Markers of neurodevelopmental impairments in early-onset psychosis

Directory of Open Access Journals (Sweden)

Petruzzelli MG

2015-07-01

Full Text Available Maria Giuseppina Petruzzelli,1 Lucia Margari,1 Francesco Craig,1 Maria Gloria Campa,1 Domenico Martinelli,2 Adriana Pastore,3 Marta Simone,1 Francesco Margari3 1Child and Adolescence Neuropsychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University “Aldo Moro” of Bari, 2Department of Medical and Surgical Sciences; University of Foggia, Foggia, 3Psychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organ, University “Aldo Moro” of Bari, Bari, Italy Background: The aim of this study was to assess the association between the clinical and neurobiological markers of neurodevelopmental impairments and early-onset schizophrenia spectrum psychosis. Methods: A sample of 36 patients with early-onset schizophrenia spectrum psychosis was compared to a control sample of 36 patients with migraine. We assessed early childhood neurodevelopmental milestones using a modified version of the General Developmental Scale, general intellectual ability using the Wechsler Intelligence Scale for Children–Revised or Leiter International Performance Scale–Revised for patients with speech and language abnormalities, and neurological soft signs with specific regard to subtle motor impairment. Results: Subjects with early-onset psychosis had a higher rate of impaired social development (P=0.001, learning difficulties (P=0.04, enuresis (P=0.0008, a lower intelligence quotient (P<0.001, and subtle motor impairments (P=0.005 than control subjects. Conclusion: We suggest that neurodevelopment in early-onset psychosis is characterized by a global impairment of functional and adaptive skills that manifests from early childhood, rather than a delay or limitation in language and motor development. The current evidence is based on a small sample and should be investigated in larger samples in future research. Keywords: early-onset psychosis, early-onset schizophrenia, neurodevelopment, social cognition

Cessation of cannabis use by patients with recent-onset schizophrenia and related disorders

NARCIS (Netherlands)

Dekker, Nienke; de Haan, Lieuwe; van den Berg, Sake; de Gier, Martin; Becker, Hiske; Linzen, Don H.

2008-01-01

Cannabis abuse has been found to be a component risk factor for the onset and poor outcome during the early course of schizophrenia and related disorders. Cannabis use has become a target for prevention and treatment of schizophrenia patients. Therefore, knowledge of factors that influence

Cognitive deficits and levels of IQ in adolescent onset schizophrenia and other psychotic disorders

DEFF Research Database (Denmark)

Fagerlund, Birgitte; Pagsberg, A Katrine; Hemmingsen, Ralf

2006-01-01

of intelligence, executive functions, memory, attention and processing speed was global or specific. First-episode psychotic adolescents (N = 39) between the ages 11 and 17 years were included, 18 of whom were diagnosed with schizophrenia, and 21 with other non-organic, non-affective psychoses, using ICD-10...... of attention, executive functions, reaction time, and memory in the schizophrenic and psychotic adolescent groups. However, analyses of WISC-III factor profiles suggested that early onset schizophrenia patients may have more global IQ deficits than non-organic, non-affective psychoses when examined recently...... the profile and severity of cognitive impairments in first-episode early onset psychotic patients who received the schizophrenia diagnosis to those diagnosed with other non-organic, non-affective psychotic disorders. The secondary purpose was to examine whether the profile of cognitive deficits, in terms...

Voxel-based structural magnetic resonance imaging (MRI study of patients with early onset schizophrenia

Directory of Open Access Journals (Sweden)

