regionally specific dysfunction, in order to understand neurological and neuropsychiatric disease, and to evaluate the mechanisms of effective therapies.

Linguistic ability in early life and the neuropathology of Alzheimer's disease and cerebrovascular disease. Findings from the Nun Study.

Science.gov (United States)

Snowdon, D A; Greiner, L H; Markesbery, W R

2000-04-01

Findings from the Nun Study indicate that low linguistic ability in early life has a strong association with dementia and premature death in late life. In the present study, we investigated the relationship of linguistic ability in early life to the neuropathology of Alzheimer's disease and cerebrovascular disease. The analyses were done on a subset of 74 participants in the Nun Study for whom we had handwritten autobiographies completed some time between the ages of 19 and 37 (mean = 23 years). An average of 62 years after writing the autobiographies, when the participants were 78 to 97 years old, they died and their brains were removed for our neuropathologic studies. Linguistic ability in early life was measured by the idea (proposition) density of the autobiographies, i.e., a standard measure of the content of ideas in text samples. Idea density scores from early life had strong inverse correlations with the severity of Alzheimer's disease pathology in the neocortex: Correlations between idea density scores and neurofibrillary tangle counts were -0.59 for the frontal lobe, -0.48 for the temporal lobe, and -0.49 for the parietal lobe (all p values < 0.0001). Idea density scores were unrelated to the severity of atherosclerosis of the major arteries at the base of the brain and to the presence of lacunar and large brain infarcts. Low linguistic ability in early life may reflect suboptimal neurological and cognitive development, which might increase susceptibility to the development of Alzheimer's disease pathology in late life.

Neuropathological changes in mouse models of cardiovascular diseases

NARCIS (Netherlands)

Bink, D.I.

2016-01-01

Mild cognitive impairment and dementia are common disorders in the elderly. As the life span of the population in the Western world is increasing, the prevalence of cognitive disorders and the social and economic burden that coincide with that will increase. Recent data indicate that cardiovascular

Interactions of the histamine and hypocretin systems in CNS disorders.

Science.gov (United States)

Shan, Ling; Dauvilliers, Yves; Siegel, Jerome M

2015-07-01

Histamine and hypocretin neurons are localized to the hypothalamus, a brain area critical to autonomic function and sleep. Narcolepsy type 1, also known as narcolepsy with cataplexy, is a neurological disorder characterized by excessive daytime sleepiness, impaired night-time sleep, cataplexy, sleep paralysis and short latency to rapid eye movement (REM) sleep after sleep onset. In narcolepsy, 90% of hypocretin neurons are lost; in addition, two groups reported in 2014 that the number of histamine neurons is increased by 64% or more in human patients with narcolepsy, suggesting involvement of histamine in the aetiology of this disorder. Here, we review the role of the histamine and hypocretin systems in sleep-wake modulation. Furthermore, we summarize the neuropathological changes to these two systems in narcolepsy and discuss the possibility that narcolepsy-associated histamine abnormalities could mediate or result from the same processes that cause the hypocretin cell loss. We also review the changes in the hypocretin and histamine systems, and the associated sleep disruptions, in Parkinson disease, Alzheimer disease, Huntington disease and Tourette syndrome. Finally, we discuss novel therapeutic approaches for manipulation of the histamine system.

Progress in understanding mood disorders: optogenetic dissection of neural circuits.

Science.gov (United States)

Lammel, S; Tye, K M; Warden, M R

2014-01-01

Major depression is characterized by a cluster of symptoms that includes hopelessness, low mood, feelings of worthlessness and inability to experience pleasure. The lifetime prevalence of major depression approaches 20%, yet current treatments are often inadequate both because of associated side effects and because they are ineffective for many people. In basic research, animal models are often used to study depression. Typically, experimental animals are exposed to acute or chronic stress to generate a variety of depression-like symptoms. Despite its clinical importance, very little is known about the cellular and neural circuits that mediate these symptoms. Recent advances in circuit-targeted approaches have provided new opportunities to study the neuropathology of mood disorders such as depression and anxiety. We review recent progress and highlight some studies that have begun tracing a functional neuronal circuit diagram that may prove essential in establishing novel treatment strategies in mood disorders. First, we shed light on the complexity of mesocorticolimbic dopamine (DA) responses to stress by discussing two recent studies reporting that optogenetic activation of midbrain DA neurons can induce or reverse depression-related behaviors. Second, we describe the role of the lateral habenula circuitry in the pathophysiology of depression. Finally, we discuss how the prefrontal cortex controls limbic and neuromodulatory circuits in mood disorders. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Scientific conception on mechanisms of calcium homeostasis disorders under low dose effect of ionizing radiation

International Nuclear Information System (INIS)

Abylaev, Zh.A.; Dospolova, Zh.G.

1997-01-01

Scientific conception of probable consequences of calcium homeostasis disorders in personals, exposed to low dose effect of ionizing radiation has been developed. Principle positions of the conception is that pathologic processes development have different ways of conducting. During predominance of low doses of external gamma-radiation there is leading pathologic mechanism (mechanism 1) of disorder neuroendocrine regulation of both the calcium and the phosphor. In this case sicks have disorders of both the vegetative tonus and the endocrine status. Under internal irradiation (mechanism 2) there is disfunction of organs and systems (bore changes and disorders of hormone status). These changes are considered as consequence of negative action on organism of incorporated long-living radionuclides. Radio-toxic factors action (mechanism 3) provokes the excess of hormones, which acting on bone tissue and could be cause of steroid osteoporosis. Influence of chronic stress factor (mechanism 4) enlarges and burden action on organism of low radiation doses. It is emphasized, that decisive role in development of pathologic processes has mechanism of disturbance of neuroendocrine regulation of calcium exchange

Fronto-striatal glutamate in children with Tourette's disorder and attention-deficit/hyperactivity disorder

Directory of Open Access Journals (Sweden)

Jilly Naaijen

2017-01-01

Conclusion: We found no evidence for glutamatergic neuropathology in TD or ADHD within the fronto-striatal circuits. However, the correlation of OC-symptoms with ACC glutamate concentrations suggests that altered glutamatergic transmission is involved in OC-symptoms within TD, but this needs further investigation.

Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study

International Nuclear Information System (INIS)

Delgado, Anna F.; Nilsson, Markus; Latini, Francesco; Mårtensson, Johanna; Zetterling, Maria; Berntsson, Shala G.; Alafuzoff, Irina; Lätt, Jimmy; Larsson, Elna-Marie

2016-01-01

Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T). The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas) on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA) and mean diffusivity (rMD) in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.). Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement

Linking neuroscience with modern concepts of impulse control disorders in Parkinson’s disease

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Napier, T. Celeste; Corvol, Jean-Christophe; Grace, Anthony A.; Roitman, Jamie D.; Rowe, James; Voon, Valerie; Strafella, Antonio P.

2014-01-01

Patients with Parkinson’s disease (PD) may experience impulse control disorders (ICDs) when on dopamine agonist therapy for their motor symptoms. In the last few years, there has been a rapid growth of interest for the recognition of these aberrant behaviors and their neurobiological correlates. Recent advances in neuroimaging are helping to identify the neuroanatomical networks responsible for these ICDs, and together with psychopharmacological assessments are providing new insights into the brain status of impulsive behavior. The genetic associations that may be unique to ICDs in PD are also being identified. Complementing human studies, electrophysiological and biochemical studies in animal models are providing insights into neuropathological mechanisms associated with these disorders. New animal models of ICDs in PD patients are being implemented that should provide critical means to identify efficacious therapies for PD-related motor deficits while avoiding ICD side effects. Here, we provide an overview of these recent advances, with a particular emphasis on the neurobiological correlates reported in animal models and patients along with their genetic underpinnings. PMID:25476402

Glucocerebrosidase expression patterns in the non-human primate brain

OpenAIRE

Dopeso-Reyes, Iria G.; Sucunza, Diego; Rico, Alberto J.; Pignataro, Diego; Marín-Ramos, David; Roda, Elvira; Rodríguez-Pérez, Ana I.; Labandeira-García, José L.; Lanciego, José L.

2017-01-01

Glucocerebrosidase (GCase) is a lysosomal enzyme encoded by the GBA1 gene. Mutations in GBA1 gene lead to Gaucher’s disease, the most prevalent lysosomal storage disorder. GBA1 mutations reduce GCase activity, therefore promoting the aggregation of alpha-synuclein, a common neuropathological finding underlying Parkinson’s disease (PD) and dementia with Lewy bodies. However, it is also worth noting that a direct link between GBA1 mutations and alpha-synuclein aggregation indicating cause and e...

[Comorbidity of substance use with mental disorders].

Science.gov (United States)

Leonidaki, V; Maliori, M

2009-01-01

This contribution reviews the international literature about dual diagnosis, meaning patients who have simultaneously mental health problems and substance use disorders and discusses epidemiology, clinical characteristics, but primarily etiopathogenesis and different treatment models and interventions. The epidemiological data coming from large-scale studies in the general population in USA, Australia and UK demonstrate the close relationship between mental health problems and substance use disorders. Also, the results from Greek research projects support this close relationship, but their research designs have significant limitations. Multiple and high risks are common in this population, like violent or suicidal behavior, self-harm, physical problems, while they appear less responsive to treatment. Subsequently, different models for etiopathogenesis of dual diagnosis have been suggested: (a) Causal relationship: secondary substance use disorder is subsequent of primary mental illness (self-medication hypothesis, supersenstivity model) or vice versa (alcohol, cannabis, and cocaine use trigger or contribute to development of mental illness). (b) Third factor as the cause of both mental and substance use disorders (genetic factor, neuropathology, traumatic experience, personality characteristics, multiple factors). (c) Comorbidty is due to chance. (d) Each disorder mutually exacerbates the other, regardless the cause. Here, the relationship between alcohol and depression is discussed further as example. The ideas and the research-evidence which support each of these models are presented. Also there is an overview of different treatment models: (a) Consecutive treatment: mental health treatment and substance misuse treatment are provided consecutively. (b) Parallel treatments: the patient attends programs of both mental health and substance use services simultaneously. (c) Integrated treatment: the same clinical team addresses both mental health issues and substance

A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Abeta25-35

DEFF Research Database (Denmark)

Klementiev, B; Novikova, T; Novitskaya, V

2007-01-01

death and brain atrophy in response to Abeta25-35. Finally, the Abeta25-35-administration led to a reduced short-term memory as determined by the social recognition test. A synthetic peptide termed FGL derived from the neural cell adhesion molecule (NCAM) was able to prevent or, if already manifest......, strongly reduce all investigated signs of Abeta25-35-induced neuropathology and cognitive impairment. The FGL peptide was recently demonstrated to be able to cross the blood-brain-barrier. Accordingly, we found that the beneficial effects of FGL were achieved not only by intracisternal, but also...... and cognitive impairment involves the modulation of intracellular signal-transduction mediated through GSK3beta....

Quantum thermostatted disordered systems and sensitivity under compression

Science.gov (United States)

Vanzan, Tommaso; Rondoni, Lamberto

2018-03-01

A one-dimensional quantum system with off diagonal disorder, consisting of a sample of conducting regions randomly interspersed within potential barriers is considered. Results mainly concerning the large N limit are presented. In particular, the effect of compression on the transmission coefficient is investigated. A numerical method to simulate such a system, for a physically relevant number of barriers, is proposed. It is shown that the disordered model converges to the periodic case as N increases, with a rate of convergence which depends on the disorder degree. Compression always leads to a decrease of the transmission coefficient which may be exploited to design nano-technological sensors. Effective choices for the physical parameters to improve the sensitivity are provided. Eventually large fluctuations and rate functions are analysed.

A model-based analysis of decision making under risk in obsessive-compulsive and hoarding disorders.

Science.gov (United States)

Aranovich, Gabriel J; Cavagnaro, Daniel R; Pitt, Mark A; Myung, Jay I; Mathews, Carol A

2017-07-01

Attitudes towards risk are highly consequential in clinical disorders thought to be prone to "risky behavior", such as substance dependence, as well as those commonly associated with excessive risk aversion, such as obsessive-compulsive disorder (OCD) and hoarding disorder (HD). Moreover, it has recently been suggested that attitudes towards risk may serve as a behavioral biomarker for OCD. We investigated the risk preferences of participants with OCD and HD using a novel adaptive task and a quantitative model from behavioral economics that decomposes risk preferences into outcome sensitivity and probability sensitivity. Contrary to expectation, compared to healthy controls, participants with OCD and HD exhibited less outcome sensitivity, implying less risk aversion in the standard economic framework. In addition, risk attitudes were strongly correlated with depression, hoarding, and compulsion scores, while compulsion (hoarding) scores were associated with more (less) "rational" risk preferences. These results demonstrate how fundamental attitudes towards risk relate to specific psychopathology and thereby contribute to our understanding of the cognitive manifestations of mental disorders. In addition, our findings indicate that the conclusion made in recent work that decision making under risk is unaltered in OCD is premature. Copyright © 2017 Elsevier Ltd. All rights reserved.

Disorder effects on helical edge transport in graphene under a strong tilted magnetic field

Science.gov (United States)

Huang, Chunli; Cazalilla, Miguel A.

2015-10-01

In a recent experiment, Young et al. [Nature (London) 505, 528 (2014), 10.1038/nature12800] observed a metal to insulator transition as well as transport through helical edge states in monolayer graphene under a strong, tilted magnetic field. Under such conditions, the bulk is a magnetic insulator which can exhibit metallic conduction through helical edges. It was found that the two-terminal conductance of the helical channels deviates from the expected quantized value (=e2/h per edge, at zero temperature). Motivated by this observation, we study the effect of disorder on the conduction through the edge channels. We show that, unlike for helical edges of topological insulators in semiconducting quantum wells, a disorder Rashba spin-orbit coupling does not lead to backscattering, at least to leading order. Instead, we find that the lack of perfect antialignment of the electron spins in the helical channels to be the most likely cause for backscattering arising from scalar (i.e., spin-independent) impurities. The intrinsic spin-orbit coupling and other time-reversal symmetry-breaking and/or sublattice parity-breaking potentials also lead to (subleading) corrections to the channel conductance.

Demography and disorders of the French Bulldog population under primary veterinary care in the UK in 2013.

Science.gov (United States)

O'Neill, Dan G; Baral, Lauren; Church, David B; Brodbelt, Dave C; Packer, Rowena M A

2018-01-01

Despite its Gallic name, the French Bulldog is a breed of both British and French origin that was first recognised by The Kennel Club in 1906. The French Bulldog has demonstrated recent rapid rises in Kennel Club registrations and is now (2017) the second most commonly registered pedigree breed in the UK. However, the breed has been reported to be predisposed to several disorders including ocular, respiratory, neurological and dermatological problems. The VetCompass™ Programme collates de-identified clinical data from primary-care veterinary practices in the UK for epidemiological research. Using VetCompass™ clinical data, this study aimed to characterise the demography and common disorders of the general population of French Bulldogs under veterinary care in the UK. French Bulldogs comprised 2228 (0.49%) of 445,557 study dogs under veterinary care during 2013. Annual proportional birth rates showed that the proportional ownership of French Bulldog puppies rose steeply from 0.02% of the annual birth cohort attending VetCompass™ practices in 2003 to 1.46% in 2013. The median age of the French Bulldogs overall was 1.3 years (IQR 0.6-2.5, range 0.0-13.0). The most common colours of French Bulldogs were brindle (solid or main) (32.36%) and fawn (solid or main) (29.9%). Of the 2228 French Bulldogs under veterinary care during 2013, 1612 (72.4%) had at least one disorder recorded. The most prevalent fine-level precision disorders recorded were otitis externa (14.0%, 95% CI: 12.6-15.5), diarrhoea (7.5%, 95% CI: 6.4-8.7), conjunctivitis (3.2%, 95% CI: 2.5-4.0), nails overlong (3.1%, 95% CI% 2.4-3.9) and skin fold dermatitis (3.0%, 95% CI% 2.3-3.8). The most prevalent disorder groups were cutaneous (17.9%, 95% CI: 16.3-19.6), enteropathy (16.7%, 95% CI: 15.2-18.3), aural (16.3%, 95% CI: 14.8-17.9), upper respiratory tract (12.7%, 95% CI: 11.3-14.1) and ophthalmological (10.5%, 95% CI: 9.3-11.9). Ownership of French Bulldogs in the UK is rising steeply. This means

Contribution of spinal cord biopsy to diagnosis of aquaporin-4 antibody positive neuromyelitis optica spectrum disorder.

Science.gov (United States)

Ringelstein, M; Metz, I; Ruprecht, K; Koch, A; Rappold, J; Ingwersen, J; Mathys, C; Jarius, S; Brück, W; Hartung, H-P; Paul, F; Aktas, O

2014-06-01

Longitudinally extensive transverse myelitis is characteristic but not pathognomonic for neuromyelitis optica spectrum disorders (NMOSDs) and may mimic local tumors. In this retrospective study based on a cohort of 175 NMOSD patients we identified seven patients who initially presented with a longitudinally extensive spinal cord lesion and underwent spinal cord biopsy due to magnetic resonance imaging (MRI)-suspected malignancies. Remarkably, routine neuropathology was inconclusive and did not guide the diagnostic process to anti-aquaporin-4 (AQP4)-seropositive NMOSD. Serious postoperative complications occurred in 5/7 patients and persisted during follow-up in 2/7 patients (29%). Considering these sequelae, AQP4-antibody testing should be mandatory in patients with inconclusive longitudinally extensive spinal cord lesions prior to biopsy. © The Author(s) 2013.

Julius Hallervorden's wartime activities: implications for science under dictatorship.

Science.gov (United States)

Shevell, M I; Peiffer, J

2001-08-01

The eponym Hallervorden-Spatz syndrome recalls Julius Hallervorden's and Hugo Spatz's original description of this pediatric neurodegenerative disorder. Julius Hallervorden's important contribution to the practice of neuropathology over a long career cannot be underestimated. However, his work as a pathologist during the Third Reich put him in close proximity with the implementation of biologic solutions (i.e., euthanasia) targeting those individuals with significant intellectual or physical disabilities in chronic-care facilities. The Nazi program of active euthanasia provided a scientific opportunity to gain quick access to pathologic materials. This opportunity was recognized and used by Hallervorden to achieve personal scientific objectives and research efforts. These efforts resulted in a number of postwar scientific publications using materials obtained through the euthanasia program. The participation of distinguished academic physicians in such a program provides a cautionary tale of the potential results of ethical compromise and the effects of the abrogation of personal autonomy in the setting of a totalitarian dictatorship.

Autism spectrum disorders and neuropathology of the cerebellum

OpenAIRE

Hampson, David R.; Blatt, Gene J.

2015-01-01

The cerebellum contains the largest number of neurons and synapses of any structure in the central nervous system. The concept that the cerebellum is solely involved in fine motor function has become outdated; substantial evidence has accumulated linking the cerebellum with higher cognitive functions including language. Cerebellar deficits have been implicated in autism for more than two decades. The computational power of the cerebellum is essential for many, if not most of the processes ...

Self-disorders in schizophrenia-spectrum disorders

DEFF Research Database (Denmark)

Nordgaard, Julie; Nilsson, Lars Siersbæk; Sæbye, Ditte

2017-01-01

Self-disorders have been hypothesized to be an underlying and trait-like core feature of schizophrenia-spectrum disorders and a certain degree of temporal stability of self-disorders would therefore be expected. The aim of the study was to examine the persistence of self-disorders measured...... by the Examination of Anomalous Self Experiences over a time span of 5 years. 48 patients with schizophrenia-spectrum disorders were thoroughly assessed for psychopathology at baseline and 5 years later. Self-disorders were assessed by the Examination of Anomalous Self Experiences. The level of self-disorders...... was same at the two occasions for the full Examination of Anomalous Self Disorders and for four out of the five domains. For one domain, the level of self-disorders increased slightly from baseline to follow-up. The correlations between baseline and follow-up were moderate. 9 out of the 13 most...

Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway.

Science.gov (United States)

Lahiri, Debomoy K; Sokol, Deborah K; Erickson, Craig; Ray, Balmiki; Ho, Chang Y; Maloney, Bryan

2013-01-01

Autism is a neurodevelopmental disorder marked by social skills and communication deficits and interfering repetitive behavior. Intellectual disability often accompanies autism. In addition to behavioral deficits, autism is characterized by neuropathology and brain overgrowth. Increased intracranial volume often accompanies this brain growth. We have found that the Alzheimer's disease (AD) associated amyloid-β precursor protein (APP), especially its neuroprotective processing product, secreted APP α, is elevated in persons with autism. This has led to the "anabolic hypothesis" of autism etiology, in which neuronal overgrowth in the brain results in interneuronal misconnections that may underlie multiple autism symptoms. We review the contribution of research in brain volume and of APP to the anabolic hypothesis, and relate APP to other proteins and pathways that have already been directly associated with autism, such as fragile X mental retardation protein, Ras small GTPase/extracellular signal-regulated kinase, and phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin. We also present additional evidence of magnetic resonance imaging intracranial measurements in favor of the anabolic hypothesis. Finally, since it appears that APP's involvement in autism is part of a multi-partner network, we extend this concept into the inherently interactive realm of epigenetics. We speculate that the underlying molecular abnormalities that influence APP's contribution to autism are epigenetic markers overlaid onto potentially vulnerable gene sequences due to environmental influence.

The prevalence of underlying bleeding disorders in patients with heavy menstrual bleeding with and without gynecologic abnormalities

NARCIS (Netherlands)

Knol, H. Marieke; Mulder, Andre; Bogchelman, Dick H.; Kluin-Nelemans, Hanneke C.; van der Zee, Ate G. J.; Meijer, Karina

OBJECTIVE: The purpose of this study was to assess the prevalence of underlying bleeding disorders in women with heavy menstrual bleeding (HMB) with and without gynecologic abnormalities. STUDY DESIGN: We performed a single-center prospective cohort study of 112 consecutive patients who were

Under-reporting of work-related musculoskeletal disorders in the Veterans Administration.

Science.gov (United States)

Siddharthan, Kris; Hodgson, Michael; Rosenberg, Deborah; Haiduven, Donna; Nelson, Audrey

2006-01-01

Work-related musculoskeletal disorders following patient contact represent a major concern for health care workers. Unfortunately, research and prevention have been hampered by difficulties ascertaining true prevalence rates owing to under-reporting of these injuries. The purpose of this study is to determine the predictors for under-reporting work-related musculoskeletal injuries and their reasons. Multivariate analysis using data obtained in a survey of Veterans Administration employees in the USA was used to determine underreporting patterns among registered nurses, licensed practical nurses and nursing assistants. Focus groups among health care workers were conducted at one of the largest Veterans Administration hospitals to determine reasons for under-reporting. A significant number of workers reported work-related musculoskeletal pain, which was not reported as an injury but required rescheduling work such as changing shifts and taking sick leave to recuperate. The findings indicate that older health care workers and those with longer service were less likely to report as were those working in the evening and night shifts. Hispanic workers and personnel who had repetitive injuries were prone to under-reporting, as were workers in places that lack proper equipment to move and handle patients. Reasons for under-reporting include the time involved, peer pressure not to report and frustration with workers' compensation procedures. This study provides insights into under-reporting musculoskeletal injuries in a major US government organization. The research indicates that current reporting procedures appear to be overtly cumbersome in time and effort. More flexible work assignments are needed to cover staff shortfalls owing to injuries. Health education on the detrimental long-term effects of ergonomic injuries and the need for prompt attention to injuries should prove useful in improving rates of reporting.

α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology

Directory of Open Access Journals (Sweden)

Tetsade Piermartiri

2015-11-01

Full Text Available α-Linolenic acid (ALA is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB, brain-derived neurotrophic factor (BDNF, a major neuroprotective protein in brain, and downstream signaling pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In this review, we discuss possible mechanisms of ALA efficacy against the highly toxic OP nerve agent soman. Organophosphate (OP nerve agents are highly toxic chemical warfare agents and a threat to military and civilian populations. Once considered only for battlefield use, these agents are now used by terrorists to inflict mass casualties. OP nerve agents inhibit the critical enzyme acetylcholinesterase (AChE that rapidly leads to a cholinergic crisis involving multiple organs. Status epilepticus results from the excessive accumulation of synaptic acetylcholine which in turn leads to the overactivation of muscarinic receptors; prolonged seizures cause the neuropathology and long-term consequences in survivors. Current countermeasures mitigate symptoms and signs as well as reduce brain damage, but must be given within minutes after exposure to OP nerve agents supporting interest in newer and more effective therapies. The pleiotropic properties of ALA result in a coordinated molecular and cellular program to restore neuronal networks and improve cognitive function in soman-exposed animals. Collectively, ALA should be brought to the clinic to treat the long-term consequences of nerve agents in survivors. ALA may be an effective therapy for other acute and chronic neurodegenerative disorders.

Involvement of the endosomal-lysosomal system correlates with regional pathology in Creutzfeldt-Jakob disease

DEFF Research Database (Denmark)

Kovács, Gábor G; Gelpi, Ellen; Ströbel, Thomas

2007-01-01

The endosomal-lysosomal system (ELS) has been suggested to play a role in the pathogenesis of prion diseases. The purpose of this study was to examine how experimental observations can be translated to human neuropathology and whether alterations of the ELS relate to neuropathologic changes...... correlate with regional pathology. Overloading of this system might impair the function of lysosomal enzymes and thus may mimic some features of lysosomal storage disorders. Udgivelsesdato: 2007-Jul...

Temporomandibular disorders and painful comorbidities: clinical association and underlying mechanisms.

Science.gov (United States)

Costa, Yuri Martins; Conti, Paulo César Rodrigues; de Faria, Flavio Augusto Cardoso; Bonjardim, Leonardo Rigoldi

2017-03-01

The association between temporomandibular disorders (TMDs) and headaches, cervical spine dysfunction, and fibromyalgia is not artefactual. The aim of this review is to describe the comorbid relationship between TMD and these three major painful conditions and to discuss the clinical implications and the underlying pain mechanisms involved in these relationships. Common neuronal pathways and central sensitization processes are acknowledged as the main factors for the association between TMD and primary headaches, although the establishment of cause-effect mechanisms requires further clarification and characterization. The biomechanical aspects are not the main factors involved in the comorbid relationship between TMD and cervical spine dysfunction, which can be better explained by the neuronal convergence of the trigeminal and cervical spine sensory pathways as well as by central sensitization processes. The association between TMD and fibromyalgia also has supporting evidence in the literature, and the proposed main mechanism underlying this relationship is the impairment of the descending pain inhibitory system. In this particular scenario, a cause-effect relationship is more likely to occur in one direction, that is, fibromyalgia as a risk factor for TMD. Therefore, clinical awareness of the association between TMD and painful comorbidities and the support of multidisciplinary approaches are required to recognize these related conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain activation for response inhibition under gaming cue distraction in internet gaming disorder

Directory of Open Access Journals (Sweden)

Gin-Chung Liu

2014-01-01

Full Text Available We evaluated neural substrates related to the loss of control in college students with internet gaming disorder (IGD. We hypothesized that deficit in response inhibition under gaming cue distraction was the possible mechanism for the loss of control internet use. Eleven cases of IGD and 11 controls performed Go/NoGo tasks with/without gaming distraction in the functional magnetic resonance imaging scanner. When the gaming picture was shown as background while individuals were performing Go/NoGo tasks, the IGD group committed more commission errors. The control group increased their brain activations more over the right dorsolateral prefrontal cortex (DLPFC and superior parietal lobe under gaming cue distraction in comparison with the IGD group. Furthermore, brain activation of the right DLPFC and superior parietal lobe were negatively associated with performance of response inhibition among the IGD group. The results suggest that the function of response inhibition was impaired under gaming distraction among the IGD group, and individuals with IGD could not activate right DLPFC and superior parietal lobe to keep cognitive control and attention allocation for response inhibition under gaming cue distraction. This mechanism should be addressed in any intervention for IGD.

Common and distinct brain networks underlying panic and social anxiety disorders.

Science.gov (United States)

Kim, Yong-Ku; Yoon, Ho-Kyoung

2018-01-03

Although panic disorder (PD) and phobic disorders are independent anxiety disorders with distinct sets of diagnostic criteria, there is a high level of overlap between them in terms of pathogenesis and neural underpinnings. Functional connectivity research using resting-state functional magnetic resonance imaging (rsfMRI) shows great potential in identifying the similarities and differences between PD and phobias. Understanding common and distinct networks between PD and phobic disorders is critical for identifying both specific and general neural characteristics of these disorders. We review recent rsfMRI studies and explore the clinical relevance of resting-state functional connectivity (rsFC) in PD and phobias. Although findings differ between studies, there are some meaningful, consistent findings. Social anxiety disorder (SAD) and PD share common default mode network alterations. Alterations within the sensorimotor network are observed primarily in PD. Increased connectivity in the salience network is consistently reported in SAD. This review supports hypotheses that PD and phobic disorders share common rsFC abnormalities and that the different clinical phenotypes between the disorders come from distinct brain functional network alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnosis, prevention and correction of boundary states, psychosomatic disorders in the personnel of the Kombinat industrial association under chronic stress conditions

International Nuclear Information System (INIS)

Tabachnikov, S.I.; Aleksandrovskij, Yu.A.; Shcherbina, E.A.; Roslyakov, V.S.; Cherenkov, V.N.; Bero, M.P.; Mukhamadieva, R.A.; Rymar', I.B.; Polonskij, V.G.; Dubritij, L.S.

1989-01-01

Dynamics of different psychogenetic impacts on the great number of people turned out under hazardous conditions for life was presented. Psychogenetic disorders in the personnel and human population following the Chernobyl' accident were studied. Personnel taking part in the emergency response and having no signs of radiation disease were found to have nervous-mental adaptation disorders at all stages of accident. Combination of measures on the preventive and therapeutic-reabilitative procedures was presented. Obtained results have shown that the proposed preventive and psychotherapeutic measures are the most effective and effications ones under chronic stress conditions. tab. 1

Functional convergence of histone methyltransferases EHMT1 and KMT2C involved in intellectual disability and autism spectrum disorder.

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Tom S Koemans

2017-10-01

Full Text Available Kleefstra syndrome, caused by haploinsufficiency of euchromatin histone methyltransferase 1 (EHMT1, is characterized by intellectual disability (ID, autism spectrum disorder (ASD, characteristic facial dysmorphisms, and other variable clinical features. In addition to EHMT1 mutations, de novo variants were reported in four additional genes (MBD5, SMARCB1, NR1I3, and KMT2C, in single individuals with clinical characteristics overlapping Kleefstra syndrome. Here, we present a novel cohort of five patients with de novo loss of function mutations affecting the histone methyltransferase KMT2C. Our clinical data delineates the KMT2C phenotypic spectrum and reinforces the phenotypic overlap with Kleefstra syndrome and other related ID disorders. To elucidate the common molecular basis of the neuropathology associated with mutations in KMT2C and EHMT1, we characterized the role of the Drosophila KMT2C ortholog, trithorax related (trr, in the nervous system. Similar to the Drosophila EHMT1 ortholog, G9a, trr is required in the mushroom body for short term memory. Trr ChIP-seq identified 3371 binding sites, mainly in the promoter of genes involved in neuronal processes. Transcriptional profiling of pan-neuronal trr knockdown and G9a null mutant fly heads identified 613 and 1123 misregulated genes, respectively. These gene sets show a significant overlap and are associated with nearly identical gene ontology enrichments. The majority of the observed biological convergence is derived from predicted indirect target genes. However, trr and G9a also have common direct targets, including the Drosophila ortholog of Arc (Arc1, a key regulator of synaptic plasticity. Our data highlight the clinical and molecular convergence between the KMT2 and EHMT protein families, which may contribute to a molecular network underlying a larger group of ID/ASD-related disorders.

The comparition of Personality Patterns, irrational beliefs and impulsivity in males with with drug abuse disorder under Treatment

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samere asadi

2015-03-01

Full Text Available Objective: the aim of this research was to determine the difference between personality Patterns, irrational beliefs and impulsivity in men with drug abuse disorder under Treatment. Method: in this casual- comparative research, 80 men ( 40 males with drug abuse under Treatment and 40 of normal males that were selected with available sampling .Groups were matched in terms of demoghraphy characteristics ( age, sexuality, education level and marital status and were valued with means of Eysenk Perceived Stress Inventory, Jonze Irrational Beliefs Scale and Baret Impulsivity Inventory. Results: The result of variance analysis showed that addicts compared to normal people, get more scores on extraversion, neuroticism and psychosis. Addicts group had Higher men scores in irrational beliefs compare of other group. There was significant difference between groups in impulsivity and impulsivity in addicts persons is the most. Conclussion: The traits of Personality, irrational beliefs and Unrealistic and high level impulsivity are factors that propel individuals toward more drug abuse and finally addict and aiming this factors in individuals with abuse disorder under Treatment can lead to prevent of Substance Abuse Relapse.

Neuropathological changes following experimental stereotactic irradiation. Progressive injuries of oligodendrocytes

International Nuclear Information System (INIS)

Ohtsuka, Takashi; Seiki, Yoshikatsu; Nakano, Jiro; Shibata, Iekado; Terao, Hideo

1997-01-01

This report describes the results of neuropathological examinations in 14 rabbit brains after 100 Gy of linear stereotactic irradiation. The tissue around the area of radiation necrosis was subjected to special examination. Fourteen rabbits were given a single dose of 100 Gy by a linear accelerator with a use of the 10 mm collimator. Animals were sacrificed serially after irradiation. Brains were removed and formalin treated paraffin sections were made. All sections were stained by H and E, GFAP and TUNEL (TdT-mediated dUTP-biotin nick end labeling method) stain. Pathological changes of vessels and neural tissue around the area of necrosis were examined. Three months after irradiation, TUNEL-positive oligodendrocytes were seen scattered in the white matter or the radiated field, and after 6 months, these changes extended around the radiating field, but vessels and neurons appeared to be intact. Two years after irradiation, massive necrosis had occurred in the radiated area. Thickness and fibrinoid degeneration of the vessel walls were evident in the area around the necrosis. These vessel changes were recognized in the zone of the 40 Gy radiated region. TUNEL-positive oligodendrocytes were also observed around the necrosis, and were scattered in the white matter and corpus callosum over the region of vascular changes. These findings suggested the following: In the later period after irradiation, oligodendrocytes in the peripheral zone of necrosis are damaged by ischemia and edema, which are caused by vascular changes. TUNEL-positive oligodendrocytes which exsisted in the white matter and corpus callosum distal to the radiated area may exhibit development of serial damage of oligodendrocytes in those regions. (author)

Hypothesis review: are clathrin-mediated endocytosis and clathrin-dependent membrane and protein trafficking core pathophysiological processes in schizophrenia and bipolar disorder?

LENUS (Irish Health Repository)

2012-02-01

Clathrin-mediated endocytosis (CME) is the best-characterized mechanism governing cellular membrane and protein trafficking. In this hypothesis review, we integrate recent evidence implicating CME and related cellular trafficking mechanisms in the pathophysiology of psychotic disorders such as schizophrenia and bipolar disorder. The evidence includes proteomic and genomic findings implicating proteins and genes of the clathrin interactome. Additionally, several important candidate genes for schizophrenia, such as dysbindin, are involved in processes closely linked to CME and membrane trafficking. We discuss that key aspects of psychosis neuropathology such as synaptic dysfunction, white matter changes and aberrant neurodevelopment are all influenced by clathrin-dependent processes, and that other cellular trafficking mechanisms previously linked to psychoses interact with the clathrin interactome in important ways. Furthermore, many antipsychotic drugs have been shown to affect clathrin-interacting proteins. We propose that the targeted pharmacological manipulation of the clathrin interactome may offer fruitful opportunities for novel treatments of schizophrenia.Molecular Psychiatry advance online publication, 11 October 2011; doi:10.1038\\/mp.2011.123.

White Matter Changes in Bipolar Disorder, Alzheimer Disease, and Mild Cognitive Impairment: New Insights from DTI

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Aikaterini Xekardaki

2011-01-01

Full Text Available Neuropathological and neuroimaging studies have reported significant changes in white matter in psychiatric and neurodegenerative diseases. Diffusion tensor imaging (DTI, a recently developed technique, enables the detection of microstructural changes in white matter. It is a noninvasive in vivo technique that assesses water molecules' diffusion in brain tissues. The most commonly used parameters are axial and radial diffusivity reflecting diffusion along and perpendicular to the axons, as well as mean diffusivity and fractional anisotropy representing global diffusion. Although the combination of these parameters provides valuable information about the integrity of brain circuits, their physiological meaning still remains controversial. After reviewing the basic principles of DTI, we report on recent contributions that used this technique to explore subtle structural changes in white matter occurring in elderly patients with bipolar disorder and Alzheimer disease.

Möbius syndrome. A clinical, radiological, neurophysiological, genetic and neuropathological study.

NARCIS (Netherlands)

Verzijl, H.T.F.M.

2005-01-01

The overall conclusion of this study is that the Möbius condition contains two distinct disorders: Firstly, an autosomal disorder which can be best described as hereditary congenital facial palsy. Secondly, a disorder for which we reserve the name Möbius syndrome and is characterized by congenital

Topographic distribution of brain iron deposition and small cerebrovascular lesions in amyotrophic lateral sclerosis and in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates.

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De Reuck, Jacques; Devos, David; Moreau, Caroline; Auger, Florent; Durieux, Nicolas; Deramecourt, Vincent; Pasquier, Florence; Maurage, Claude-Alain; Cordonnier, Charlotte; Leys, Didier; Bordet, Regis

2017-12-01

Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal lobar degeneration (FTLD) in 15% of the cases. A neuropathological continuity between ALS and FTLD-TDP is suspected. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) study compares the topographic distribution of iron (Fe) deposition and the incidence of small cerebrovascular lesions in ALS and in FTLD brains. Seventy-eight post-mortem brains underwent 7.0-tesla MRI. The patients consisted of 12 with ALS, 38 with FTLD, and 28 controls. Three ALS brains had minor FTLD features. Three coronal sections of a cerebral hemisphere were submitted to T2 and T2* MRI sequences. The amount of Fe deposition in the deep brain structures and the number of small cerebrovascular lesions was determined in ALS and the subtypes of FTLD compared to control brains, with neuropathological correlates. A significant increase of Fe deposition was observed in the claustrum, caudate nucleus, globus pallidus, thalamus, and subthalamic nucleus of the FTLD-FUS and FTLD-TDP groups, while in the ALS one, the Fe increase was only observed in the caudate and the subthalamic nuclei. White matter changes were only significantly more severe in the FTLD compared to those in ALS and in controls brains. Cortical micro-bleeds were increased in the frontal and temporal lobes of FTLD as well as of ALS brains compared to controls. Cortical micro-infarcts were, on the other hand, more frequent in the control compared to the ALS and FTLD groups. The present study supports the assumption of a neuropathological continuity between ALS and FTLD and illustrates the favourable vascular risk profile in these diseases.

Amino acids as dietary excitotoxins: a contribution to understanding neurodegenerative disorders.

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Meldrum, B

1993-01-01

The possibility that some acidic amino acids occurring naturally or as additives in the diet can act as excitotoxins producing central nervous system pathology has been the subject of extensive debate in the last 20 years and is here reviewed. High doses of glutamate, aspartate or related excitatory amino acids given in isolation to neonatal rodents produce acute degeneration organs. Neuropathology resulting from consumption of glutamate or aspartate has not been described in man. Various unusual amino acids of plant origin can produce acute excitotoxic syndromes. In man domoate (consumed in mussels that have fed on (Nitschia pungens) can produce an acute syndrome associated with limbic system lesions and anterograde amnesia. Kainate and domoate produce similar syndromes in rodents; acromelate produces spinal pathology. The mechanisms and manifestations of chronic excitotoxicity are less clearly established. A combination of impaired energy metabolism or impaired buffering of calcium and free radicals and endogenous or exogenous excitotoxins may contribute to neuronal loss in human neurodegenerative disorders.

Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

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Daniele Bertoglio

2017-11-01

Full Text Available The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE. As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE. Wistar Han (Charles River, France and Sprague-Dawley (Harlan, The Netherlands rats were subjected to KASE using the Hellier kainic acid (KA and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG in a subgroup of animals, while animals were sacrificed 1 week (subacute phase and 12 weeks (chronic phase post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei, microglial activation (OX-42 and translocator protein, and neurodegeneration (Fluorojade C were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001 in SD/H (median 8.3 days animals compared to WH/CR (median 15.4 days. During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01. However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure

Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

Science.gov (United States)

Bertoglio, Daniele; Amhaoul, Halima; Van Eetveldt, Annemie; Houbrechts, Ruben; Van De Vijver, Sebastiaan; Ali, Idrish; Dedeurwaerdere, Stefanie

2017-01-01

The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE) rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE). As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE). Wistar Han (Charles River, France) and Sprague-Dawley (Harlan, The Netherlands) rats were subjected to KASE using the Hellier kainic acid (KA) and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG) in a subgroup of animals, while animals were sacrificed 1 week (subacute phase) and 12 weeks (chronic phase) post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei), microglial activation (OX-42 and translocator protein), and neurodegeneration (Fluorojade C) were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001) in SD/H (median 8.3 days) animals compared to WH/CR (median 15.4 days). During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01). However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure burden

International recommendation for a comprehensive neuropathologic workup of epilepsy surgery brain tissue: A consensus Task Force report from the ILAE Commission on Diagnostic Methods.