Suzuki Katsuaki

2008-12-01

Full Text Available Abstract Background Investigation into the whole brain morphology of early onset schizophrenia (EOS to date has been sparse. We studied the regional brain volumes in EOS patients, and the correlations between regional volume measures and symptom severity. Methods A total of 18 EOS patients (onset under 16 years and 18 controls matched for age, gender, parental socioeconomic status, and height were examined. Voxel-based morphometric analysis using the Brain Analysis Morphological Mapping (BAMM software package was employed to explore alterations of the regional grey (GM and white matter (WM volumes in EOS patients. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS. Results EOS patients had significantly reduced GM volume in the left parahippocampal, inferior frontal, and superior temporal gyri, compared with the controls. They also had less WM volume in the left posterior limb of the internal capsule and the left inferior longitudinal fasciculus. The positive symptom score of PANSS (higher values corresponding to more severe symptoms was negatively related to GM volume in the bilateral posterior cingulate gyrus. The negative symptom score was positively correlated with GM volume in the right thalamus. As for the association with WM volume, the positive symptom score of PANSS was positively related to cerebellar WM (vermis region, and negatively correlated with WM in the brain stem (pons and in the bilateral cerebellum (hemisphere region. Conclusion Our findings of regional volume alterations of GM and WM in EOS patients coincide with those of previous studies of adult onset schizophrenia patients. However, in brain regions that had no overall structural differences between EOS patients and controls (that is, the bilateral posterior cingulate gyrus, the right thalamus, the cerebellum, and the pons, within-subject analysis of EOS patients alone revealed that there were significant associations of the volume in these areas

The neuropsychology and neurobiology of late-onset schizophrenia and very-late-onset schizophrenia-like psychosis : a critical review

OpenAIRE

Assche, Van, Lies; Morrens, Manuel; Luyten, Patrick; Ven, Van de, Luc; Vandenbulcke, Mathieu

2017-01-01

Abstract: OBJECTIVE: The current review discusses neuropsychological profiles and the longitudinal course of cognitive dysfunction in Late Onset Schizophrenia (LOS) and Very-late-onset schizophrenia-like psychosis (VLOSLP), and attempts to clarify its neurobiological underpinnings. METHOD: A systematic literature search resulted in 29 publications describing original research on the neuropsychology of LOS/VLOSLP and 46 studies focussing on neurobiology. RESULTS: Although mildly progressive co...

The rationale for early intervention in schizophrenia and related disorders

DEFF Research Database (Denmark)

Nordentoft, Merete; Jeppesen, Pia; Petersen, Lone

2009-01-01

, adherence to treatment, comorbid drug abuse, relapse and readmission. Some benefits persist after cessation of the intervention. Conclusions: Early intervention in schizophrenia is justified to reduce the negative personal and social impact of prolonged periods of untreated symptoms. Furthermore, phase......Abstract Aim: To examine the rationale and evidence supporting an early intervention approach in schizophrenia. Methods: A selective literature review was conducted. Results: During the onset of schizophrenia, there is often a significant delay between the emergence of psychotic symptoms...

Structural brain abnormalities in early onset first-episode psychosis

DEFF Research Database (Denmark)

Pagsberg, A K; Baaré, William Frans Christian; Raabjerg Christensen, A M

2007-01-01

BACKGROUND: Brain morphometry in children and adolescents with first-episode psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We compared high-resolution 3D T1-weighted magnetic resonance images of the brain in 29 patients (schizophrenia, schizotypal disorder...... that schizophrenia patients (n = 15) had significantly larger lateral ventricles as compared to controls. Duration and dose of antipsychotics correlated negatively with global gray matter volume in minimally medicated patients (n = 18). CONCLUSION: Findings of white matter changes and enlarged lateral ventricles...... already at illness onset in young schizophrenia spectrum patients, suggests aberrant neurodevelopmental processes in the pathogenesis of these disorders. Gray matter volume changes, however, appear not to be a key feature in early onset first-episode psychosis....

Environmental risk factors and their impact on the age of onset of schizophrenia: Comparing familial to non-familial schizophrenia.

Science.gov (United States)

Scherr, Martin; Hamann, Melanie; Schwerthöffer, Dirk; Froböse, Teresa; Vukovich, Ruth; Pitschel-Walz, Gabriele; Bäuml, Josef

2012-04-01

Several risk factors for schizophrenia have yet been identified. The aim of our study was to investigate how certain childhood and adolescent risk factors predict the age of onset of psychosis in patients with and without a familial component (i.e. a relative with schizophrenia or schizoaffective disorder). Aside from the age of onset of psychosis, we examined the risk factors for schizophrenia including obstetric complications, birth during winter or spring, behavioral deviances or delayed motor and speech development, exposure to adverse life events and exposure to substance use within a group of 100 patients (45 female, 55 male) with a mean age (± standard deviation) of 35.15 ± 13.21. Birth complications and cannabis abuse are predictors for an earlier onset of schizophrenia in patients with non-familial schizophrenia. No environmental risk factors for an earlier age of onset in familial schizophrenia have been identified. Certain environmental risk factors for schizophrenia seem to have an impact on the age of onset of psychosis in non-familial schizophrenia, they do not seem to have an impact on familial schizophrenia.

A CASE OF ADOLESCENT SCHIZOPHRENIA WHOSE REFRACTORY OBSESSIVE-COMPULSIVE SYMPTOMS IN THE PRODROMAL PERIOD CHANGED TO RESPONSIVE AFTER THE ONSET AND WERE INPROVED

OpenAIRE

澤田, 将幸; 根來, 秀樹; 永嶌, 朋久; 岸本, 年史; 大西, 貴子; 飯田, 順三

2009-01-01

Several psychiatric disorders have obsessive-compulsive symptoms. These symptoms have been noticed in schizophrenia since old times. Early-onset schizophrenia had obsessive-compulsive symptoms as premonitory symptoms only rarely. Arienti S. suggested that obsessive-compulsive symptoms prevented the onset of schizophrenia in patients with these symptoms. Matsumoto suggested that the patients had not good clinical courses because of these symptoms. In addition, it is said that the earlier onset...

Accumulated environmental risk determining age at schizophrenia onset: a deep phenotyping-based study.

Science.gov (United States)

Stepniak, Beata; Papiol, Sergi; Hammer, Christian; Ramin, Anna; Everts, Sarah; Hennig, Lena; Begemann, Martin; Ehrenreich, Hannelore

2014-11-01

Schizophrenia is caused by a combination of genetic and environmental factors, as first evidenced by twin studies. Extensive efforts have been made to identify the genetic roots of schizophrenia, including large genome-wide association studies, but these yielded very small effect sizes for individual markers. In this study, we aimed to assess the relative contribution of genome-wide association study-derived genetic versus environmental risk factors to crucial determinants of schizophrenia severity: disease onset, disease severity, and socioeconomic measures. In this parallel analysis, we studied 750 male patients from the Göttingen Research Association for Schizophrenia (GRAS) dataset (Germany) with schizophrenia for whom both genome-wide coverage of single-nucleotide polymorphisms and deep clinical phenotyping data were available. Specifically, we investigated the potential effect of schizophrenia risk alleles as identified in the most recent large genome-wide association study versus the effects of environmental hazards (ie, perinatal brain insults, cannabis use, neurotrauma, psychotrauma, urbanicity, and migration), alone and upon accumulation, on age at disease onset, age at prodrome, symptom expression, and socioeconomic parameters. In this study, we could show that frequent environmental factors become a major risk for early schizophrenia onset when accumulated (prodrome begins up to 9 years earlier; p=2·9×10(-10)). In particular, cannabis use-an avoidable environmental risk factor-is highly significantly associated with earlier age at prodrome (p=3·8×10(-20)). By contrast, polygenic genome-wide association study risk scores did not have any detectable effects on schizophrenia phenotypes. These findings should be translated to preventive measures to reduce environmental risk factors, since age at onset of schizophrenia is a crucial determinant of an affected individual's fate and the total socioeconomic cost of the illness. German Research Foundation

Early trauma, attachment experiences and comorbidities in schizophrenia

Directory of Open Access Journals (Sweden)