Science.gov (United States)

Blümcke, Ingmar; Aronica, Eleonora; Miyata, Hajime; Sarnat, Harvey B; Thom, Maria; Roessler, Karl; Rydenhag, Bertil; Jehi, Lara; Krsek, Pavel; Wiebe, Samuel; Spreafico, Roberto

2016-03-01

Epilepsy surgery is an effective treatment in many patients with drug-resistant focal epilepsies. An early decision for surgical therapy is facilitated by a magnetic resonance imaging (MRI)-visible brain lesion congruent with the electrophysiologically abnormal brain region. Recent advances in the pathologic diagnosis and classification of epileptogenic brain lesions are helpful for clinical correlation, outcome stratification, and patient management. However, application of international consensus classification systems to common epileptic pathologies (e.g., focal cortical dysplasia [FCD] and hippocampal sclerosis [HS]) necessitates standardized protocols for neuropathologic workup of epilepsy surgery specimens. To this end, the Task Force of Neuropathology from the International League Against Epilepsy (ILAE) Commission on Diagnostic Methods developed a consensus standard operational procedure for tissue inspection, distribution, and processing. The aims are to provide a systematic framework for histopathologic workup, meeting minimal standards and maximizing current and future opportunities for morphofunctional correlations and molecular studies for both clinical care and research. Whenever feasible, anatomically intact surgical specimens are desirable to enable systematic analysis in selective hippocampectomies, temporal lobe resections, and lesional or nonlesional neocortical samples. Correct orientation of sample and the sample's relation to neurophysiologically aberrant sites requires good communication between pathology and neurosurgical teams. Systematic tissue sampling of 5-mm slabs along a defined anatomic axis and application of a limited immunohistochemical panel will ensure a reliable differential diagnosis of main pathologies encountered in epilepsy surgery. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Excitatory/inhibitory imbalance in autism spectrum disorders: Implications for interventions and therapeutics.

Science.gov (United States)

Uzunova, Genoveva; Pallanti, Stefano; Hollander, Eric

2016-04-01

Imbalance between excitation and inhibition and increased excitatory-inhibitory (E-I) ratio is a common mechanism in autism spectrum disorders (ASD) that is responsible for the learning and memory, cognitive, sensory, motor deficits, and seizures occurring in these disorders. ASD are very heterogeneous and better understanding of E-I imbalance in brain will lead to better diagnosis and treatments. We perform a critical literature review of the causes and presentations of E-I imbalance in ASD. E-I imbalance in ASD is due primarily to abnormal glutamatergic and GABAergic neurotransmission in key brain regions such as neocortex, hippocampus, amygdala, and cerebellum. Other causes are due to dysfunction of neuropeptides (oxytocin), synaptic proteins (neuroligins), and immune system molecules (cytokines). At the neuropathological level E-I imbalance in ASD is presented as a "minicolumnopathy". E-I imbalance alters the manner by which the brain processes information and regulates behaviour. New developments for investigating E-I imbalance such as optogenetics and transcranial magnetic stimulation (TMS) are presented. Non-invasive brain stimulation methods such as TMS for treatment of the core symptoms of ASD are discussed. Understanding E-I imbalance has important implications for developing better pharmacological and behavioural treatments for ASD, including TMS, new drugs, biomarkers and patient stratification.

The values underlying team decision-making in work rehabilitation for musculoskeletal disorders.

Science.gov (United States)

Loisel, Patrick; Falardeau, Marlène; Baril, Raymond; José-Durand, Marie; Langley, Ann; Sauvé, Sandrine; Gervais, Julie

2005-05-20

This paper presents the results of a qualitative study on the values underlying the decision-making process of an interdisciplinary team working in a work rehabilitation facility of a Québec teaching hospital. In order to document the values underlying the decision-making process, a single case observational study was conducted. Interdisciplinary team weekly discussions on ongoing cases of 22 workers absent from work due to musculoskeletal disorders were videotaped. All discourses were transcribed and analyzed following an inductive and iterative approach. The values identified were validated by feedback from team members. Ten common decision values emerged from the data: (1) team unity and credibility, (2) collaboration with stakeholders, (3) worker's internal motivation, (4) worker's adherence to the program, (5) worker's reactivation, (6) single message, (7) reassurance, (8) graded intervention, (9) pain management and (10) return to work as a therapy. The analysis of these values led to the design of a model describing interrelations between them. This study throws light on some mechanisms underlying the decisions made by the team and determining its action. This improves understanding of the actions taken by an interdisciplinary team in work rehabilitation and may facilitate knowledge transfer in the training of other teams.

Advectional enhancement of eddy diffusivity under parametric disorder

International Nuclear Information System (INIS)

Goldobin, Denis S

2010-01-01

Frozen parametric disorder can lead to the appearance of sets of localized convective currents in an otherwise stable (quiescent) fluid layer heated from below. These currents significantly influence the transport of an admixture (or any other passive scalar) along the layer. When the molecular diffusivity of the admixture is small in comparison to the thermal one, which is quite typical in nature, disorder can enhance the effective (eddy) diffusivity by several orders of magnitude in comparison to the molecular diffusivity. In this paper, we study the effect of an imposed longitudinal advection on the delocalization of convective currents, both numerically and analytically, and report a subsequent drastic boost of the effective diffusivity for weak advection.

Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway

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Debomoy K Lahiri

2013-06-01

Full Text Available Autism is a neurodevelopmental disorder marked by social skills and communication deficits and interfering repetitive behavior. Intellectual disability often accompanies autism. In addition to behavioral deficits, autism is characterized by neuropathology and brain overgrowth. Increased intracranial volume often accompanies this brain growth. We have found that the Alzheimer’s disease (AD associated amyloid-β precursor protein (APP, especially its neuroprotective processing product, secreted APP α (sAPPα, is elevated in persons with autism. This has led to the anabolic hypothesis of autism etiology, in which neuronal overgrowth in the brain results in interneuronal misconnections that may underlie multiple autism symptoms. We review the contribution of research in brain volume and of APP to the anabolic hypothesis, and relate APP to other proteins and pathways that have already been directly associated with autism, such as fragile X mental retardation protein (FMRP, Ras small GTPase/Extracellular Signal-Regulated Kinase (Ras/ERK, and phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR. We also present additional evidence of MRI intracranial measurements in favor of the anabolic hypothesis. Finally, since it appears that APP’s involvement in autism is part of a multi-partner network, we extend this concept into the inherently interactive realm of epigenetics. We speculate that the underlying molecular abnormalities that influence APP’s contribution to autism are epigenetic markers overlaid onto potentially vulnerable gene sequences due to environmental influence.

Application and Evaluation of Independent Component Analysis Methods to Generalized Seizure Disorder Activities Exhibited in the Brain.

Science.gov (United States)

George, S Thomas; Balakrishnan, R; Johnson, J Stanly; Jayakumar, J

2017-07-01

EEG records the spontaneous electrical activity of the brain using multiple electrodes placed on the scalp, and it provides a wealth of information related to the functions of brain. Nevertheless, the signals from the electrodes cannot be directly applied to a diagnostic tool like brain mapping as they undergo a "mixing" process because of the volume conduction effect in the scalp. A pervasive problem in neuroscience is determining which regions of the brain are active, given voltage measurements at the scalp. Because of which, there has been a surge of interest among the biosignal processing community to investigate the process of mixing and unmixing to identify the underlying active sources. According to the assumptions of independent component analysis (ICA) algorithms, the resultant mixture obtained from the scalp can be closely approximated by a linear combination of the "actual" EEG signals emanating from the underlying sources of electrical activity in the brain. As a consequence, using these well-known ICA techniques in preprocessing of the EEG signals prior to clinical applications could result in development of diagnostic tool like quantitative EEG which in turn can assist the neurologists to gain noninvasive access to patient-specific cortical activity, which helps in treating neuropathologies like seizure disorders. The popular and proven ICA schemes mentioned in various literature and applications were selected (which includes Infomax, JADE, and SOBI) and applied on generalized seizure disorder samples using EEGLAB toolbox in MATLAB environment to see their usefulness in source separations; and they were validated by the expert neurologist for clinical relevance in terms of pathologies on brain functionalities. The performance of Infomax method was found to be superior when compared with other ICA schemes applied on EEG and it has been established based on the validations carried by expert neurologist for generalized seizure and its clinical

Subcortical neuromorphometry in schizophrenia spectrum and bipolar disorders

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Daniel Mamah

2016-01-01

Conclusions: Few similarities in surface deformation patterns were seen across groups, which may reflect differing neuropathologies. Posterior thalamic contraction in SCZ and BP suggest common genetic or environmental antecedents. Surface deformities in SCZ basal ganglia may have been due to antipsychotic drug effects.

Disrupted Cerebro-cerebellar Intrinsic Functional Connectivity in Young Adults with High-functioning Autism Spectrum Disorder: A Data-driven, Whole-brain, High Temporal Resolution fMRI Study.

Science.gov (United States)

Arnold Anteraper, Sheeba; Guell, Xavier; D'Mello, Anila; Joshi, Neha; Whitfield-Gabrieli, Susan; Joshi, Gagan

2018-06-13

To examine the resting-state functional-connectivity (RsFc) in young adults with high-functioning autism spectrum disorder (HF-ASD) using state-of-the-art fMRI data acquisition and analysis techniques. Simultaneous multi-slice, high temporal resolution fMRI acquisition; unbiased whole-brain connectome-wide multivariate pattern analysis (MVPA) techniques for assessing RsFc; and post-hoc whole-brain seed-to-voxel analyses using MVPA results as seeds. MVPA revealed two clusters of abnormal connectivity in the cerebellum. Whole-brain seed-based functional connectivity analyses informed by MVPA-derived clusters showed significant under connectivity between the cerebellum and social, emotional, and language brain regions in the HF-ASD group compared to healthy controls. The results we report are coherent with existing structural, functional, and RsFc literature in autism, extend previous literature reporting cerebellar abnormalities in the neuropathology of autism, and highlight the cerebellum as a potential target for therapeutic, diagnostic, predictive, and prognostic developments in ASD. The description of functional connectivity abnormalities using whole-brain, data-driven analyses as reported in the present study may crucially advance the development of ASD biomarkers, targets for therapeutic interventions, and neural predictors for measuring treatment response.

Less Is More: Substrate Reduction Therapy for Lysosomal Storage Disorders

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Maria Francisca Coutinho

2016-07-01

Full Text Available Lysosomal storage diseases (LSDs are a group of rare, life-threatening genetic disorders, usually caused by a dysfunction in one of the many enzymes responsible for intralysosomal digestion. Even though no cure is available for any LSD, a few treatment strategies do exist. Traditionally, efforts have been mainly targeting the functional loss of the enzyme, by injection of a recombinant formulation, in a process called enzyme replacement therapy (ERT, with no impact on neuropathology. This ineffectiveness, together with its high cost and lifelong dependence is amongst the main reasons why additional therapeutic approaches are being (and have to be investigated: chaperone therapy; gene enhancement; gene therapy; and, alternatively, substrate reduction therapy (SRT, whose aim is to prevent storage not by correcting the original enzymatic defect but, instead, by decreasing the levels of biosynthesis of the accumulating substrate(s. Here we review the concept of substrate reduction, highlighting the major breakthroughs in the field and discussing the future of SRT, not only as a monotherapy but also, especially, as complementary approach for LSDs.

Heterogeneity in Red Wine Polyphenolic Contents Differentially Influences Alzheimer's Disease-type Neuropathology and Cognitive Deterioration

Science.gov (United States)

Ho, Lap; Chen, Ling Hong; Wang, Jun; Zhao, Wei; Talcott, Stephen T.; Ono, Kenjiro; Teplow, David; Humala, Nelson; Cheng, Alice; Percival, Susan S.; Ferruzzi, Mario; Janle, Elsa; Dickstein, Dara L.; Pasinetti, Giulio Maria

2009-01-01

We recently found that moderate consumption of two unrelated red wines generate from different grape species, a Cabernet Sauvignon and a muscadine wine that are characterized by distinct component composition of polyphenolic compounds, significantly attenuated the development of Alzheimer's disease (AD)-type brain pathology and memory deterioration in a transgenic AD mouse model. Interestingly, our evidence suggests that the two red wines attenuated AD phenotypes through independent mechanisms. In particular, we previously found that treatment with Cabernet Sauvignon reduced the generation of AD-type amyloid-β (Aβ) peptides. In contrast, evidence from our present study suggests that muscadine treatment attenuates Aβ neuropathology and Aβ-related cognitive deterioration in Tg2576 mice by interfering with the oligomerization of Aβ molecules to soluble high-molecular-weight Aβ oligomer species that are responsible for initiating a cascade of cellular events resulting in cognitive decline. Collectively, our observations suggest that distinct polyphenolic compounds from red wines may be bioavailable at the organism level and beneficially modulate AD phenotypes through multiple Aβ-related mechanisms. Results from these studies suggest the possibility of developing a “combination” of dietary polyphenolic compounds for AD prevention and/or therapy by modulating multiple Aβ-related mechanisms. PMID:19158422

Using the mood disorder questionnaire and bipolar spectrum diagnostic scale to detect bipolar disorder and borderline personality disorder among eating disorder patients

Science.gov (United States)

2013-01-01

Background Screening scales for bipolar disorder including the Mood Disorder Questionnaire (MDQ) and Bipolar Spectrum Diagnostic Scale (BSDS) have been plagued by high false positive rates confounded by presence of borderline personality disorder. This study examined the accuracy of these scales for detecting bipolar disorder among patients referred for eating disorders and explored the possibility of simultaneous assessment of co-morbid borderline personality disorder. Methods Participants were 78 consecutive female patients who were referred for evaluation of an eating disorder. All participants completed the mood and eating disorder sections of the SCID-I/P and the borderline personality disorder section of the SCID-II, in addition to the MDQ and BSDS. Predictive validity of the MDQ and BSDS was evaluated by Receiver Operating Characteristic analysis of the Area Under the Curve (AUC). Results Fifteen (19%) and twelve (15%) patients fulfilled criteria for bipolar II disorder and borderline personality disorder, respectively. The AUCs for bipolar II disorder were 0.78 (MDQ) and 0.78 (BDSD), and the AUCs for borderline personality disorder were 0.75 (MDQ) and 0.79 (BSDS). Conclusions Among patients being evaluated for eating disorders, the MDQ and BSDS show promise as screening questionnaires for both bipolar disorder and borderline personality disorder. PMID:23443034

Alcohol use disorder

Science.gov (United States)

... have problems with alcohol if you: Are a young adult under peer pressure Have depression, bipolar disorder , anxiety disorders , or schizophrenia Can easily obtain alcohol Have low self-esteem Have problems with relationships Live a stressful lifestyle ...

Sexual Desire Disorders

OpenAIRE

Montgomery, Keith A.

2008-01-01

Hypoactive sexual desire disorder (HSDD) and sexual aversion disorder (SAD) are an under-diagnosed group of disorders that affect men and women. Despite their prevalence, these two disorders are often not addressed by healthcare providers and patients due their private and awkward nature. As physicians, we need to move beyond our own unease in order to adequately address our patients’ sexual problems and implement appropriate treatment. Using the Sexual Response Cycle as the model of the phys...

Fragile X-associated tremor/ataxia syndrome: phenotypic comparisons with other movement disorders.

Science.gov (United States)

Robertson, Erin E; Hall, Deborah A; McAsey, Andrew R; O'Keefe, Joan A

2016-08-01

The purpose of this paper is to review the typical cognitive and motor impairments seen in fragile X-associated tremor/ataxia syndrome (FXTAS), essential tremor (ET), Parkinson disease (PD), spinocerebellar ataxias (SCAs), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) in order to enhance diagnosis of FXTAS patients. We compared the cognitive and motor phenotypes of FXTAS with each of these other movement disorders. Relevant neuropathological and neuroimaging findings are also reviewed. Finally, we describe the differences in age of onset, disease severity, progression rates, and average lifespan in FXTAS compared to ET, PD, SCAs, MSA, and PSP. We conclude with a flow chart algorithm to guide the clinician in the differential diagnosis of FXTAS. By comparing the cognitive and motor phenotypes of FXTAS with the phenotypes of ET, PD, SCAs, MSA, and PSP we have clarified potential symptom overlap while elucidating factors that make these disorders unique from one another. In summary, the clinician should consider a FXTAS diagnosis and testing for the Fragile X mental retardation 1 (FMR1) gene premutation if a patient over the age of 50 (1) presents with cerebellar ataxia and/or intention tremor with mild parkinsonism, (2) has the middle cerebellar peduncle (MCP) sign, global cerebellar and cerebral atrophy, and/or subcortical white matter lesions on MRI, or (3) has a family history of fragile X related disorders, intellectual disability, autism, premature ovarian failure and has neurological signs consistent with FXTAS. Peripheral neuropathy, executive function deficits, anxiety, or depression are supportive of the diagnosis. Distinct profiles in the cognitive and motor domains between these movement disorders may guide practitioners in the differential diagnosis process and ultimately lead to better medical management of FXTAS patients.

Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features

Science.gov (United States)

Mahoney, Colin J.; Beck, Jon; Rohrer, Jonathan D.; Lashley, Tammaryn; Mok, Kin; Shakespeare, Tim; Yeatman, Tom; Warrington, Elizabeth K.; Schott, Jonathan M.; Fox, Nick C.; Rossor, Martin N.; Hardy, John; Collinge, John; Revesz, Tamas; Mead, Simon

2012-01-01

An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as a major cause of familial frontotemporal lobar degeneration and motor neuron disease, including cases previously identified as linked to chromosome 9. Here we present a detailed retrospective clinical, neuroimaging and histopathological analysis of a C9ORF72 mutation case series in relation to other forms of genetically determined frontotemporal lobar degeneration ascertained at a specialist centre. Eighteen probands (19 cases in total) were identified, representing 35% of frontotemporal lobar degeneration cases with identified mutations, 36% of cases with clinical evidence of motor neuron disease and 7% of the entire cohort. Thirty-three per cent of these C9ORF72 cases had no identified relevant family history. Families showed wide variation in clinical onset (43–68 years) and duration (1.7–22 years). The most common presenting syndrome (comprising a half of cases) was behavioural variant frontotemporal dementia, however, there was substantial clinical heterogeneity across the C9ORF72 mutation cohort. Sixty per cent of cases developed clinical features consistent with motor neuron disease during the period of follow-up. Anxiety and agitation and memory impairment were prominent features (between a half to two-thirds of cases), and dominant parietal dysfunction was also frequent. Affected individuals showed variable magnetic resonance imaging findings; however, relative to healthy controls, the group as a whole showed extensive thinning of frontal, temporal and parietal cortices, subcortical grey matter atrophy including thalamus and cerebellum and involvement of long intrahemispheric, commissural and corticospinal tracts. The neuroimaging profile of the C9ORF72 expansion was significantly more symmetrical than progranulin mutations with significantly less temporal lobe involvement than microtubule-associated protein tau mutations. Neuropathological examination in six cases

Regional cerebral glucose metabolic changes in oculopalatal myoclonus: implication for neural pathways, underlying the disorder

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Cho, Sang Soo; Moon, So Young; Kim, Ji Soo; Kim, Sang Eun [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

2004-07-01

Palatal myoclonus (PM) is characterized by rhythmic involuntary jerky movements of the soft palate of the throat. When associated with eye movements, it is called oculopalatal myoclonus (OPM). Ordinary PM is characterized by hypertrophic olivary degeneration, a trans-synaptic degeneration following loss of neuronal input to the inferior olivary nucleus due to an interruption of the Guillain-Mollaret triangle usually by a hemorrhage. However, the neural pathways underlying the disorder are uncertain. In an attempt to understand the pathologic neural pathways, we examined the metabolic correlates of this tremulous condition. Brain FDG PET scans were acquired in 8 patients with OPM (age, 49.9{+-}4.6 y: all males: 7 with pontine hemorrhage, 1 with diffuse brainstem infarction) and age-matched 50 healthy males (age, 50.7{+-} 9.0) and the regional glucose metabolism compared using SPM99. For group analysis, the hemispheres containing lesions were assigned to the right side of the brain. Patients with OPM had significant hypometabolism in the ipsilateral (to the lesion) brainstem and superior temporal and parahippocampal gyri (P < 0.05 corrected, k = 100). By contrast, there was significant hypermetabolism in the contralateral middle and inferior temporal gyri, thalamus, middle frontal gyrus and precuneus (P < 0.05 corrected, k=l00). Our data demonstrate the distinct metabolic changes between several ipsilateral and contralateral brain regions (hypometabolism vs. hypermetabolism) in patients with OPM. This may provide clues for understanding the neural pathways underlying the disorder.

Regional cerebral glucose metabolic changes in oculopalatal myoclonus: implication for neural pathways, underlying the disorder

International Nuclear Information System (INIS)

Cho, Sang Soo; Moon, So Young; Kim, Ji Soo; Kim, Sang Eun

2004-01-01

Palatal myoclonus (PM) is characterized by rhythmic involuntary jerky movements of the soft palate of the throat. When associated with eye movements, it is called oculopalatal myoclonus (OPM). Ordinary PM is characterized by hypertrophic olivary degeneration, a trans-synaptic degeneration following loss of neuronal input to the inferior olivary nucleus due to an interruption of the Guillain-Mollaret triangle usually by a hemorrhage. However, the neural pathways underlying the disorder are uncertain. In an attempt to understand the pathologic neural pathways, we examined the metabolic correlates of this tremulous condition. Brain FDG PET scans were acquired in 8 patients with OPM (age, 49.9±4.6 y: all males: 7 with pontine hemorrhage, 1 with diffuse brainstem infarction) and age-matched 50 healthy males (age, 50.7± 9.0) and the regional glucose metabolism compared using SPM99. For group analysis, the hemispheres containing lesions were assigned to the right side of the brain. Patients with OPM had significant hypometabolism in the ipsilateral (to the lesion) brainstem and superior temporal and parahippocampal gyri (P < 0.05 corrected, k = 100). By contrast, there was significant hypermetabolism in the contralateral middle and inferior temporal gyri, thalamus, middle frontal gyrus and precuneus (P < 0.05 corrected, k=l00). Our data demonstrate the distinct metabolic changes between several ipsilateral and contralateral brain regions (hypometabolism vs. hypermetabolism) in patients with OPM. This may provide clues for understanding the neural pathways underlying the disorder

Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy?

Science.gov (United States)

Washington, Patricia M; Villapol, Sonia; Burns, Mark P

2016-01-01

Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer's disease (AD), while repeat mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position-examining epidemiological and case control human studies, neuropathological evidence, and preclinical data. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson's disease. Further, human post-mortem studies on both single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a 'polypathology'. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI is viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of apolipoprotein E genotype on cortical neuropathology in senile dementia of the Lewy body and Alzheimer's disease.

Science.gov (United States)

Benjamin, R; Leake, A; Ince, P G; Perry, R H; McKeith, I G; Edwardson, J A; Morris, C M

1995-12-01

Apolipoprotein E (APO E) genotypes were determined in a UK population of neuropathologically confirmed control cases, and in cases of Lewy body dementia (SDLT) and late onset Alzheimer's disease (AD). APO E epsilon 4 allele frequency was significantly elevated in both SDLT and AD groups with a concomitant reduction in the APO E epsilon 3 allele frequency. The epsilon 2 allele frequency in the AD group was only 25% of the control population, though because of the relatively small sample size this reduction was not significant; the epsilon 2 allele frequency in the SDLT group was normal. No significant association was found between senile plaque density and neurofibrillary tangle density in the neocortex and APO E allele dose in either SDLT or AD. Although the possession of APO E epsilon 4 is associated with an increased risk of developing SDLT and AD, actual APO E genotype does not appear to affect the burden of pathology.

The serotonergic anatomy of the developing human medulla oblongata: implications for pediatric disorders of homeostasis.

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Kinney, Hannah C; Broadbelt, Kevin G; Haynes, Robin L; Rognum, Ingvar J; Paterson, David S

2011-07-01

The caudal serotonergic (5-HT) system is a critical component of a medullary "homeostatic network" that regulates protective responses to metabolic stressors such as hypoxia, hypercapnia, and hyperthermia. We define anatomically the caudal 5-HT system in the human medulla as 5-HT neuronal cell bodies located in the raphé (raphé obscurus, raphé magnus, and raphé pallidus), extra-raphé (gigantocellularis, paragigantocellularis lateralis, intermediate reticular zone, lateral reticular nucleus, and nucleus subtrigeminalis), and ventral surface (arcuate nucleus). These 5-HT neurons are adjacent to all of the respiratory- and autonomic-related nuclei in the medulla where they are positioned to modulate directly the responses of these effector nuclei. In the following review, we highlight the topography and development of the caudal 5-HT system in the human fetus and infant, and its inter-relationships with nicotinic, GABAergic, and cytokine receptors. We also summarize pediatric disorders in early life which we term "developmental serotonopathies" of the caudal (as well as rostral) 5-HT domain and which are associated with homeostatic imbalances. The delineation of the development and organization of the human caudal 5-HT system provides the critical foundation for the neuropathologic elucidation of its disorders directly in the human brain. Copyright © 2011 Elsevier B.V. All rights reserved.

Stroke and sleep-disordered breathing: A relationship under construction.

Science.gov (United States)

Parra, Olga; Arboix, Adrià

2016-02-16

The association between sleep-disordered breathing (SDB) and cardiovascular risk has been the focus of attention in recent years. Sleep disorders are emerging risk factors for cardiovascular disease and have been related to the whole spectrum of stroke, including transient ischemic attack, ischemic cerebral infarction and intracerebral haemorrhage. It has been shown that lacunar stroke or lacunar infarctions affecting the internal capsule or the protuberance are associated with a higher frequency of SDB. Acute stroke patients with associated SDB have a worse prognosis and a higher mortality as compared to patients with first-ever stroke without SDB. Preliminary studies provide evidence of the usefulness of treatment with continuous positive airway pressure when SDB is present in stroke patients.

Psychogenic Balance Disorders: Is It a New Entity of Psychogenic Movement Disorders?

Directory of Open Access Journals (Sweden)

Jong Sam Baik

2012-05-01

Full Text Available The various reported psychogenic dyskinesias include tremor, dystonia, myoclonus, gait disorder, Parkinsonism, tics, and chorea. It is not easy to diagnose psychogenic movement disorders, especially in patients with underlying organic disease. We describe three patients with balance and/or posture abnormalities that occur when they stand up, start to move, or halt from walking, although their gaits are normal. One had an underlying unilateral frontal lobe lesion. All patients improved dramatically after receiving a placebo-injection or medication. These abnormal features differ from the previously reported features of astasia without abasia and of psychogenic gait disorders, including recumbent gait. We describe and discuss the patients’ unique clinical characteristics.

[Conversion disorder : functional neuroimaging and neurobiological mechanisms].

Science.gov (United States)

Lejeune, J; Piette, C; Salmon, E; Scantamburlo, G

2017-04-01

Conversion disorder is a psychiatric disorder often encountered in neurology services. This condition without organic lesions was and still is sometimes referred as an imaginary illness or feigning. However, the absence of organic lesions does not exclude the possibility of cerebral dysfunction. The etiologic mechanisms underlying this disorder remain uncertain even today.The advent of cognitive and functional imaging opens up a field of exploration for psychiatry in understanding the neurobiological mechanisms underlying mental disorders and especially the conversion disorder. This article reports several neuroimaging studies of conversion disorder and attempts to generate hypotheses about neurobiological mechanisms.

Influence of post-traumatic stress disorder on neuroinflammation and cell proliferation in a rat model of traumatic brain injury.

Directory of Open Access Journals (Sweden)

Sandra A Acosta

Full Text Available Long-term consequences of traumatic brain injury (TBI are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD, yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long

Influence of post-traumatic stress disorder on neuroinflammation and cell proliferation in a rat model of traumatic brain injury.

Science.gov (United States)

Acosta, Sandra A; Diamond, David M; Wolfe, Steven; Tajiri, Naoki; Shinozuka, Kazutaka; Ishikawa, Hiroto; Hernandez, Diana G; Sanberg, Paul R; Kaneko, Yuji; Borlongan, Cesar V

2013-01-01

Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long-term inflammation and suppressed

Influence of Post-Traumatic Stress Disorder on Neuroinflammation and Cell Proliferation in a Rat Model of Traumatic Brain Injury

Science.gov (United States)

Diamond, David M.; Shinozuka, Kazutaka; Ishikawa, Hiroto; Hernandez, Diana G.; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesar V.

2013-01-01

Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long-term inflammation and suppressed

SHANK3 as an autism spectrum disorder-associated gene.

Science.gov (United States)

Uchino, Shigeo; Waga, Chikako

2013-02-01

SHANK3 is a synaptic scaffolding protein enriched in the postsynaptic density of excitatory synapses, and plays important roles in the formation, maturation, and maintenance of synapses. Haploinsufficiency of the SHANK3 gene causes a developmental disorder, 22q13.3 deletion syndrome (known as Phelan-McDermid syndrome), that is characterized by severe expressive language and speech delay, hypotonia, global developmental delay, and autistic behavior. Since several SHANK3 mutations have been identified in a particular phenotypic group in patients with autism spectrum disorder (ASD), the SHANK3 is strongly suspected of being involved in the pathogenesis and neuropathology of ASD. Five CpG-islands have been identified in the SHANK3 gene, and tissue-specific expression of SHANK3 is regulated by DNA methylation in an epigenetic manner. Cumulative evidence has shown that several SHANK3 variants are expressed in the developing rodent brain and that their expression is regulated by DNA methylation of intragenic promoters. We identified novel SHANK3 transcripts whose transcription started at the vicinity of the CpG-island 2 in the mouse brain. Shank3 mutant mice exhibit autistic-like behaviors, including impaired social interaction and repetitive behaviors. In this article we review recent findings in regard to higher brain functions of SHANK3, epigenetic regulation of SHANK3 expression, and SHANK3-related ASD that were obtained from genetic analyses in ASD patients, molecular biological studies using developing mouse brains, and studies of Shank3 mutant mice. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Dyslipidemia in Dermatological Disorders

Science.gov (United States)

Shenoy, Chetana; Shenoy, Manjunath Mala; Rao, Gururaja K.

2015-01-01

Dyslipidemias are one of the common metabolic disorders. A link between dermatological disorders like psoriasis and dyslipidemia has been established in the recent past. Many dermatological disorders could have a systemic inflammatory component which explains such association. Chronic inflammatory dermatological disorders could also have other metabolic imbalances that may contribute to dyslipidemia. Presence of such abnormal metabolism may justify routine screening of these disorders for associated dyslipidemia and other metabolic abnormalities and early treatment of such comorbidities to improve quality of life. Some of the drugs used by dermatologists such as retinoids are also likely to be a cause of dyslipidemia. Hence, it is imperative that the dermatologists obtain scientific knowledge on the underlying mechanisms involved in dyslipidemia and understand when to intervene with therapies. A systematic review of the English language literature was done by using Google Scholar and PubMed. In this review, attempts are made to list the dermatological disorders associated with dyslipidemia; to simplify the understanding of underlying mechanisms; and to give a brief idea about the interventions. PMID:26713286

A Single Neonatal Exposure to BMAA in a Rat Model Produces Neuropathology Consistent with Neurodegenerative Diseases

Directory of Open Access Journals (Sweden)

Laura Louise Scott

2017-12-01

Full Text Available Although cyanobacterial β-N-methylamino-l-alanine (BMAA has been implicated in the development of Alzheimer’s Disease (AD, Parkinson’s Disease (PD and Amyotrophic Lateral Sclerosis (ALS, no BMAA animal model has reproduced all the neuropathology typically associated with these neurodegenerative diseases. We present here a neonatal BMAA model that causes β-amyloid deposition, neurofibrillary tangles of hyper-phosphorylated tau, TDP-43 inclusions, Lewy bodies, microbleeds and microgliosis as well as severe neuronal loss in the hippocampus, striatum, substantia nigra pars compacta, and ventral horn of the spinal cord in rats following a single BMAA exposure. We also report here that BMAA exposure on particularly PND3, but also PND4 and 5, the critical period of neurogenesis in the rodent brain, is substantially more toxic than exposure to BMAA on G14, PND6, 7 and 10 which suggests that BMAA could potentially interfere with neonatal neurogenesis in rats. The observed selective toxicity of BMAA during neurogenesis and, in particular, the observed pattern of neuronal loss observed in BMAA-exposed rats suggest that BMAA elicits its effect by altering dopamine and/or serotonin signaling in rats.

Control psychophysical children’s development under the correction movement disorder

Directory of Open Access Journals (Sweden)

B O Bukhovets

2016-02-01

  Abstract   This article deals with the problem of determining the effectiveness of the method Bobath, as the main methods of psychophysical condition correction of children with movement disorders. Given the drawbacks of the proposed test detailed rating scale of psychomotor development of children "Map test of motor abilities of children" was adapted and implemented together with the Munich diagnostic testing cards of mental skills and motor abilities of children. The basis of the experiment became the evaluation of basic motor skills in certain positions and determine the true psychophysical age at the beginning and at the end of the course on corrective exercises by Bobath method. Considering the universality, accessibility of data and informative test quality it became possible to assess the stages of psychomotor development and mental qualities forming with the true definition of real psychophysical children age with movement disorders 3-4 years.   Key words: Bobath method, Munich diagnosis, psychomotor development, preschool children, motor disorders.

Community-Acquired Pneumonia Hospitalization among Children with Neurologic Disorders.

Science.gov (United States)

Millman, Alexander J; Finelli, Lyn; Bramley, Anna M; Peacock, Georgina; Williams, Derek J; Arnold, Sandra R; Grijalva, Carlos G; Anderson, Evan J; McCullers, Jonathan A; Ampofo, Krow; Pavia, Andrew T; Edwards, Kathryn M; Jain, Seema

2016-06-01

To describe and compare the clinical characteristics, outcomes, and etiology of pneumonia among children hospitalized with community-acquired pneumonia (CAP) with neurologic disorders, non-neurologic underlying conditions, and no underlying conditions. Children children's hospitals. Neurologic disorders included cerebral palsy, developmental delay, Down syndrome, epilepsy, non-Down syndrome chromosomal abnormalities, and spinal cord abnormalities. We compared the epidemiology, etiology, and clinical outcomes of CAP in children with neurologic disorders with those with non-neurologic underlying conditions, and those with no underlying conditions using bivariate, age-stratified, and multivariate logistic regression analyses. From January 2010-June 2012, 2358 children with radiographically confirmed CAP were enrolled; 280 (11.9%) had a neurologic disorder (52.1% of these individuals also had non-neurologic underlying conditions), 934 (39.6%) had non-neurologic underlying conditions only, and 1144 (48.5%) had no underlying conditions. Children with neurologic disorders were older and more likely to require intensive care unit (ICU) admission than children with non-neurologic underlying conditions and children with no underlying conditions; similar proportions were mechanically ventilated. In age-stratified analysis, children with neurologic disorders were less likely to have a pathogen detected than children with non-neurologic underlying conditions. In multivariate analysis, having a neurologic disorder was associated with ICU admission for children ≥2 years of age. Children with neurologic disorders hospitalized with CAP were less likely to have a pathogen detected and more likely to be admitted to the ICU than children without neurologic disorders. Published by Elsevier Inc.

Administration of a selective β2 adrenergic receptor antagonist exacerbates neuropathology and cognitive deficits in a mouse model of Alzheimer's disease.

Science.gov (United States)

Branca, Caterina; Wisely, Elena V; Hartman, Lauren K; Caccamo, Antonella; Oddo, Salvatore

2014-12-01

Currently, there are no available approaches to cure or slow down the progression of Alzheimer's disease (AD), which is characterized by the accumulation of extracellular amyloid-β (Aβ) deposits and intraneuronal tangles that comprised hyperphosphorylated tau. The β2 adrenergic receptors (β2ARs) are expressed throughout the cortex and hippocampus and play a key role in cognitive functions. Alterations in the function of these receptors have been linked to AD; however, these data remain controversial as apparent contradicting reports have been published. Given the current demographics of growing elderly population and the high likelihood of concurrent β-blocker use for other chronic conditions, more studies into the role of this receptor in AD animal models are needed. Here, we show that administration of ICI 118,551 (ICI), a selective β2AR antagonist, exacerbates cognitive deficits in a mouse model of AD, the 3xTg-AD mice. Neuropathologically, ICI increased Aβ levels and Aβ plaque burden. Concomitantly, ICI-treated 3xTg-AD mice showed an increase in tau phosphorylation and accumulation. Mechanistically, these changes were linked to an increase in amyloidogenic amyloid precursor protein processing. These results suggest that under the conditions used here, selective pharmacologic inhibition of β2ARs has detrimental effects on AD-like pathology in mice. Overall, these studies strengthen the notion that the link between β2ARs and AD is likely highly complex and suggest caution in generalizing the beneficial effects of β blockers on AD. Copyright © 2014 Elsevier Inc. All rights reserved.

Associations in the Course of Personality Disorders and Axis I Disorders Over Time

Science.gov (United States)

Shea, M. Tracie; Yen, Shirley; Pagano, Maria E.; Morey, Leslie C.; McGlashan, Thomas H.; Grilo, Carlos M.; Sanislow, Charles A.; Stout, Robert L.; Skodol, Andrew E.; Gunderson, John G.; Bender, Donna S.; Zanarini, Mary C.

2012-01-01

In this study, the authors examined time-varying associations between schizotypal (STPD), borderline (BPD), avoidant (AVPD), or obsessive–compulsive (OCPD) personality disorders and co-occurring Axis I disorders in 544 adult participants from the Collaborative Longitudinal Personality Disorders Study. The authors tested predictions of specific longitudinal associations derived from a model of crosscutting psychobiological dimensions (L. J. Siever & K. L. Davis, 1991) with participants with the relevant Axis I disorders. The authors assessed participants at baseline and at 6-, 12-, and 24-month follow-up evaluations. BPD showed significant longitudinal associations with major depressive disorder and posttraumatic stress disorder. AVPD was significantly associated with anxiety disorders (specifically social phobia and obsessive–compulsive disorder). Two of the four personality disorders under examination (STPD and OCPD) showed little or no association with Axis I disorders. PMID:15535783

Slower EEG alpha generation, synchronization and "flow"-possible biomarkers of cognitive impairment and neuropathology of minor stroke.

Science.gov (United States)

Petrovic, Jelena; Milosevic, Vuk; Zivkovic, Miroslava; Stojanov, Dragan; Milojkovic, Olga; Kalauzi, Aleksandar; Saponjic, Jasna

2017-01-01

We investigated EEG rhythms, particularly alpha activity, and their relationship to post-stroke neuropathology and cognitive functions in the subacute and chronic stages of minor strokes. We included 10 patients with right middle cerebral artery (MCA) ischemic strokes and 11 healthy controls. All the assessments of stroke patients were done both in the subacute and chronic stages. Neurological impairment was measured using the National Institute of Health Stroke Scale (NIHSS), whereas cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) and MoCA memory index (MoCA-MIS). The EEG was recorded using a 19 channel EEG system with standard EEG electrode placement. In particular, we analyzed the EEGs derived from the four lateral frontal (F3, F7, F4, F8), and corresponding lateral posterior (P3, P4, T5, T6) electrodes. Quantitative EEG analysis included: the group FFT spectra, the weighted average of alpha frequency (αAVG), the group probability density distributions of all conventional EEG frequency band relative amplitudes (EEG microstructure), the inter- and intra-hemispheric coherences, and the topographic distribution of alpha carrier frequency phase potentials (PPs). Statistical analysis was done using a Kruskal-Wallis ANOVA with a post-hoc Mann-Whitney U two-tailed test, and Spearman's correlation. We demonstrated transient cognitive impairment alongside a slower alpha frequency ( α AVG) in the subacute right MCA stroke patients vs. the controls. This slower alpha frequency showed no amplitude change, but was highly synchronized intra-hemispherically, overlying the ipsi-lesional hemisphere, and inter-hemispherically, overlying the frontal cortex. In addition, the disturbances in EEG alpha activity in subacute stroke patients were expressed as a decrease in alpha PPs over the frontal cortex and an altered "alpha flow", indicating the sustained augmentation of inter-hemispheric interactions. Although the stroke induced slower alpha was a

Autism counts. Stereological studies on human postmortem brains and a mouse model for autism

NARCIS (Netherlands)

van Kooten, I.A.J.

2008-01-01

Autism is a neurodevelopmental disorder with a strong genetic component and several known environmental risk factors. Classical neuropathology studies have reported consistent findings in the limbic system, cerebellum and cerebral cortex of patients with autism. However, the neurobiological

A systematic evaluation of dendritic and neuronal (MAP2, SMI-311) immunolabelling within the cerebral cortex in autism

OpenAIRE

Del Valle Suarez, E.; Schmitz, C; Rezaie, P.; Gabbott, P.

2009-01-01

Autism Spectrum Disorders (ASD) are pervasive eurodevelopmental disorders clinically characterised by deficits in three core behavioural parameters: social interaction, communication and repetitive behaviours. There are currently no biological markers for ASD. Diagnosis is based solely on behavioural characteristics that vary considerably in severity. Neuropathology is varied and inconsistent amongst cases. The spatial arrangement of neurons is reportedly altered within cortical areas whose f...

Post-traumatic stress disorder and opioid use disorder: A narrative review of conceptual models.

Science.gov (United States)

Danovitch, Itai

2016-01-01

Post-traumatic stress disorder is highly prevalent among individuals who suffer from opioid use disorder. Compared to individuals with opioid use disorder alone, those with post-traumatic stress disorder have a worse course of illness, occupational functioning, and physical health. The neurobiological pathways underlying each disorder overlap substantially, and there are multiple pathways through which these disorders may interact. This narrative review explores evidence underpinning 3 explanatory perspectives on comorbid post-traumatic stress disorder and opioid use disorder: The opioid susceptibility model (a.k.a.: the Self-Medication Hypothesis), the post-traumatic stress disorder susceptibility model, and the common factors model. Diagnostic implications, treatment implications, and directions for future research are discussed.

Oppositional Defiant Disorder Is Better Conceptualized as a Disorder of Emotional Regulation.

Science.gov (United States)

Cavanagh, Monica; Quinn, Declan; Duncan, Don; Graham, Tom; Balbuena, Lloyd

2017-03-01

It has been reported that Oppositional Defiant Disorder (ODD) can be differentiated into distinct subtypes associated with different outcomes in adulthood. We examined whether ODD is conceptually independent and coherent, and whether ODD and Conduct Disorder (CD) are expressions of the same core deficit. The data come from a sample of 4,380 children for whom SNAP rating scales were available. Parallel analysis was performed on the eight-item ODD diagnostic items and on the SNAP-90 scale. These were factor analyzed and the components were correlated. ODD has one underlying factor, whereas the parent-rated SNAP has nine underlying factors. ODD items grouped together with emotional lability and irritability items, which did not group with CD. Confirmatory factor analysis supported the separation of ODD and CD but not ODD and emotion dysregulation. The expanded ODD factor more likely captures a disorder of emotion regulation, rather than a disruptive behavior disorder.

Stem cells and neurogenesis in relation to Alzheimer's disease Models

NARCIS (Netherlands)

Lucassen, P.J.; Jacobs, E.H.; Hoeijmakers, L.; Lesuis, S.L.; Krugers, H.; Korosi, A.; Kuhn, H.G.; Boekhoorn, K.; Kuhn, H.G.; Eisch, A.J.

2015-01-01

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder associated with progressive cognitive decline and extensive neuropathology throughout the brain. Its main features include limited cell loss in selected subregions, generalized brain atrophy, and gradual accumulation of β-amyloid

Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy

NARCIS (Netherlands)

G. Hoglinger (Gunter); N.M. Melhem (Nadine); D. Dickson (Dennis); P.M.A. Sleiman (Patrick); L.-S. Wang; L. Klei (Lambertus); R. Rademakers (Rosa); R. de Silva (Rohan); I. Litvan (Irene); D.E. Riley (David); J.C. van Swieten (John); P. Heutink (Peter); Z.K. Wszolek (Zbigniew); R.J. Uitti (Ryan); J. Vandrovcova (Jana); H.I. Hurtig (Howard); R.G. Gross (Rachel); W. Maetzler (Walter); S. Goldwurm (Stefano); E. Tolosa; B. Borroni (Barbara); P. Pastor (Pau); L.B. Cantwell (Laura); M.R. Han; A. Dillman (Allissa); M.P. van der Brug (Marcel); J. Gibbs (Raphael); M.R. Cookson (Mark); D.G. Hernandez (Dena); A. Singleton (Andrew); M.J. Farrer (Matthew); C.-E. Yu (Changen); L.I. Golbe (Lawrence); T. Revesz (Tamas); J. Hardy (John); A.J. Lees (Andrew); B. Devlin (Bernie); H. Hakonarson (Hakon); U. Müller (Ulrich); G.D. Schellenberg (Gerard); R.L. Albin (Roger); E. Alonso (Elena); M. Apfelbacher (Manuela); S.E. Arnold (Steven); J. Avila (Jesús); T.G. Beach (Thomas); S. Beecher (Sherry); D. Berg (Daniela); T.D. Bird (Thomas); N. Bogdanović (Nenad); A.J.W. Boon (Andrea); Y. Bordelon (Yvette); A. Brice (Alexis); H. Budka (Herbert); M. Canesi (Margherita); W.Z. Chiu (Wang Zheng); R. Cilia (Roberto); C. Colosimo (Carlo); P.P. de Deyn (Peter); J.G. de Yebenes; L. Donker Kaat (Laura); R. Duara (Ranjan); A. Durr; S. Engelborghs (Sebastiaan); G. Fabbrini (Giovanni); N.A. Finch (Nicole); R. Flook (Robyn); M.P. Frosch (Matthew); C. Gaig; D. Galasko (Douglas); T. Gasser (Thomas); M. Gearing (Marla); E.T. Geller (Evan); B. Ghetti (Bernardino); N.R. Graff-Radford (Neill); M. Grossman (Murray); D.A. Hall (Deborah); L.-N. Hazrati; M. Höllerhage (Matthias); J. Jankovic (Joseph); J.L. Juncos (Jorge); A. Karydas (Anna); H.A. Kretzschmar (Hans); I. Leber (Isabelle); V.M.Y. Lee (Virginia); A.P. Lieberman (Andrew); K.E. Lyons (Kelly); C. Mariani (Claudio); E. Masliah (Eliezer); L.A. Massey (Luke); C.A. McLean (Catriona); N. Meucci (Nicoletta); B.L. Miller (Bruce); B. Mollenhauer (Brit); J.C. Möller (Jens); H. Morris (Huw); S.S. O'Sullivan (Sean); W. Oertel; D. Ottaviani (Donatella); A. Padovani (Alessandro); R. Pahwa (Rajesh); G. Pezzoli (Gianni); S. Pickering-Brown (Stuart); W. Poewe (Werner); A. Rabano (Alberto); A. Rajput (Alex); S.G. Reich (Stephen); G. Respondek (Gesine); S. Roeber (Sigrun); J.D. Rohrer (Jonathan Daniel); O.A. Ross (Owen); M. Rossor (Martin); G. Sacilotto (Giorgio); W.W. Seeley (William); K. Seppi (Klaus); L. Silveira-Moriyama (Laura); S. Spina (Salvatore); K. Srulijes (Karin); P. St. George-Hyslop (Peter); M. Stamelou (Maria); D.G. Standaert (David); S. Tesei (Silvana); W.W. Tourtellotte (Wallace); C. Trenkwalder (Claudia); C. Troakes (Claire); J.Q. Trojanowski (John); J.C. Troncoso (Juan); V.M. Deerlin (Vivianna); J.P.G. Vonsattel; G.K. Wenning (Gregor); C.L. White III (Charles); P. Winter (Pia); C. Zarow (Chris); A.L. Zecchinelli (Anna); A. Antonini (Angelo)

2011-01-01

textabstractProgressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated

Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.

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Yuen-Shan Ho

Full Text Available Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD. To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.

Cigarette Smoking Accelerated Brain Aging and Induced Pre-Alzheimer-Like Neuropathology in Rats

Science.gov (United States)

Ho, Yuen-Shan; Yang, Xifei; Yeung, Sze-Chun; Chiu, Kin; Lau, Chi-Fai; Tsang, Andrea Wing-Ting; Mak, Judith Choi-Wo; Chang, Raymond Chuen-Chung

2012-01-01

Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD). To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP) processing by increasing the production of sAPPβ and accumulation of β–amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia. PMID:22606286

Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment.

Science.gov (United States)

Skrobot, Olivia A; Attems, Johannes; Esiri, Margaret; Hortobágyi, Tibor; Ironside, James W; Kalaria, Rajesh N; King, Andrew; Lammie, George A; Mann, David; Neal, James; Ben-Shlomo, Yoav; Kehoe, Patrick G; Love, Seth

2016-11-01

There are no generally accepted protocols for post-mortem assessment in cases of suspected vascular cognitive impairment. Neuropathologists from seven UK centres have collaborated in the development of a set of vascular cognitive impairment neuropathology guidelines (VCING), representing a validated consensus approach to the post-mortem assessment and scoring of cerebrovascular disease in relation to vascular cognitive impairment. The development had three stages: (i) agreement on a sampling protocol and scoring criteria, through a series of Delphi method surveys; (ii) determination of inter-rater reliability for each type of pathology in each region sampled (Gwet's AC2 coefficient); and (iii) empirical testing and validation of the criteria, by blinded post-mortem assessment of brain tissue from 113 individuals (55 to 100 years) without significant neurodegenerative disease who had had formal cognitive assessments within 12 months of death. Fourteen different vessel and parenchymal pathologies were assessed in 13 brain regions. Almost perfect agreement (AC2 > 0.8) was found when the agreed criteria were used for assessment of leptomeningeal, cortical and capillary cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microhaemorrhage, larger haemorrhage, fibrinoid necrosis, microaneurysms, perivascular space dilation, perivascular haemosiderin leakage, and myelin loss. There was more variability (but still reasonably good agreement) in assessment of the severity of arteriolosclerosis (0.45-0.91) and microinfarcts (0.52-0.84). Regression analyses were undertaken to identify the best predictors of cognitive impairment. Seven pathologies-leptomeningeal cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microinfarcts, arteriolosclerosis, perivascular space dilation and myelin loss-predicted cognitive impairment. Multivariable logistic regression determined the best predictive models of cognitive impairment. The preferred model included moderate

Alterations in white matter volume and its correlation with clinical characteristics in patients with generalized anxiety disorder

International Nuclear Information System (INIS)

Moon, Chung-Man; Jeong, Gwang-Woo

2015-01-01

Only a few morphological studies have focused on changes in white matter (WM) volume in patients with generalized anxiety disorder (GAD). We evaluated alterations in WM volume and its correlation with symptom severity and duration of illness in adults with GAD. The 44 subjects were comprised of 22 patients with GAD (13 males and nine females) diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and 22 age-matched healthy controls (13 males and nine females). High-resolution magnetic resonance imaging (MRI) data were processed by voxel-based morphometry (VBM) analysis based on diffeomorphic anatomical registration using the exponentiated Lie algebra (DARTEL) algorithm in SPM8. Patients with GAD showed significantly reduced WM volume, particularly in the dorsolateral prefrontal cortex (DLPFC), anterior limb of the internal capsule (ALIC), and midbrain. In addition, DLPFC volume was negatively correlated with GAD-7 score and illness duration. ALIC volume was negatively correlated with GAD-7 score. Female patients had significantly less orbitofrontal cortex volume compared to that in male patients. The findings demonstrate localized changes in WM volume associated with cognitive and emotional dysfunction in patients with GAD. The finding will be helpful for understanding the neuropathology in patients with GAD. (orig.)

Alterations in white matter volume and its correlation with clinical characteristics in patients with generalized anxiety disorder

Energy Technology Data Exchange (ETDEWEB)

Moon, Chung-Man [Chonnam National University Hospital, Research Institute for Medical Imaging, Gwangju (Korea, Republic of); Jeong, Gwang-Woo [Chonnam National University Hospital, Research Institute for Medical Imaging, Gwangju (Korea, Republic of); Chonnam National University Medical School, Department of Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of)

2015-11-15

Only a few morphological studies have focused on changes in white matter (WM) volume in patients with generalized anxiety disorder (GAD). We evaluated alterations in WM volume and its correlation with symptom severity and duration of illness in adults with GAD. The 44 subjects were comprised of 22 patients with GAD (13 males and nine females) diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and 22 age-matched healthy controls (13 males and nine females). High-resolution magnetic resonance imaging (MRI) data were processed by voxel-based morphometry (VBM) analysis based on diffeomorphic anatomical registration using the exponentiated Lie algebra (DARTEL) algorithm in SPM8. Patients with GAD showed significantly reduced WM volume, particularly in the dorsolateral prefrontal cortex (DLPFC), anterior limb of the internal capsule (ALIC), and midbrain. In addition, DLPFC volume was negatively correlated with GAD-7 score and illness duration. ALIC volume was negatively correlated with GAD-7 score. Female patients had significantly less orbitofrontal cortex volume compared to that in male patients. The findings demonstrate localized changes in WM volume associated with cognitive and emotional dysfunction in patients with GAD. The finding will be helpful for understanding the neuropathology in patients with GAD. (orig.)

Neurotransmitters and neuropeptides in depression

NARCIS (Netherlands)

Bao, A.-M.; Ruhé, H. G.; Gao, S.-F.; Swaab, D. F.

2012-01-01

There are no specific structural neuropathological hallmarks found in the brain of patients with mood disorders. The described alterations confirm, however, a neurodevelopmental underpinning, which is in agreement with the genetic and developmental risk factors. The effect of developmental sequelae

Neuroinflammation in Alzheimer's disease and prion disease

NARCIS (Netherlands)

Eikelenboom, P.; Bate, C.; van Gool, W. A.; Hoozemans, J. J. M.; Rozemuller, J. M.; Veerhuis, R.; Williams, A.

2002-01-01

Alzheimer's disease (AD) and prion disease are characterized neuropathologically by extracellular deposits of Abeta and PrP amyloid fibrils, respectively. In both disorders, these cerebral amyloid deposits are co-localized with a broad variety of inflammation-related proteins (complement factors,

Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy

NARCIS (Netherlands)

Hoglinger, G.U.; Melhem, N.M.; Dickson, D.W.; Sleiman, P.M.A.; Wang, L.S.; Klei, L.; Rademakers, R.; de Silva, R.; Litvan, I.; Riley, D.E.; van Swieten, J.C.; Heutink, P.; Wszolek, Z.K.; Uitti, R.J.; Vandrovcova, J.; Hurtig, H.I.; Gross, R.G.; Maetzler, W.; Goldwurm, S.; Tolosa, E.; Borroni, B.; Pastor, P.; Cantwell, L.B.; Han, M.R.; Dillman, A.; van der Brug, M.P.; Gibbs, J.R.; Cookson, M.R.; Hernandez, D.G.; Singleton, A.B.; Farrer, M.J.; Yu, C.E.; Golbe, L.I.; Revesz, T.; Hardy, J.; Lees, A.J.; Devlin, B.; Hakonarson, H.; Muller, U.; Schellenberg, G.D.

2011-01-01

Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some

The anxiety disorders and suicidal ideation: accounting for co-morbidity via underlying personality traits.

Science.gov (United States)

Naragon-Gainey, K; Watson, D

2011-07-01

The anxiety disorders are robust correlates/predictors of suicidal ideation, but it is unclear whether (a) the anxiety disorders are specifically associated with suicidal ideation or (b) the association is due to co-morbidity with depression and other disorders. One means of modeling co-morbidity is through the personality traits neuroticism/negative emotionality (N/NE) and extraversion/positive emotionality (E/PE), which account for substantial shared variance among the internalizing disorders. The current study examines the association between the internalizing disorders and suicidal ideation, after controlling for co-morbidity via N/NE and E/PE. The sample consisted of 327 psychiatric out-patients. Multiple self-report and interview measures were collected for internalizing disorders [depression, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), social anxiety, panic and specific phobia] and suicidal ideation, as well as self-report measures for N/NE and E/PE. A model was hypothesized in which each disorder and suicidal ideation was regressed on N/NE, and depression and social anxiety were regressed on E/PE. Structural equation modeling (SEM) was used to examine the unique association of suicidality with each disorder, beyond shared variance with N/NE and E/PE. The hypothesized model was an acceptable fit to the data. Although zero-order analyses indicated that suicidal ideation was moderately to strongly correlated with all of the disorders, only depression and PTSD remained significantly associated with suicidal ideation in the SEM analyses. In a latent variable model that accounts for measurement error and a broad source of co-morbidity, only depression and PTSD were uniquely associated with suicidal ideation; panic, GAD, social anxiety and specific phobia were not.

Pathophysiology of mood disorders in temporal lobe epilepsy Fisiopatologia dos transtornos de humor na epilepsia do lobo temporal

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Ludmyla Kandratavicius

2012-10-01

Full Text Available OBJECTIVE: There is accumulating evidence that the limbic system is pathologically involved in cases of psychiatric comorbidities in temporal lobe epilepsy (TLE patients. Our objective was to develop a conceptual framework describing how neuropathological, neurochemical and electrophysiological aspects might contribute to the development of psychiatric symptoms in TLE and the putative neurobiological mechanisms that cause mood disorders in this patient subgroup. METHODS: In this review, clinical, experimental and neuropathological findings, as well as neurochemical features of the limbic system were examined together to enhance our understanding of the association between TLE and psychiatric comorbidities. Finally, the value of animal models in epilepsy and mood disorders was discussed. CONCLUSIONS:TLE and psychiatric symptoms coexist more frequently than chance would predict. Alterations and neurotransmission disturbance among critical anatomical networks, and impaired or aberrant plastic changes might predispose patients with TLE to mood disorders. Clinical and experimental studies of the effects of seizures on behavior and electrophysiological patterns may offer a model of how limbic seizures increase the vulnerability of TLE patients to precipitants of psychiatric symptoms.OBJETIVO: Há evidências crescentes do envolvimento do sistema límbico nas comorbidades psiquiátricas associadas à epilepsia do lobo temporal (ELT. Nosso objetivo foi descrever o panorama atual das alterações neuropatológicas, neuroquímicas e eletrofisiológicas que podem contribuir para o desenvolvimento de sintomas psiquiátricos na ELT e explorar possíveis mecanismos neurobiológicos que podem levar ao aparecimento das desordens de humor nesse subgrupo de pacientes. MÉTODOS: Achados clínicos, de modelos experimentais e neuropatológicos foram revistos, assim como características neuroquímicas do sistema límbico foram examinadas em conjunto para auxiliar

Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study.

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Stuart G Snowden

2017-03-01

Full Text Available The metabolic basis of Alzheimer disease (AD pathology and expression of AD symptoms is poorly understood. Omega-3 and -6 fatty acids have previously been linked to both protective and pathogenic effects in AD. However, to date little is known about how the abundance of these species is affected by differing levels of disease pathology in the brain.We performed metabolic profiling on brain tissue samples from 43 individuals ranging in age from 57 to 95 y old who were stratified into three groups: AD (N = 14, controls (N = 14 and "asymptomatic Alzheimer's disease" (ASYMAD, i.e., individuals with significant AD neuropathology at death but without evidence for cognitive impairment during life (N = 15 from the autopsy sample of the Baltimore Longitudinal Study of Aging (BLSA. We measured 4,897 metabolite features in regions both vulnerable in the middle frontal and inferior temporal gyri (MFG and ITG and resistant (cerebellum to classical AD pathology. The levels of six unsaturated fatty acids (UFAs in whole brain were compared in controls versus AD, and the differences were as follows: linoleic acid (p = 8.8 x 10-8, FC = 0.52, q = 1.03 x 10-6, linolenic acid (p = 2.5 x 10-4, FC = 0.84, q = 4.03 x 10-4, docosahexaenoic acid (p = 1.7 x 10-7, FC = 1.45, q = 1.24 x 10-6, eicosapentaenoic acid (p = 4.4 x 10-4, FC = 0.16, q = 6.48 x 10-4, oleic acid (p = 3.3 x 10-7, FC = 0.34, q = 1.46 x 10-6, and arachidonic acid (p = 2.98 x 10-5, FC = 0.75, q = 7.95 x 10-5. These fatty acids were strongly associated with AD when comparing the groups in the MFG and ITG, respectively: linoleic acid (p ASYMAD>AD and increases in docosahexanoic acid (AD>ASYMAD>control may represent regionally specific threshold levels of these metabolites beyond which the accumulation of AD pathology triggers the expression of clinical symptoms. The main limitation of this study is the relatively small sample size. There are few cohorts with extensive longitudinal cognitive assessments

A comparative study of computerized tomograms and neuropathological findings in cerebrovascular diseases

International Nuclear Information System (INIS)

Tohgi, Hideo; Mochizuki, Hiroshi; Yamanouchi, Hiroshi; Iio, Masahiro; Yamada, Hideo

1979-01-01

The reliability of computed tomography (CT) in the diagnosis of cerebrovascular diseases was studied by comparing CT images and neuropathological findings in 38 autopsied cases. Our special concern was directed toward several factors which caused false positive and false negative results in CT: the size and location of lesions, and the interval between the onset of the disease and the time of CT studies. Infarctions smaller than 5 mm should be interpreted as such with great care, because only 32.1% of them could be detected in CT, and 81.0% of small low density areas supposed to be small infarctions in CT films proved to be false positive in postmortem examination. 41.9% of middle-sized infarctions were detected in CT and 40.9% of middle-sized low density areas were false positive. Most of false positive low density areas appeared on the surface of the cerebrum where deep sulci join, or in the white matter anterior to the anterior horn or posterior to the posterior horn of the lateral ventricles. The possibility of false positive findings became far less, when the number of slices showing low density areas increased. All of the large infarctions were detected in CT. However, immediately after stroke they did not stand out as low density areas. In such cases, the decrease of cerebral sulci due to brain edema and signs of compression in the ventricular system could be the clues to make the diagnosis of large infarctions. The diagnosis of hemorrhagic infarctions was often difficult. Cerebral bleeding could be diagnosed easily by CT in its early period. However, old hematomas which rapidly resolved and became shrunken, could hardly be identified in CT. (author)

Genome-Wide Prediction of Intrinsic Disorder; Sequence Alignment of Intrinsically Disordered Proteins

Science.gov (United States)

Midic, Uros

2012-01-01

Intrinsic disorder (ID) is defined as a lack of stable tertiary and/or secondary structure under physiological conditions in vitro. Intrinsically disordered proteins (IDPs) are highly abundant in nature. IDPs possess a number of crucial biological functions, being involved in regulation, recognition, signaling and control, e.g. their functional…

Mood disorder history and personality assessment in premenstrual dysphoric disorder.

Science.gov (United States)

Critchlow, D G; Bond, A J; Wingrove, J

2001-09-01

Menstrually related dysphoria is known to be associated with other affective disorders, notably major depressive disorder and puerperal depression. The relationship between premenstrual dysphoric disorder (PMDD) and maladaptive personality disorders and traits, however, is less established, at least in part because of the methodological and nosologic difficulties in the diagnosis of both PMDD and personality disorders. This study seeks to address this problem to elucidate the relationship between PMDD, other affective disturbances commonly experienced by women, and maladaptive personality. Axis I and II disorders were examined using standardized instruments and stringent diagnostic criteria (DSM-IV and the International Personality Disorders Examination) in 34 women with DSM-IV PMDD and 22 healthy women without severe premenstrual mood changes. Seventy-seven percent of the PMDD group had suffered from a past Axis I disorder in comparison with 17% of the control group. Two thirds of the parous women with PMDD had suffered from major depressive disorder in the puerperium. Personality disorder diagnoses were not highly represented in either group of women. The women with PMDD had significantly more obsessional personality traits (p personality disorder diagnoses. Obsessional symptoms are known to cluster with the affective disorders and may reflect underlying temperamental and biological vulnerability. This study provides further evidence of the link between serotonergic dysregulation, personality vulnerability, and mood changes related to the female reproductive cycle.

Prefrontal NAA and Glx Levels in Different Stages of Psychotic Disorders: a 3T 1H-MRS Study.

Science.gov (United States)

Liemburg, Edith; Sibeijn-Kuiper, Anita; Bais, Leonie; Pijnenborg, Gerdina; Knegtering, Henderikus; van der Velde, Jorien; Opmeer, Esther; de Vos, Annerieke; Dlabac-De Lange, Jozarni; Wunderink, Lex; Aleman, André

2016-02-23

H-Magnetic Resonance Spectroscopy ((1)H-MRS) can offer insights in various neuropathologies by measuring metabolite levels in the brain. In the current study we investigated the levels of glutamate + glutamine (Glx, neurotransmitter and precursor) and N-Acetyl Aspartate + glutamic acid (NAA + NAAG; neuronal viability) in the prefrontal cortex of patients with a psychotic disorder and people at Ultra High Risk (UHR) for psychosis. A (1)H-MRS spectrum was acquired in 31 patients with a recent onset psychotic disorder and 60 with a chronic state, 16 UHR patients and 36 healthy controls. Absolute metabolite levels were calculated using LCModel with a reference water peak. Groups were compared while taking into account age and partial volume effects. Moreover, we investigated associations with positive and negative symptoms, duration of illness, and antipsychotic treatment in patients. The most notable finding is that chronicity of schizophrenia was related to decreased levels of Glx and NAA. On the other hand, although on an exploratory note, UHR showed increased levels of prefrontal Glx and NAA levels with increasing age. Our results may indicate an initial Glx and NAA increase and subsequent decrease during illness progression that may be related to the neurotoxic effects of glutamate.

Binge-Eating Disorder: Between Eating Disorders and Obesity? A Cognitive-Behavioral Perspective

OpenAIRE

Gempeler Rueda, Juanita

2005-01-01

Abstract This article reviews the available literature on binge-eating disorder, currently included in the DSM IV as an Eating Disorder NOS. Its inclusion in the DSM V is under discussion. Conceptualization of this disorder is examined, as well as implications for clinical interventions from a cognitive-behavioral perspective. Resumen El presente artículo tiene por objeto revisar la bibliografía actualizada disponible sobre el tema del trastorno por atracones de la alimentación, que hasta ...

Characteristics of female mentally disordered offenders culpable under the new legislation in Japan: A gender comparison study.

Science.gov (United States)

Nagata, Takako; Nakagawa, Atsuo; Matsumoto, Satoko; Shiina, Akihiro; Iyo, Masaomi; Hirabayashi, Naotsugu; Igarashi, Yoshito

2016-02-01

Although a substantial increase in the number of female offenders has drawn interest towards understanding their unique characteristics, few studies have investigated the characteristics of female mentally disordered offenders in Japan and none since the legislation enacted in 2005 in Japan, which provided for special services for them. The aim of this study is to identify those characteristics of people detained under this legislation, which distinguish the women from the men and may indicate special needs among the women. A retrospective records-based study of all patients admitted to one secure unit in the 8 years since its opening in July 2005 until a census date of 31 October 2013. Thirty-six (15%) of the patients were women. Marriage, mood disorders, past suicide attempts and homicide were more common among the women than the men. Six of the female offender-patients had committed filicides, of which four were infanticides. There appears to be a particularly vulnerable sub-group of women with severe mood disorders, a history of serious suicide attempts and young children at risk of harming those children. Our sample was small and from a single unit so, given the potential importance of improving understanding of who is at risk in such circumstances, extending our study nationally seems indicated. Copyright © 2015 John Wiley & Sons, Ltd.

Influence of taste disorders on dietary behaviors in cancer patients under chemotherapy

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Laviano Alessandro

2010-03-01

Full Text Available Abstract Objectives To determine the relationship between energy and nutrient consumption with chemosensory changes in cancer patients under chemotherapy. Methods We carried out a cross-sectional study, enrolling 60 subjects. Cases were defined as patients with cancer diagnosis after their second chemotherapy cycle (n = 30, and controls were subjects without cancer (n = 30. Subjective changes of taste during treatment were assessed. Food consumption habits were obtained with a food frequency questionnaire validated for Mexican population. Five different concentrations of three basic flavors --sweet (sucrose, bitter (urea, and a novel basic taste, umami (sodium glutamate-- were used to measure detection thresholds and recognition thresholds (RT. We determine differences between energy and nutrient consumption in cases and controls and their association with taste DT and RT. Results No demographic differences were found between groups. Cases showed higher sweet DT (6.4 vs. 4.4 μmol/ml; p = 0.03 and a higher bitter RT (100 vs. 95 μmol/ml; p = 0.04 than controls. Cases with sweet DT above the median showed significant lower daily energy (2,043 vs.1,586 kcal; p = 0.02, proteins (81.4 vs. 54 g/day; p = 0.01, carbohydrates (246 vs.192 g/day; p = 0.05, and zinc consumption (19 vs.11 mg/day; p = 0.01 compared to cases without sweet DT alteration. Cases with sweet DT and RT above median were associated with lower completion of energy requirements and consequent weight loss. There was no association between flavors DT or RT and nutrient ingestion in the control group. Conclusion Changes of sweet DT and bitter RT in cancer patients under chemotherapy treatment were associated with lower energy and nutrient ingestion. Taste detection and recognition thresholds disorders could be important factors in malnutrition development on patients with cancer under chemotherapy treatment.

Disorder-induced stiffness degradation of highly disordered porous materials

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Laubie, Hadrien; Monfared, Siavash; Radjaï, Farhang; Pellenq, Roland; Ulm, Franz-Josef

2017-09-01

The effective mechanical behavior of multiphase solid materials is generally modeled by means of homogenization techniques that account for phase volume fractions and elastic moduli without considering the spatial distribution of the different phases. By means of extensive numerical simulations of randomly generated porous materials using the lattice element method, the role of local textural properties on the effective elastic properties of disordered porous materials is investigated and compared with different continuum micromechanics-based models. It is found that the pronounced disorder-induced stiffness degradation originates from stress concentrations around pore clusters in highly disordered porous materials. We identify a single disorder parameter, φsa, which combines a measure of the spatial disorder of pores (the clustering index, sa) with the pore volume fraction (the porosity, φ) to scale the disorder-induced stiffness degradation. Thus, we conclude that the classical continuum micromechanics models with one spherical pore phase, due to their underlying homogeneity assumption fall short of addressing the clustering effect, unless additional texture information is introduced, e.g. in form of the shift of the percolation threshold with disorder, or other functional relations between volume fractions and spatial disorder; as illustrated herein for a differential scheme model representative of a two-phase (solid-pore) composite model material.

Hoarding Disorder Trough Three Case, A New Mental Disorder in DSM-5

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Süheyla DODAN BULUT

2014-03-01

Full Text Available Compulsive hoarding is a problem characterized with excessive collection and accumulation, failure to discard the excess amount of collected items. Although it is considered to be a symptom of obsessive-compulsive disorder in DSMIV- TR (Diagnostic and statistical manual of mental disorders fourth edition text revision, it is thought that compulsive hoarding and OCD may have different biological, cognitive and behavioral mechanisms and compulsive hoarding may be associated with many other psychological illnesses. For these reasons, in DSM-5 (Diagnostic and statistical manual of mental disorders fifth edition hoarding disorder diagnosis is located under the classification of obsessive-compulsive and related disorders. In this case report, three cases classified in different diagnostic categories according to DSM-IV-TR will be mentioned and hoarding disorder will be discussed.

Spatiotemporal dissociation of brain activity underlying threat and reward in social anxiety disorder.

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A Richey, John; Ghane, Merage; Valdespino, Andrew; Coffman, Marika C; Strege, Marlene V; White, Susan W; Ollendick, Thomas H

2017-01-01

Social anxiety disorder (SAD) involves abnormalities in social motivation, which may be independent of well-documented differences in fear and arousal systems. Yet, the neurobiology underlying motivational difficulties in SAD is not well understood. The aim of the current study was to spatiotemporally dissociate reward circuitry dysfunction from alterations in fear and arousal-related neural activity during anticipation and notification of social and non-social reward and punishment. During fMRI acquisition, non-depressed adults with social anxiety disorder (SAD; N = 21) and age-, sex- and IQ-matched control subjects (N = 22) completed eight runs of an incentive delay task, alternating between social and monetary outcomes and interleaved in alternating order between gain and loss outcomes. Adults with SAD demonstrated significantly reduced neural activity in ventral striatum during the anticipation of positive but not negative social outcomes. No differences between the SAD and control groups were observed during anticipation of monetary gain or loss outcomes or during anticipation of negative social images. However, consistent with previous work, the SAD group demonstrated amygdala hyper-activity upon notification of negative social outcomes. Degraded anticipatory processing in bilateral ventral striatum in SAD was constrained exclusively to anticipation of positive social information and dissociable from the effects of negative social outcomes previously observed in the amygdala. Alterations in anticipation-related neural signals may represent a promising target for treatment that is not addressed by available evidence-based interventions, which focus primarily on fear extinction and habituation processes. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Chronic idiopathic urticaria and post-traumatic stress disorder (PTSD): an under-recognized comorbidity.

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Gupta, Madhulika A; Gupta, Aditya K

2012-01-01

A large body of literature supports the role of psychologic stress in urticaria; however, the comorbidity between chronic idiopathic urticaria (CIU) and post-traumatic stress disorder (PTSD), a classic stress-mediated syndrome, has received little attention. The underlying etiology of urticaria is not identifiable in about 70% of patients, possibly because of difficulties with identification of a direct cause-and-effect relationship between a potential causative factor and the onset of urticaria. The core features of PTSD (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision [DSMIV-TR]) that are important in urticaria include (1) autonomic nervous system reactivity and state of sympathetic hyperarousal that can manifest as CIU, and (2) the persistent re-experiencing of the traumatic events in PTSD, which can manifest as urticaria or angioedema, or both, affecting a previously traumatized body region (eg, urticarial wheals affecting the body region where the patient had been stabbed years earlier). The following features of PTSD make it difficult to use the cause-and-effect model for the determination of causation: (1) PTSD may first emerge years after the initial trauma and is classified as PTSD with Delayed Onset (DSMIV-TR); and (2) the traumatic triggers that precipitate the PTSD symptoms may be unique and idiosyncratic to the patient and not even qualify as stressful or traumatic by standard criteria (eg, precipitating events for the PTSD may include smell of a certain cologne that was used by the perpetrator or witnessing a scene in a movie that was reminiscent of the location where the abuse occurred). Finally, in PTSD with Delayed Onset, patients may not make a conscious association between their recurrent urticaria and their earlier traumas because they can develop classically conditioned associations between stimuli that are reminiscent of the original abuse situation and their somatic reactions such as urticaria. The clinician

Adult separation anxiety disorder in the DSM-5

NARCIS (Netherlands)

Bögels, S.M.; Knappe, S.; Clark, L.A.

2013-01-01

Unlike other DSM-IV anxiety disorders, separation anxiety disorder (SAD) has been considered a disorder that typically begins in childhood, and could be diagnosed only in adults "if onset is before 18." Moreover, SAD is the only DSM-IV anxiety disorder placed under "Disorders Usually First Diagnosed

Sleep and Eating Disorders.

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Allison, Kelly C; Spaeth, Andrea; Hopkins, Christina M

2016-10-01

Insomnia is related to an increased risk of eating disorders, while eating disorders are related to more disrupted sleep. Insomnia is also linked to poorer treatment outcomes for eating disorders. However, over the last decade, studies examining sleep and eating disorders have relied on surveys, with no objective measures of sleep for anorexia nervosa or bulimia nervosa, and only actigraphy data for binge eating disorder. Sleep disturbance is better defined for night eating syndrome, where sleep efficiency is reduced and melatonin release is delayed. Studies that include objectively measured sleep and metabolic parameters combined with psychiatric comorbidity data would help identify under what circumstances eating disorders and sleep disturbance produce an additive effect for symptom severity and for whom poor sleep would increase risk for an eating disorder. Cognitive behavior therapy for insomnia may be a helpful addition to treatment of those with both eating disorder and insomnia.

Meta-analysis of gray matter abnormalities in autism spectrum disorder: should Asperger disorder be subsumed under a broader umbrella of autistic spectrum disorder?

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Via, Esther; Radua, Joaquim; Cardoner, Narcis; Happé, Francesca; Mataix-Cols, David

2011-04-01

Studies investigating abnormalities of regional gray matter volume in autism spectrum disorder (ASD) have yielded contradictory results. It is unclear whether the current subtyping of ASD into autistic disorder and Asperger disorder is neurobiologically valid. To conduct a quantitative meta-analysis of voxel-based morphometry studies exploring gray matter volume abnormalities in ASD, to examine potential neurobiological differences among ASD subtypes, and to create an online database to facilitate replication and further analyses by other researchers. We retrieved studies from PubMed, ScienceDirect, Scopus, and Web of Knowledge databases between June 3, 1999, the date of the first voxel-based morphometry study in ASD, and October 31, 2010. Studies were also retrieved from reference lists and review articles. We contacted authors soliciting additional data. Twenty-four data sets met inclusion criteria, comprising 496 participants with ASD and 471 healthy control individuals. Peak coordinates of clusters of regional gray matter differences between participants with ASD and controls, as well as demographic, clinical, and methodologic variables, were extracted from each study or obtained from the authors. No differences in overall gray matter volume were found between participants with ASD and healthy controls. Participants with ASD were found to have robust decreases of gray matter volume in the bilateral amygdala-hippocampus complex and the bilateral precuneus. A small increase of gray matter volume in the middle-inferior frontal gyrus was also found. No significant differences in overall or regional gray matter volumes were found between autistic disorder and Asperger disorder. Decreases of gray matter volume in the right precuneus were statistically higher in adults than in adolescents with ASD. These results confirm the crucial involvement of structures linked to social cognition in ASD. The absence of significant differences between ASD subtypes may have

Forensic Psychiatric Aspects of Impulse Control Disorders

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Huseyin Soysal

2015-03-01

Full Text Available Impulse control disorders is an important psychiatric disorder group which draws attention in recent years. Attention deficit hyperactivity disorder and other classical disorders like pyromania, kleptomania, intermittent explosive disorder and compulsive buying could be evasuated under this topic. The aim of this article is to review forensic psychiatric aspects of impulse control disorders and evaluate the disorders in terms of their legal status. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(1: 16-29

Major depressive disorder, panic disorder, and post-traumatic stress disorder in Korean subway drivers.

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Kim, Hyoung-Ryoul; Yim, Hyeon Woo; Jo, Sun-Jin; Choi, Bongkyoo; Jeong, Seung Hee; Lee, Kang Sook; Park, Jong-Ik; Chang, Sung Man

2013-05-01

The purposes of this study are to investigate the prevalence of major depressive disorder, panic disorder, and post-traumatic stress disorder (PTSD) in Korean subway drivers, and find the association between these disorders and the drivers' person-under-train (PUT) experiences. A total of 826 subway drivers who participated in a cross-sectional work and health survey were included for this study. The Korean version of the Composite International Diagnostic Interview 2.1 was applied to assess major depressive disorder, panic disorder, and PTSD. The date of PUT, whether victim died, and how many PUTs the drivers experienced were asked using a structured questionnaire. The standardized prevalence ratios (SPRs) for lifetime prevalence of panic disorder and PTSD in subway drivers were 13.3 (95 % confidence interval [CI] 6.6-22.4) and 2.1 (95 % CI 1.1-3.4), respectively. In lifetime prevalence, after adjusting for age, education, income, and working career, the drivers who experienced PUT had significantly higher risks for panic disorder (odds ratio [OR] = 4.2, 95 % CI 1.2-16.6) and PTSD (OR = 4.4, 95 % CI 1.3-16.4). In 1-year prevalence, the drivers who experienced PUT had a significantly higher risk for PTSD (OR = 11.7, 95 % CI 1.9-225.8). There was no significant value of SPR and OR in major depressive disorder. This study suggests that Korean subway drivers are at higher risk for panic disorder and PTSD compared to the general population, and PUT experience is associated with panic disorder and PTSD. Drivers who have experienced PUT should be treated quickly, sympathetically, and sensitively by a psychological professional and their colleagues, so they can return to work soon.

Massively parallel sequencing and targeted exomes in familial kidney disease can diagnose underlying genetic disorders.