Thalita Gabínio

2018-04-01

Full Text Available Abstract Objective To evaluate attachment patterns in subjects with schizophrenia and their relationships to early traumatic events, psychotic symptoms and comorbidities. Methods Twenty patients diagnosed with schizophrenia according to criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5 underwent retrospective symptom assessment and careful assessment of the number and manner of childhood caregiver changes. The Diagnostic Interview for Psychosis and Affective Disorders (DI-PAD was used to assess symptoms related to schizophrenia (positive and negative symptoms, depression and mania. Anxiety disorder comorbidities were assessed by the Liebowitz Social Anxiety Scale (LSAS, Yale-Brown Obsessions and Compulsions Scale (Y-BOCS and Panic and Schizophrenia Interview (PaSI. Experience in Close Relationships – Relationship Structures (ECR-RS and Early Trauma Inventory Self Report-Short Form (ETISR-SF were used to assess attachment patterns and traumatic history, respectively. Results Moderate and significant correlations between attachment patterns and early trauma showed that greater severity of anxious attachment was predicted by a higher frequency of total early traumas (Spearman ρ = 0.446, p = 0.04, mainly general traumas (ρ = 0.526, p = 0.017; including parental illness and separation, as well as natural disaster and serious accidents. Among the correlations between early trauma and comorbid symptoms, panic attacks occurring before the onset of schizophrenia showed significant and positive correlations with ETISR-SF total scores and the sexual trauma subscale. Conclusion Children with an unstable early emotional life are more vulnerable to the development of psychopathology, such as panic anxiety symptoms. Traumatic events may also predict later schizophrenia.

Inflexible minds: impaired attention switching in recent-onset schizophrenia.

Directory of Open Access Journals (Sweden)

Henderikus G O M Smid

Full Text Available Impairment of sustained attention is assumed to be a core cognitive abnormality in schizophrenia. However, this seems inconsistent with a recent hypothesis that in schizophrenia the implementation of selection (i.e., sustained attention is intact but the control of selection (i.e., switching the focus of attention is impaired. Mounting evidence supports this hypothesis, indicating that switching of attention is a bigger problem in schizophrenia than maintaining the focus of attention. To shed more light on this hypothesis, we tested whether schizophrenia patients are impaired relative to controls in sustaining attention, switching attention, or both. Fifteen patients with recent-onset schizophrenia and fifteen healthy volunteers, matched on age and intelligence, performed sustained attention and attention switching tasks, while performance and brain potential measures of selective attention were recorded. In the sustained attention task, patients did not differ from the controls on these measures. In the attention switching task, however, patients showed worse performance than the controls, and early selective attention related brain potentials were absent in the patients while clearly present in the controls. These findings support the hypothesis that schizophrenia is associated with an impairment of the mechanisms that control the direction of attention (attention switching, while the mechanisms that implement a direction of attention (sustained attention are intact.

Brain volume in male patients with recent onset schizophrenia with and without cannabis use disorders

NARCIS (Netherlands)

Koenders, L.; Machielsen, M.W.; van der Meer, F.J.; van Gasselt, A.C.; Meijer, C.J.; van den Brink, W.; Koeter, M.W.; Caan, M.W.; Cousijn, J.; den Braber, A.; van 't Ent, D.; Rive, M.M.; Schene, A.H.; van de Giessen, E.; Huyser, C.; de Kwaasteniet, B.P.; Veltman, D.J.; de Haan, L.

2014-01-01

BACKGROUND: Schizophrenia is highly comorbid with cannabis use disorders (CUDs), and this comorbidity is associated with an unfavourable course. Early onset or frequent cannabis use may influence brain structure. A key question is whether comorbid CUDs modulate brain morphology alterations

Processing speed and executive functions predict real-world everyday living skills in adolescents with early-onset schizophrenia.

Science.gov (United States)

Puig, O; Penadés, R; Baeza, I; Sánchez-Gistau, V; De la Serna, E; Fonrodona, L; Andrés-Perpiñá, S; Bernardo, M; Castro-Fornieles, J