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Mallett, Andrew J; McCarthy, Hugh J; Ho, Gladys; Holman, Katherine; Farnsworth, Elizabeth; Patel, Chirag; Fletcher, Jeffery T; Mallawaarachchi, Amali; Quinlan, Catherine; Bennetts, Bruce; Alexander, Stephen I

2017-12-01

Inherited kidney disease encompasses a broad range of disorders, with both multiple genes contributing to specific phenotypes and single gene defects having multiple clinical presentations. Advances in sequencing capacity may allow a genetic diagnosis for familial renal disease, by testing the increasing number of known causative genes. However, there has been limited translation of research findings of causative genes into clinical settings. Here, we report the results of a national accredited diagnostic genetic service for familial renal disease. An expert multidisciplinary team developed a targeted exomic sequencing approach with ten curated multigene panels (207 genes) and variant assessment individualized to the patient's phenotype. A genetic diagnosis (pathogenic genetic variant[s]) was identified in 58 of 135 families referred in two years. The genetic diagnosis rate was similar between families with a pediatric versus adult proband (46% vs 40%), although significant differences were found in certain panels such as atypical hemolytic uremic syndrome (88% vs 17%). High diagnostic rates were found for Alport syndrome (22 of 27) and tubular disorders (8 of 10), whereas the monogenic diagnostic rate for congenital anomalies of the kidney and urinary tract was one of 13. Quality reporting was aided by a strong clinical renal and genetic multidisciplinary committee review. Importantly, for a diagnostic service, few variants of uncertain significance were found with this targeted, phenotype-based approach. Thus, use of targeted massively parallel sequencing approaches in inherited kidney disease has a significant capacity to diagnose the underlying genetic disorder across most renal phenotypes. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Are We Under-Estimating the Association between Autism Symptoms?: The Importance of Considering Simultaneous Selection When Using Samples of Individuals Who Meet Diagnostic Criteria for an Autism Spectrum Disorder

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Murray, Aja Louise; McKenzie, Karen; Kuenssberg, Renate; O'Donnell, Michael

2014-01-01

The magnitude of symptom inter-correlations in diagnosed individuals has contributed to the evidence that autism spectrum disorders (ASD) is a fractionable disorder. Such correlations may substantially under-estimate the population correlations among symptoms due to simultaneous selection on the areas of deficit required for diagnosis. Using…

[Panic disorder--psychobiological aspects of personality dimensions].

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Draganić-Rajić, Saveta; Lecić-Tosevski, Dusica; Paunović, Vladimir R; Cvejić, Vesna; Svrakić, Dragan

2005-01-01

Attempts to understand the underlying mechanisms of association between psychological factors and panic disorder have been mostly based on psychodynamic description. Evidence of the importance of serotonergic (5-HT) system in panic disorder (PD), however, has substanti ally increased in recent years. The objective of our study was to determine whether there was a specific personality profile of panic disorder patients and how it was related to possible neurobiological mechanisms underlying personality dimensions. Sample consisted of 14 inpatients with ICD-X diagnosis of panic disorder and 34 healthy control subjects. Personality dimensions were assessed by Minnesota Multiphasic Personality Inventory (MMPI-201) and Tridimensional Personality Questionnaire (TPQ). To assess central 5-HT function, platelet monoamine-oxidase (MAO) activity was measured. In panic disorder group, higher scores of histrionic, depressive and hypochondriac subscales and significant increase of harm avoidance (HA) scale as well as low MAO activity were found. Negative correlation was established between MAO activity and psychopathic deviance MMPI scale. The obtained results might indicate a specific personality profile of patients with panic disorder, which is characterized by high neuroticism, fearfulness, inhibition, shyness and apprehensive worry. Low MAO activity and high HA scores possibly indicate underlying hyperserotonergic state. The observed correlation between personality traits and MAO activity provide additional support for the hypothesized functional relationship between underlying central monoaminergic activity and temperament traits associated with anxiety, depression and impulsivity.

The effectiveness of anticonvulsants in psychiatric disorders

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Grunze, Heinz C. R.

2008-01-01

Anticonvulsant drugs are widely used in psychiatric indications. These include mainly alcohol and benzodiazepine withdrawal syndromes, panic and anxiety disorders, dementia, schizophrenia, affective disorders, bipolar affective disorders in particular, and, to some extent, personality disorders, A further area in which neurology and psychiatry overlap is pain conditions, in which some anticonvulsants, and also typical psychiatric medications such as antidepressants, are helpful. From the beginning of their psychiatric use, anticonvulsants have also been used to ameliorate specific symptoms of psychiatric disorders independently of their causality and underlying illness, eg, aggression, and, more recently, cognitive impairment, as seen in affective disorders and schizophrenia. With new anticonvulsants currently under development, it is likely that their use in psychiatry will further increase, and that psychiatrists need to learn about their differential efficacy and safety profiles to the same extent as do neurologists. PMID:18472486

Evolutionary Conservation in Genes Underlying Human Psychiatric Disorders

Directory of Open Access Journals (Sweden)

Lisa Michelle Ogawa

2014-05-01

Full Text Available Many psychiatric diseases observed in humans have tenuous or absent analogs in other species. Most notable among these are schizophrenia and autism. One hypothesis has posited that these diseases have arisen as a consequence of human brain evolution, for example, that the same processes that led to advances in cognition, language, and executive function also resulted in novel diseases in humans when dysfunctional. Here, the molecular evolution of genes associated with these and other psychiatric disorders are compared among species. Genes associated with psychiatric disorders are drawn from the literature and orthologous sequences are collected from eleven primate species (human, chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, baboon, marmoset, squirrel monkey, and galago and thirty one non-primate mammalian species. Evolutionary parameters, including dN/dS, are calculated for each gene and compared between disease classes and among species, focusing on humans and primates compared to other mammals and on large-brained taxa (cetaceans, rhinoceros, walrus, bear, and elephant compared to their small-brained sister species. Evidence of differential selection in primates supports the hypothesis that schizophrenia and autism are a cost of higher brain function. Through this work a better understanding of the molecular evolution of the human brain, the pathophysiology of disease, and the genetic basis of human psychiatric disease is gained.

Autism Spectrum Disorders

Directory of Open Access Journals (Sweden)

Rebecca E. Rosenberg

2011-01-01

Full Text Available We used a national online registry to examine variation in cumulative prevalence of community diagnosis of psychiatric comorbidity in 4343 children with autism spectrum disorders (ASD. Adjusted multivariate logistic regression models compared influence of individual, family, and geographic factors on cumulative prevalence of parent-reported anxiety disorder, depression, bipolar disorder, and attention deficit/hyperactivity disorder or attention deficit disorder. Adjusted odds of community-assigned lifetime psychiatric comorbidity were significantly higher with each additional year of life, with increasing autism severity, and with Asperger syndrome and pervasive developmental disorder—not otherwise specified compared with autistic disorder. Overall, in this largest study of parent-reported community diagnoses of psychiatric comorbidity, gender, autistic regression, autism severity, and type of ASD all emerged as significant factors correlating with cumulative prevalence. These findings could suggest both underlying trends in actual comorbidity as well as variation in community interpretation and application of comorbid diagnoses in ASD.

At the crossroads: the intersection of substance use disorders, anxiety disorders, and posttraumatic stress disorder.

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Ruglass, Lesia M; Lopez-Castro, Teresa; Cheref, Soumia; Papini, Santiago; Hien, Denise A

2014-11-01

The co-occurrence of substance use disorders with anxiety disorders and/or posttraumatic stress disorder has been widely documented and when compared to each disorder alone, consistently linked to increased risk for a host of negative outcomes including greater impairment, poorer treatment response, and higher rates of symptom relapse. This article focuses on recent advances in the understanding and effective treatment of this common and highly complex comorbidity. Prevalence and epidemiological data are introduced, followed by a review of contemporary models of etiology and associative pathways. Conceptualizations of effective treatment approaches are discussed alongside evidence from the past decade of clinical research trials. Highlighted are ongoing questions regarding the benefit of sequential, parallel, and integrated approaches and the necessity of further investigation into the mechanisms underlying treatment efficacy. Lastly, recent contributions from neuroscience research are offered as a promising bridge for the development and testing of novel, interdisciplinary treatment approaches.

Egon Schiele: Autoportréty z let 1910 a 1911 v kontextu psychopatologie

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Zdislava Ryantová

2017-09-01

Society gazed at photographs of exalted women (hysteria and deformed male bodies (neuropathology with voyeuristic interest. The language of the “pathological body” was supposedly comprehensible in general and the “pathological body” was perceived as a symptom of the times. Egon Schiele employed the extreme expression of the deformed bodies in his self-portraits as well as in the portraits of his benefactors and collectors. The quick succession of Schiele’s self-portraits can be seen as an obsession to extensively document bodies of people with neuropathological disorders to map out and characterize the disease. At the same time, Egon Schiele was evidently attempting to fully encompass himself.

Alzheimer’s disease is not “brain aging”: neuropathological, genetic, and epidemiological human studies

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Head, Elizabeth; Schmitt, Frederick A.; Davis, Paulina R.; Neltner, Janna H.; Jicha, Gregory A.; Abner, Erin L.; Smith, Charles D.; Van Eldik, Linda J.; Kryscio, Richard J.; Scheff, Stephen W.

2011-01-01

Human studies are reviewed concerning whether “aging”-related mechanisms contribute to Alzheimer’s disease (AD) pathogenesis. AD is defined by specific neuropathology: neuritic amyloid plaques and neocortical neurofibrillary tangles. AD pathology is driven by genetic factors related not to aging per se, but instead to the amyloid precursor protein (APP). In contrast to genes involved in APP-related mechanisms, there is no firm connection between genes implicated in human “accelerated aging” diseases (progerias) and AD. The epidemiology of AD in advanced age is highly relevant but deceptively challenging to address given the low autopsy rates in most countries. In extreme old age, brain diseases other than AD approximate AD prevalence while the impact of AD pathology appears to peak by age 95 and decline thereafter. Many distinct brain diseases other than AD afflict older human brains and contribute to cognitive impairment. Additional prevalent pathologies include cerebrovascular disease and hippocampal sclerosis, both high-morbidity brain diseases that appear to peak in incidence later than AD chronologically. Because of these common brain diseases of extreme old age, the epidemiology differs between clinical “dementia” and the subset of dementia cases with AD pathology. Additional aging-associated mechanisms for cognitive decline such as diabetes and synapse loss have been linked to AD and these hypotheses are discussed. Criteria are proposed to define an “aging-linked” disease, and AD fails all of these criteria. In conclusion, it may be most fruitful to focus attention on specific pathways involved in AD rather than attributing it to an inevitable consequence of aging. PMID:21516511

Functional neuroimaging of sleep disorders

International Nuclear Information System (INIS)

Qiu Chun; Zhao Jun; Guan Yihui

2013-01-01

Sleep disorders may affect the health and normal life of human badly. However, the pathophysiology underlying adult sleep disorders is still unclear. Functional neuroimaging can be used to investigate whether sleep disorders are associated with specific changes in brain structure or regional activity. This paper reviews functional brain imaging findings in major intrinsic sleep disorders (i.e., idiopathic insomnia, narcolepsy, and obstructive sleep apnea) and in abnormal motor behavior during sleep (i.e., periodic limb movement disorder and REM sleep behavior disorder). Metabolic/functional investigations (positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging) are mainly reviewed, as well as neuroanatomical assessments (voxel-based morphometry, magnetic resonance spectroscopy). Meanwhile, here are some brief introduction of different kinds of sleep disorders. (authors)

Association between severity of behavioral phenotype and comorbid attention deficit hyperactivity disorder symptoms in children with autism spectrum disorders

OpenAIRE

Rao, Patricia A; Landa, Rebecca J

2013-01-01

Autism spectrum disorder and attention deficit hyperactivity disorder are neurodevelopmental disorders that cannot be codiagnosed under existing diagnostic guidelines (Diagnostic and Statistical Manual of the American Psychiatric Association, 4th ed., text rev.). However, reports are emerging that attention deficit hyperactivity disorder is sometimes comorbid with autism spectrum disorder. In the current study, we examined rates of parent-reported clinically significant symptoms of attention ...

Association between Severity of Behavioral Phenotype and Comorbid Attention Deficit Hyperactivity Disorder Symptoms in Children with Autism Spectrum Disorders

Science.gov (United States)

Rao, Patricia A.; Landa, Rebecca J.

2014-01-01

Autism spectrum disorder and attention deficit hyperactivity disorder are neurodevelopmental disorders that cannot be codiagnosed under existing diagnostic guidelines ("Diagnostic and Statistical Manual of the American Psychiatric Association," 4th ed., text rev.). However, reports are emerging that attention deficit hyperactivity…

XVIII WFN World Congress on Parkinson’s Disease and Related Disorders Synopsis

NARCIS (Netherlands)

Frei, K.; Wolters, E.C.

2010-01-01

Several interesting concepts regarding Parkinson's disease were recently presented at the XVIII World Congress on Parkinson's disease. The theory of α-synuclein acting as a prion, resulting in the spread of Parkinson's disease, was presented and related to the Braak hypothesis of neuropathology of

DSM-IV antisocial personality disorder and conduct disorder: evidence for taxonic structures among individuals with and without substance use disorders in the general population.

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Kerridge, Bradley T; Saha, Tulshi D; Hasin, Deborah S

2014-05-01

The categorical-dimensional status of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) conduct disorder (CD) and antisocial personality disorder (ASPD) is a source of controversy. This study examined whether the underlying structure of DSM-IV CD and ASPD was dimensional or categorical (taxonic) among individuals with and without substance use disorders. Using a national large representative survey of U.S. adults (n = 43,093), taxometric analyses of DSM-IV CD and ASPD diagnostic criteria were conducted on the total sample and among those with and without substance use disorders. Results of three taxometric procedures were consistent in showing that the structures underlying DSM-IV CD and ASPD were clearly taxonic in the total sample and among individuals with and without substance use disorders. Comparison curve fit indices exceeded 0.57 for each model. Taxonic findings of the present study were in contrast to the dimensional results of prior taxometric research among incarcerated samples with substantial comorbidity of antisocial syndromes and substance use disorders. Results supported the categorical representation and diagnostic thresholds of ASPD and CD as defined in DSM-IV and DSM-5. That the structure of ASPD and CD may be taxonic suggests that further research on these disorders use group comparative designs in which samples with and without these disorders are compared in terms of sociodemographic and clinical correlates, comorbidity, and treatment utilization. The taxonic structure of ASPD and CD may contribute to future research on causal processes through which these antisocial syndromes develop.

DSM-IV Antisocial Personality Disorder and Conduct Disorder: Evidence for Taxonic Structures Among Individuals With and Without Substance Use Disorders in the General Population

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Kerridge, Bradley T; Saha, Tulshi D; Hasin, Deborah S

2014-01-01

Objective: The categorical-dimensional status of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) conduct disorder (CD) and antisocial personality disorder (ASPD) is a source of controversy. This study examined whether the underlying structure of DSM-IV CD and ASPD was dimensional or categorical (taxonic) among individuals with and without substance use disorders. Method: Using a national large representative survey of U.S. adults (n = 43,093), taxometric analyses of DSM-IV CD and ASPD diagnostic criteria were conducted on the total sample and among those with and without substance use disorders. Results: Results of three taxometric procedures were consistent in showing that the structures underlying DSM-IV CD and ASPD were clearly taxonic in the total sample and among individuals with and without substance use disorders. Comparison curve fit indices exceeded 0.57 for each model. Conclusions: Taxonic findings of the present study were in contrast to the dimensional results of prior taxometric research among incarcerated samples with substantial comorbidity of antisocial syndromes and substance use disorders. Results supported the categorical representation and diagnostic thresholds of ASPD and CD as defined in DSM-IV and DSM-5. That the structure of ASPD and CD may be taxonic suggests that further research on these disorders use group comparative designs in which samples with and without these disorders are compared in terms of sociodemographic and clinical correlates, comorbidity, and treatment utilization. The taxonic structure of ASPD and CD may contribute to future research on causal processes through which these antisocial syndromes develop. PMID:24766762

Attention Deficit Hyperactivity Disorder, Tic Disorder, and Allergy: Is There a Link? A Nationwide Population-Based Study

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Chen, Mu-Hong; Su, Tung-Ping; Chen, Ying-Sheue; Hsu, Ju-Wei; Huang, Kai-Lin; Chang, Wen-Han; Bai, Ya-Mei

2013-01-01

Background: Attention deficit hyperactivity disorder (ADHD) and tic disorder usually co-occur in the same individuals, but the underlying mechanisms remain unclear. Previous evidence has shown that a frequent coexistence of allergic diseases was noted in patients with ADHD or tic disorder. We attempted to investigate the possible link among ADHD,…

[The cerebellum as a major player in motor disturbances related to Autistic Syndrome Disorders].

Science.gov (United States)

Jaber, M

2017-04-01

Autism spectrum disorders (ASD) are neurodevelopmental disorders associated with disturbances in communication, social interactions, cognition and affect. ASD are also accompanied by complex movement disorders, including ataxia. A special focus of recent research in this area is made on the striatum and the cerebellum, two structures known not only to control movement but also to be involved in cognitive functions such as memory and language. Dysfunction within the motor system may be associated with abnormal movements in ASD that are translated into ataxia, abnormal pattern of righting, gait sequencing, development of walking, and hand positioning. This line of study may generate new knowledge and understanding of motor symptoms associated with ASD and aims to deliver fresh perspectives for early diagnosis and therapeutic strategies against ASD. Despite the relative paucity of research in this area (compared to the social, linguistic, and behavioural disturbances in ASD), there is evidence that the frontostriatal motor system and/or the cerebellar motor systems may be the site of dysfunction in ASD. Indeed, the cerebellum seems to be essential in the development of basic social capabilities, communication, repetitive/restrictive behaviors, and motor and cognitive behaviors that are all impaired in ASD. Cerebellar neuropathology including cerebellar hypoplasia and reduced cerebellar Purkinje cell numbers are the most consistent neuropathologies linked to ASD. The functional state of the cerebellum and its impact on brain function in ASD is the focus of this review. This review starts by recapitulating historical findings pointing towards an implication of the cerebellum, and to a lesser extent the basal ganglia structures, in TSA. We then detail the structure/function of the cerebellum at the regional and cellular levels before describing human and animal findings indicating a role of the cerebellum and basal ganglia in ASD. Several studies have attempted to

Post traumatic stress disorder: undiagnosed cases in a tertiary ...

African Journals Online (AJOL)

Posttraumatic stress disorder (PTSD) may develop after a ... with other mood- and anxiety disorders, we postulated that this disorder may be under- diagnosed in therapeutic wards ..... disorder and major depression with greater risk for suicidal.

Linking blast physics to biological outcomes in mild traumatic brain injury: Narrative review and preliminary report of an open-field blast model.

Science.gov (United States)

Song, Hailong; Cui, Jiankun; Simonyi, Agnes; Johnson, Catherine E; Hubler, Graham K; DePalma, Ralph G; Gu, Zezong

2018-03-15

Blast exposures are associated with traumatic brain injury (TBI) and blast-induced TBIs are common injuries affecting military personnel. Department of Defense and Veterans Administration (DoD/VA) reports for TBI indicated that the vast majority (82.3%) has been mild TBI (mTBI)/concussion. mTBI and associated posttraumatic stress disorders (PTSD) have been called "the invisible injury" of the current conflicts in Iraq and Afghanistan. These injuries induce varying degrees of neuropathological alterations and, in some cases, chronic cognitive, behavioral and neurological disorders. Appropriate animal models of blast-induced TBI will not only assist the understanding of physical characteristics of the blast, but also help to address the potential mechanisms. This report provides a brief overview of physical principles of blast, injury mechanisms related to blast exposure, current blast animal models, and the neurological behavioral and neuropathological findings related to blast injury in experimental settings. We describe relationships between blast peak pressures and the observed injuries. We also report preliminary use of a highly reproducible and intensity-graded blast murine model carried out in open-field with explosives, and describe physical and pathological findings in this experimental model. Our results indicate close relationships between blast intensities and neuropathology and behavioral deficits, particularly at low level blast intensities relevant to mTBI. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessing the Role of Dopamine in Limb and Cranial-Oromotor Control in a Rat Model of Parkinson's Disease

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Kane, Jacqueline R.; Ciucci, Michelle R.; Jacobs, Amber N.; Tews, Nathan; Russell, John A.; Ahrens, Allison M.; Ma, Sean T.; Britt, Joshua M.; Cormack, Lawrence K.; Schallert, Timothy

2011-01-01

Parkinson's disease (PD) is a neurodegenerative disorder primarily characterized by sensorimotor dysfunction. The neuropathology of PD includes a loss of dopamine (DA) neurons of the nigrostriatal pathway. Classic signs of the disease include rigidity, bradykinesia, and postural instability. However, as many as 90% of patients also experience…

Disease: H01211 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available H01211 MECP2-related severe neonatal encephalopathy MECP2-related severe neonatal encephalopathy... is a rare disorder of males characterized by a static encephalopathy, severe developmental de...BC ... TITLE ... MECP2 mutation in a boy with severe neonatal encephalopathy: clinical, neuropathological and

Neuropsychological Evaluation in the Diagnosis and Treatment of Tourette's Syndrome

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Osmon, David C.; Smerz, Jessica M.

2005-01-01

The neurobiological basis of Tourettes syndrome is reviewed for the purpose of presenting a clinically relevant account of the neuropsychology of the disorder for the clinician who is behaviorally oriented. The neuropathology and neuropsychological deficits typically found in Tourettes are reviewed, and a neuropsychological test battery is…

Dietary interventions that reduce mTOR activity rescue autistic-like behavioral deficits in mice

NARCIS (Netherlands)

Wu, Jiangbo; de Theije, Caroline G M; da Silva, Sofia Lopes; Abbring, Suzanne; van der Horst, Hilma; Broersen, Laus M; Willemsen, Linette; Kas, Martien; Garssen, Johan; Kraneveld, Aletta D

Enhanced mammalian target of rapamycin (mTOR) signaling in the brain has been implicated in the pathogenesis of autism spectrum disorder (ASD). Inhibition of the mTOR pathway improves behavior and neuropathology in mouse models of ASD containing mTOR-associated single gene mutations. The current

Effects of hematopoietic stem cell transplantation on acyl-CoA oxidase deficiency: a sibling comparison study

NARCIS (Netherlands)

Wang, Raymond Y.; Monuki, Edwin S.; Powers, James; Schwartz, Phillip H.; Watkins, Paul A.; Shi, Yang; Moser, Ann; Shrier, David A.; Waterham, Hans R.; Nugent, Diane J.; Abdenur, Jose E.

2014-01-01

Acyl-CoA oxidase (ACOX1) deficiency is a rare disorder of peroxisomal very-long chain fatty acid oxidation. No reports detailing attempted treatment, longitudinal imaging, or neuropathology exist. We describe the natural history of clinical symptoms and brain imaging in two siblings with ACOX1

Defining Oppositional Defiant Disorder

Science.gov (United States)

Rowe, Richard; Maughan, Barbara; Costello, E. Jane; Angold, Adrian

2005-01-01

Background: ICD-10 and DSM-IV include similar criterial symptom lists for conduct disorder (CD) and oppositional defiant disorder (ODD), but while DSM-IV treats each list separately, ICD-10 considers them jointly. One consequence is that ICD-10 identifies a group of children with ODD subtype who do not receive a diagnosis under DSM-IV. Methods: We…

Addictive Disorders in Adolescents.

Science.gov (United States)

Truong, Anh; Moukaddam, Nidal; Toledo, Alexander; Onigu-Otite, Edore

2017-09-01

Addictive disorders in youth represent a dynamic field characterized by shifting patterns of substance use and high rates of experimentation, while retaining the risky behaviors and negative outcomes associated with established drug classes. Youth/adolescents are also at the forefront of use of new technologies, and non-substance-related disorders are pertinent. These disorders present with similar pictures of impairment, and can be diagnosed following the same principles. An underlying mental disorder and the possibility of a dual diagnosis need to be assessed carefully, and optimal treatment includes psychosocial treatments with applicable pharmacologic management, the latter representing an expanding field. Copyright © 2017 Elsevier Inc. All rights reserved.

Panic disorder: Psychobiological aspects of personality dimensions

Directory of Open Access Journals (Sweden)

Draganić-Gajić Saveta

2005-01-01

Full Text Available Attempts to understand the underlying mechanisms of association between psychological factors and panic disorder have been mostly based on psychodynamic description. Evidence of the importance of serotonergic (5-HT system in panic disorder (PD, however, has substanti ally increased in recent years. OBJECTIVE The objective of our study was to determine whether there was a specific personality profile of panic disorder patients and how it was related to possible neurobiological mechanisms underlying personality dimensions. PATIENTS AND METHODS Sample consisted of 14 inpatients with ICD-X diagnosis of panic disorder and 34 healthy control subjects. Personality dimensions were assessed by Minnesota Multiphasic Personality Inventory (MMPI-201 and Tridimensional Personality Questionnaire (TPQ. To assess central 5-HT function, platelet monoamine-oxidase (MAO activity was measured. RESULTS In panic disorder group, higher scores of histrionic, depressive and hypochondriac subscales and significant increase of harm avoidance (HA scale as well as low MAO activity were found. Negative correlation was established between MAO activity and psychopathic deviance MMPI scale. CONCLUSION The obtained results might indicate a specific personality profile of patients with panic disorder, which is characterized by high neuroticism, fearfulness, inhibition, shyness and apprehensive worry. Low MAO activity and high HA scores possibly indicate underlying hyperserotonergic state. The observed correlation between personality traits and MAO activity provide additional support for the hypothesized functional relationship between underlying central monoaminergic activity and temperament traits associated with anxiety, depression and impulsivity.

HOW TO DIFFERENTIATE FRONTOTEMPORAL FROMALZHEIMER’S DEMENTIA? RECENT DEVELOPMENTS INMOLECULAR GENETICS AND NEUROPATHOLOGY

Directory of Open Access Journals (Sweden)

Rajko Liščić

2008-05-01

Full Text Available Frontotemporal dementia is a major cause of non-Alzheimer dementia (AD. Frontotemporal lobar degeneration (FTLD is used here as an umbrella term for both clinical andneuropathological entities starting before age of 65 years. FTLD differs clinically from ADbecause memory loss is rarely an early symptom. Instead, the dementia of FTLD is usuallydenoted by behavioral and language difficulties, although clinical and cognitive featuresof FTLD may overlap with AD. Aphasia may be prominent, either fluent or nonfluent.Clinical FTLD is associated with a variety of different neuropathological entities, whichshare common feature of preferential degeneration of the frontal and temporal lobes. Whereas, in the past, most attention focused on FTLD pathology associated with tau-positive inclusions and microtubule associated protein tau gene (MAPT mutations (tauopathies,there has recently been greater attention paid to non-tau, ubiquitin positive inclusions(FTLD-U or non-tauopathies. It is now recognized that FTLD-U is the most common pathology associated with clinical FTLD. Clinically, cases with FTLD-U may additionally presentwith or without motor neuron disease and parkinsonism. Majority of familial cases ofFTLD-U have mutations in the progranulin (PRGN gene. Some families of FTLD-U withPGRN mutation (hereditary dysphasic disinhibition dementia 1 and 2 are characterized,besides behavior and language difficulties, by additional memory loss and AD-type pathology. Recently, the ubiquitinated pathological protein in FTLD-U has been identified asTAR DNA binding protein (TDP 43 and found in an increasing number of neurodegenerative diseases, including AD. The overlap between FTLD-U and AD is important since asmany as 20 % of AD cases show some FTLD-U type TDP-43 pathology. Recent developmentshave helped to clarify the relationship between different types of FTLD and related conditions. Understanding and differentiating between FTLD and AD is very important for

Regional homogeneity and functional connectivity patterns in major depressive disorder, cognitive vulnerability to depression and healthy subjects.

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Sun, Hui; Luo, Lizhu; Yuan, Xinru; Zhang, Lu; He, Yini; Yao, Shuqiao; Wang, Jiaojian; Xiao, Jing

2018-08-01

Cognitive vulnerability to depression (CVD) is a high risk for depressive disorder. Recent studies focus on individuals with CVD to determine the neural basis of major depressive disorder (MDD) neuropathology. However, whether CVD showed specific or similar brain functional activity and connectivity patterns, compared to MDD, remain largely unknown. Here, using resting-state functional magnetic resonance imaging in subjects with CVD, healthy controls (HC) and MDD, regional homogeneity (ReHo) and resting-state functional connectivity (R-FC) analyses were conducted to assess local synchronization and changes in functional connectivity patterns. Significant ReHo differences were found in right posterior lobe of cerebellum (PLC), left lingual gyrus (LG) and precuneus. Compared to HC, CVD subjects showed increased ReHo in the PLC, which was similar to the difference found between MDD and HC. Compared to MDD patients, CVD subjects showed decreased ReHo in PLC, LG, and precuneus. R-FC analyses found increased functional connections between LG and left inferior parietal lobule, posterior cingulate cortex, and dorsolateral prefrontal cortex in CVD compared to both HC and MDD. Moreover, Regional mean ReHo values were positively correlated with Center for Epidemiologic Studies Depression Scale scores. These analyses revealed that PLC and functional connections between LG and left inferior parietal lobule, posterior cingulate cortex, and dorsolateral prefrontal cortex may be a potential marker for CVD. Copyright © 2018 Elsevier B.V. All rights reserved.

Neuropathological Changes and Clinical Features of Autism Spectrum Disorder Participants Are Similar to that Reported in Congenital and Chronic Cerebral Toxoplasmosis in Humans and Mice

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Prandota, Joseph

2010-01-01

Anatomic, histopathologic, and MRI/SPET studies of autistic spectrum disorders (ASD) patients' brains confirm existence of very early developmental deficits. In congenital and chronic murine toxoplasmosis several cerebral anomalies also have been reported, and worldwide, approximately two billion people are chronically infected with T. "gondii"…

Emotional Reactivity in Posttraumatic Stress Disorder: Behavioural and Neurobiological Correlates of Underlying Mechanisms and the Role of Emotional Memory Modification

OpenAIRE

Thome, Janine

2017-01-01

The symptom pattern of posttraumatic stress disorder (PTSD) comprises four clusters: “involuntary distressing memories”, “persistent avoidance of stimuli related to the traumatic event”, “negative alterations in cognition and mood”, and “in arousal and reactivity” (DSM 5, American Psychological Association). Increasing evidence points towards enhanced emotional reactivity as an underlying mechanism of the latter mentioned symptom pattern in individuals with PTSD. From a process oriented persp...

Association among depressive disorder, adjustment disorder, sleep disturbance, and suicidal ideation in Taiwanese adolescent.

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Chung, Ming-Shun; Chiu, Hsien-Jane; Sun, Wen-Jung; Lin, Chieh-Nan; Kuo, Chien-Cheng; Huang, Wei-Che; Chen, Ying-Sheue; Cheng, Hui-Ping; Chou, Pesus

2014-09-01

The aim of this study is to investigate the association among depressive disorder, adjustment disorder, sleep disturbance, and suicidal ideation in Taiwanese adolescent. We recruited 607 students (grades 5-9) to fill out the investigation of basic data and sleep disturbance. Psychiatrists then used the Mini International Neuropsychiatric Interview-Kid to interview these students to assess their suicidal ideation and psychiatric diagnosis. Multiple logistic regression with forward conditionals was used to find the risk factors for multivariate analysis. Female, age, depressive disorder, adjustment disorder, and poor sleep all contributed to adolescent suicidal ideation in univariate analysis. However, poor sleep became non-significant under the control of depressive disorder and adjustment disorder. We found that both depressive disorder and adjustment disorder play important roles in sleep and adolescent suicidal ideation. After controlling both depressive disorder and adjustment disorder, sleep disturbance was no longer a risk of adolescent suicidal ideation. We also confirm the indirect influence of sleep on suicidal ideation in adolescent. © 2013 Wiley Publishing Asia Pty Ltd.

Dissociative disorder manifesting for underlying adolescent hemi-parkinsonism: New chronology for old mummies.

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Jha, Shailesh; Garg, Amit; Khanna, Amit

2015-08-01

Dissociative symptoms can be induced by a variety of conditions that can either coexist or mimic each other in clinical presentation. In coexisting dissociative disorder with medical illness, the causality remains uncertain, but sometime its role as nidus for dissociative symptoms just cannot be ruled out. The origin of "organic dissociative disorder" is undoubtedly found by various authors who demonstrated that a high percentage of patients with dissociative symptoms present with some form of neurological insult before developing the symptom. Herein we report on a case of adolescent onset hemi-parkinsonism with coexisting dissociative disorder. Copyright © 2015 Elsevier B.V. All rights reserved.

Eating Disorders as Coping Mechanisms

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Wagener, Amy M.; Much, Kari

2010-01-01

This article focuses on the complex nature of eating disorders, specifically highlighting their use as coping mechanisms for underlying emotional and psychological concerns. Case examples of college counseling center clients are discussed in order to illustrate common ways in which eating disorders are utilized by clients with varying…

Sleep-related movement disorders.

Science.gov (United States)

Merlino, Giovanni; Gigli, Gian Luigi

2012-06-01

Several movement disorders may occur during nocturnal rest disrupting sleep. A part of these complaints is characterized by relatively simple, non-purposeful and usually stereotyped movements. The last version of the International Classification of Sleep Disorders includes these clinical conditions (i.e. restless legs syndrome, periodic limb movement disorder, sleep-related leg cramps, sleep-related bruxism and sleep-related rhythmic movement disorder) under the category entitled sleep-related movement disorders. Moreover, apparently physiological movements (e.g. alternating leg muscle activation and excessive hypnic fragmentary myoclonus) can show a high frequency and severity impairing sleep quality. Clinical and, in specific cases, neurophysiological assessments are required to detect the presence of nocturnal movement complaints. Patients reporting poor sleep due to these abnormal movements should undergo non-pharmacological or pharmacological treatments.

Treatment of personality disorder.

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Bateman, Anthony W; Gunderson, John; Mulder, Roger

2015-02-21

The evidence base for the effective treatment of personality disorders is insufficient. Most of the existing evidence on personality disorder is for the treatment of borderline personality disorder, but even this is limited by the small sample sizes and short follow-up in clinical trials, the wide range of core outcome measures used by studies, and poor control of coexisting psychopathology. Psychological or psychosocial intervention is recommended as the primary treatment for borderline personality disorder and pharmacotherapy is only advised as an adjunctive treatment. The amount of research about the underlying, abnormal, psychological or biological processes leading to the manifestation of a disordered personality is increasing, which could lead to more effective interventions. The synergistic or antagonistic interaction of psychotherapies and drugs for treating personality disorder should be studied in conjunction with their mechanisms of change throughout the development of each. Copyright © 2015 Elsevier Ltd. All rights reserved.

Myelination and myelin disorders

International Nuclear Information System (INIS)

Knaap, M.S. van der.

1991-01-01

The first part of this thesis contains the results of a study into the capabilities of MR in the assessment of normal cerebral development. The process of normal myelination under the age of 1 year is divided into stages with specific MRI characteristics. An indication of normal age limits for each stage is given. The relationships between changes in signal intensities and biochemical background, and between progress of myelination and psychomotor development are discussed. The latter in the light of a study performed in hydrocephalic children, prior to and repeatedly after shunt implantation. Normal changes in 1 H and 31 P spectra of the brain in infants and children are described. The relationship between observed spectral changes and cerebral maturational processes is discussed. The second part deals with assessment of myelin disorders with MRI. Basic information about demyelinating disorders and biochemical background are reviewed. A new classification of myelin disorders, underlying the development of an MRI pattern recognition scheme, is proposed based on the most recent scientific developments. Common histological characteristics are described for all main categories of myelin disorders. Extensive information is presented about MRI patterns of abnormalities in patients in whom the disease is predominantly or exclusively located in the white matter. On the basis of the data of these patients a global MRI pattern recognition scheme has been developed covering all white matter disorders that were encountered. Also an example of an in-depth pattern recognition in a circumscribed category of disorders is presented. Finally a study of MRS in demyelinating disorders as opposed to neuronal disorders is described. While MRI provides information about the extent of the process of demyelination and about the disease category, MRS turns out to provide information about the severity of the demyelination and of the concomitant neuronal damage. (H.W.). 725 refs.; 53 figs

Alcohol and Substance Use Disorders in DSM-5

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Gulcan Gulec

2015-12-01

Full Text Available When we compare the categories about alcohol, and substance-related disorders in DSM-IV and DSM-5, the new category, named addictive disorders is the most striking change. Only gambling disorder have been identified currently in this category. This may be the most remarkable change among the changes in the DSM-5. Because the expansion of the existing diagnostic criteria may cause the assessment of and lsquo;normal behavior' as a disorder. Additionally, withdrawal of caffeine and cannabis are defined in the DSM-5. Disorders collected under the title of substance-related disorders in the DSM-IV were collected under the name of substance-related and addictive disorders in the DSM-5. Specific criterias for substance abuse and substance addiction have been combined into the name of "substance use disorders". In substance abuse, "experienced legal problems" criteria was removed and "a strong desire or urge or craving for substance use" criteria has been introduced. Henceforth, substance abuse is defined as a mild form of substance use disorders in the DSM-5. A change in the prevalence of substance use disorders should be investigated by the new researches.

Hypereosinophilic Atopic Transverse Myelitis

African Journals Online (AJOL)

2018-06-11

4 days ago ... Atopic transverse myelitis is a rare disorder that is defined as a ... was commenced on prednisolone and had good response to treatment. .... Atopic myelitis is more common in male sex such as .... their identity, but anonymity cannot be guaranteed. ... useful diagnostic clue in surgical neuropathology.

Adaptive plasticity during stress and depression and the role of ...

African Journals Online (AJOL)

This paper will review pre-clinical and clinical evidence supporting a role for the glutamatenitric oxide pathway as a putative mediator of the neuropathological changes evident in depression and stress-related disorders, particularly PTSD, and its potential as a novel target for psychotropic activity. South African Psychiatry ...

Beyond Symptom Counts for Diagnosing Oppositional Defiant Disorder and Conduct Disorder?

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Lindhiem, Oliver; Bennett, Charles B; Hipwell, Alison E; Pardini, Dustin A

2015-10-01

Conduct Disorder (CD) and Oppositional Defiant Disorder (ODD) are among the most commonly diagnosed childhood behavioral health disorders. Although there is substantial evidence of heterogeneity of symptom presentations, DSM diagnoses of CD and ODD are formally diagnosed on the basis of symptom counts without regard to individual symptom patterns. We used unidimensional item response theory (IRT) two-parameter logistic (2PL) models to examine item parameters for the individual symptoms of CD and ODD using data on 6,491 adolescents (ages 13-17) from the National Comorbidity Study: Adolescent Supplement (NCS-A). For each disorder, the symptoms differed in terms of severity and discrimination parameters. As a result, some adolescents who were above DSM diagnostic thresholds for disruptive behavior disorders exhibited lower levels of the underlying construct than others below the thresholds, based on their unique symptom profile. In terms of incremental benefit, our results suggested an advantage of latent trait scores for CD but not ODD.

Circadian Rhythms, Sleep, and Disorders of Aging.

Science.gov (United States)

Mattis, Joanna; Sehgal, Amita

2016-04-01

Sleep-wake cycles are known to be disrupted in people with neurodegenerative disorders. These findings are now supported by data from animal models for some of these disorders, raising the question of whether the disrupted sleep/circadian regulation contributes to the loss of neural function. As circadian rhythms and sleep consolidation also break down with normal aging, changes in these may be part of what makes aging a risk factor for disorders like Alzheimer's disease (AD). Mechanisms underlying the connection between circadian/sleep dysregulation and neurodegeneration remain unclear, but several recent studies provide interesting possibilities. While mechanistic analysis is under way, it is worth considering treatment of circadian/sleep disruption as a means to alleviate symptoms of neurodegenerative disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

DMFT+Σ approach to disordered Hubbard model

International Nuclear Information System (INIS)

Kuchinskii, E. Z.; Sadovskii, M. V.

2016-01-01

We briefly review the generalized dynamic mean-field theory DMFT+Σ applied to both repulsive and attractive disordered Hubbard models. We examine the general problem of metal–insulator transition and the phase diagram in the repulsive case, as well as the BCS–BEC crossover region of the attractive model, demonstrating a certain universality of single-electron properties under disordering in both models. We also discuss and compare the results for the density of states and dynamic conductivity in the repulsive and attractive cases and the generalized Anderson theorem behavior of the superconducting critical temperature in the disordered attractive case. A brief discussion of the behavior of Ginzburg–Landau coefficients under disordering in the BCS–BEC crossover region is also presented.

The Emergence of Network Inefficiencies in Infants With Autism Spectrum Disorder.

Science.gov (United States)

Lewis, John D; Evans, Alan C; Pruett, John R; Botteron, Kelly N; McKinstry, Robert C; Zwaigenbaum, Lonnie; Estes, Annette M; Collins, D Louis; Kostopoulos, Penelope; Gerig, Guido; Dager, Stephen R; Paterson, Sarah; Schultz, Robert T; Styner, Martin A; Hazlett, Heather C; Piven, Joseph

2017-08-01

Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral features that emerge during the first years of life. Research indicates that abnormalities in brain connectivity are associated with these behavioral features. However, the inclusion of individuals past the age of onset of the defining behaviors complicates interpretation of the observed abnormalities: they may be cascade effects of earlier neuropathology and behavioral abnormalities. Our recent study of network efficiency in a cohort of 24-month-olds at high and low familial risk for ASD reduced this confound; we reported reduced network efficiencies in toddlers classified with ASD. The current study maps the emergence of these inefficiencies in the first year of life. This study uses data from 260 infants at 6 and 12 months of age, including 116 infants with longitudinal data. As in our earlier study, we use diffusion data to obtain measures of the length and strength of connections between brain regions to compute network efficiency. We assess group differences in efficiency within linear mixed-effects models determined by the Akaike information criterion. Inefficiencies in high-risk infants later classified with ASD were detected from 6 months onward in regions involved in low-level sensory processing. In addition, within the high-risk infants, these inefficiencies predicted 24-month symptom severity. These results suggest that infants with ASD, even before 6 months of age, have deficits in connectivity related to low-level processing, which contribute to a developmental cascade affecting brain organization and eventually higher-level cognitive processes and social behavior. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Mitochondrial recessive ataxia syndrome mimicking dominant spinocerebellar ataxia.

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Palin, Eino J H; Hakonen, Anna H; Korpela, Mari; Paetau, Anders; Suomalainen, Anu

2012-04-15

We studied the genetic background of a family with SCA, showing dominant inheritance and anticipation. Muscle histology, POLG1 gene sequence, neuropathology and mitochondrial DNA analyses in a mother and a son showed typical findings for a mitochondrial disorder, and both were shown to be homozygous for a recessive POLG1 mutation, underlying mitochondrial recessive ataxia syndrome, MIRAS. The healthy father was a heterozygous carrier for the same mutation. Recessively inherited MIRAS mutations should be tested in dominantly inherited SCAs cases of unknown cause, as the high carrier frequency of MIRAS may result in two independent introductions of the mutant allele in the family and thereby mimic dominant inheritance. Copyright © 2011 Elsevier B.V. All rights reserved.

Neuroimaging of tic disorders with co-existing attention-deficit/hyperactivity disorder

DEFF Research Database (Denmark)

Plessen, Kerstin J; Royal, Jason M; Peterson, Bradley S

2007-01-01

BACKGROUND: Tourette syndrome (TS) and Attention-Deficit/Hyperactivity Disorder (ADHD) are common and debilitating neuropsychiatric illnesses that typically onset in the preschool years. Recently, both conditions have been subject to neuroimaging studies, with the aim of understanding...... contrast these findings with those in ADHD without comorbid tic disorders. RESULTS: The frequent comorbidity of TS and ADHD may reflect a common underlying neurobiological substrate, and studies confirm the hypothesized involvement of fronto-striatal circuits in both TS and ADHD. However, poor inhibitory...... their underlying neurobiological correlates. OBJECTIVE: The relation of TS and ADHD is discussed against the background of findings from previous Magnetic Resonance Imaging (MRI) studies. METHODS: We review the designs and major findings of previous studies that have examined TS with comorbid ADHD, and we briefly...

Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells--possible relevance to autism spectrum disorders.

Directory of Open Access Journals (Sweden)

Bistra B Nankova

Full Text Available Alterations in gut microbiome composition have an emerging role in health and disease including brain function and behavior. Short chain fatty acids (SCFA like propionic (PPA, and butyric acid (BA, which are present in diet and are fermentation products of many gastrointestinal bacteria, are showing increasing importance in host health, but also may be environmental contributors in neurodevelopmental disorders including autism spectrum disorders (ASD. Further to this we have shown SCFA administration to rodents over a variety of routes (intracerebroventricular, subcutaneous, intraperitoneal or developmental time periods can elicit behavioral, electrophysiological, neuropathological and biochemical effects consistent with findings in ASD patients. SCFA are capable of altering host gene expression, partly due to their histone deacetylase inhibitor activity. We have previously shown BA can regulate tyrosine hydroxylase (TH mRNA levels in a PC12 cell model. Since monoamine concentration is known to be elevated in the brain and blood of ASD patients and in many ASD animal models, we hypothesized that SCFA may directly influence brain monoaminergic pathways. When PC12 cells were transiently transfected with plasmids having a luciferase reporter gene under the control of the TH promoter, PPA was found to induce reporter gene activity over a wide concentration range. CREB transcription factor(s was necessary for the transcriptional activation of TH gene by PPA. At lower concentrations PPA also caused accumulation of TH mRNA and protein, indicative of increased cell capacity to produce catecholamines. PPA and BA induced broad alterations in gene expression including neurotransmitter systems, neuronal cell adhesion molecules, inflammation, oxidative stress, lipid metabolism and mitochondrial function, all of which have been implicated in ASD. In conclusion, our data are consistent with a molecular mechanism through which gut related environmental signals

Identification of risk loci with shared effects on five major psychiatric disorders

DEFF Research Database (Denmark)

Steinhausen, Hans-Christoph E.; Strauss, John; Strohmaier, Jana

2013-01-01

Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: a......: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia.......Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium...

Research progress of BOLD-functional MRI of hepatic encephalopathy

International Nuclear Information System (INIS)

Ni Ling; Zhang Longjiang; Lu Guangming

2013-01-01

Hepatic encephalopathy (HE), characterized by a wide spectrum of clinical manifestations, ranging from behavior abnormality, conscious disorder and even coma, is a consequence of liver dysfunction in both acute and chronic hepatic diseases. Minimal hepatic encephalopathy (MHE) refers to a subgroup of cirrhotic patients without clinical overt hepatic encephalopathy symptoms hut with abnormalities in neuro -cognitive functions. HE/MHE can have a far-reaching impact on quality of life and prognosis. The exact neuropathology mechanism was still unclear. Recently, functional MRI (fMRI) has been increasingly applied for investigating the neuro-pathophysiological mechanism of HE. This paper will review the fMRI research applied on uncovering the neuropathology mechanism of HE. (authors)

Genetic variants associated with sleep disorders

OpenAIRE

Kripke, Daniel F.; Kline, Lawrence E.; Nievergelt, Caroline M.; Murray, Sarah S.; Shadan, Farhad F.; Dawson, Arthur; Poceta, J. Steven; Cronin, John; Jamil, Shazia M.; Tranah, Gregory J.; Loving, Richard T.; Grizas, Alexandra P.; Hahn, Elizabeth K.

2015-01-01

© 2014 The Authors. Objective: The diagnostic boundaries of sleep disorders are under considerable debate. The main sleep disorders are partly heritable therefore, defining heritable pathophysiologic mechanisms could delineate diagnoses and suggest treatment. We collected clinical data and DNA from consenting patients scheduled to undergo clinical polysomnograms, to expand our understanding of the polymorphisms associated with the phenotypes of particular sleep disorders. Methods: Patients at...

Temporomandibular disorders and tension-type headache.

Science.gov (United States)

Mongini, Franco

2007-12-01

Pathologies currently defined as temporomandibular disorders may be different in nature. Temporomandibular joint (TMJ) disorders and craniofacial and cervical myogenous pain (MP) are distinct pathologies but may be superimposed and share some etiologic factors. Tension-type headache (TTH) may often be associated with craniofacial and cervical pain, and the same pharmacologic and nonpharmacologic treatment may be efficacious for both. Psychiatric comorbidity (depression and/or anxiety disorder) is less frequent in sheer TMJ disorders, compared with MP and TTH. A screening for the presence of an underlying psychiatric disorder should be part of the clinical evaluation in patients suffering from headache and facial pain.

A Belief Rule Based Expert System to Assess Mental Disorder under Uncertainty

DEFF Research Database (Denmark)

Hossain, Mohammad Shahadat; Afif Monrat, Ahmed; Hasan, Mamun

2016-01-01

to ignorance, incompleteness, and randomness. So, a belief rule-based expert system (BRBES) has been designed and developed with the capability of handling the uncertainties mentioned. Evidential reasoning works as the inference engine and the belief rule base as the knowledge representation schema......Mental disorder is a change of mental or behavioral pattern that causes sufferings and impairs the ability to function in ordinary life. In psychopathology, the assessment methods of mental disorder contain various types of uncertainties associated with signs and symptoms. This study identifies...

Actual neurosis as the underlying psychic structure of panic disorder, somatization, and somatoform disorder: an integration of Freudian and attachment perspectives.

Science.gov (United States)

Verhaeghe, Paul; Vanheule, Stijn; De Rick, Ann

2007-10-01

Starting from a contemporary critique of the DSM-IV, this paper argues that the diagnostic categories of panic disorder somatization, and undifferentiated somatoform disorders can be understood as belonging to a common type of psychopathology--i.e., the Freudian actual neuroses. In addition to their strong clinical similarity, these disorders share an etiological similarity; and the authors propose a combination of Freud's focus on this type of patient's inability to represent an endogenous drive arousal with the post-Freudian focus on separation anxiety. An etiological hypothesis is put forward based on contemporary psychoanalytic attachment theory, highlighting mentalization. Concrete implications for a psychoanalytically based treatment are proposed.

Integrating genetic and toxicogenomic information for determining underlying susceptibility to developmental disorders.

Science.gov (United States)

Robinson, Joshua F; Port, Jesse A; Yu, Xiaozhong; Faustman, Elaine M

2010-10-01

To understand the complex etiology of developmental disorders, an understanding of both genetic and environmental risk factors is needed. Human and rodent genetic studies have identified a multitude of gene candidates for specific developmental disorders such as neural tube defects (NTDs). With the emergence of toxicogenomic-based assessments, scientists now also have the ability to compare and understand the expression of thousands of genes simultaneously across strain, time, and exposure in developmental models. Using a systems-based approach in which we are able to evaluate information from various parts and levels of the developing organism, we propose a framework for integrating genetic information with toxicogenomic-based studies to better understand gene-environmental interactions critical for developmental disorders. This approach has allowed us to characterize candidate genes in the context of variables critical for determining susceptibility such as strain, time, and exposure. Using a combination of toxicogenomic studies and complementary bioinformatic tools, we characterize NTD candidate genes during normal development by function (gene ontology), linked phenotype (disease outcome), location, and expression (temporally and strain-dependent). In addition, we show how environmental exposures (cadmium, methylmercury) can influence expression of these genes in a strain-dependent manner. Using NTDs as an example of developmental disorder, we show how simple integration of genetic information from previous studies into the standard microarray design can enhance analysis of gene-environment interactions to better define environmental exposure-disease pathways in sensitive and resistant mouse strains. © Wiley-Liss, Inc.

Why gamblers fail to win: a review of cognitive and neuroimaging findings in pathological gambling

NARCIS (Netherlands)

van Holst, Ruth J.; van den Brink, Wim; Veltman, Dick J.; Goudriaan, Anna E.

2010-01-01

The purpose of this review is to gain more insight in the neuropathology of pathological gambling (PG) and problem gambling, and to discuss challenges in this research area. Results from the reviewed PG studies show that PG is more than just an impulse control disorder. PG seems to fit very well

[Hereditary factors in attention deficit hyperactivity disorder

NARCIS (Netherlands)

Fliers, E.A.; Franke, B.

2005-01-01

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by concentration problems, hyperactivity and impulsivity. Disturbances in dopamine and/or noradrenalin neurotransmission are probably the underlying pathophysiological mechanisms of ADHD. Around 80% of

Association between abnormal serum myelin-specific protein levels and white matter integrity in first-episode and drug-naïve patients with major depressive disorder.

Science.gov (United States)

Jiang, Linling; Cheng, Yuqi; Jiang, Hongyan; Xu, Jian; Lu, Jin; Shen, Zonglin; Lu, Yi; Liu, Fang; Li, Luqiong; Xu, Xiufeng

2018-05-01

Although the structural abnormalities of white matter (WM) have been described in patients with major depressive disorder (MDD), the neuropathological changes remain unclear. The current study aimed to investigate the myelin oligodendrocyte glycoprotein (MOG) and myelin-associated glycoprotein (MAG) levels and their correlations with WM integrity in first-episode, drug-naïve MDD patients. We obtained diffusion tensor images of 102 first-episode, drug-naïve MDD patients and 81 age- and sex-matched controls. Serum MOG and MAG levels of all participants were measured and compared between the two groups. The correlations between WM integrity and MOG and MAG levels were examined. MOG and MAG serum levels were significantly higher in MDD patients than in controls. Patients with MDD also showed decreased fractional anisotropy (FA) and axial diffusivity in the WM of the bilateral thalamus, right hippocampus, right temporal lobe, and left pulvinar. At the whole-brain level, no regions showed any correlations of diffusivity parameters with MOG or MAG levels in healthy subjects. However, we observed two-way correlations between the MOG and MAG levels and the FA and mean diffusivity values in the WM of the left middle frontal lobe, right inferior parietal lobe, and right supplementary motor area in MDD patients. Further investigation with a larger sample size and longitudinal studies are required to better understand the neuropathology of WM integrity in MDD. Our findings represent the first evidence of a relationship between abnormal serum myelin-specific protein levels and impaired WM integrity, which may help to better understand the neurobiological mechanisms of MDD. Copyright © 2018 Elsevier B.V. All rights reserved.

Mechanisms underlying the comorbidity between depressive and addictive disorders in adolescents: interactions between stress and HPA activity.

Science.gov (United States)

Rao, Uma; Hammen, Constance L; Poland, Russell E

2009-03-01

Depression may be a precursor to substance use disorder in some youngsters, and substance abuse might complicate the subsequent course of depression. This study examined whether hypothalamic-pituitary-adrenal (HPA) activity and stressful life experiences are related to the development of substance use disorder in depressed and nondepressed adolescents, and whether substance use disorder predicts a worsening course of depression. Urinary-free cortisol was measured for 3 nights in 151 adolescents with no prior history of substance use disorder (55 depressed, 48 at high risk for depression, and 48 normal subjects). Information was obtained on recent stressful life experiences. The participants were followed for up to 5 years to assess the onset of substance use disorder, course of depression, and stressful experiences. The relationships among depression, cortisol as a measure of HPA activity, stressful experiences, and substance use disorder were examined. Elevated cortisol was associated with onset of substance use disorder. Stressful life experiences moderated this relationship. Cortisol and stress accounted for the effects of a history or risk of depression on the development of substance use disorder. Substance use disorder was associated with higher frequency of subsequent depressive episodes. Higher cortisol prior to the onset of substance use disorder may indicate vulnerability to substance use disorder. Stressful experiences increase the risk for substance use disorder in such vulnerable youth. The high prevalence of substance use disorders in depressed individuals may be explained, in part, by high levels of stress and increased HPA activity.

Developmental pathway genes and neural plasticity underlying emotional learning and stress-related disorders.

Science.gov (United States)

Maheu, Marissa E; Ressler, Kerry J

2017-09-01

The manipulation of neural plasticity as a means of intervening in the onset and progression of stress-related disorders retains its appeal for many researchers, despite our limited success in translating such interventions from the laboratory to the clinic. Given the challenges of identifying individual genetic variants that confer increased risk for illnesses like depression and post-traumatic stress disorder, some have turned their attention instead to focusing on so-called "master regulators" of plasticity that may provide a means of controlling these potentially impaired processes in psychiatric illnesses. The mammalian homolog of Tailless (TLX), Wnt, and the homeoprotein Otx2 have all been proposed to constitute master regulators of different forms of plasticity which have, in turn, each been implicated in learning and stress-related disorders. In the present review, we provide an overview of the changing distribution of these genes and their roles both during development and in the adult brain. We further discuss how their distinct expression profiles provide clues as to their function, and may inform their suitability as candidate drug targets in the treatment of psychiatric disorders. © 2017 Maheu and Ressler; Published by Cold Spring Harbor Laboratory Press.

Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson's disease

NARCIS (Netherlands)

Doppler, Kathrin; Jentschke, Hanna-Maria; Schulmeyer, Lena; Vadasz, David; Janzen, Annette; Luster, Markus; Höffken, Helmut; Mayer, Geert; Brumberg, Joachim; Booij, Jan; Musacchio, Thomas; Klebe, Stephan; Sittig-Wiegand, Elisabeth; Volkmann, Jens; Sommer, Claudia; Oertel, Wolfgang H.

2017-01-01

Phosphorylated alpha-synuclein (p-alpha-syn) deposits, one of the neuropathological hallmarks of Parkinson's disease (PD), have recently been detected in dermal nerve fibres in PD patients with good specificity and sensitivity. Here, we studied whether p-alpha-syn may serve as a biomarker in

Psychotherapy and Pharmacotherapy for Patients with Dissociative Identity Disorder

OpenAIRE

Gentile, Julie P.; Dillon, Kristy S.; Gillig, Paulette Marie

2013-01-01

There is a wide variety of what have been called “dissociative disorders,” including dissociative amnesia, dissociative fugue, depersonalization disorder, dissociative identity disorder, and forms of dissociative disorder not otherwise specified. Some of these diagnoses, particularly dissociative identity disorder, are controversial and have been questioned by many clinicians over the years. The disorders may be under-diagnosed or misdiagnosed, but many persons who have experienced trauma rep...

Neuroimaging of tic disorders with co-existing attention-deficit/hyperactivity disorder

DEFF Research Database (Denmark)

Plessen, Kerstin J; Royal, Jason M; Peterson, Bradley S

2007-01-01

BACKGROUND: Tourette syndrome (TS) and Attention-Deficit/Hyperactivity Disorder (ADHD) are common and debilitating neuropsychiatric illnesses that typically onset in the preschool years. Recently, both conditions have been subject to neuroimaging studies, with the aim of understanding...... contrast these findings with those in ADHD without comorbid tic disorders. RESULTS: The frequent comorbidity of TS and ADHD may reflect a common underlying neurobiological substrate, and studies confirm the hypothesized involvement of fronto-striatal circuits in both TS and ADHD. However, poor inhibitory...

Genotyping Sleep Disorders Patients

OpenAIRE

Kripke, Daniel F.; Shadan, Farhad F.; Dawson, Arthur; Cronin, John W.; Jamil, Shazia M.; Grizas, Alexandra P.; Koziol, James A.; Kline, Lawrence E.

2010-01-01

Objective The genetic susceptibility factors underlying sleep disorders might help us predict prognoses and responses to treatment. Several candidate polymorphisms for sleep disorders have been proposed, but there has as yet inadequate replication or validation that the candidates may be useful in the clinical setting. Methods To assess the validity of several candidate associations, we obtained saliva deoxyribonucleic acid (DNA) samples and clinical information from 360 consenting research p...

Quantitative measurement of Nerve Growth Factor in rat brain after acute and chronic application of lithium and carbamazepine

OpenAIRE

Nagel, Michael

2010-01-01

Bipolar affective disorder is a frequent, recurring affective disease with a high rate of mortality and co-morbidity. Manic as well as depressive episodes occur in its course. There are some indicators, that patients with bipolar affective disorder show a decrease in volume and metabolism of certain areas of the brain. This is accompanied by neuronal atrophy or loss of neurons. This assumption is supported by radiological as well as neuropathological findings of this patient group. A possi...

Slower EEG alpha generation, synchronization and “flow”—possible biomarkers of cognitive impairment and neuropathology of minor stroke

Directory of Open Access Journals (Sweden)

Jelena Petrovic

2017-09-01

Full Text Available Background We investigated EEG rhythms, particularly alpha activity, and their relationship to post-stroke neuropathology and cognitive functions in the subacute and chronic stages of minor strokes. Methods We included 10 patients with right middle cerebral artery (MCA ischemic strokes and 11 healthy controls. All the assessments of stroke patients were done both in the subacute and chronic stages. Neurological impairment was measured using the National Institute of Health Stroke Scale (NIHSS, whereas cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA and MoCA memory index (MoCA-MIS. The EEG was recorded using a 19 channel EEG system with standard EEG electrode placement. In particular, we analyzed the EEGs derived from the four lateral frontal (F3, F7, F4, F8, and corresponding lateral posterior (P3, P4, T5, T6 electrodes. Quantitative EEG analysis included: the group FFT spectra, the weighted average of alpha frequency (αAVG, the group probability density distributions of all conventional EEG frequency band relative amplitudes (EEG microstructure, the inter- and intra-hemispheric coherences, and the topographic distribution of alpha carrier frequency phase potentials (PPs. Statistical analysis was done using a Kruskal–Wallis ANOVA with a post-hoc Mann–Whitney U two-tailed test, and Spearman’s correlation. Results We demonstrated transient cognitive impairment alongside a slower alpha frequency (αAVG in the subacute right MCA stroke patients vs. the controls. This slower alpha frequency showed no amplitude change, but was highly synchronized intra-hemispherically, overlying the ipsi-lesional hemisphere, and inter-hemispherically, overlying the frontal cortex. In addition, the disturbances in EEG alpha activity in subacute stroke patients were expressed as a decrease in alpha PPs over the frontal cortex and an altered “alpha flow”, indicating the sustained augmentation of inter-hemispheric interactions

Cerebrospinal fluid biomarkers profile of idiopathic normal pressure hydrocephalus.

Science.gov (United States)

Schirinzi, Tommaso; Sancesario, Giulia Maria; Di Lazzaro, Giulia; D'Elia, Alessio; Imbriani, Paola; Scalise, Simona; Pisani, Antonio

2018-04-01

Idiopathic normal pressure hydrocephalus (iNPH) is a disabling neurological disorder whose potential treatability is significantly limited by diagnostic uncertainty. In fact, typical clinical presentation occurs at late phases of disease, when CSF shunting could be ineffective. In recent years, measurement of different CSF proteins, whose concentration directly reflects neuropathological changes of CNS, has significantly improved both diagnostic timing and accuracy of neurodegenerative disease. Unfortunately iNPH lacks neuropathological hallmarks allowing the identification of specific disease biomarkers. However, neuropathology of iNPH is so rich and heterogeneous that many processes can be tracked in CSF, including Alzheimer's disease core pathology, subcortical degeneration, neuroinflammation and vascular dysfunction. Indeed, a huge number of CSF biomarkers have been analyzed in iNPH patients, but a unifying profile has not been provided yet. In this brief survey, we thus attempted to summarize the main findings in the field of iNPH CSF biomarkers, aimed at outlining a synthetic model. Although defined cut-off values for biomarkers are not available, a better knowledge of CSF characteristics may definitely assist in diagnosing the disease.

The development of psychotic disorders in adolescence: a potential role for hormones.

Science.gov (United States)

Trotman, Hanan D; Holtzman, Carrie W; Ryan, Arthur T; Shapiro, Daniel I; MacDonald, Allison N; Goulding, Sandra M; Brasfield, Joy L; Walker, Elaine F

2013-07-01

This article is part of a Special Issue "Puberty and Adolescence". The notion that adolescence is characterized by dramatic changes in behavior, and often by emotional upheaval, is widespread and longstanding in popular western culture. In recent decades, this notion has gained increasing support from empirical research showing that the peri- and post-pubertal developmental stages are associated with a significant rise in the rate of psychiatric symptoms and syndromes. As a result, interest in adolescent development has burgeoned among researchers focused on the origins of schizophrenia and other psychotic disorders. Two factors have fueled this trend: 1) increasing evidence from longitudinal research that adolescence is the modal period for the emergence of "prodromal" manifestations, or precursors of psychotic symptoms, and 2) the rapidly accumulating scientific findings on brain structural and functional changes occurring during adolescence and young adulthood. Further, gonadal and adrenal hormones are beginning to play a more prominent role in conceptualizations of adolescent brain development, as well as in the origins of psychiatric symptoms during this period (Walker and Bollini, 2002; Walker et al., 2008). In this paper, we begin by providing an overview of the nature and course of psychotic disorders during adolescence/young adulthood. We then turn to the role of hormones in modulating normal brain development, and the potential role they might play in the abnormal brain changes that characterize youth at clinical high-risk (CHR) for psychosis. The activational and organizational effects of hormones are explored, with a focus on how hormone-induced changes might be linked with neuropathological processes in the emergence of psychosis. Copyright © 2013 Elsevier Inc. All rights reserved.

X-ray diffraction study of the Y{sub 2}Ti{sub 2}O{sub 7} pyrochlore disordering sequence under irradiation

Energy Technology Data Exchange (ETDEWEB)

Soulié, Aurélien, E-mail: aurelien.soulie@cea.fr [CEA, DEN, Service de Recherches de Métallurgie Physique, Université Paris-Saclay, F-91191 Gif sur Yvette (France); CEA, DEN, Service de Recherches de Métallurgie Appliqué, Université Paris-Saclay, F-91191 Gif sur Yvette (France); Menut, Denis [CEA, DEN, Service de Recherches de Métallurgie Appliqué, Université Paris-Saclay, F-91191 Gif sur Yvette (France); Crocombette, Jean-Paul [CEA, DEN, Service de Recherches de Métallurgie Physique, Université Paris-Saclay, F-91191 Gif sur Yvette (France); Chartier, Alain [CEA, DEN, Service de la Corrosion et du Comportement des Matériaux dans leur Environnement, Laboratoire de Modélisation, de Thermodynamique et de Thermochimie, Université Paris-Saclay, F-91191 Gif sur Yvette (France); Sellami, Neila [Univ. Paris Sud, ICMMO-SP2M, Bât. 410, F-91405 Orsay (France); Sattonnay, Gaël [Univ. Paris-Sud, CSNSM, CNRS, IN2P3, Bât. 108, F-91405 Orsay (France); Monnet, Isabelle [CIMAP, CEA, CNRS, Université de Caen, BP 5133, F-14070 Caen Cedex 5 (France); and others

2016-11-15

The disordering sequence of Y{sub 2}Ti{sub 2}O{sub 7} pyrochlore, a nano-oxide phase that strengthens ODS steels under irradiation is studied in the experimental and modeling framework. XRD analysis has been performed considering both swift heavy ion and low energy/low mass ion irradiations. The simulation within molecular dynamics of Frenkel pair accumulation proves able to reproduce the variation of the amorphization fluence with temperature. XRD patterns calculated from the simulations reproduce well the patterns observed experimentally in the literature. Both experiments and calculations point to a first transition from pyrochlore to fluorite before an eventual amorphization. For swift heavy ion irradiations with 93 MeV Xe ions, tracks of direct impact amorphization are visible by HRTEM. Advanced refinement shows that one third of the pyrochlore impacted by an ion transforms into fluorite, while two third are directly amorphized. - Highlights: • A comparison between swift heavy ion and low energy/low mass ion irradiation of Y{sub 2}Ti{sub 2}O{sub 7} pyrochlore is performed. • Simulations of the irradiation with Molecular dynamics reproduce the amorphization dose at low energy/mass ion irradiation. • Advanced refinement of X-ray diffraction patterns gives the evolution of phase fractions in pyrochlore under irradiation. • The disordering sequence a transition from pyrochlore to defect fluorite before an eventual amorphization.

[Specificities of the logopenic variant of primary progressive aphasia].

Science.gov (United States)

Magnin, E; Teichmann, M; Martinaud, O; Moreaud, O; Ryff, I; Belliard, S; Pariente, J; Moulin, T; Vandel, P; Démonet, J-F

2015-01-01

The logopenic variant of primary progressive aphasia is a syndrome with neuropsychological and linguistic specificities, including phonological loop impairment for which diagnosis is currently mainly based on the exclusion of the two other variants, semantic and nonfluent/agrammatic primary progressive aphasia. The syndrome may be underdiagnosed due (1) to mild language difficulties during the early stages of the disease or (2) to being mistaken for mild cognitive impairment or Alzheimer's disease when the evaluation of episodic memory is based on verbal material and (3) finally, it is not uncommon that the disorders are attributed to psychiatric co-morbidities such as, for example, anxiety. Moreover, compared to other variants of primary progressive aphasia, brain abnormalities are different. The left temporoparietal junction is initially affected. Neuropathology and biomarkers (cerebrospinal fluid, molecular amyloid nuclear imaging) frequently reveal Alzheimer's disease. Consequently this variant of primary progressive aphasia does not fall under the traditional concept of frontotemporal lobar degeneration. These distinctive features highlight the utility of correct diagnosis, classification, and use of biomarkers to show the neuropathological processes underlying logopenic primary progressive aphasia. The logopenic variant of primary progressive aphasia is a specific form of Alzheimer's disease frequently presenting a rapid decline; specific linguistic therapies are needed. Further investigation of this syndrome is needed to refine screening, improve diagnostic criteria and better understand the epidemiology and the biological mechanisms involved. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Quantitative neuropathological study of Alzheimer-type pathology in the hippocampus: comparison of senile dementia of Alzheimer type, senile dementia of Lewy body type, Parkinson's disease and non-demented elderly control patients.

Science.gov (United States)

Ince, P; Irving, D; MacArthur, F; Perry, R H

1991-12-01

A Lewy body dementing syndrome in the elderly has been recently described and designated senile dementia of Lewy body type (SDLT) on the basis of a distinct clinicopathological profile. The pathological changes seen in SDLT include the presence of cortical Lewy bodies (LB) frequently, but not invariably, associated with senile plaque (SP) formation. Whilst neocortical neurofibrillary tangles (NFT) are sparse or absent, a proportion of these cases show involvement of the temporal archicortex by lesions comprising Alzheimer-type pathology (ATP, i.e. NFT, SP and granulovacuolar degeneration [GVD]). Thus the relationship between SDLT and senile dementia of Alzheimer type (SDAT) is complex and controversial. In this study quantitative neuropathology was used to compare the intensity and distribution of ATP in the hippocampus and entorhinal cortex of 53 patients from 3 disease groups (SDLT, SDAT, Parkinson's disease (PD)) and a group of neurologically and mentally normal elderly control patients. For most brain areas examined the extent of ATP between the patient groups followed the trend SDAT greater than SDLT greater than PD greater than control. Statistical comparison of these groups revealed significant differences between the mean densities of NFT, SP and GVD although individual cases showed considerable variability. These results confirm additional pathological differences between SDAT and SDLT regarding the intensity of involvement of the temporal archicortex by ATP. Many patients with Lewy body disorders (LBdis) show a predisposition to develop ATP albeit in a more restricted distribution (e.g. low or absent neocortical NFT) and at lower densities than is found in SDAT. Some cases of SDLT show minimal SP and NFT formation in both neocortex and archicortex supporting previously published data distinguishing this group from Alzheimer's disease.

New systems of care for substance use disorders: treatment, finance, and technology under health care reform.

Science.gov (United States)

Pating, David R; Miller, Michael M; Goplerud, Eric; Martin, Judith; Ziedonis, Douglas M

2012-06-01

This article outlined ways in which persons with addiction are currently underserved by our current health care system. However, with the coming broad scale reforms to our health care system, the access to and availability of high-quality care for substance use disorders will increase. Addiction treatments will continue to be offered through traditional substance abuse care systems, but these will be more integrated with primary care, and less separated as treatment facilities leverage opportunities to blend services, financing mechanisms, and health information systems under federally driven incentive programs. To further these reforms, vigilance will be needed by consumers, clinicians, and policy makers to assure that the unmet treatment needs of individuals with addiction are addressed. Embedded in this article are essential recommendations to facilitate the improvement of care for substance use disorders under health care reform. Ultimately, as addiction care acquires more of the “look and feel” of mainstream medicine, it is important to be mindful of preexisting trends in health care delivery overall that are reflected in recent health reform legislation. Within the world of addiction care, clinicians must move beyond their self-imposed “stigmatization” and sequestration of specialty addiction treatment. The problem for addiction care, as it becomes more “mainstream,” is to not comfortably feel that general slogans like “Treatment Works,” as promoted by Substance Abuse and Mental Health Services Administration’s Center for Substance Abuse Treatment during its annual Recovery Month celebrations, will meet the expectations of stakeholders outside the specialty addiction treatment community. Rather, the problem is to show exactly how addiction treatment works, and to what extent it works-there have to be metrics showing changes in symptom level or functional outcome, changes in health care utilization, improvements in workplace attendance and

White matter tract integrity in treatment-resistant gambling disorder

DEFF Research Database (Denmark)

Chamberlain, Samuel R.; Derbyshire, Katherine; Daws, Richard E.

2016-01-01

Background: Gambling disorder is a relatively common psychiatric disorder recently re-classified within the DSM-5 under the category of ‘substance-related and addictive disorders’. Aims: To compare white matter integrity in patients with gambling disorder with healthy controls; to explore...

Selective layer disordering in III-nitrides with a capping layer

Science.gov (United States)

Wierer, Jr., Jonathan J.; Allerman, Andrew A.

2016-06-14

Selective layer disordering in a doped III-nitride superlattice can be achieved by depositing a dielectric capping layer on a portion of the surface of the superlattice and annealing the superlattice to induce disorder of the layer interfaces under the uncapped portion and suppress disorder of the interfaces under the capped portion. The method can be used to create devices, such as optical waveguides, light-emitting diodes, photodetectors, solar cells, modulators, laser, and amplifiers.

Evaluation of Planning Dysfunction in Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorders Using the Zoo Map Task

Science.gov (United States)

Salcedo-Marin, M. D.; Moreno-Granados, J. M.; Ruiz-Veguilla, M.; Ferrin, M.

2013-01-01

Attention-Deficit-Hyperactivity-Disorders (ADHD) and Autistic-Spectrum-Disorders (ASD) share overlapping clinical and cognitive features that may confuse the diagnosis. Evaluation of executive problems and planning dysfunction may aid the clinical diagnostic process and help disentangle the neurobiological process underlying these conditions. This…

Microglia Responses in Acute and Chronic Neurological Diseases: What Microglia-Specific Transcriptomic Studies Taught (and did Not Teach Us

Directory of Open Access Journals (Sweden)

Hélène E. Hirbec

2017-07-01

Full Text Available Over the last decade, microglia have been acknowledged to be key players in central nervous system (CNS under both physiological and pathological conditions. They constantly survey the CNS environment and as immune cells, in pathological contexts, they provide the first host defense and orchestrate the immune response. It is well recognized that under pathological conditions microglia have both sequential and simultaneous, beneficial and detrimental effects. Cell-specific transcriptomics recently became popular in Neuroscience field allowing concurrent monitoring of the expression of numerous genes in a given cell population. Moreover, by comparing two or more conditions, these approaches permit to unbiasedly identify deregulated genes and pathways. A growing number of studies have thus investigated microglial transcriptome remodeling over the course of neuropathological conditions and highlighted the molecular diversity of microglial response to different diseases. In the present work, we restrict our review to microglia obtained directly from in vivo samples and not cell culture, and to studies using whole-genome strategies. We first critically review the different methods developed to decipher microglia transcriptome. In particular, we compare advantages and drawbacks of flow cytometry and laser microdissection to isolate pure microglia population as well as identification of deregulated microglial genes obtained via RNA sequencing (RNA-Seq vs. microarrays approaches. Second, we summarize insights obtained from microglia transcriptomes in traumatic brain and spinal cord injuries, pain and more chronic neurological conditions including Amyotrophic lateral sclerosis (ALS, Alzheimer disease (AD and Multiple sclerosis (MS. Transcriptomic responses of microglia in other non-neurodegenerative CNS disorders such as gliomas and sepsis are also addressed. Third, we present a comparison of the most activated pathways in each neuropathological condition

Whiplash-Associated Disorders

DEFF Research Database (Denmark)

Ferrara, S. D.; Ananian, V.; Baccino, E.

2016-01-01

The manuscript presents the International Guidelines developed by the Working Group on Personal Injury and Damage under the patronage of the International Academy of Legal Medicine (IALM) regarding the Methods of Ascertainment of any suspected Whiplash-Associated Disorders (WAD). The document...

The relation among perfectionism, obsessive-compulsive personality disorder and obsessive-compulsive disorder in individuals with eating disorders.

Science.gov (United States)

Halmi, Katherine A; Tozzi, Federica; Thornton, Laura M; Crow, Scott; Fichter, Manfred M; Kaplan, Allan S; Keel, Pamela; Klump, Kelly L; Lilenfeld, Lisa R; Mitchell, James E; Plotnicov, Katherine H; Pollice, Christine; Rotondo, Alessandro; Strober, Michael; Woodside, D Blake; Berrettini, Wade H; Kaye, Walter H; Bulik, Cynthia M

2005-12-01

Perfectionism and obsessionality are core features of eating disorders (ED), yet the nature of their relation remains unknown. Understanding the relation between these traits may enhance our ability to identify relevant behavioral endophenotypes for ED. Six-hundred seven individuals with anorexia and bulimia nervosa from the International Price Foundation Genetic Study were assessed for perfectionism, obsessive-compulsive personality disorder (OCPD), and obsessive-compulsive disorder (OCD). No differences were found across ED subtypes in the prevalence of OCPD and OCD, nor with the association between OCD and OCPD. Perfectionism scores were highest in individuals with OCPD whether alone or in combination with OCD. Perfectionism appears to be more closely associated with obsessive-compulsive personality symptoms rather than OCD. The pairing of perfectionism with OCPD may be a relevant core behavioral feature underlying vulnerability to ED. Copyright 2005 by Wiley Periodicals, Inc.

Specific learning disorder: prevalence and gender differences.

Directory of Open Access Journals (Sweden)

Kristina Moll

Full Text Available Comprehensive models of learning disorders have to consider both isolated learning disorders that affect one learning domain only, as well as comorbidity between learning disorders. However, empirical evidence on comorbidity rates including all three learning disorders as defined by DSM-5 (deficits in reading, writing, and mathematics is scarce. The current study assessed prevalence rates and gender ratios for isolated as well as comorbid learning disorders in a representative sample of 1633 German speaking children in 3rd and 4th Grade. Prevalence rates were analysed for isolated as well as combined learning disorders and for different deficit criteria, including a criterion for normal performance. Comorbid learning disorders occurred as frequently as isolated learning disorders, even when stricter cutoff criteria were applied. The relative proportion of isolated and combined disorders did not change when including a criterion for normal performance. Reading and spelling deficits differed with respect to their association with arithmetic problems: Deficits in arithmetic co-occurred more often with deficits in spelling than with deficits in reading. In addition, comorbidity rates for arithmetic and reading decreased when applying stricter deficit criteria, but stayed high for arithmetic and spelling irrespective of the chosen deficit criterion. These findings suggest that the processes underlying the relationship between arithmetic and reading might differ from those underlying the relationship between arithmetic and spelling. With respect to gender ratios, more boys than girls showed spelling deficits, while more girls were impaired in arithmetic. No gender differences were observed for isolated reading problems and for the combination of all three learning disorders. Implications of these findings for assessment and intervention of learning disorders are discussed.

Stereotyped movement disorder in ICD-11.

Science.gov (United States)

Stein, Dan J; Woods, Douglas W

2014-01-01

According to current proposals for ICD-11, stereotyped movement disorder will be classified in the grouping of neurodevelopmental disorders, with a qualifier to indicate whether self-injury is present, similar to the classification of stereotypic movement disorder in DSM-5. At the same time, the WHO ICD-11 Working Group on the Classification of Obsessive-Compulsive and Related Disorders has proposed a grouping of body-focused repetitive behavior disorders within the obsessive-compulsive and related disorders (OCRD) cluster to include trichotillomania and skin-picking disorder. DSM-5 has taken a slightly different approach: trichotillomania and excoriation (skin picking) disorder are included in the OCRD grouping, while body-focused repetitive behavior disorder is listed under other specified forms of OCRD. DSM-5 also includes a separate category of nonsuicidal self-injury in the section on "conditions for further study." There are a number of unresolved nosological questions regarding the relationships among stereotyped movement disorder, body-focused repetitive behavior disorders, and nonsuicidal self-injury. In this article, we attempt to provide preliminary answers to some of these questions as they relate to the ICD-11 classification of mental and behavioral disorders.

Potentiating mGluR5 Function with a Positive Allosteric Modulator Enhances Adaptive Learning

Science.gov (United States)

Xu, Jian; Zhu, Yongling; Kraniotis, Stephen; He, Qionger; Marshall, John J.; Nomura, Toshihiro; Stauffer, Shaun R.; Lindsley, Craig W.; Conn, P. Jeffrey; Contractor, Anis

2013-01-01

Metabotropic glutamate receptor 5 (mGluR5) plays important roles in modulating neural activity and plasticity and has been associated with several neuropathological disorders. Previous work has shown that genetic ablation or pharmacological inhibition of mGluR5 disrupts fear extinction and spatial reversal learning, suggesting that mGluR5…

Disorders of water homeostasis in neurosurgical patients.