2012-06-01

Cognition and clinical variables are known to be among the most predictive factors of real-world social functioning and daily living skills in adult-onset schizophrenia. Fewer studies have focused on their impact in adolescents with early-onset schizophrenia (EOS). The aim of this study is to examine the relationships and the predictive value of cognition and clinical variables on real-world daily living skills in a sample of adolescents with EOS. Cognitive, clinical and real-world everyday living skills measures were administered to 45 clinically and pharmacologically stabilized adolescent outpatients with EOS and 45 healthy control subjects matched by age and sex. Multi-variant analyses to compare cognitive and real-world functioning profiles between patients and controls and regression analysis to identify predictors of real-world functioning scores in patients were used. Adolescents with EOS showed a generalized cognitive and real-world daily living skills dysfunction. Several cognitive and clinical variables significantly correlated with real-world daily living skills functioning but only the processing speed and executive functions emerged as independent predictors of everyday living skills scores, explaining 25.1% of the variance. Slowness in processing information and executive dysfunction showed a significant impact on real-world daily living skills in EOS, independently from clinical symptoms and other cognitive variables. Nevertheless, much of the variance in the daily living skills measure remained unaccounted for, suggesting that other factors were involved as well in this young population.

The neuropsychology and neurobiology of late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: A critical review.

Science.gov (United States)

Van Assche, Lies; Morrens, Manuel; Luyten, Patrick; Van de Ven, Luc; Vandenbulcke, Mathieu

2017-12-01

The current review discusses neuropsychological profiles and the longitudinal course of cognitive dysfunction in Late Onset Schizophrenia (LOS) and Very-late-onset schizophrenia-like psychosis (VLOSLP), and attempts to clarify its neurobiological underpinnings. A systematic literature search resulted in 29 publications describing original research on the neuropsychology of LOS/VLOSLP and 46 studies focussing on neurobiology. Although mildly progressive cognitive impairment is usually present, only a subgroup of LOS/VLOSLP develops dementia during a 10-year follow-up succeeding the onset of psychosis. This coincides with the absence of neuropathological evidence for neurodegeneration in many cases. Cognitive deterioration is characterized by deficits in (working) memory, language, psychomotor speed and executive functioning. Underlying neurobiological changes encompass white matter pathology, increased ventricle-to-brain ratio (VBR) with coinciding atrophy and hypo-metabolism of frontal, temporal and subcortical areas. Multiple changes in neurobiology and cognition contributing to LOS/VLOSLP may reflect stress-related accelerated brain aging rather than neurodegenerative pathology. Their involvement in the onset of illness, however, might be inversely proportional to pre-existing (psychosocial and/or genetic) vulnerability to psychosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Frequency and pattern of childhood symptom onset reported by first episode schizophrenia and clinical high risk youth.

Science.gov (United States)

Woodberry, Kristen A; Serur, Rachael A; Hallinan, Sean B; Mesholam-Gately, Raquelle I; Giuliano, Anthony J; Wojcik, Joanne D; Keshavan, Matcheri S; Frazier, Jean A; Goldstein, Jill M; Shenton, Martha E; McCarley, Robert W; Seidman, Larry J

2014-09-01

Psychosis prevention and early intervention efforts in schizophrenia have focused increasingly on sub-threshold psychotic symptoms in adolescents and young adults. Although many youth report symptom onset prior to adolescence, the childhood incidence of prodromal-level symptoms in those with schizophrenia or related psychoses is largely unknown. This study reports on the retrospective recall of prodromal-level symptoms from 40 participants in a first-episode of schizophrenia (FES) and 40 participants at "clinical high risk" (CHR) for psychosis. Onset of positive and non-specific symptoms was captured using the Structured Interview for Prodromal Syndromes. Frequencies are reported according to onset during childhood (prior to age 13), adolescence (13-17), or adulthood (18+). Childhood-onset of attenuated psychotic symptoms was not rare. At least 11% of FES and 23% of CHR reported specific recall of childhood-onset of unusual or delusional ideas, suspiciousness, or perceptual abnormalities. Most recalled experiencing non-specific symptoms prior to positive symptoms. CHR and FES did not differ significantly in the timing of positive and non-specific symptom onset. Other than being younger at assessment, those with childhood onset did not differ demographically from those with later onset. Childhood-onset of initial psychotic-like symptoms may be more common than previous research has suggested. Improved characterization of these symptoms and a focus on their predictive value for subsequent schizophrenia and other major psychoses are needed to facilitate screening of children presenting with attenuated psychotic symptoms. Accurate detection of prodromal symptoms in children might facilitate even earlier intervention and the potential to alter pre-illness trajectories. Copyright © 2014 Elsevier B.V. All rights reserved.