LENUS (Irish Health Repository)

Hannon, Mark J

2012-05-01

Context: Disorders of water balance are common in neurosurgical patients and usually manifest as hypo- or hypernatremia. They are most commonly seen after subarachnoid hemorrhage, traumatic brain injury, with intracranial tumors, and after pituitary surgery. Setting: We reviewed the experience of endocrine evaluation and management of disorders of salt and water balance in a large cohort of inpatients attending the national neurosciences referral centre in Dublin, Ireland, and compared this experience with findings from other studies. Patients: The study group included unselected neurosurgical patients admitted to our centre and requiring endocrine evaluation. Interventions: We conducted investigations to determine the underlying mechanistic basis for disorders of salt and water balance in neurosurgical patients and treatment to restore normal metabolism. Main Outcome Measures: Morbidity and mortality associated with deranged salt and water balance were measured. Results: The underlying pathophysiology of disordered water balance in neurosurgical patients is complex and varied and dictates the optimal therapeutic approach. Conclusions: A systematic and well-informed approach is needed to properly diagnose and manage disorders of salt and water balance in neurosurgical patients.

Factors affecting increased risk for substance use disorders following traumatic brain injury: What we can learn from animal models.

Science.gov (United States)

Merkel, Steven F; Cannella, Lee Anne; Razmpour, Roshanak; Lutton, Evan; Raghupathi, Ramesh; Rawls, Scott M; Ramirez, Servio H

2017-06-01

Recent studies have helped identify multiple factors affecting increased risk for substance use disorders (SUDs) following traumatic brain injury (TBI). These factors include age at the time of injury, repetitive injury and TBI severity, neurocircuits, neurotransmitter systems, neuroinflammation, and sex differences. This review will address each of these factors by discussing 1) the clinical and preclinical data identifying patient populations at greatest risk for SUDs post-TBI, 2) TBI-related neuropathology in discrete brain regions heavily implicated in SUDs, and 3) the effects of TBI on molecular mechanisms that may drive substance abuse behavior, like dopaminergic and glutamatergic transmission or neuroimmune signaling in mesolimbic regions of the brain. Although these studies have laid the groundwork for identifying factors that affect risk of SUDs post-TBI, additional studies are required. Notably, preclinical models have been shown to recapitulate many of the behavioral, cellular, and neurochemical features of SUDs and TBI. Therefore, these models are well suited for answering important questions that remain in future investigations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Frontostriatal Dysfunction During Decision Making in Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder.

Science.gov (United States)

Norman, Luke J; Carlisi, Christina O; Christakou, Anastasia; Murphy, Clodagh M; Chantiluke, Kaylita; Giampietro, Vincent; Simmons, Andrew; Brammer, Michael; Mataix-Cols, David; Rubia, Katya

2018-03-24

The aim of the current paper is to provide the first comparison of computational mechanisms and neurofunctional substrates in adolescents with attention-deficit/hyperactivity disorder (ADHD) and adolescents with obsessive-compulsive disorder (OCD) during decision making under ambiguity. Sixteen boys with ADHD, 20 boys with OCD, and 20 matched control subjects (12-18 years of age) completed a functional magnetic resonance imaging version of the Iowa Gambling Task. Brain activation was compared between groups using three-way analysis of covariance. Hierarchical Bayesian analysis was used to compare computational modeling parameters between groups. Patient groups shared reduced choice consistency and relied less on reinforcement learning during decision making relative to control subjects, while adolescents with ADHD alone demonstrated increased reward sensitivity. During advantageous choices, both disorders shared underactivation in ventral striatum, while OCD patients showed disorder-specific underactivation in the ventromedial orbitofrontal cortex. During outcome evaluation, shared underactivation to losses in patients relative to control subjects was found in the medial prefrontal cortex and shared underactivation to wins was found in the left putamen/caudate. ADHD boys showed disorder-specific dysfunction in the right putamen/caudate, which was activated more to losses in patients with ADHD but more to wins in control subjects. The findings suggest shared deficits in using learned reward expectancies to guide decision making, as well as shared dysfunction in medio-fronto-striato-limbic brain regions. However, findings of unique dysfunction in the ventromedial orbitofrontal cortex in OCD and in the right putamen in ADHD indicate additional, disorder-specific abnormalities and extend similar findings from inhibitory control tasks in the disorders to the domain of decision making under ambiguity. Copyright © 2018 Society of Biological Psychiatry. Published by

A possible common basis for MDD, bipolar disorder and schizophrenia: Lessons from electrophysiology

Directory of Open Access Journals (Sweden)

Goded eShahaf

2016-06-01

Full Text Available There is ample electrophysiological evidence of attention dysfunction in the EEG/ERP signal of various psychopathologies such as major depressive disorder (MDD, bipolar disorder, and schizophrenia. The reduced attention-related ERP waves show much similarity between MDD, bipolar disorder, and schizophrenia, raising the question whether there are similarities in the neurophysiologic process that underlies attention dysfunction in these pathologies. The present work suggests that there is such a unified underlying neurophysiologic process, which results in reduced attention in the three pathologies. Naturally, as these pathologies involve different clinical manifestations, we expect differences in their underlying neurophysiology. These differences and their subtle manifestation in the ERP marker for attention are also discussed.MDD, bipolar disorder and schizophrenia are just three of multiple neuropsychiatric disorders, which involve changes in the EEG/ERP manifestations of attention. Further work should expand the basic model presented here to offer comprehensive modeling of these multiple disorders and to emphasize similarities and dissimilarities of the underlying neurophysiologic processes.

Regional glucose utilization and blood flow following graded forebrain ischemia in the rat: correlation with neuropathology

International Nuclear Information System (INIS)

Ginsberg, M.D.; Graham, D.I.; Busto, R.

1985-01-01

Regional patterns of cerebral glucose utilization (rCMRglc) and blood flow (rCBF) were examined in the early recovery period following transient forebrain ischemia in order to correlate early postischemic physiological events with regionally selective patterns of ischemic neuropathology. Wistar rats were subjected to 30 or 60 minutes of graded forebrain ischemia by a method combining unilateral occlusion of the common carotid artery with moderate elevation of intracranial pressure and mild hypotension; this procedure results in a high-grade ischemic deficit affecting chiefly the lateral neocortex, striatum, and hippocampus ipsilateral to the carotid occlusion. Simultaneous measurements of rCMRglc and rCBF made in regional tissue samples after 2 and 4 hours of postischemic recirculation using a double-tracer radioisotopic strategy revealed a disproportionately high level of glucose metabolism relative to blood flow in the early postischemic striatum, owing to the resumption of nearly normal rCMRglc in the face of depressed flow. In contrast, the neocortex, which had been equally ischemic, showed parallel depressions of both metabolism and blood flow during early recovery. Light microscopy at 4 and 8 hours after recovery revealed the striatum to be the predominant locus of ischemic neuronal alterations, whereas neocortical lesions were much less prominent in extent and severity at this time. The resumption of normal levels of metabolism in the setting of a disproportionate depression of rCBF in the early postischemic period may accentuate the process of neuronal injury initiated by ischemia and may contribute to the genesis of neuronal necrosis in selectively vulnerable areas of the forebrain

Attention Deficit Hyperactivity Disorder

Science.gov (United States)

Matthews, Marguerite; Nigg, Joel T.

2014-01-01

Over the last two decades, there have been numerous technical and methodological advances available to clinicians and researchers to better understand attention deficit hyperactivity disorder (ADHD) and its etiology. Despite the growing body of literature investigating the disorder’s pathophysiology, ADHD remains a complex psychiatric disorder to characterize. This chapter will briefly review the literature on ADHD, with a focus on its history, the current genetic insights, neurophysiologic theories, and the use of neuroimaging to further understand the etiology. We address some of the major concerns that remain unclear about ADHD, including subtype instability, heterogeneity, and the underlying neural correlates that define the disorder. We highlight that the field of ADHD is rapidly evolving; the descriptions provided here will hopefully provide a sturdy foundation for which to build and improve our understanding of the disorder. PMID:24214656

Diagnosis, treatment, and neurobiology of autism in children.

Science.gov (United States)

Lainhart, J E; Piven, J

1995-08-01

Autism is a developmental neuropsychiatric disorder defined by the presence of social and communicative deficits, restricted and repetitive behaviors and interests, and a characteristic course. Research suggests that hereditary factors play a principal role in the etiology of most cases. A phenotype broader than autism, including milder social and language-based cognitive deficits, appears to be inherited. Although the pathogenesis is unknown, neurobiologic mechanisms clearly underlie the disorder. Neuropathologic studies have demonstrated abnormalities in limbic structures, the cerebellum, and the cortex. New advances in behavioral therapies and pharmacologic treatment are important components of successful multidisciplinary treatment of this disorder.

Selenomethionine Ameliorates Neuropathology in the Olfactory Bulb of a Triple Transgenic Mouse Model of Alzheimer’s Disease

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Zhong-Hao Zhang

2016-09-01

Full Text Available Olfactory dysfunction is an early and common symptom in Alzheimer′s disease (AD and is reported to be related to several pathologic changes, including the deposition of Aβ and hyperphosphorylated tau protein as well as synaptic impairment. Selenomethionine (Se-Met, the major form of selenium in animals and humans, may be a promising therapeutic option for AD as it decreases the deposition of Aβ and tau hyperphosphorylation in a triple transgenic mouse model of AD (3× Tg-AD. In this study, 4-month-old AD mice were treated with 6 µg/mL Se-Met in drinking water for 12 weeks and the effect of Se-Met on neuropathological deficits in olfactory bulb (OB of 3× Tg-AD mice was investigated. The administration of Se-Met effectively decreased the production and deposition of Aβ by inhibiting β-site amyloid precursor protein cleaving enzyme 1 (BACE1-regulated amyloid precursor protein (APP processing and reduced the level of total tau and phosphorylated tau, which depended on depressing the activity and expression of glycogen synthase kinase-3β (GSK-3β and cyclin-dependent kinase 5 (CDK5. Meanwhile, Se-Met reduced glial activation, relieved neuroinflammation and attenuated neuronal cell death in the OB of AD mice. So Se-Met could improve pathologic changes of AD in the OB, which further demonstrated the potential therapeutic effect of Se-Met in AD.

Effects of three months treatment with sertraline on intraocular pressure and cup-to-disc ratio in patients with anxiety disorders/mixed anxiety and depressive disorder/major depressive disorder and without underlying eye disease

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Narjes Hendouei

2017-09-01

Full Text Available Exposure to selective serotonin reuptake inhibitors causes pupillary dilator muscle stimulation, active mydriasis, rapid rise in the level of the intraocular pressure (IOP, damage to the optic nerve at the back of the eye, and ultimately leads to acute angle closure glaucoma. The aim of this study was to assess the effects of sertraline on the levels of IOP and cup-to-disc ratio (CDR in patients with anxiety disorders or mixed anxiety and depressive disorder or major depressive under daily treatment with sertraline and without underlying eye disease for three months. In this study,30 eligible patients in the sertraline group and 30 healthy volunteers in the control group include the study and were referred to an ophthalmologist. Ophthalmologic examinations were assessed at the baseline and on the first and third months of the study. The average daily dose of sertraline was 95±2.5 mg.During the study, the IOP changes in the sertraline and control groups were 0.26±0.43 and 0.00±0.00 mmHg (p<0.001, p=NS respectively and the CDR changes in sertraline and control groups were 0.03±0.05 and -0.01±0.05 (p=0.002, p=0.03 respectively. There was a significant difference in the IOP and CDR increasement between two groups ([F (1.7, 104.2 = 3.7, p = 0.03] and [F (2, 116 = 8.3, p < 0.001] respectively. In the present study, although changes in the IOP and CDR  levels in the sertraline group were significant and was equal the daily change in the persons without glaucoma or patients with normal-tension glaucoma, but the slight and continuous increase in the IOP level associated with changes in pupil size and CDR, especially in patients at risk of glaucoma in the long term, can cause a disruption in hydrodynamic homeostasis. More studies with longer duration and different dosage of sertraline need to confirm our results.     

Impaired decision-making under risk is associated with gaming-specific inhibition deficits among college students with Internet gaming disorder.

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Yao, Yuan-Wei; Wang, Ling-Jiao; Yip, Sarah W; Chen, Pin-Ru; Li, Song; Xu, Jiansong; Zhang, Jin-Tao; Deng, Lin-Yuan; Liu, Qin-Xue; Fang, Xiao-Yi

2015-09-30

A growing body of evidence indicates that both inhibition and decision-making deficits play essential roles in the development and maintenance of Internet gaming disorder (IGD). Clarifying whether impaired decision-making among individuals with IGD is related to poor inhibition will advance our understanding of IGD and contribute to intervention development. However, the relationship between these two functions remains unclear. In this study, we sought to systemically examine inhibitory processes, decision-making and the relationship between the two among individuals with IGD. Thirty-four individuals with IGD and 32 matched healthy controls (HCs) were recruited. In comparison to HCs, IGD subjects demonstrated inhibition deficits during performance of the gaming-related Go/No-Go task and impaired decision-making under risk. In addition, errors on No-Go trials during the gaming-related Go/No-Go task were positively associated with decision-making impairments under risk but not under ambiguity among IGD subjects. These results suggest individuals with IGD are impaired in some aspects of inhibition and decision-making functions, and that decision-making deficits under risk are linked to poor inhibition specifically related to gaming cues, which has implications for the development of novel intervention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Sleep disorders in cerebellar ataxias

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José L. Pedroso

2011-04-01

Full Text Available Cerebellar ataxias comprise a wide range of etiologies leading to central nervous system-related motor and non-motor symptoms. Recently, a large body of evidence has demonstrated a high frequency of non-motor manifestations in cerebellar ataxias, specially in autosomal dominant spinocerebellar ataxias (SCA. Among these non-motor dysfunctions, sleep disorders have been recognized, although still under or even misdiagnosed. In this review, we highlight the main sleep disorders related to cerebellar ataxias focusing on REM sleep behavior disorder (RBD, restless legs syndrome (RLS, periodic limb movement in sleep (PLMS, excessive daytime sleepiness (EDS, insomnia and sleep apnea.

Spin diffusion in disordered organic semiconductors

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Li, Ling; Gao, Nan; Lu, Nianduan; Liu, Ming; Bässler, Heinz

2015-12-01

An analytical theory for spin diffusion in disordered organic semiconductors is derived. It is based on percolation theory and variable range hopping in a disordered energy landscape with a Gaussian density of states. It describes universally the dependence of the spin diffusion on temperature, carrier density, material disorder, magnetic field, and electric field at the arbitrary magnitude of the Hubbard energy of charge pairs. It is found that, compared to the spin transport carried by carriers hopping, the spin exchange will hinder the spin diffusion process at low carrier density, even under the condition of a weak electric field. Importantly, under the influence of a bias voltage, anomalous spreading of the spin packet will lead to an abnormal temperature dependence of the spin diffusion coefficient and diffusion length. This explains the recent experimental data for spin diffusion length observed in Alq3.

Are we under-estimating the association between autism symptoms?: The importance of considering simultaneous selection when using samples of individuals who meet diagnostic criteria for an autism spectrum disorder.

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Murray, Aja Louise; McKenzie, Karen; Kuenssberg, Renate; O'Donnell, Michael

2014-11-01

The magnitude of symptom inter-correlations in diagnosed individuals has contributed to the evidence that autism spectrum disorders (ASD) is a fractionable disorder. Such correlations may substantially under-estimate the population correlations among symptoms due to simultaneous selection on the areas of deficit required for diagnosis. Using statistical simulations of this selection mechanism, we provide estimates of the extent of this bias, given different levels of population correlation between symptoms. We then use real data to compare domain inter-correlations in the Autism Spectrum Quotient, in those with ASD versus a combined ASD and non-ASD sample. Results from both studies indicate that samples restricted to individuals with a diagnosis of ASD potentially substantially under-estimate the magnitude of association between features of ASD.

Personality disorders in eating disorder not otherwise specified and binge eating disorder: a meta-analysis of comorbidity studies.

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Friborg, Oddgeir; Martinussen, Monica; Kaiser, Sabine; Øvergård, Karl Tore; Martinsen, Egil W; Schmierer, Phöbe; Rosenvinge, Jan Harald

2014-02-01

A meta-analysis was conducted to identify the proportion of comorbid personality disorders (PDs) in patients with eating disorder not otherwise specified (EDNOS) and binge eating disorder (BED). A search identified 20 articles in the period of 1987 to 2010. For EDNOS and BED, the comorbid proportions for any PD were 0.38 and 0.29, respectively; for cluster C PDs, 0.38 and 0.30, respectively (avoidant PD, 0.18 and 0.12, and obsessive-compulsive PD, 0.11 and 0.10, respectively); and for cluster B PDs, 0.25 and 0.11, respectively (borderline, 0.12 and 0.10). This pattern converged with findings on anorexia nervosa and bulimia nervosa, except being lower. Because the comorbidity profiles for EDNOS and BED were highly similar, their underlying PD pathology seems similar. Few moderators were significant, except for interviews yielding lower estimates than that of questionnaires. The variance statistic for any PD comorbidity was wide for EDNOS and narrow for BED, thus partly supporting BED as a distinct eating disorder category and EDNOS as a potentially more severe condition than BED.

Disorders presenting with headache as the sole symptom ...

African Journals Online (AJOL)

Disorders presenting with headache as the sole symptom. ... Log in or Register to get access to full text downloads. ... probably do not require sophisticated neurological skills or investigations, failure to recognise an underlying disorder or an ...

White Matter Integrity in Adolescents with Histories of Marijuana Use and Binge Drinking

OpenAIRE

Jacobus, J.; McQueeny, T.; Bava, S.; Schweinsburg, B. C.; Frank, L.R.; Yang, T. T.; Tapert, S. F.

2009-01-01

Structural brain abnormalities have been observed in adolescents with alcohol use disorders but less is known about neuropathological brain characteristics of teens with subdiagnostic binge drinking or the common pattern of binge drinking combined with marijuana use. The goal of this study was to examine white matter integrity in adolescents with histories of binge drinking and marijuana use.

Boys with Oppositional Defiant Disorder/Conduct Disorder Show Impaired Adaptation During Stress: An Executive Functioning Study.

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Schoorl, Jantiene; van Rijn, Sophie; de Wied, Minet; van Goozen, Stephanie; Swaab, Hanna

2018-04-01

Evidence for problems in executive functioning (EF) in children with oppositional defiant disorder/conduct disorder (ODD/CD) is mixed and the impact stress may have on EF is understudied. Working memory, sustained attention, inhibition and cognitive flexibility of boys with ODD/CD (n = 65) and non-clinical controls (n = 32) were examined under typical and stressful test conditions. Boys with ODD/CD showed impaired working memory under typical testing conditions, and impairments in working memory and sustained attention under stressful conditions. In contrast to controls, performance on sustained attention, cognitive flexibility and inhibition was less influenced by stress in boys with ODD/CD. These results suggest that boys with ODD/CD show impairments in adaptation to the environment whereas typically developing boys show adaptive changes in EF.

Cognitive-analytical therapy for a patient with functional neurological symptom disorder-conversion disorder (psychogenic myopia: A case study

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Hamid Nasiri

2015-01-01

Full Text Available Functional neurological symptom disorder commonly presents with symptoms and defects of sensory and motor functions. Therefore, it is often mistaken for a medical condition. It is well known that functional neurological symptom disorder more often caused by psychological factors. There are three main approaches namely analytical, cognitive and biological to manage conversion disorder. Any of such approaches can be applied through short-term treatment programs. In this case, study a 12-year-old boy with the diagnosed functional neurological symptom disorder (psychogenic myopia was put under a cognitive-analytical treatment. The outcome of this treatment modality was proved successful.

Cognitive-analytical therapy for a patient with functional neurological symptom disorder-conversion disorder (psychogenic myopia): A case study.

Science.gov (United States)

Nasiri, Hamid; Ebrahimi, Amrollah; Zahed, Arash; Arab, Mostafa; Samouei, Rahele

2015-05-01

Functional neurological symptom disorder commonly presents with symptoms and defects of sensory and motor functions. Therefore, it is often mistaken for a medical condition. It is well known that functional neurological symptom disorder more often caused by psychological factors. There are three main approaches namely analytical, cognitive and biological to manage conversion disorder. Any of such approaches can be applied through short-term treatment programs. In this case, study a 12-year-old boy with the diagnosed functional neurological symptom disorder (psychogenic myopia) was put under a cognitive-analytical treatment. The outcome of this treatment modality was proved successful.

Cross-Species Studies on the Mechanisms Underlying Abnormal Behavior in Bipolar Disorder: A Dopaminergic Focus

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van Enkhuizen, J.

2014-01-01

Bipolar disorder (BD) is a severe neuropsychiatric disorder, affecting approximately 2% of the worldwide population. It is characterized by euphoric states of mania and opposite mood states of depression, which are devastating to the patients’ quality of life. Current treatment options are poor and

The structure and stability of common mental disorders - The NEMESIS Study

NARCIS (Netherlands)

Vollebergh, W.A.M.; Iedema, J; Bijl, R.V.; de Graaf, R.; Smit, F.; Ormel, J.

Background: We analyzed the underlying latent structure of 12-month DSM-III-R diagnoses of 9 common disorders for the general population in the Netherlands. In addition, we sought to establish (1) the stability of the latent structure underlying mental disorders across a 1-year period (structural

Clinical Reasoning in the Assessment and Intervention Planning for Writing Disorder

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Harrison, Gina L.; McManus, Kelly L.

2017-01-01

The incidence of writing disorder is as common as reading disorder, but it is frequently under-identified and rarely targeted for intervention. Increasing clinical understanding on various subtypes of writing disorder through assessment guided by data-driven decision making may alleviate this disparity for students with writing disorders. The…

Nail disorders in children, a clinical study

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Ayşe Akbaş

2016-04-01

Full Text Available Introduction: Aims of the study to investigate the frequency and the nature ofnail disorders in children significant clinical data is available. Nail disorders although common in children in some parts of our country. This study was carried out to document the clinical and demographic pattern of nail disorders in a dermatology outpatient clinic of a pediatric hospital in Ankara, Turkey. Material and Methods: All consecutive patients a total of 3000 children from age 0-16 were admitted to dermatology outpatient clinic of Ankara Pediatric Hematology and Oncology Education and Research Hospital during January 2011 to December 2011 were studied and retrospectively evaluated for age, gender, drug use, diseases, systemic or genetic disorders and demographic features. Diagnostic evaluation results were noted and patients were categorized for demographic features and diagnosis. Results: These 133 patients (M: F 58:75, %44 vs 56, respectively were under 16 years of age and have 17 different dermatological disorders related with nail symptoms. Fifty three of (39,8% these patient were under 2 years of age, 31 (23.3% were between 3-5 years, 30 (22.5% were between 6-11 years old, 19 of 133 (14%, 2 were between 11-16 years of age. Through all of ages and independent of gender the most etiologies of nail disorders were, onychomadesis, paronychia, onycholysis, onychomycosis and systemic nail presentation of systemic dermatosis. Conclusion: Nail disorders are different in children than in adults. In our study, the first 5 years of age was found in 53% of nail disorders. Nail disorders are uncommon but may be seen as a part of a systemic disease and may be associated with cosmetic and psychologic problem.

Genetics of bipolar disorder

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Kerner B

2014-02-01

Full Text Available Berit Kerner Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA Abstract: Bipolar disorder is a common, complex genetic disorder, but the mode of transmission remains to be discovered. Many researchers assume that common genomic variants carry some risk for manifesting the disease. The research community has celebrated the first genome-wide significant associations between common single nucleotide polymorphisms (SNPs and bipolar disorder. Currently, attempts are under way to translate these findings into clinical practice, genetic counseling, and predictive testing. However, some experts remain cautious. After all, common variants explain only a very small percentage of the genetic risk, and functional consequences of the discovered SNPs are inconclusive. Furthermore, the associated SNPs are not disease specific, and the majority of individuals with a “risk” allele are healthy. On the other hand, population-based genome-wide studies in psychiatric disorders have rediscovered rare structural variants and mutations in genes, which were previously known to cause genetic syndromes and monogenic Mendelian disorders. In many Mendelian syndromes, psychiatric symptoms are prevalent. Although these conditions do not fit the classic description of any specific psychiatric disorder, they often show nonspecific psychiatric symptoms that cross diagnostic boundaries, including intellectual disability, behavioral abnormalities, mood disorders, anxiety disorders, attention deficit, impulse control deficit, and psychosis. Although testing for chromosomal disorders and monogenic Mendelian disorders is well established, testing for common variants is still controversial. The standard concept of genetic testing includes at least three broad criteria that need to be fulfilled before new genetic tests should be introduced: analytical validity, clinical validity, and clinical utility. These criteria are

Metabolic disorders with typical alterations in MRI

International Nuclear Information System (INIS)

Warmuth-Metz, M.

2010-01-01

The classification of metabolic disorders according to the etiology is not practical for neuroradiological purposes because the underlying defect does not uniformly transform into morphological characteristics. Therefore typical MR and clinical features of some easily identifiable metabolic disorders are presented. Canavan disease, Pelizaeus-Merzbacher disease, Alexander disease, X-chromosomal adrenoleukodystrophy and adrenomyeloneuropathy, mitochondrial disorders, such as MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) and Leigh syndrome as well as L-2-hydroxyglutaric aciduria are presented. (orig.) [de

Childhood Traumatic Experiences, Dissociative Symptoms, and Dissociative Disorder Comorbidity Among Patients With Panic Disorder: A Preliminary Study.

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Ural, Cenk; Belli, Hasan; Akbudak, Mahir; Tabo, Abdulkadir

2015-01-01

This study assessed childhood trauma history, dissociative symptoms, and dissociative disorder comorbidity in patients with panic disorder (PD). A total of 92 psychotropic drug-naive patients with PD, recruited from outpatient clinics in the psychiatry department of a Turkish hospital, were involved in the study. Participants were assessed using the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D), Dissociation Questionnaire, Panic and Agoraphobia Scale, Panic Disorder Severity Scale, and Childhood Trauma Questionnaire. Of the patients with PD, 18 (19%) had a comorbid dissociative disorder diagnosis on screening with the SCID-D. The most prevalent disorders were dissociative disorder not otherwise specified, dissociative amnesia, and depersonalization disorders. Patients with a high degree of dissociation symptoms and dissociative disorder comorbidity had more severe PD than those without (p dissociation and PD. Among all of the subscales, the strongest relationship was with childhood emotional abuse. Logistic regression analysis showed that emotional abuse and severity of PD were independently associated with dissociative disorder. In our study, a significant proportion of the patients with PD had concurrent diagnoses of dissociative disorder. We conclude that the predominance of PD symptoms at admission should not lead the clinician to overlook the underlying dissociative process and associated traumatic experiences among these patients.

Dissociative symptoms and dissociative disorder comorbidity in patients with obsessive-compulsive disorder.

Science.gov (United States)

Belli, Hasan; Ural, Cenk; Vardar, Melek Kanarya; Yesılyurt, Sema; Oncu, Fatıh

2012-10-01

The present study attempted to assess the dissociative symptoms and overall dissociative disorder comorbidity in patients with obsessive-compulsive disorder (OCD). In addition, we examined the relationship between the severity of obsessive-compulsive symptoms and dissociative symptoms. All patients admitted for the first time to the psychiatric outpatient unit were included in the study. Seventy-eight patients had been diagnosed as having OCD during the 2-year study period. Patients had to meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD. Most (76.9%; n = 60) of the patients were female, and 23.1% (n = 18) of the patients were male. Dissociation Questionnaire was used to measure dissociative symptoms. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Dissociative Disorders interviews and Yale-Brown Obsessive Compulsive Checklist and Severity Scale were used. Eleven (14%) of the patients with OCD had comorbid dissociative disorder. The most prevalent disorder in our study was dissociative depersonalization disorder. Dissociative amnesia and dissociative identity disorder were common as well. The mean Yale-Brown score was 23.37 ± 7.27 points. Dissociation Questionnaire scores were between 0.40 and 3.87 points, and the mean was 2.23 ± 0.76 points. There was a statistically significant positive correlation between Yale-Brown points and Dissociation Questionnaire points. We conclude that dissociative symptoms among patients with OCD should alert clinicians for the presence of a chronic and complex dissociative disorder. Clinicians may overlook an underlying dissociative process in patients who have severe symptoms of OCD. However, a lack of adequate response to cognitive-behavioral and drug therapy may be a consequence of dissociative process. Copyright © 2012 Elsevier Inc. All rights reserved.

The Root Cause of Post-Traumatic and Developmental Stress Disorder (Phase 1)

Science.gov (United States)

2015-04-01

Table 1). Both gross andmicroscopic neuropathology examswere conducted by a neuropathologist and all specimens were found to be free of confounding... psychological stress was associated with spine changes in the hippocampal CA3 region. Individuals reporting high levels of anxiety and depression had...it will also be interesting to ascertain whether the mitochondrial pathways identified as abnormal in that study might be related to the changes in

Comparing psychological disorders in addicts treated under NA Association and TC Centers

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Safoura Jamshidi

2018-02-01

Results: Findings obtained from the analysis of comparing two independent groups showed that NA group had better conditions than TC clients group in terms of psychological and personality disorders and they had significant difference statistically (P

Binge or control? : assessment of the validity, treatment and underlying mechanisms of Binge Eating Disorder

NARCIS (Netherlands)

Dingemans, Alexandra

2009-01-01

This thesis focuses on patients with Binge Eating Disorder. The thesis consists of three parts. In the first part the validity of the diagnosis of BED will be discussed. The results of two literature reviews and an empirical cross-sectional study suggested that BED is a distinct eating disorder and

The structure of Diagnostic and Statistical Manual of Mental Disorders (4th edition, text revision) personality disorder symptoms in a large national sample.

Science.gov (United States)

Trull, Timothy J; Vergés, Alvaro; Wood, Phillip K; Jahng, Seungmin; Sher, Kenneth J

2012-10-01

We examined the latent structure underlying the criteria for DSM-IV-TR (American Psychiatric Association, 2000, Diagnostic and statistical manual of mental disorders (4th ed., text revision). Washington, DC: Author.) personality disorders in a large nationally representative sample of U.S. adults. Personality disorder symptom data were collected using a structured diagnostic interview from approximately 35,000 adults assessed over two waves of data collection in the National Epidemiologic Survey on Alcohol and Related Conditions. Our analyses suggested that a seven-factor solution provided the best fit for the data, and these factors were marked primarily by one or at most two personality disorder criteria sets. A series of regression analyses that used external validators tapping Axis I psychopathology, treatment for mental health problems, functioning scores, interpersonal conflict, and suicidal ideation and behavior provided support for the seven-factor solution. We discuss these findings in the context of previous studies that have examined the structure underlying the personality disorder criteria as well as the current proposals for DSM-5 personality disorders. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Autism Spectrum Disorder (ASD) and Fragile X Syndrome (FXS): Two Overlapping Disorders Reviewed through Electroencephalography—What Can be Interpreted from the Available Information?

Science.gov (United States)

Mc Devitt, Niamh; Gallagher, Louise; Reilly, Richard B.

2015-01-01

Autism Spectrum Disorder (ASD) and Fragile X syndrome (FXS) are neurodevelopmental disorders with different but potentially related neurobiological underpinnings, which exhibit significant overlap in their behavioural symptoms. FXS is a neurogenetic disorder of known cause whereas ASD is a complex genetic disorder, with both rare and common genetic risk factors and likely genetic and environmental interaction effects. A comparison of the phenotypic presentation of the two disorders may highlight those symptoms that are more likely to be under direct genetic control, for example in FXS as opposed to shared symptoms that are likely to be under the control of multiple mechanisms. This review is focused on the application and analysis of electroencephalography data (EEG) in ASD and FXS. Specifically, Event Related Potentials (ERP) and resting state studies (rEEG) studies investigating ASD and FXS cohorts are compared. This review explores the electrophysiological similarities and differences between the two disorders in addition to the potentially associated neurobiological mechanisms at play. A series of pertinent research questions which are suggested in the literature are also posed within the review. PMID:25826237

Autism Spectrum Disorder (ASD and Fragile X Syndrome (FXS: Two Overlapping Disorders Reviewed through Electroencephalography—What Can be Interpreted from the Available Information?

Directory of Open Access Journals (Sweden)

Niamh Mc Devitt

2015-03-01

Full Text Available Autism Spectrum Disorder (ASD and Fragile X syndrome (FXS are neurodevelopmental disorders with different but potentially related neurobiological underpinnings, which exhibit significant overlap in their behavioural symptoms. FXS is a neurogenetic disorder of known cause whereas ASD is a complex genetic disorder, with both rare and common genetic risk factors and likely genetic and environmental interaction effects. A comparison of the phenotypic presentation of the two disorders may highlight those symptoms that are more likely to be under direct genetic control, for example in FXS as opposed to shared symptoms that are likely to be under the control of multiple mechanisms. This review is focused on the application and analysis of electroencephalography data (EEG in ASD and FXS. Specifically, Event Related Potentials (ERP and resting state studies (rEEG studies investigating ASD and FXS cohorts are compared. This review explores the electrophysiological similarities and differences between the two disorders in addition to the potentially associated neurobiological mechanisms at play. A series of pertinent research questions which are suggested in the literature are also posed within the review.

Glutamate synapses in human cognitive disorders.

Science.gov (United States)

Volk, Lenora; Chiu, Shu-Ling; Sharma, Kamal; Huganir, Richard L

2015-07-08

Accumulating data, including those from large genetic association studies, indicate that alterations in glutamatergic synapse structure and function represent a common underlying pathology in many symptomatically distinct cognitive disorders. In this review, we discuss evidence from human genetic studies and data from animal models supporting a role for aberrant glutamatergic synapse function in the etiology of intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ), neurodevelopmental disorders that comprise a significant proportion of human cognitive disease and exact a substantial financial and social burden. The varied manifestations of impaired perceptual processing, executive function, social interaction, communication, and/or intellectual ability in ID, ASD, and SCZ appear to emerge from altered neural microstructure, function, and/or wiring rather than gross changes in neuron number or morphology. Here, we review evidence that these disorders may share a common underlying neuropathy: altered excitatory synapse function. We focus on the most promising candidate genes affecting glutamatergic synapse function, highlighting the likely disease-relevant functional consequences of each. We first present a brief overview of glutamatergic synapses and then explore the genetic and phenotypic evidence for altered glutamate signaling in ID, ASD, and SCZ.

History, Present, and Progress of Frontotemporal Dementia in China: A Systematic Review

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Ru-Jing Ren

2012-01-01

Full Text Available We aim to provide an overview of clinical and demographical features and neuropathological research on frontotemporal dementia (FTD from China over the past decade. We reviewed the demographic features, clinical presentations, and neuropathology of the FTD-spectrum disorders from the 49 cases in China published since 1998. On the basis of these findings, we retrospect the history and speculate on future progress in terms of FTD in China. We found that most published papers comprise case reports with a few retrospective studies with small sample sizes. Behavior variant FTD (bvFTD was the most common diagnostic subtype, of which 35% were associated with amyotrophic lateral sclerosis or Parkinsonian syndrome. More than 47% patients with FTD had age onset before 65. There were no differences in age of onset and sex distribution between diagnostic subtypes. The spectrum of neuropathological diagnosis of bvFTD was frontotemporal lobe degeneration (FTLD with tau protein or ubiquitin-immunopositive inclusions, and FTLD without intracellular inclusions. Median survival in bvFTD was 14 years. This paper provides an overview of the current status and pointers for future research directions of FTD in China.

Autism Spectrum Disorders and Schizophrenia Spectrum Disorders: Excitation/Inhibition Imbalance and Developmental Trajectories

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Roberto Canitano

2017-05-01

Full Text Available Autism spectrum disorders (ASD and schizophrenia spectrum disorders (SSD share clinical and genetic components that have long been recognized. The two disorders co-occur more frequently than would be predicted by their respective prevalence, suggesting that a complex, multifactor association is involved. However, DSM-5 maintains the distinction between ASD, with core social and communication impairments, and SSD, including schizophrenia (SCZ, with hallucinations, delusions, and thought disorder as essential features. ASD and SSD have common biological underpinnings that may emerge early in development and unfold over time. One of the hypotheses supporting the similarities in the social and cognitive disturbances of ASD and SSD relates to abnormalities in the ratio of excitatory to inhibitory cortical activity (E/I imbalance. E/I imbalance in neurodevelopmental disorders could be the consequence of abnormalities in genes coding for glutamatergic and GABAergic receptors or synaptic proteins followed by system derangements. SSD and ASD have been characterized as polygenic disorders in which to the onset and progression of disease is triggered by interactions among multiple genes. Mammalian target of rapamycin signaling is under intense investigation as a convergent altered pathway in the two spectrum disorders. Current understanding of shared and divergent patterns between ASD and SSD from molecular to clinical aspects is still incomplete and may be implemented by the research domain criteria approach.

Prefrontal NAA and Glx Levels in Different Stages of Psychotic Disorders : a 3T 1H-MRS Study

NARCIS (Netherlands)

Liemburg, Edith; Sibeijn-Kuiper, Anita; Bais, Leonie; Pijnenborg, Gerdina; Knegtering, Henderikus; van der Velde, Jorien; Opmeer, Esther; de Vos, Annerieke; Dlabac-De Lange, Jozarni; Wunderink, Lex; Aleman, André

2016-01-01

H-Magnetic Resonance Spectroscopy ((1)H-MRS) can offer insights in various neuropathologies by measuring metabolite levels in the brain. In the current study we investigated the levels of glutamate + glutamine (Glx, neurotransmitter and precursor) and N-Acetyl Aspartate + glutamic acid (NAA + NAAG;

Regional thalamic neuropathology in patients with hippocampal sclerosis and epilepsy: A postmortem study

Science.gov (United States)

Sinjab, Barah; Martinian, Lillian; Sisodiya, Sanjay M; Thom, Maria

2013-01-01

Purpose Clinical, experimental, and neuroimaging data all indicate that the thalamus is involved in the network of changes associated with temporal lobe epilepsy (TLE), particularly in association with hippocampal sclerosis (HS), with potential roles in seizure initiation and propagation. Pathologic changes in the thalamus may be a result of an initial insult, ongoing seizures, or retrograde degeneration through reciprocal connections between thalamic and limbic regions. Our aim was to carry out a neuropathologic analysis of the thalamus in a postmortem (PM) epilepsy series, to assess the distribution, severity, and nature of pathologic changes and its association with HS. Methods Twenty-four epilepsy PM cases (age range 25–87 years) and eight controls (age range 38–85 years) were studied. HS was classified as unilateral (UHS, 11 cases), bilateral (BHS, 4 cases) or absent (No-HS, 9 cases). Samples from the left and right sides of the thalamus were stained with cresyl violet (CV), and for glial firbillary acidic protein (GFAP) and synaptophysin. Using image analysis, neuronal densities (NDs) or field fraction staining values (GFAP, synaptophysin) were measured in four thalamic nuclei: anteroventral nucleus (AV), lateral dorsal nucleus (LD), mediodorsal nucleus (MD), and ventrolateral nucleus (VL). The results were compared within and between cases. Key Findings The severity, nature, and distribution of thalamic pathology varied between cases. A pattern that emerged was a preferential involvement of the MD in UHS cases with a reduction in mean ND ipsilateral to the side of HS (p = 0.05). In UHS cases, greater field fraction values for GFAP and lower values for synaptophysin and ND were seen in the majority of cases in the MD ipsilateral to the side of sclerosis compared to other thalamic nuclei. In addition, differences in the mean ND between classical HS, atypical HS, and No-HS cases were noted in the ipsilateral MD (p < 0.05), with lower values observed in

Similarities and differences between children and adolescents with autism spectrum disorder and those with obsessive compulsive disorder: executive functioning and repetitive behaviour.

NARCIS (Netherlands)

Scheeren, Anke M; Begeer, Sander; Banerjee, Robin; Meerum Terwogt, Mark; Koot, Hans M

2010-01-01

In order to examine hypothesized underlying neurocognitive processes in repetitive behaviour, children and adolescents (7-16 years) with autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) were compared on a range of executive function (EF) measures. Performance on

Neuropathology

International Nuclear Information System (INIS)

Kaufman, M.A.; Roizin, L.; Gold, G.

1971-01-01

The etiology of neuropathies in man and animals is reviewed. X-irradiation of rabbits on the 18th day of fetal life with 150 r disturbed the normal developmental changes of tissue respiration and anaerobic glycolysis of brain during ontogenesis. X-irradiation of the brain of 7-day-old rats (600 r) resulted in a large selective deficit of cerebellar weight at 7 1 / 2 months with a substantial increase of cellularity. A reduction in the cellular response to superficial freezing injury was dependent on the dosage of previous local brain x-irradiation, but independent of the time interval between irradiation and injury. It was suggested that radiation damage was stored up in local cells until they were stimulated to divide, when they died. Similar modifications were also induced in the response to subsequent intracerebral infection with Bacillus pertussis and were believed to support the view that brain macrophages are of local origin. The similarity of mast cell changes induced by compound 48/80 in both acute and chronic stages to those in irradiated monkey brains suggested that some of the lesions may reflect a process of delayed hypersensitivity with antigen provided by some component of the mast cells. (U.S.)

Impulse control disorder in patients with Parkinson's disease under dopamine agonist therapy: a multicentre study.

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Garcia-Ruiz, Pedro J; Martinez Castrillo, Juan Carlos; Alonso-Canovas, Araceli; Herranz Barcenas, Antonio; Vela, Lydia; Sanchez Alonso, Pilar; Mata, Marina; Olmedilla Gonzalez, Nuria; Mahillo Fernandez, Ignacio

2014-08-01

Impulse control disorders (ICDs) encompass a wide spectrum of abnormal behaviour frequently found in cases of Parkinson's disease (PD) treated with dopamine agonists (DAs). The main aim of this study was to analyse ICD prevalence with different DAs. We carried out a multicentre transversal study to evaluate the presence of ICDs in patients with PD chronically treated (>6 months) with a single non-ergolinic DA (pramipexole, ropinirole, or rotigotine). Clinical assessment of ICD was performed using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease. Thirty-nine per cent of patients (91/233) fulfilled the clinical criteria for ICD. The group of patients with ICD symptoms (ICD+) differed from those without ICD symptoms (ICD-) in younger age and type of DA intake. Oral DA treatment (pramipexole and ropinirole) was associated with higher risk of ICDs compared with transdermal DA (rotigotine): 84/197 (42%) patients treated with oral DA developed ICD, versus 7/36 (19%) patients treated with transdermal DA (Fisher's exact text <0.01). In univariate analysis, a younger age (p<0.01), treatment with rasagiline (p<0.05), and especially treatment with an oral DA (pramipexole or ropinirole) (p<0.01) were significantly associated with ICD. Multivariate analysis confirmed that oral DA remained significantly associated with ICD (p: 0.014, OR: 3.14; 1.26-7.83). ICD was significantly associated with the use of the non-ergolinic oral DA (pramipexole and ropinirole) when compared with transdermal non-ergolinic DA (rotigotine). Since pramipexole, ropinirole and rotigotine are non-ergolinic DAs with very similar pharmacodynamic profiles, it is likely that other factors including route of administration (transdermal vs oral) explain the difference in risk of ICD development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Memory-Based Model of Posttraumatic Stress Disorder: Evaluating Basic Assumptions Underlying the PTSD Diagnosis

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Rubin, David C.; Berntsen, Dorthe; Bohni, Malene Klindt

2008-01-01

In the mnemonic model of posttraumatic stress disorder (PTSD), the current memory of a negative event, not the event itself, determines symptoms. The model is an alternative to the current event-based etiology of PTSD represented in the "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.; American Psychiatric Association,…

Clinical imaging and neuropathological correlations in an unusual case of cerebrotendinous xanthomatosis.

NARCIS (Netherlands)

Wallon, D.; Guyant-Marechal, L.; Laquerriere, A.; Wevers, R.A.; Martinaud, O.; Kluijtmans, L.A.J.; Yntema, H.G.; Saugier-Veber, P.; Hannequin, D.

2010-01-01

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disorder due to a deficiency of the mitochondrial enzyme sterol 27-hydroxylase (CYP 27) with reduced or no chenodeoxycholic synthesis. This deficiency leads to an accumulation of cholestanol in different sites such as

Regional correlations between [11C]PIB PET and post-mortem burden of amyloid-beta pathology in a diverse neuropathological cohort

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Sang Won Seo

2017-01-01

Full Text Available Imaging-pathological correlation studies show that in vivo amyloid-β (Aβ positron emission tomography (PET strongly predicts the presence of significant Aβ pathology at autopsy. We sought to determine whether regional PiB-PET uptake would improve sensitivity for amyloid detection in comparison with global measures (experiment 1, and to estimate the relative contributions of different Aβ aggregates to in vivo PET signal (experiment 2. In experiment 1, 54 subjects with [11C] PiB-PET during life and postmortem neuropathologic examination (85.2% with dementia, interval from PET to autopsy 3.1 ± 1.9 years were included. We assessed Thal amyloid phase (N = 36 and CERAD score (N = 54 versus both global and regional PiB SUVRs. In experiment 2 (N = 42, PiB SUVR and post-mortem amyloid β burden was analyzed in five customized regions of interest matching regions sampled at autopsy. We assessed the relative contribution of neuritic plaques (NPs, diffuse plaques (DPs and cerebral amyloid angiopathy (CAA to regional PIB SUVR using multi-linear regression. In experiment 1, there were no differences in Area Under the Curve for amyloid phase ≥ A2 and CERAD score ≥ C2 between global and highest regional PiB SUVR (p = 0.186 and 0.230. In experiment 2, when NPs, DPs, and/or CAA were included in the same model, moderate to severe NPs were independently correlated with PiB SUVR in all regions except for the inferior temporal and calcarine ROI (β = 0.414–0.804, p < 0.05, whereas DPs were independently correlated with PiB SUVR in the angular gyrus ROI (β = 0.446, p = 0.010. CAA was also associated with PiB SUVR in the inferior temporal and calcarine ROI (β = 0.222–0.355, p < 0.05. In conclusion, global PiB-PET SUVR performed as well as regional values for amyloid detection in our cohort. The substrate-specific binding of PiB might differ among the brain specific regions.

Response to emotional expressions in generalized social phobia and generalized anxiety disorder: evidence for separate disorders.

Science.gov (United States)

Blair, Karina; Shaywitz, Jonathan; Smith, Bruce W; Rhodes, Rebecca; Geraci, Marilla; Jones, Matthew; McCaffrey, Daniel; Vythilingam, Meena; Finger, Elizabeth; Mondillo, Krystal; Jacobs, Madeline; Charney, Dennis S; Blair, R J R; Drevets, Wayne C; Pine, Daniel S

2008-09-01

Generalized social phobia involves fear/avoidance, specifically of social situations, whereas generalized anxiety disorder involves intrusive worry about diverse circumstances. It remains unclear the degree to which these two, often comorbid, conditions represent distinct disorders or alternative presentations of a single, core underlying pathology. Functional magnetic resonance imaging assessed the neural response to facial expressions in generalized social phobia and generalized anxiety disorder. Individuals matched on age, IQ, and gender with generalized social phobia without generalized anxiety disorder (N=17), generalized anxiety disorder (N=17), or no psychopathology (N=17) viewed neutral, fearful, and angry expressions while ostensibly making a simple gender judgment. The patients with generalized social phobia without generalized anxiety disorder showed increased activation to fearful relative to neutral expressions in several regions, including the amygdala, compared to healthy individuals. This increased amygdala response related to self-reported anxiety in patients with generalized social phobia without generalized anxiety disorder. In contrast, patients with generalized anxiety disorder showed significantly less activation to fearful relative to neutral faces compared to the healthy individuals. They did show significantly increased response to angry expressions relative to healthy individuals in a lateral region of the middle frontal gyrus. This increased lateral frontal response related to self-reported anxiety in patients with generalized anxiety disorder. These results suggest that neural circuitry dysfunctions differ in generalized social phobia and generalized anxiety disorder.

Microendophenotypes of psychiatric disorders: phenotypes of psychiatric disorders at the level of molecular dynamics, synapses, neurons, and neural circuits.

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Kida, S; Kato, T

2015-01-01

Psychiatric disorders are caused not only by genetic factors but also by complicated factors such as environmental ones. Moreover, environmental factors are rarely quantitated as biological and biochemical indicators, making it extremely difficult to understand the pathological conditions of psychiatric disorders as well as their underlying pathogenic mechanisms. Additionally, we have actually no other option but to perform biological studies on postmortem human brains that display features of psychiatric disorders, thereby resulting in a lack of experimental materials to characterize the basic biology of these disorders. From these backgrounds, animal, tissue, or cell models that can be used in basic research are indispensable to understand biologically the pathogenic mechanisms of psychiatric disorders. In this review, we discuss the importance of microendophenotypes of psychiatric disorders, i.e., phenotypes at the level of molecular dynamics, neurons, synapses, and neural circuits, as targets of basic research on these disorders.

Chondromyxoid fibroma of the frontal bone in a teenager

International Nuclear Information System (INIS)

Kadom, Nadja; Rushing, Elisabeth J.; Yaun, Amanda; Santi, Mariarita

2009-01-01

We report a skull chondromyxoid fibroma with symptomatic intracranial extension causing initial misdiagnosis as a psychiatric disorder in a 14-year-old child. CT performed for work-up of the patient's ''stuffy nose'' revealed a large calcified frontal bone mass with extensive intracranial growth. We present this child with the diagnosis of intracranial chondromyxoid fibroma with detailed neuroimaging and neuropathology correlations. (orig.)

Management of Current Psychiatric Disorders

Science.gov (United States)

Carbonnel, François; David, Michel; Norton, Joanna; Bourrel, Gérard; Boulenger, Jean-Philippe; Capdevielle, Delphine

2016-01-01

Objective: Describe and analyse the experience of family physicians in managing current psychiatric disorders to obtain a better understanding of the underlying reasons of under-detection and inadequate prescribing identified in studies. Methods: A qualitative study using in-depth interviews. Sample of 15 practicing family physicians, recruited by telephone from a precedent cohort (Sesame1) with a maximum variation: sex, age, single or group practice, urban or rural. Qualitative method is inspired by the completed grounded theory of a verbatim semiopragmatic analysis from 2 experts in this approach. Results: Family physicians found that current psychiatric disorders were related to psychological symptoms in reaction to life events. Their role was to make patients aware of a psychiatric symptom rather than establish a diagnosis. Their management responsibility was considered in contrasting ways: it was claimed or endured. They defined their position as facilitating compliance to psychiatrist consultations, while assuring a complementary psychotherapeutic approach. Prescribing medication was not a priority for them. Conclusions: The identified under-detection is essentially due to inherent frontline conditions and complexity of clinical forms. The family physician role, facilitating compliance to psychiatrist consultations while assuring a support psychotherapy is the main result of this study. More studies should be conducted to define more accurately the clinical reality, management and course of current psychiatric disorders in primary care.

Psychotherapy and pharmacotherapy for patients with dissociative identity disorder.

Science.gov (United States)

Gentile, Julie P; Dillon, Kristy S; Gillig, Paulette Marie

2013-02-01

There is a wide variety of what have been called "dissociative disorders," including dissociative amnesia, dissociative fugue, depersonalization disorder, dissociative identity disorder, and forms of dissociative disorder not otherwise specified. Some of these diagnoses, particularly dissociative identity disorder, are controversial and have been questioned by many clinicians over the years. The disorders may be under-diagnosed or misdiagnosed, but many persons who have experienced trauma report "dissociative" symptoms. Prevalence of dissociative disorders is unknown, but current estimates are higher than previously thought. This paper reviews clinical, phenomenological, and epidemiological data regarding diagnosis in general, and illustrates possible treatment interventions for dissociative identity disorder, with a focus on psychotherapy interventions and a review of current psychopharmacology recommendations as part of a comprehensive multidisciplinary treatment plan.

The cognitive psychology of Internet gaming disorder.

Science.gov (United States)

King, Daniel L; Delfabbro, Paul H

2014-06-01

Internet gaming disorder (IGD) has received nomenclatural recognition as a potential mental health disorder, despite evident variability in its core psychopathology and psychometric assessment. Although cognitive-behavioural therapy (CBT) is considered an efficacious treatment for IGD, the underlying cognitions of the disorder are not well understood. This review aimed to synthesise research evidence on Internet gaming cognition toward identification of cognitive factors underlying IGD. A systematic review of 29 quantitative studies on Internet gaming cognition and 7 treatment studies employing cognitive therapy for IGD was conducted. Four cognitive factors underlying IGD were identified. Factors included (a) beliefs about game reward value and tangibility, (b) maladaptive and inflexible rules about gaming behaviour, (c) over-reliance on gaming to meet self-esteem needs, and (d) gaming as a method of gaining social acceptance. It is proposed that IGD-related cognition may be more complex than "preoccupation" (i.e., criterion A of IGD). IGD cognition may involve the persistent overvaluation of video gaming rewards, activities, and identities, combined with a need to adhere to maladaptive rules governing use and completion of video games. Greater understanding of the proposed cognitive factors may advance clinical research agendas on identification of individuals with IGD, as well as the expansion and improvement of cognitive therapies for the disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

Under-reactive but easily distracted: An fMRI investigation of attentional capture in autism spectrum disorder

Directory of Open Access Journals (Sweden)

Brandon Keehn

2016-02-01

Full Text Available For individuals with autism spectrum disorder (ASD, salient behaviorally-relevant information often fails to capture attention, while subtle behaviorally-irrelevant details commonly induce a state of distraction. The present study used functional magnetic resonance imaging (fMRI to investigate the neurocognitive networks underlying attentional capture in sixteen high-functioning children and adolescents with ASD and twenty-one typically developing (TD individuals. Participants completed a rapid serial visual presentation paradigm designed to investigate activation of attentional networks to behaviorally-relevant targets and contingent attention capture by task-irrelevant distractors. In individuals with ASD, target stimuli failed to trigger bottom-up activation of the ventral attentional network and the cerebellum. Additionally, the ASD group showed no differences in behavior or occipital activation associated with contingent attentional capture. Rather, results suggest that to-be-ignored distractors that shared either task-relevant or irrelevant features captured attention in ASD. Results indicate that individuals with ASD may be under-reactive to behaviorally-relevant stimuli, unable to filter irrelevant information, and that both top-down and bottom-up attention networks function atypically in ASD. Lastly, deficits in target-related processing were associated with autism symptomatology, providing further support for the hypothesis that non-social attentional processes and their neurofunctional underpinnings may play a significant role in the development of sociocommunicative impairments in ASD.

The Dysregulated Brain : A psychoimmunological approach to bipolar disorder

NARCIS (Netherlands)

Haarman, Bartholomeus Cornelius Maria

2017-01-01

An important problem with psychiatric disorders is that much remains unknown about the underlying disease mechanisms, thereby delaying sometimes for many years the diagnosis bipolar disorder, with significant implications for treatment. In recent years, the neuroinflammation theory, which assumes

Advanced paternal age effects in neurodevelopmental disorders-review of potential underlying mechanisms.

Science.gov (United States)

Janecka, M; Mill, J; Basson, M A; Goriely, A; Spiers, H; Reichenberg, A; Schalkwyk, L; Fernandes, C

2017-01-31

Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events. Here we provide a review of the epidemiological and molecular findings to date. Focusing on the latter, we present the evidence for genetic and epigenetic mechanisms underpinning the association between late fatherhood and disorder in offspring. We also discuss the limitations of the APA literature. We propose that different hypotheses relating to the origins of the APA effects are not mutually exclusive. Instead, multiple mechanisms likely contribute, reflecting the etiological complexity of neurodevelopmental disorders.

Dysfunctional affect regulation in borderline personality disorder and in somatoform disorder

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Annemiek van Dijke

2012-09-01

Full Text Available Background: Although affect dysregulation is considered a core component of borderline personality disorder (BPD and somatoform disorders (SoD, remarkably little research has focused on the prevalence and nature of affect dysregulation in these disorders. Also, despite apparent similarities, little is known about how dysfunctional under- and overregulation of affect and positive and negative somatoform and psychoform dissociative experiences inter-relate. Prior studies suggest a clear relationship between early childhood psychological trauma and affect dysregulation, especially when the caretaker is emotionally, sexually, or physically abusing the child, but how these relate to under- and overregulation while differentiating for developmental epochs is not clear. Although an elevated risk of childhood trauma exposure or complex posttraumatic stress disorder (CPTSD symptoms has been reported in BPD and SoD, trauma histories, dysfunctional affect regulation, dissociation, PTSD, and CPTSD were never assessed in unison in BPD and/or SoD. Method: BPD and/or SoD diagnoses were confirmed or ruled out in 472 psychiatric inpatients using clinical interviews. Dysfunctional under- and overregulation of affect and somatoform and psychoform dissociation, childhood trauma-by-primary-caretaker (TPC, PTSD, and CPTSD were all measured using self reports. Results: No disorder-specific form of dysfunctional affect regulation was found. Although both BPD and SoD can involve affect dysregulation and dissociation, there is a wide range of intensity of dysfunctional regulation phenomena in patients with these diagnoses. Evidence was found for the existence of three qualitatively different forms of experiencing states: inhibitory experiencing states (overregulation of affect and negative psychoform dissociation most commonly found in SoD, excitatory experiencing states (underregulation of affect and positive psychoform dissociation most commonly found in BPD, and

Conceptual Relations between Anxiety Disorder and Fearful Temperament

Science.gov (United States)

Rapee, Ronald M.; Coplan, Robert J.

2010-01-01

Fearful temperaments have been identified as a major risk factor for anxiety disorders. However, descriptions of fearful temperament and several forms of anxiety disorder show strong similarities. This raises the question whether these terms may simply refer to different aspects of the same underlying construct. The current review examines…

Neural correlates of intolerance of uncertainty in clinical disorders

NARCIS (Netherlands)

Wever, Mirjam; Smeets, Paul; Sternheim, Lot

2015-01-01

Intolerance of uncertainty is a key contributor to anxiety-related disorders. Recent studies highlight its importance in other clinical disorders. The link between its clinical presentation and the underlying neural correlates remains unclear. This review summarizes the emerging literature on the

Neural Correlates of Intolerance of Uncertainty in Clinical Disorders

NARCIS (Netherlands)

Wever, M.; Smeets, P.A.M.; Sternheim, L.

2015-01-01

Intolerance of uncertainty is a key contributor to anxiety-related disorders. Recent studies highlight its importance in other clinical disorders. The link between its clinical presentation and the underlying neural correlates remains unclear. This review summarizes the emerging literature on the

The neural bases of cognitive processes in gambling disorder

OpenAIRE

Potenza, Marc N.

2014-01-01

Functional imaging is offering powerful new tools to investigate the neurobiology of cognitive functioning in people with and without psychiatric conditions like gambling disorder. Based on similarities between gambling and substance-use disorders in neurocognitive and other domains, gambling disorder has recently been classified in DSM-5 as a behavioral addiction. Despite the advances in understanding, there exist multiple unanswered questions about the pathophysiology underlying gambling di...

Dysthymic disorder: forlorn and overlooked?

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Sansone, Randy A; Sansone, Lori A

2009-05-01

This ongoing column is dedicated to the challenging clinical interface between psychiatry and primary care-two fields that are inexorably linked.Dysthymic disorder is a smoldering mood disturbance characterized by a long duration (at least two years in adults) as well as transient periods of normal mood. The disorder is fairly common in the US general population (3-6%) as well as in primary care (7%) and mental health settings (up to one-third of psychiatric outpatients). While the etiology of dysthymia remains unknown, there appears to be a genetic susceptibility, which may manifest in the presence of various psychosocial stressors. While the Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria are fairly clear, the disorder can be easily under-recognized for a variety of reasons. Treatment may include pharmacotherapy and psychotherapy, although the overall treatment course is oftentimes characterized by protracted symptoms and relapses.

Protein secondary structure appears to be robust under in silico evolution while protein disorder appears not to be.

KAUST Repository

Schaefer, Christian

2010-01-16

MOTIVATION: The mutation of amino acids often impacts protein function and structure. Mutations without negative effect sustain evolutionary pressure. We study a particular aspect of structural robustness with respect to mutations: regular protein secondary structure and natively unstructured (intrinsically disordered) regions. Is the formation of regular secondary structure an intrinsic feature of amino acid sequences, or is it a feature that is lost upon mutation and is maintained by evolution against the odds? Similarly, is disorder an intrinsic sequence feature or is it difficult to maintain? To tackle these questions, we in silico mutated native protein sequences into random sequence-like ensembles and monitored the change in predicted secondary structure and disorder. RESULTS: We established that by our coarse-grained measures for change, predictions and observations were similar, suggesting that our results were not biased by prediction mistakes. Changes in secondary structure and disorder predictions were linearly proportional to the change in sequence. Surprisingly, neither the content nor the length distribution for the predicted secondary structure changed substantially. Regions with long disorder behaved differently in that significantly fewer such regions were predicted after a few mutation steps. Our findings suggest that the formation of regular secondary structure is an intrinsic feature of random amino acid sequences, while the formation of long-disordered regions is not an intrinsic feature of proteins with disordered regions. Put differently, helices and strands appear to be maintained easily by evolution, whereas maintaining disordered regions appears difficult. Neutral mutations with respect to disorder are therefore very unlikely.

Protein secondary structure appears to be robust under in silico evolution while protein disorder appears not to be.

KAUST Repository

Schaefer, Christian; Schlessinger, Avner; Rost, Burkhard

2010-01-01

MOTIVATION: The mutation of amino acids often impacts protein function and structure. Mutations without negative effect sustain evolutionary pressure. We study a particular aspect of structural robustness with respect to mutations: regular protein secondary structure and natively unstructured (intrinsically disordered) regions. Is the formation of regular secondary structure an intrinsic feature of amino acid sequences, or is it a feature that is lost upon mutation and is maintained by evolution against the odds? Similarly, is disorder an intrinsic sequence feature or is it difficult to maintain? To tackle these questions, we in silico mutated native protein sequences into random sequence-like ensembles and monitored the change in predicted secondary structure and disorder. RESULTS: We established that by our coarse-grained measures for change, predictions and observations were similar, suggesting that our results were not biased by prediction mistakes. Changes in secondary structure and disorder predictions were linearly proportional to the change in sequence. Surprisingly, neither the content nor the length distribution for the predicted secondary structure changed substantially. Regions with long disorder behaved differently in that significantly fewer such regions were predicted after a few mutation steps. Our findings suggest that the formation of regular secondary structure is an intrinsic feature of random amino acid sequences, while the formation of long-disordered regions is not an intrinsic feature of proteins with disordered regions. Put differently, helices and strands appear to be maintained easily by evolution, whereas maintaining disordered regions appears difficult. Neutral mutations with respect to disorder are therefore very unlikely.

The neurogenetics of atypical parkinsonian disorders.

Science.gov (United States)

Fogel, Brent L; Clark, Mary C; Geschwind, Daniel H

2014-04-01

Although classic Parkinson disease is the disorder most commonly associated with the clinical feature of parkinsonism, there is in fact a broader spectrum of disease represented by a collection of phenotypically similar neurodegenerative conditions that mimic many of its core features. These atypical parkinsonian disorders most commonly include progressive supranuclear palsy and corticobasal degeneration, disorders both associated with frontotemporal dementia, as well as multiple system atrophy and dementia with Lewy bodies. Although the clinical distinction of these disorders still remains a challenge to physicians, recent advances in genetics are poised to tease apart the differences. Insights into the molecular etiologies underlying these conditions will improve diagnosis, yield a better understanding of the underlying disease pathology, and ultimately lend stimulation to the development of potential treatments. At the same time, the wide range of phenotypes observed from mutations in a single gene warrants broad testing facilitated by advances in DNA sequencing. These expanding genomic approaches, ranging from the use of next-generation sequencing to identify causative or risk-associated gene variations to the study of epigenetic modification linking human genetics to environmental factors, are poised to lead the field into a new age of discovery. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Decreased pyramidal neuron size in Brodmann areas 44 and 45 in patients with autism.

Science.gov (United States)

Jacot-Descombes, Sarah; Uppal, Neha; Wicinski, Bridget; Santos, Micaela; Schmeidler, James; Giannakopoulos, Panteleimon; Heinsen, Helmut; Heinsein, Helmut; Schmitz, Christoph; Hof, Patrick R

2012-07-01

Autism is a neurodevelopmental disorder characterized by deficits in social interaction and social communication, as well as by the presence of repetitive and stereotyped behaviors and interests. Brodmann areas 44 and 45 in the inferior frontal cortex, which are involved in language processing, imitation function, and sociality processing networks, have been implicated in this complex disorder. Using a stereologic approach, this study aims to explore the presence of neuropathological differences in areas 44 and 45 in patients with autism compared to age- and hemisphere-matched controls. Based on previous evidence in the fusiform gyrus, we expected to find a decrease in the number and size of pyramidal neurons as well as an increase in volume of layers III, V, and VI in patients with autism. We observed significantly smaller pyramidal neurons in patients with autism compared to controls, although there was no difference in pyramidal neuron numbers or layer volumes. The reduced pyramidal neuron size suggests that a certain degree of dysfunction of areas 44 and 45 plays a role in the pathology of autism. Our results also support previous studies that have shown specific cellular neuropathology in autism with regionally specific reduction in neuron size, and provide further evidence for the possible involvement of the mirror neuron system, as well as impairment of neuronal networks relevant to communication and social behaviors, in this disorder.

Obsessive-compulsive disorder, impulse control disorders and drug addiction: common features and potential treatments.

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Fontenelle, Leonardo F; Oostermeijer, Sanne; Harrison, Ben J; Pantelis, Christos; Yücel, Murat

2011-05-07

The basic concepts underlying compulsive, impulsive and addictive behaviours overlap, which may help explain why laymen use these expressions interchangeably. Although there has been a large research effort to better characterize and disentangle these behaviours, clinicians and scientists are still unable to clearly differentiate them. Accordingly, obsessive-compulsive disorder (OCD), impulse control disorders (ICD) and substance-related disorders (SUD) overlap on different levels, including phenomenology, co-morbidity, neurocircuitry, neurocognition, neurochemistry and family history. In this review we summarize these issues with particular emphasis on the role of the opioid system in the pathophysiology and treatment of OCD, ICD and SUD. We postulate that with progression and chronicity of OCD, the proportion of the OCD-related behaviours (e.g. checking, washing, ordering and hoarding, among others) that are driven by impulsive 'rash' processes increase as involvement of more ventral striatal circuits becomes prominent. In contrast, as SUD and ICD progress, the proportion of the SUD- and ICD-related behaviours that are driven by compulsive 'habitual' processes increase as involvement of more dorsal striatal circuits become prominent. We are not arguing that, with time, ICD becomes OCD or vice versa. Instead, we are proposing that these disorders may acquire qualities of the other with time. In other words, while patients with ICD/SUD may develop 'compulsive impulsions', patients with OCD may exhibit 'impulsive compulsions'. There are many potential implications of our model. Theoretically, OCD patients exhibiting impulsive or addictive features could be managed with drugs that address the quality of the underlying drives and the involvement of neural systems. For example, agents for the reduction or prevention of relapse of addiction (e.g. heavy drinking), which modulate the cortico-mesolimbic dopamine system through the opioid (e.g. buprenorphine and naltrexone

Should OCD leave the anxiety disorders in DSM-V? The case for obsessive compulsive-related disorders.

Science.gov (United States)

Hollander, Eric; Braun, Ashley; Simeon, Daphne

2008-01-01

Recently in 2006, a group of experts in obsessive compulsive disorder (OCD) and obsessive compulsive-related disorders (OCRDs) convened in Washington, DC, to review existing data on the relationships between these various disorders, and to suggest approaches to address the gaps in our knowledge, in preparation for the upcoming Diagnostic and Statistical Manual (Fifth Edition) (DSM-V). As a result of this meeting, the Research Planning Agenda for DSM-V: OCRD Work Group suggested removing OCD from the anxiety disorders, where it is currently found. This proposal is in accordance with the current International Classification of Mental Disorders (ICD-10) classification of OCD as a separate category from the anxiety disorders. Although the ICD-10 places both OCD and the anxiety disorders under the umbrella category of "neurotic, stress-related, and somatoform disorders," they are two separate categories, distinct from one another. As OCD and other putative OCRDs share aspects of phenomenology, comorbidity, neurotransmitter/peptide systems, neurocircuitry, familial and genetic factors, and treatment response, it was proposed to create a new category in DSM-V entitled OCRDs. Alternatively, the OCRDs might be conceptualized as a new category within the broader category of anxiety disorders. Future studies are needed to better define the relationships among these disorders, and to study boundary issues for this proposed category. There are both advantages and disadvantages in creating a new diagnostic category in DSM-V, and these are discussed in this article.

Obsessive-compulsive disorder in children and adolescents.

Science.gov (United States)

Krebs, Georgina; Heyman, Isobel

2015-05-01

Obsessive-compulsive disorder (OCD) in childhood and adolescence is an impairing condition, associated with a specific set of distressing symptoms incorporating repetitive, intrusive thoughts (obsessions) and distressing, time-consuming rituals (compulsions). This review considers current knowledge of causes and mechanisms underlying OCD, as well as assessment and treatment. Issues relating to differential diagnosis are summarised, including the challenges of distinguishing OCD from autism spectrum disorders and tic disorders in youth. The recommended treatments, namely cognitive behaviour therapy and serotonin reuptake inhibiting/selective serotonin reuptake inhibitor medications, are outlined along with the existing evidence-based and factors associated with treatment resistance. Finally, novel clinical developments that are emerging in the field and future directions for research are discussed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Evaluation of Avulsion-Induced Neuropathology in Rat Spinal Cords with 18F-FDG Micro-PET/CT.

Directory of Open Access Journals (Sweden)

Ze-Min Ling

Full Text Available Brachial plexus root avulsion (BPRA leads to dramatic motoneuron death and glial reactions in the corresponding spinal segments at the late stage of injury. To protect spinal motoneurons, assessment of the affected spinal segments should be done at an earlier stage of the injury. In this study, we employed 18F-FDG small-animal PET/CT to assess the severity of BPRA-induced cervical spinal cord injuries. Adult Sprague-Dawley rats were randomly treated and divided into three groups: Av+NS (brachial plexus root avulsion (Av treated with normal saline, Av+GM1 (treated with monosialoganglioside, and control. At time points of 3 day (d, 1 week (w, 2 w, 4 w and 8 w post-injury, 18F-FDG micro-PET/CT scans and neuropathology assessments of the injured spinal roots, as well as the spinal cord, were performed. The outcomes of the different treatments were compared. The results showed that BPRA induced local bleeding and typical Wallerian degeneration of the avulsed roots accompanied by 18F-FDG accumulations at the ipsilateral cervical intervertebral foramen. BPRA-induced astrocyte reactions and overexpression of neuronal nitric oxide synthase in the motoneurons correlated with higher 18F-FDG uptake in the ipsilateral cervical spinal cord during the first 2 w post-injury. The GM1 treatment reduced BPRA-induced astrocyte reactions and inhibited the de novo nNOS expressions in spinal motoneurons. The GM1 treatment also protected spinal motoneurons from avulsion within the first 4 w post-injury. The data from this study suggest that 18F-FDG PET/CT could be used to assess the severity of BPRA-induced primary and secondary injuries in the spinal cord. Furthermore, GM1 is an effective drug for reducing primary and secondary spinal cord injuries following BPRA.

DSM-5 under-Identifies PDDNOS: Diagnostic Agreement between the DSM-5, DSM-IV, and Checklist for Autism Spectrum Disorder

Science.gov (United States)

Mayes, Susan Dickerson; Black, Amanda; Tierney, Cheryl D.

2013-01-01

Agreement between the DSM-5, DSM-IV, and Checklist for Autism Spectrum Disorder was assessed in 125 children with autism spectrum disorder (ASD), which included high and low functioning autism (HFA and LFA) and pervasive developmental disorder not otherwise specified (PDDNOS), and children with other clinical disorders (e.g., ADHD, mental…

Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons.

Science.gov (United States)

Rodriguez-Rodriguez, Patricia; Sandebring-Matton, Anna; Merino-Serrais, Paula; Parrado-Fernandez, Cristina; Rabano, Alberto; Winblad, Bengt; Ávila, Jesús; Ferrer, Isidre; Cedazo-Minguez, Angel

2017-12-01

Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression. Furthermore, cells accumulating insulin show signs of insulin resistance and decreased insulin receptor levels. These results suggest that insulin retention in hyperphosphorylated tau-bearing neurons is a causative factor for the insulin resistance observed in tauopathies, and describe a novel neuropathological concept with important therapeutic implications. © 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.

Psychiatric disorders associated with Cushing's syndrome.

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Bratek, Agnieszka; Koźmin-Burzyńska, Agnieszka; Górniak, Eliza; Krysta, Krzysztof

2015-09-01

Cushing's syndrome is the term used to describe a set of symptoms associated with hypercortisolism, which in most cases is caused by hypophysial microadenoma over-secreting adrenocorticotropic hormone. This endocrine disorder is often associated with psychiatric comorbidities. The most important include mood disorders, psychotic disorders, cognitive dysfunctions and anxiety disorders. The aim of this article was to review the prevalence, symptoms and consequences of psychiatric disorders in the course of Cushing's syndrome. We therefore performed a literature search using the following keywords: Cushing's syndrome and psychosis, Cushing's syndrome and mental disorders, Cushing's syndrome and depression, Cushing's syndrome and anxiety. The most prevalent psychiatric comorbidity of Cushing's syndrome is depression. Psychiatric manifestations can precede the onset of full-blown Cushing's syndrome and therefore be misdiagnosed. Despite the fact that treatment of the underlying endocrine disease in most cases alleviates psychiatric symptoms, the loss of brain volume persists. It is important to be alert to the symptoms of hypercortisolism in psychiatric patients to avoid misdiagnosis and enable them receiving adequate treatment.

Conversion Disorder- Mind versus Body: A Review.

Science.gov (United States)

Ali, Shahid; Jabeen, Shagufta; Pate, Rebecca J; Shahid, Marwah; Chinala, Sandhya; Nathani, Milankumar; Shah, Rida

2015-01-01

In this article, the authors accentuate the signs and symptoms of conversion disorder and the significance of clinical judgment and expertise in order to reach the right diagnosis. The authors review the literature and provide information on the etiology, prevalence, diagnostic criteria, and the treatment methods currently employed in the management of conversion disorder. Of note, the advancements of neuropsychology and brain imaging have led to emergence of a relatively sophisticated picture of the neuroscientific psychopathology of complex mental illnesses, including conversion disorder. The available evidence suggests new methods with which to test hypotheses about the neural circuits underlying conversion symptoms. In context of this, the authors also explore the neurobiological understanding of conversion disorder.

The neural bases of cognitive processes in gambling disorder.

Science.gov (United States)

Potenza, Marc N

2014-08-01

Functional imaging is offering powerful new tools to investigate the neurobiology of cognitive functioning in people with and without psychiatric conditions like gambling disorder. Based on similarities between gambling and substance-use disorders in neurocognitive and other domains, gambling disorder has recently been classified in the Diagnostic and Statistical Manual of Mental Disorders (5th edn) (DSM-5) as a behavioral addiction. Despite the advances in understanding, there exist multiple unanswered questions about the pathophysiology underlying gambling disorder and the promise for translating the neurobiological understanding into treatment advances remains largely unrealized. Here we review the neurocognitive underpinnings of gambling disorder with a view to improving prevention, treatment, and policy efforts. Copyright © 2014 Elsevier Ltd. All rights reserved.

The structure of common and uncommon mental disorders.

Science.gov (United States)

Forbush, K T; Watson, D

2013-01-01

Co-morbidity patterns in epidemiological studies of mental illness consistently demonstrate that a latent internalizing factor accounts for co-morbidity patterns among unipolar mood and anxiety disorders, whereas a latent externalizing factor underlies the covariation of substance-use disorders and antisocial behaviors. However, this structure needs to be extended to include a broader range of disorders. Exploratory and confirmatory factor analyses were used to examine the structure of co-morbidity using data from the Collaborative Psychiatric Epidemiological Surveys (n = 16 233). In the best-fitting model, eating and bipolar disorders formed subfactors within internalizing, impulse control disorders were indicators of externalizing, and factor-analytically derived personality disorder scales split between internalizing and externalizing. This was the first large-scale nationally representative study that has included uncommon mental disorders with sufficient power to examine their fit within a structural model of psychopathology. The results of this study have important implications for conceptualizing myriad mental disorders.

Brain Responses Underlying Anthropomorphism, Agency, and Social Attribution in Autism Spectrum Disorder.

Science.gov (United States)

Ammons, Carla J; Doss, Constance F; Bala, David; Kana, Rajesh K

2018-01-01

Theory of Mind (ToM), the ability to attribute mental states to oneself and others, is frequently impaired in Autism Spectrum Disorder (ASD) and may result from altered activation of social brain regions. Conversely, Typically Developing (TD) individuals overextend ToM and show a strong tendency to anthropomorphize and interpret biological motion in the environment. Less is known about how the degree of anthropomorphism influences intentional attribution and engagement of the social brain in ASD. This fMRI study examines the extent of anthropomorphism, its role in social attribution, and the underlying neural responses in ASD and TD using a series of human stick figures and geometrical shapes. 14 ASD and 14 TD adults watched videos of stick figures and triangles interacting in random or socially meaningful ways while in an fMRI scanner. In addition, they completed out-of-scanner measures of ToM skill and real-world social deficits. Whole brain statistical analysis was performed for regression and within and between group comparisons of all conditions using SPM12's implementation of the general linear model. ToM network regions were activated in response to social movement and human-like characters in ASD and TD. In addition, greater ToM ability was associated with increased TPJ and MPFC activity while watching stick figures; whereas more severe social symptoms were associated with reduced right TPJ activation in response to social movement. These results suggest that degree of anthropomorphism does not differentially affect social attribution in ASD and highlights the importance of TPJ in ToM and social attribution.

[Schizophrenia: neurodevelopmental disorder or degenerative brain process?].

Science.gov (United States)

Gross, G; Huber, G

2008-05-01

In the last two decades schizophrenia is viewed increasingly as a neurodevelopmental (ND) disorder; as indicators are discussed f.e. premorbid personality, behaviour anomalies, premorbid somatic signs, deviations shown by brain imaging methods, neuropathological findings or neuropsychological deficits. Premorbid personality and behaviour anomalies have to be distinguished from precursor syndromes (prodromes and outpost syndromes), preceding the first psychotic episode many years. Moreover, only a minority of patients, later developing schizophrenia, reveal abnormal premorbid personality traits. Explanations why clinical expression of the disorder is delayed until adult life or at least adolescence, remain speculative. Findings of neocortical and limbic maldevelopment, e.g. in parahippocampal cortex, are hitherto not yet conclusive. As an argument for the ND hypothesis is claimed that ventricular enlargement already is present at the onset of positive symptoms and does not progress on follow-ups. But, if a ND disorder would have caused the ventricular enlargement, cranial volume and head size must be decreased, what is not the case in schizophrenia. Furtheron, there are findings of progressive increase in ventricular size and also of gliosis, especially in subcortical and periventricular areas. Anomalies of cerebral asymmetry; also distinct ND brain anomalies such as cavum septi pellucidi or dysgenesis of corpus callosum do not occur more frequently than expected in schizophrenia. As to the rate of obstetric complications (OCs) and viral infections sufficiently reliable data are missing; the great majority of schizophrenics have no OCs. Altogether, attempts to correlate brain findings, regarded as expression of an aberrant brain development with clinical subgroups of schizophrenia, were not very successful. This is also valid for ND concepts confined to male, early onset or sporadic schizophrenias. Only a distinct psychopathological remission type with the component

Cognitive neuroscience of obsessive-compulsive disorder.

Science.gov (United States)

Stern, Emily R; Taylor, Stephan F

2014-09-01

Cognitive neuroscience investigates neural responses to cognitive and emotional probes, an approach that has yielded critical insights into the neurobiological mechanisms of psychiatric disorders. This article reviews some of the major findings from neuroimaging studies using a cognitive neuroscience approach to investigate obsessive-compulsive disorder (OCD). It evaluates the consistency of results and interprets findings within the context of OCD symptoms, and proposes a model of OCD involving inflexibility of internally focused cognition. Although further research is needed, this body of work probing cognitive-emotional processes in OCD has already shed considerable light on the underlying mechanisms of the disorder. Copyright © 2014 Elsevier Inc. All rights reserved.

Gene expression deficits in pontine locus coeruleus astrocytes in men with major depressive disorder.

Science.gov (United States)

Chandley, Michelle J; Szebeni, Katalin; Szebeni, Attila; Crawford, Jessica; Stockmeier, Craig A; Turecki, Gustavo; Miguel-Hidalgo, Jose Javier; Ordway, Gregory A

2013-07-01

Norepinephrine and glutamate are among several neurotransmitters implicated in the neuropathology of major depressive disorder (MDD). Glia deficits have also been demonstrated in people with MDD, and glia are critical modulators of central glutamatergic transmission. We studied glia in men with MDD in the region of the brain (locus coeruleus; LC) where noradrenergic neuronal cell bodies reside and receive glutamatergic input. The expression of 3 glutamate-related genes (SLC1A3, SLC1A2, GLUL) concentrated in glia and a glia gene (GFAP) were measured in postmortem tissues from men with MDD and from paired psychiatrically healthy controls. Initial gene expression analysis of RNA isolated from homogenized tissue (n = 9-10 pairs) containing the LC were followed by detailed analysis of gene expressions in astrocytes and oligodendrocytes (n = 6-7 pairs) laser captured from the LC region. We assessed protein changes in GFAP using immunohistochemistry and immunoblotting (n = 7-14 pairs). Astrocytes, but not oligodendrocytes, demonstrated robust reductions in the expression of SLC1A3 and SLC1A2, whereas GLUL expression was unchanged. GFAP expression was lower in astrocytes, and we confirmed reduced GFAP protein in the LC using immunostaining methods. Reduced expression of protein products of SLC1A3 and SLC1A2 could not be confirmed because of insufficient amounts of LC tissue for these assays. Whether gene expression abnormalities were associated with only MDD and not with suicide could not be confirmed because most of the decedents who had MDD died by suicide. Major depressive disorder is associated with unhealthy astrocytes in the noradrenergic LC, characterized here by a reduction in astrocyte glutamate transporter expression. These findings suggest that increased glutamatergic activity in the LC occurs in men with MDD.

[Psychosocial Characteristics of Adolescent Girls with Posttraumatic Stress Disorders and Substance Use Disorders].

Science.gov (United States)

Thomsen, Monika; Baldus, Christiane; Herschelmann, Susanne; Schäfer, Ingo; Thomasius, Rainer

2016-09-01

Psychosocial Characteristics of Adolescent Girls with Posttraumatic Stress Disorders and Substance Use Disorders Already in adolescence posttraumatic stress disorder (PTSD) and substance use disorders (SUD) often occur comorbid. SUD is usually in the focus of treatment and underlying PTSD is not always recognized. To date there is no explicit offer for the simultaneous treatment of both clinical pictures in adolescence. In the present study we tested whether the group intervention Seeking Safety, that is implemented successfully in adulthood, would also be interesting for the youth clientele. In addition we analyzed the characteristics of a target group of girls and young women between 14 and 21 years, that could be reached for such a program in a German city. In the present study we conducted 39 complete interviews that enable an estimation of the various strains and symptoms of those affected. The results clarify that female adolescents with a dual diagnosis PTSD and SUD are currently not sufficiently addressed by the supply system and could benefit from a specific treatment like Seeking Safety.

Embodying Emotional Disorders: New Hypotheses about Possible Emotional Consequences of Motor Disorders in Parkinson's Disease and Tourette's Syndrome.

Science.gov (United States)

Mermillod, Martial; Vermeulen, Nicolas; Droit-Volet, Sylvie; Jalenques, Isabelle; Durif, Franck; Niedenthal, Paula

2011-01-01

Parkinson's disease (PD) and Tourette's syndrome (TS) lead to important motor disorders among patients such as possible facial amimia in PD and tics in Tourette's syndrome. Under the grounded cognition framework that shows the importance of motor embodiment in emotional feeling (Niedenthal, 2007), both types of pathology with motor symptoms should be sufficient to induce potential impairments for these patients when recognizing emotional facial expressions (EFE). In this opinion paper, we describe a theoretical framework that assumes potential emotional disorders in Parkinson's disease and Tourette's syndrome based on motor disorders characterizing these two pathologies. We also review different methodological barriers in previous experimental designs that could enable the identification of emotional facial expressions despite emotional disorders in PD and TS.

Autism Spectrum Disorders in Africa : Current Challenges in Identification, Assessment, and Treatment

NARCIS (Netherlands)

Ruparelia, Kavita; Abubakar, Amina; Badoe, Eben; Bakare, Muideen; Visser, Karren; Chugani, Diane C.; Chugani, Harry T.; Donald, Kirsten A.; Wilmshurst, Jo M.; Shih, Andy; Skuse, David; Newton, Charles R.

2016-01-01

Prevalence of autism spectrum disorders has increased over recent years, however, little is known about the identification and management of autism spectrum disorder in Africa. This report summarizes a workshop on autism spectrum disorder in Africa under the auspices of the International Child

Als and Ftd: Insights into the disease mechanisms and therapeutic targets.

Science.gov (United States)

Liscic, Rajka M

2017-12-15

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders, related by signs of deteriorating motor and cognitive functions, and short survival. The causes are still largely unknown and no effective treatment currently exists. It has been shown that FTLD may coexist with ALS. The overlap between ALS and frontotemporal dementia (FTD), the clinical syndrome associated with FTLD, occurs at clinical, genetic, and pathological levels. The hallmark proteins of the pathognomonic inclusions are SOD-1, TDP-43 or FUS, rarely the disease is caused by mutations in the respective genes. Frontotemporal lobar degenerations (FTLD) is genetically, neuropathologically and clinically heterogeneous and may present with behavioural, language and occasionally motor disorder, respectively. Almost all cases of ALS, as well as tau-negative FTLD share a common neuropathology, neuronal and glial inclusion bodies containing abnormal TDP-43 protein, collectively called TDP-43 proteinopathy. Recent discoveries in genetics (e.g. C9orf72 hexanucleotide expansion) and the subsequent neuropathological characterization have revealed remarkable overlap between ALS and FTLD-TDP indicating common pathways in pathogenesis. For ALS, an anti-glutamate agent riluzole may be offered to slow disease progression (Level A), and a promising molecule, arimoclomol, is currently in clinical trials. Other compounds, however, are being trailed and some have shown encouraging results. As new therapeutic approaches continue to emerge by targeting SOD1, TDP-43, or GRN, we present some advances that are being made in our understanding of the molecular mechanisms of these diseases, which together with gene and stem cell therapies may translate into new treatment options. Copyright © 2017 Elsevier B.V. All rights reserved.

Renal aquaporins and water balance disorders

DEFF Research Database (Denmark)

Kortenoeven, Marleen; Fenton, Robert A.

2013-01-01

BACKGROUND: Aquaporins (AQPs) are a family of proteins that can act as water channels. Regulation of AQPs is critical to osmoregulation and the maintenance of body water homeostasis. Eight AQPs are expressed in the kidney of which five have been shown to play a role in body water balance; AQP1, A......-solute diet and diuretics. GENERAL SIGNIFICANCE: In recent years, our understanding of the underlying mechanisms of water balance disorders has increased enormously, which has opened up several possible new treatment strategies.......BACKGROUND: Aquaporins (AQPs) are a family of proteins that can act as water channels. Regulation of AQPs is critical to osmoregulation and the maintenance of body water homeostasis. Eight AQPs are expressed in the kidney of which five have been shown to play a role in body water balance; AQP1, AQP......2, AQP3, AQP4 and AQP7. AQP2 in particular is regulated by vasopressin. SCOPE OF REVIEW: This review summarizes our current knowledge of the underlying mechanisms of various water balance disorders and their treatment strategies. MAJOR CONCLUSIONS: Dysfunctions of AQPs are involved in disorders...

Attention Deficit Hyperactivity Disorder (ADHD) and disordered eating behaviour: A systematic review and a framework for future research.

Science.gov (United States)

Kaisari, Panagiota; Dourish, Colin T; Higgs, Suzanne

2017-04-01

Preliminary findings suggest that Attention Deficit Hyperactivity Disorder (ADHD) may be associated with disordered eating behaviour, but whether there is sufficient evidence to suggest an association between ADHD and specific types of disordered eating behaviour is unclear. Furthermore, it is uncertain whether specific features associated with ADHD are differentially associated with disordered eating behaviour. A systematic review of seventy-five studies was conducted to evaluate the potential association between ADHD symptomatology and disordered eating behaviour and to provide an estimate of the strength of evidence for any association. Overall, a moderate strength of evidence exists for a positive association between ADHD and disordered eating and with specific types of disordered-eating behaviour, in particular, overeating behaviour. There is consistent evidence that impulsivity symptoms of ADHD are positively associated with overeating and bulimia nervosa and more limited evidence for an association between hyperactivity symptoms and restrictive eating in males but not females. Further research is required to assess the potential direction of the relationship between ADHD and disordered eating, the underlying mechanisms and the role of specific ADHD symptoms in the development and/or maintenance of disordered eating behaviour. We propose a framework that could be used to guide the design of future studies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chronic inorganic mercury exposure induces sex-specific changes in central TNFα expression: Importance in autism?

OpenAIRE

Curtis, J. Thomas; Chen, Yue; Buck, Daniel J.; Davis, Randall L.

2011-01-01

Mercury is neurotoxic and increasing evidence suggests that environmental exposure to mercury may contribute to neuropathologies including Alzheimer's disease and autism spectrum disorders. Mercury is known to disrupt immunocompetence in the periphery, however, little is known about the effects of mercury on neuroimmune signaling. Mercury-induced effects on central immune function are potentially very important given that mercury exposure and neuroinflammation both are implicated in certain n...

Conditional loss of progranulin in neurons is not sufficient to cause neuronal ceroid lipofuscinosis-like neuropathology in mice.

Science.gov (United States)

Petkau, Terri L; Blanco, Jake; Leavitt, Blair R

2017-10-01

Progranulin deficiency due to heterozygous null mutations in the GRN gene is a common cause of familial frontotemporal lobar degeneration (FTLD), while homozygous loss-of-function GRN mutations cause neuronal ceroid lipofuscinosis (NCL). Aged progranulin-knockout mice display highly exaggerated lipofuscinosis, microgliosis, and astrogliosis, as well as mild cell loss in specific brain regions. Progranulin is a secreted glycoprotein expressed in both neurons and microglia, but not astrocytes, in the brain. We generated conditional progranulin-knockout mice that lack progranulin in nestin-expressing cells (Nes-cKO mice), which include most neurons as well as astrocytes. We confirmed near complete knockout of progranulin in neurons in Nes-cKO mice, while microglial progranulin levels remained similar to that of wild-type animals. Overall brain progranulin levels were reduced by about 50% in Nes-cKO, and no Grn was detected in primary Nes-cKO neurons. Nes-cKO mice aged to 12months did not display any increase in lipofuscin deposition, microgliosis, or astrogliosis in the four brain regions examined, though increases were observed for most of these measures in Grn-null animals. We conclude that neuron-specific loss of progranulin is not sufficient to cause similar neuropathological changes to those seen in constitutive Grn-null animals. Our results suggest that increased lipofuscinosis and gliosis in Grn-null animals are not caused by intrinsic progranulin deficiency in neurons, and that microglia-derived progranulin may be sufficient to maintain neuronal health and homeostasis in the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Interpersonal Functioning in Obsessive-Compulsive Personality Disorder

OpenAIRE

Cain, Nicole M.; Ansell, Emily B.; Simpson, H. Blair; Pinto, Anthony

2014-01-01

The core symptoms of obsessive-compulsive personality disorder (OCPD) often lead to interpersonal difficulties. However, little research has explored interpersonal functioning in OCPD. The current study examined interpersonal problems, interpersonal sensitivities, empathy, and systemizing, the drive to analyze and derive underlying rules for systems, in a sample of 25 OCPD individuals, 25 individuals with comorbid OCPD and obsessive-compulsive disorder (OCD), and 25 healthy controls. We found...

Tic disorders: administrative prevalence and co-occurrence with attention-deficit/hyperactivity disorder in a German community sample.

Science.gov (United States)

Schlander, M; Schwarz, O; Rothenberger, A; Roessner, V

2011-09-01

Coexistence of tics and attention-deficit/hyperactivity disorder (ADHD) has important clinical and scientific implications. Existing data on the co-occurrence of tic disorders, Tourette Syndrome (TS), and ADHD are largely derived from small-scale studies in selected samples and therefore heterogeneous. The Nordbaden project captures the complete outpatient claims data of more than 2.2 million persons, representing 82% of the regional population in 2003. Based upon the number of diagnosed cases of tic disorders, TS, and ADHD, we determined 12-months administrative prevalence rates as well as rates of co-occurrence. Both tic disorders and ADHD were diagnosed most often in the age group 7-12 years (any tic disorder: 0.8%; ADHD: 5.0%). With increasing age, the administrative prevalence difference in favor of males disappeared, with tic disorders being somewhat more frequently reported in females than males in the age groups above 30 years. The highest rate of ADHD co-occurring with tic disorders was found in adolescents (age 13-18 years, 15.1%). Tic disorders were observed in 2.3% of patients with ADHD. Administrative prevalence rates of tic disorders and TS were substantially lower compared to rates found in community-based epidemiological studies, suggesting that a large number of cases remain undetected and untreated under present conditions of routine outpatient care. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Subcortical pathways: Towards a better understanding of auditory disorders.

Science.gov (United States)

Felix, Richard A; Gourévitch, Boris; Portfors, Christine V

2018-05-01

Hearing loss is a significant problem that affects at least 15% of the population. This percentage, however, is likely significantly higher because of a variety of auditory disorders that are not identifiable through traditional tests of peripheral hearing ability. In these disorders, individuals have difficulty understanding speech, particularly in noisy environments, even though the sounds are loud enough to hear. The underlying mechanisms leading to such deficits are not well understood. To enable the development of suitable treatments to alleviate or prevent such disorders, the affected processing pathways must be identified. Historically, mechanisms underlying speech processing have been thought to be a property of the auditory cortex and thus the study of auditory disorders has largely focused on cortical impairments and/or cognitive processes. As we review here, however, there is strong evidence to suggest that, in fact, deficits in subcortical pathways play a significant role in auditory disorders. In this review, we highlight the role of the auditory brainstem and midbrain in processing complex sounds and discuss how deficits in these regions may contribute to auditory dysfunction. We discuss current research with animal models of human hearing and then consider human studies that implicate impairments in subcortical processing that may contribute to auditory disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Cross-Disorder Genetic Analysis of Tic Disorders, Obsessive-Compulsive, and Hoarding Symptoms.

Science.gov (United States)

Zilhão, Nuno R; Smit, Dirk J; Boomsma, Dorret I; Cath, Danielle C

2016-01-01

Hoarding, obsessive-compulsive disorder (OCD), and Tourette's disorder (TD) are psychiatric disorders that share symptom overlap, which might partly be the result of shared genetic variation. Population-based twin studies have found significant genetic correlations between hoarding and OCD symptoms, with genetic correlations varying between 0.1 and 0.45. For tic disorders, studies examining these correlations are lacking. Other lines of research, including clinical samples and GWAS or CNV data to explore genetic relationships between tic disorders and OCD, have only found very modest if any shared genetic variation. Our aim was to extend current knowledge on the genetic structure underlying hoarding, OC symptoms (OCS), and lifetime tic symptoms and, in a trivariate analysis, assess the degree of common and unique genetic factors contributing to the etiology of these disorders. Data have been gathered from participants in the Netherlands Twin Register comprising a total of 5293 individuals from a sample of adult monozygotic (n = 2460) and dizygotic (n = 2833) twin pairs (mean age 33.61 years). The data on Hoarding, OCS, and tic symptoms were simultaneously analyzed in Mplus. A liability threshold model was fitted to the twin data, analyzing heritability of phenotypes and of their comorbidity. Following the criteria for a probable clinical diagnosis in all phenotypes, 6.8% of participants had a diagnosis of probable hoarding disorder (HD), 6.3% of OCS, and 12.8% of any probable lifetime tic disorder. Genetic factors explained 50.4, 70.1, and 61.1% of the phenotypic covariance between hoarding-OCS, hoarding-tics, and OCS-tics, respectively. Substantial genetic correlations were observed between hoarding and OCS (0.41), hoarding and tics (0.35), and between OCS and tics (0.37). These results support the contribution of genetic factors in the development of these disorders and their comorbidity. Furthermore, tics were mostly influenced by specific

Cross-Disorder Genetic Analysis of Tic Disorders, Obsessive–Compulsive, and Hoarding Symptoms

Science.gov (United States)

Zilhão, Nuno R.; Smit, Dirk J.; Boomsma, Dorret I.; Cath, Danielle C.

2016-01-01

Hoarding, obsessive–compulsive disorder (OCD), and Tourette’s disorder (TD) are psychiatric disorders that share symptom overlap, which might partly be the result of shared genetic variation. Population-based twin studies have found significant genetic correlations between hoarding and OCD symptoms, with genetic correlations varying between 0.1 and 0.45. For tic disorders, studies examining these correlations are lacking. Other lines of research, including clinical samples and GWAS or CNV data to explore genetic relationships between tic disorders and OCD, have only found very modest if any shared genetic variation. Our aim was to extend current knowledge on the genetic structure underlying hoarding, OC symptoms (OCS), and lifetime tic symptoms and, in a trivariate analysis, assess the degree of common and unique genetic factors contributing to the etiology of these disorders. Data have been gathered from participants in the Netherlands Twin Register comprising a total of 5293 individuals from a sample of adult monozygotic (n = 2460) and dizygotic (n = 2833) twin pairs (mean age 33.61 years). The data on Hoarding, OCS, and tic symptoms were simultaneously analyzed in Mplus. A liability threshold model was fitted to the twin data, analyzing heritability of phenotypes and of their comorbidity. Following the criteria for a probable clinical diagnosis in all phenotypes, 6.8% of participants had a diagnosis of probable hoarding disorder (HD), 6.3% of OCS, and 12.8% of any probable lifetime tic disorder. Genetic factors explained 50.4, 70.1, and 61.1% of the phenotypic covariance between hoarding-OCS, hoarding-tics, and OCS-tics, respectively. Substantial genetic correlations were observed between hoarding and OCS (0.41), hoarding and tics (0.35), and between OCS and tics (0.37). These results support the contribution of genetic factors in the development of these disorders and their comorbidity. Furthermore, tics were mostly influenced by specific

Relationships Among Avoidant Personality Disorder, Social Anxiety Disorder, and Normative Personality Traits: A Twin Study.

Science.gov (United States)

Welander-Vatn, Audun; Torvik, Fartein Ask; Czajkowski, Nikolai; Kendler, Kenneth S; Reichborn-Kjennerud, Ted; Knudsen, Gun Peggy; Ystrom, Eivind

2018-03-05

Avoidant personality disorder (AvPD) and social anxiety disorder (SAD) share risk factors to a substantial degree, and both are characterized by the experience of anxiety in social situations. The authors investigated whether these disorders are differentially related to the Big Five personality traits. They also examined the underlying genetic and environmental influences on these associations. A population-based sample of 1,761 female twins was interviewed at baseline, and 1,471 of these were re-interviewed 10 years later. Associations between AvPD, SAD, and personality traits were investigated with multivariate biometric analyses. The authors found that AvPD and SAD are differentially related to several personality traits at the phenotypic, genetic, and environmental level. The genetic and environmental liability to AvPD could be fully accounted for by the genetic and environmental factors influencing SAD and personality. The findings may increase current etiological understanding of these disorders and inform future classification and treatment efforts.

Border Terriers under primary veterinary care in England: demography and disorders.

Science.gov (United States)

O'Neill, Dan G; Darwent, Elisabeth C; Church, David B; Brodbelt, Dave C

2017-01-01

The Border Terrier is a working terrier type that is generally considered to be a relatively healthy and hardy breed. This study aimed to characterise the demography and common disorders of Border Terriers receiving veterinary care in England using de-identified electronic patient record data within the VetCompass™ Programme. Annual birth proportion for Border Terriers showed a decreasing trend from 1.46% in 2005 to 0.78% in 2014. The median adult bodyweight for males (10.9 kg, IQR: 9.6-12.3, range: 6.3-25.0) was higher than for females (9.1 kg, IQR: 8.2-10.3, range: 5.2-21.6) ( P  skin disorder (10.17%, 95% CI: 8.60-11.93).Syndromic analysis showed that the most prevalent body locations affected were the head-and-neck (37.75%, 95% CI: 35.14-40.43), abdomen (18.61%, 95% CI: 16.55-20.81) and limb (11.53%, 95% CI: 9.86-13.37). At least one organ system was affected in 834 (62.85%) Border Terriers. The most prevalent organ systems affected were the digestive (32.03%, 95% CI: 29.52-34.61), integument (26.68%, 95% CI: 24.31-29.14), connective/soft tissue (11.15%, 95% CI: 9.51-12.97) and auditory (9.87%, 95% CI: 8.32-11.60). At least one affected pathophysiological process was described in 881 (66.39%) Border Terriers. The most prevalent pathophysiologic processes recorded were inflammation (31.65%, 95% CI: 29.15-34.23), nutritional (9.04%, 95% CI: 7.55-10.72), mass/swelling (8.89%, 95% CI: 7.42-10.55), traumatic (7.99%, 95% CI: 6.59-9.58) and infectious (7.76%, 95% CI: 6.38-9.33). This study documented a trend towards reducing ownership and relatively long-livedness in the Border Terrier. The most common disorders were periodontal disease, overweight/obesity and otitis externa. Predisposition to dental and neurological disease was suggested. These results can provide a comprehensive evidence resource to support breed-based health plans that can contribute positively to reforms to improve health and welfare within the breed.

Foreign body impaction in the esophagus: are there underlying motor disorders?

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Mazzadi, S; Salis, G B; García, A; Iannicillo, H; Fucile, V; Chiocca, J C

2017-11-01

Compared with the control group, the impacted subjects presented marked reduction in amplitude and duration of esophageal contraction in the proximal esophagus. These motor disorders could be responsible for the foreign body impaction in the esophagus. However, we believe this patient group should be further studied by 24-hour esophageal manometry to reach a more accurate diagnosis by studying each patient's entire circadian cycle. © 1998 International Society for Diseases of the Esophagus/Harcourt Brace & Co. Ltd

Knowledge of physicians about sleep disorders in Osogbo, South ...

African Journals Online (AJOL)

Background: Sleep disorders are common and global problem that affects a larger proportion of the population. The condition is significantly under diagnosed and most cases are left untreated. Objective: The presents study aims to study the knowledge of physicians about sleep disorders in suburban town in south-west ...

Sleep and gastrointestinal disturbances in autism spectrum disorder in children.

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Klukowski, Mark; Wasilewska, Jolanta; Lebensztejn, Dariusz

2015-01-01

Autism spectrum disorder (ASD), a neurodevelopmental disorder with a prevalence of 1 in 68 children, commonly presents with comorbid conditions which include sleep disorders. Sleep disorders reported in ASD include, among others, increased bedtime resistance, insomnia, parasomnia, sleep disordered breathing, morning rise problems, and daytime sleepiness. Polysomnography studies show that children with ASD have altered sleep architecture including shorter total sleep time and longer sleep latency than typically developing peers. Sleep-related problems have been shown to affect overall autism scores, social skills decits, stereotypic behavior, and cognitive performance. Additionally, problematic sleep in children with ASD has been associated with higher levels of parental stress. Underlying causes specically related to sleep disorders are not fully known. Gastrointestinal (GI) disorders are commonly associated with sleep problems in these patients. Children with ASD and GI symptoms have been found to have a higher prevalence of sleep disturbances compared with typically developing peers who do not have GI symptoms. Treatment approaches to children with sleep disorders are varied and range from lifestyle modications and behavioral interventions to drug therapies and surgical interventions. Physicians should take into account GI disorders as possible underlying causes of sleep-related problems in children with ASD. Therapeutic interventions should begin with less invasive methods before progressing to more invasive options such as pharmacotherapy and should be based on medical indications in order to provide effective care while minimizing potential adverse health effects. Evidence-based studies concerning GI and sleep disorders in children with ASD are limited and further studies are warranted.

An Underlying Common Factor, Influenced by Genetics and Unique Environment, Explains the Covariation Between Major Depressive Disorder, Generalized Anxiety Disorder, and Burnout: A Swedish Twin Study.

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Mather, Lisa; Blom, Victoria; Bergström, Gunnar; Svedberg, Pia

2016-12-01

Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005-2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69-0.74) between MDD and GAD, 0.58 (0.56-0.60) between MDD and burnout, and 0.53 (0.50-0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

[Lower urinary tract dysfunction and neuropathological findings of the neural circuits controlling micturition in familial amyotrophic lateral sclerosis with L106V mutation in the SOD1 gene].

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Hineno, Akiyo; Oyanagi, Kiyomitsu; Nakamura, Akinori; Shimojima, Yoshio; Yoshida, Kunihiro; Ikeda, Shu-Ichi

2016-01-01

We report lower urinary tract dysfunction and neuropathological findings of the neural circuits controlling micturition in the patients with familial amyotrophic lateral sclerosis having L106V mutation in the SOD1 gene. Ten of 20 patients showed lower urinary tract dysfunction and 5 patients developed within 1 year after the onset of weakness. In 8 patients with an artificial respirator, 6 patients showed lower urinary tract dysfunction. Lower urinary tract dysfunction and respiratory failure requiring an artificial respirator occurred simultaneously in 3 patients. Neuronal loss and gliosis were observed in the neural circuits controlling micturition, such as frontal lobe, thalamus, hypothalamus, striatum, periaqueductal gray, ascending spinal tract, lateral corticospinal tract, intermediolateral nucleus and Onufrowicz' nucleus. Lower urinary tract dysfunction, especially storage symptoms, developed about 1 year after the onset of weakness, and the dysfunction occurred simultaneously with artificial respirator use in the patients.

Update on common nutritional disorders of captive reptiles.

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Mans, Christoph; Braun, Jana

2014-09-01

Nutritional disorders of captive reptiles remain very common despite the increasing knowledge about reptile husbandry and nutrition. Many nutritional disorders are diagnosed late in the disease process; often secondary complications, such as pathologic fractures in reptiles suffering from nutritional secondary hyperparathyroidism have occurred. Therefore, every attempt should be made to educate reptile owners and keepers about the proper care and dietary needs of reptiles under their care because all nutritional disorders seen in captive reptiles are preventable. Copyright © 2014 Elsevier Inc. All rights reserved.

Does impaired socioemotional functioning account for behavioral dysexecutive disorders? Evidence from a transnosological study.

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Narme, Pauline; Roussel, Martine; Mouras, Harold; Krystkowiak, Pierre; Godefroy, Olivier

2017-01-01

Behavioral dysexecutive disorders are highly prevalent in patients with neurological diseases but cannot be explained by cognitive dysexecutive impairments. In fact, the underlying mechanisms are poorly understood. Given that socioemotional functioning underlies appropriate behavior, socioemotional impairments may contribute to the appearance of behavioral disorders. To investigate this issue, we performed a transnosological study. Seventy-five patients suffering from various neurological diseases (Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration, and stroke) were included in the study. The patients were comprehensively assessed in terms of cognitive and behavioral dysexecutive disorders and socioemotional processes (facial emotion recognition and theory of mind). As was seen for cognitive and behavioral dysexecutive impairments, the prevalence of socioemotional impairments varied according to the diagnosis. Stepwise logistic regressions showed that (i) only cognitive executive indices predicted hypoactivity with apathy/abulia, (ii) theory of mind impairments predicted hyperactivity-distractibility-impulsivity and stereotyped/perseverative behaviors, and (iii) impaired facial emotion recognition predicted social behavior disorders. Several dysexecutive behavioral disorders are associated with an underlying impairment in socioemotional processes but not with cognitive indices of executive functioning (except for apathy). These results strongly suggest that some dysexecutive behavioral disorders are the outward signs of an underlying impairment in socioemotional processes.

Social Cognition and Emotional Functioning in Patients with Binge Eating Disorder.

Science.gov (United States)

Aloi, Matteo; Rania, Marianna; Caroleo, Mariarita; De Fazio, Pasquale; Segura-García, Cristina

2017-05-01

This study aims to evaluate the theory of mind ability in a sample of obese patients with and without binge eating disorder (BED) and to explore the correlations between emotional and clinical assessments. Overall, 20 non-BED, 16 under-threshold BED and 22 BED obese patients completed a battery of tests assessing social cognition and eating disorder psychopathology. Binge eating disorder, non-BED and under-threshold-BED obese patients showed similar ability to recognise others' emotions, but BED obese patients exhibited a deficit in recognising their own emotions as demonstrated by more impaired levels of alexithymia and interoceptive awareness and were more depressed. High positive correlations were evident between binging, depression, interoceptive awareness and alexithymia. Binge eating disorder patients have a comparable ability to understand others' emotions but a more impaired capacity to understand and code their own emotions compared with non-BED obese patients. This impairment is highly correlated with depression. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Fragile X-associated disorders: Don't miss them.

Science.gov (United States)

Birch, Rachael C; Cohen, Jonathan; Trollor, Julian N

2017-01-01

Fragile X-associated disorders are a family of inherited disorders caused by expansions in the Fragile X Mental Retardation 1 (FMR1) gene. Premutation expansions of the FMR1 gene confer risk for fragile X-associated primary ovarian insufficiency and fragile X-associated tremor ataxia syndrome, as well as other medical and psychiatric comorbidities. Premutation expansions of the FMR1 gene are common in the general population. However, fragile X-associated disorders are frequently under-recognised and often misdiagnosed. The aim of this article is to describe fragile X-associated disorders and identify specific considerations for general practitioners (GPs) during identification and management of these disorders. GPs have a critical role in the identification of fragile X-associated disorders, as well as coordination of complex care needs. Prompt recognition and appropriate management of these disorders and potential medical and psychiatric comorbidities will have important implications not only for the affected patient, but also other family members who may be at risk.

BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology.

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Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

2017-08-01

Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer's disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD.

The study of role of stress in children with behavior disorders and orofacial lesions.

Science.gov (United States)

Baad, R K; Jagtap, Kiran

2012-07-01

(1) To study the behavior disorders in children between 5 to 15 years. (2) To study the role of stress in causing behavior disorders. (3) To interpret the orofacial findings in children with behavior disorders. (4) Correlate the orofacial findings with behavior disorder. Ninty children with behavior problems between age of 5 to 15 years along with their parents who visited the Department of Child-Guidance Clinic, BYL Nair Charitable Hospital, Mumbai. Intraoral examinations were conducted. Behavioral disorders and factors predisposing to those disorders were recorded. Behavior disorders with orofacial lesions was more common in age group of 8 to 10 years. The children were continuously under stress, which manifested in the form of various orofacial disorders or oral lesions. Most common orofacial condition was bruxism. Awareness of behavior disorders in dental treatment should guide the pediatric dentist to seek child psychiatric consultation for behavioral disorders to enable early evaluation of the underlying disorder. The present study suggested that orofacial and behavior characteristics can serve as markers to diagnose children with behavioral disorders. It also serves as a guide to dental clinicians to refer such children to psychiatrists or pediatricians for early identification, prevention and treatment.

Comorbidity of depressive and dermatologic disorders - therapeutic aspects.

Science.gov (United States)

Filaković, Pavo; Petek, Anamarija; Koić, Oliver; Radanović-Grgurić, Ljiljana; Degmecić, Dunja

2009-09-01

Depressive disorders are more common in the population affected with dermatologic disorders. Comorbidity of depression and dermatologic disorders is around 30%. The correlation between depressive and dermatologic disorders still remains unclear. In psychodermatology three disorders are described: a) psychophysiological disorders (both disorders induced and maintained by stressors), b) secondary psychiatric disorders (mental disorder as a result of skin leasions and treatment) and c) primary psychiatric disorders (skin alterations as a result of mental disorders and treatment). In depression and dermatology disorders in which certain precipitating factors are required thereby causing alteration of the patient's immunological identity causing a combination of hereditary features and ones acquired through adaptation occur to cause the disorder to develop. The cytokines are vital in the regulation of the immunology response and are also mediators of non-infective inflammatory processes leading to recurrent hormonal secretion affecting the function of the vegetative and central nervous system leading to so called "sickness behaviour", marked by loss of appetite, anhedonia, anxiety, decrease of concentration and interest along with other changes which generate a picture of depressive disorder. Treatment of depressive and dermatologic disorders is complex and requires an integral therapeutic approach encompassing all aspects of both disorders and their comorbidity. Therefore therapeutic success lies in a team approach to the patient under the auspice of consultative-liason psychiatry by setting the frame for efficient collaboration and bridging the gap between the mental and the physical in everyday clinical practice.

Pediatric anxiety disorders: from neuroscience to evidence-based clinical practice

Directory of Open Access Journals (Sweden)

Giovanni Abrahao Salum

2013-01-01

Full Text Available The objective of this narrative review of the literature is to describe the epidemiology, etiology, pathophysiology, diagnosis, and treatment of pediatric anxiety disorders. We aim to guide clinicians in understanding the biology of anxiety disorders and to provide general guidelines for the proper diagnoses and treatment of these conditions early in life. Anxiety disorders are prevalent, associated with a number of negative life outcomes, and currently under-recognized and under-treated. The etiology involves both genes and environmental influences modifying the neural substrate in a complex interplay. Research on pathophysiology is still in its infancy, but some brain regions, such as the amygdala and the prefrontal cortex, have been implicated in fear and anxiety. Current practice is to establish diagnosis based purely on clinical features, derived from clinical interviews with the child, parents, and teachers. Treatment is effective using medication, cognitive behavioral therapy, or a combination of both. An introduction to the neuroscience behind anxiety disorders combined with an evidence-based approach may help clinicians to understand these disorders and treat them properly in childhood.

Alcohol abuse, personality disorders, and aggression : The quest for a common underlying mechanism

NARCIS (Netherlands)

Garofalo, C.; Wright, Aidan G.C.

2017-01-01

Alcohol abuse and personality disorders are often comorbid, and their co-occurrence is associated with worse rognostic expectations, poor therapeutic outcomes, as well as deleterious behavioral and interpersonal consequences. The current review aims at untangling the association among alcohol abuse,

Disordered eating practices in gastrointestinal disorders.

Science.gov (United States)

Satherley, R; Howard, R; Higgs, S

2015-01-01

To systematically review evidence concerning disordered eating practices in dietary-controlled gastrointestinal conditions. Three key questions were examined: a) are disordered eating practices a feature of GI disorders?; b) what abnormal eating practices are present in those with GI disorders?; and c) what factors are associated with the presence of disordered eating in those with GI disorders? By exploring these questions, we aim to develop a conceptual model of disordered eating development in GI disease. Five key databases, Web of Science with Conference Proceedings (1900-2014) and MEDLINE (1950-2014), PubMed, PsycINFO (1967-2014) and Google Scholar, were searched for papers relating to disordered eating practices in those with GI disorders. All papers were quality assessed before being included in the review. Nine papers were included in the review. The majority of papers reported that the prevalence of disordered eating behaviours is greater in populations with GI disorders than in populations of healthy controls. Disordered eating patterns in dietary-controlled GI disorders may be associated with both anxiety and GI symptoms. Evidence concerning the correlates of disordered eating was limited. The presence of disordered eating behaviours is greater in populations with GI disorders than in populations of healthy controls, but the direction of the relationship is not clear. Implications for further research are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Feeding and eating disorders in children.

Science.gov (United States)

Bryant-Waugh, Rachel

2013-11-01

The past few years have seen a steep increase in journal articles relating to feeding and eating disorders in children, making a succinct overview timely. The relevance of this review is enhanced by the recent publication of revised feeding and eating disorder diagnostic criteria in DSM-5. These have significant implications for younger patients, in particular through the inclusion of the new diagnostic category Avoidant/Restrictive Food Intake Disorder (ARFID). It is likely that this will encourage increased research interest in this field. Recent publications included in this article cover a broad range of topics relevant to childhood feeding and eating disorders, to include: presentation, diagnosis and classification; epidemiology; risk factors; assessment measures; treatment, prognosis and outcome. The area of feeding and eating disorders in children remains relatively under-researched, with significant gaps in knowledge about epidemiology, course and prognosis as well as a limited evidence base for treatment. However, important and promising avenues are increasingly being explored. In relation to clinical practice, there is now a much better recognition of these disorders and a greater awareness of their complexity, severity and potential impact in both the short and the longer term if not appropriately managed.

Concentrated Solutions of Single-Chain Nanoparticles: A Simple Model for Intrinsically Disordered Proteins under Crowding Conditions.

Science.gov (United States)

Moreno, Angel J; Lo Verso, Federica; Arbe, Arantxa; Pomposo, José A; Colmenero, Juan

2016-03-03

By means of large-scale computer simulations and small-angle neutron scattering (SANS), we investigate solutions of single-chain nanoparticles (SCNPs), covering the whole concentration range from infinite dilution to melt density. The analysis of the conformational properties of the SCNPs reveals that these synthetic nano-objects share basic ingredients with intrinsically disordered proteins (IDPs), as topological polydispersity, generally sparse conformations, and locally compact domains. We investigate the role of the architecture of the SCNPs in their collapse behavior under macromolecular crowding. Unlike in the case of linear macromolecules, which experience the usual transition from self-avoiding to Gaussian random-walk conformations, crowding leads to collapsed conformations of SCNPs resembling those of crumpled globules. This behavior is already found at volume fractions (about 30%) that are characteristic of crowding in cellular environments. The simulation results are confirmed by the SANS experiments. Our results for SCNPs--a model system free of specific interactions--propose a general scenario for the effect of steric crowding on IDPs: collapse from sparse conformations at high dilution to crumpled globular conformations in cell environments.

EFNS guidelines for the molecular diagnosis of neurogenetic disorders: motoneuron, peripheral nerve and muscle disorders.

Science.gov (United States)

Burgunder, J-M; Schöls, L; Baets, J; Andersen, P; Gasser, T; Szolnoki, Z; Fontaine, B; Van Broeckhoven, C; Di Donato, S; De Jonghe, P; Lynch, T; Mariotti, C; Spinazzola, A; Tabrizi, S J; Tallaksen, C; Zeviani, M; Harbo, H F; Finsterer, J

2011-02-01

These EFNS guidelines on the molecular diagnosis of motoneuron disorders, neuropathies and myopathies are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated. To collect data about planning, conditions and performance of molecular diagnosis of these disorders, a literature search in various electronic databases was carried out and original papers, meta-analyses, review papers and guideline recommendations reviewed. The best level of evidence for genetic testing recommendation (B) can be found for the disorders with specific presentations, including familial amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, Charcot-Marie-Tooth 1A, myotonic dystrophy and Duchenne muscular dystrophy. For a number of less common disorders, a precise description of the phenotype, including the use of immunologic methods in the case of myopathies, is considered as good clinical practice to guide molecular genetic testing. These guidelines are provisional and the future availability of molecular-genetic epidemiological data about the neurogenetic disorders under discussion in this article will allow improved recommendation with an increased level of evidence. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.

The Stability of DSM Personality Disorders over Twelve to Eighteen Years

Science.gov (United States)

Nestadt, Gerald; Di, Chongzhi; Samuels, J F; Bienvenu, O J; Reti, I M; Costa, P; Eaton, William W; Bandeen-Roche, Karen

2009-01-01

Background Stability of personality disorders is assumed in most nomenclatures; however, the evidence for this is limited and inconsistent. The aim of this study is to investigate the stability of DSM-III personality disorders in a community sample of eastern Baltimore residents unselected for treatment. Methods Two hundred ninety four participants were examined on two occasions by psychiatrists using the same standardized examination twelve to eighteen years apart. All the DSM-III criteria for personality disorders were assessed. Item-response analysis was adapted into two approaches to assess the agreement between the personality measures on the two occasions. The first approach estimated stability in the underlying disorder, correcting for error in trait measurement, and the second approach estimated stability in the measured disorder, without correcting for item unreliability. Results Five of the ten personality disorders exhibited moderate stability in individuals: antisocial, avoidant, borderline, histrionic, and schizotypal. Associated estimated ICCs for stability of underlying disorder over time ranged between approximately 0.4 and 0.7–0.8. A sixth disorder, OCPD, exhibited appreciable stability with estimated ICC of approximately 0.2–0.3. Dependent, narcissistic, paranoid, and schizoid disorders were not demonstrably stable. Conclusions The findings suggest that six of the DSM personality disorder constructs themselves are stable, but that specific traits within the DSM categories are both of lesser importance than the constructs themselves and require additional specification. PMID:19656527

Using animal models to study post-partum psychiatric disorders.

Science.gov (United States)

Perani, C V; Slattery, D A

2014-10-01

The post-partum period represents a time during which all maternal organisms undergo substantial plasticity in a wide variety of systems in order to ensure the well-being of the offspring. Although this time is generally associated with increased calmness and decreased stress responses, for a substantial subset of mothers, this period represents a time of particular risk for the onset of psychiatric disorders. Thus, post-partum anxiety, depression and, to a lesser extent, psychosis may develop, and not only affect the well-being of the mother but also place at risk the long-term health of the infant. Although the risk factors for these disorders, as well as normal peripartum-associated adaptations, are well known, the underlying aetiology of post-partum psychiatric disorders remains poorly understood. However, there have been a number of attempts to model these disorders in basic research, which aim to reveal their underlying mechanisms. In the following review, we first discuss known peripartum adaptations and then describe post-partum mood and anxiety disorders, including their risk factors, prevalence and symptoms. Thereafter, we discuss the animal models that have been designed in order to study them and what they have revealed about their aetiology to date. Overall, these studies show that it is feasible to study such complex disorders in animal models, but that more needs to be done in order to increase our knowledge of these severe and debilitating mood and anxiety disorders. © 2014 The British Pharmacological Society.

Neural Correlates of Intolerance of Uncertainty in Clinical Disorders.