Patterns and correlates of expressed emotion, perceived criticism, and rearing style in first admitted early-onset schizophrenia spectrum disorders.

Science.gov (United States)

von Polier, Georg G; Meng, Heiner; Lambert, Martin; Strauss, Monika; Zarotti, Gianni; Karle, Michael; Dubois, Reinmar; Stark, Fritz-Michael; Neidhart, Sibylle; Zollinger, Ruedi; Bürgin, Dieter; Felder, Wilhelm; Resch, Franz; Koch, Eginhard; Schulte-Markwort, Michael; Schimmelmann, Benno G

2014-11-01

The aim of this study was to assess patterns and correlates of family variables in 31 adolescents treated for their first episode of a schizophrenia spectrum disorder (early-onset schizophrenia [EOS]). Expressed emotion, perceived criticism, and rearing style were assessed. Potential correlates were patient psychopathology, premorbid adjustment, illness duration, quality of life (QoL), sociodemographic variables, patient and caregiver "illness concept," and caregiver personality traits and support. Families were rated as critical more frequently by patients than raters (55% vs. 13%). Perceived criticism was associated with worse QoL in relationship with parents and peers. An adverse rearing style was associated with a negative illness concept in patients, particularly with less trust in their physician. Future research should examine perceived criticism as a predictor of relapse and indicator of adolescents with EOS who need extended support and treatment. Rearing style should be carefully observed because of its link with patients' illness concept and, potentially, to service engagement and medication adherence.

Impaired Verbal Learning Is Associated with Larger Caudate Volumes in Early Onset Schizophrenia Spectrum Disorders.

Directory of Open Access Journals (Sweden)

Monica Juuhl-Langseth

Full Text Available Both brain structural abnormalities and neurocognitive impairments are core features of schizophrenia. We have previously reported enlargements in subcortical brain structure volumes and impairment of neurocognitive functioning as measured by the MATRICS Cognitive Consensus Battery (MCCB in early onset schizophrenia spectrum disorders (EOS. To our knowledge, no previous study has investigated whether neurocognitive performance and volumetric abnormalities in subcortical brain structures are related in EOS.Twenty-four patients with EOS and 33 healthy controls (HC were included in the study. Relationships between the caudate nucleus, the lateral and fourth ventricles volumes and neurocognitive performance were investigated with multivariate linear regression analyses. Intracranial volume, age, antipsychotic medication and IQ were included as independent predictor-variables.The caudate volume was negatively correlated with verbal learning performance uniquely in the EOS group (r=-.454, p=.034. There were comparable positive correlations between the lateral ventricular volume and the processing speed, attention and reasoning and problem solving domains for both the EOS patients and the healthy controls. Antipsychotic medication was related to ventricular enlargements, but did not affect the brain structure-function relationship.Enlargement of the caudate volume was related to poorer verbal learning performance in patients with EOS. Despite a 32% enlargement of the lateral ventricles in the EOS group, associations to processing speed, attention and reasoning and problem solving were similar for both the EOS and the HC groups.

The When and Where of Working Memory Dysfunction in Early-Onset Schizophrenia-A Functional Magnetic Resonance Imaging Study.

Science.gov (United States)

Bittner, Robert A; Linden, David E J; Roebroeck, Alard; Härtling, Fabian; Rotarska-Jagiela, Anna; Maurer, Konrad; Goebel, Rainer; Singer, Wolf; Haenschel, Corinna

2015-09-01

Behavioral evidence indicates that working memory (WM) in schizophrenia is already impaired at the encoding stage. However, the neurophysiological basis of this primary deficit remains poorly understood. Using event-related fMRI, we assessed differences in brain activation and functional connectivity during the encoding, maintenance and retrieval stages of a visual WM task with 3 levels of memory load in 17 adolescents with early-onset schizophrenia (EOS) and 17 matched controls. The amount of information patients could store in WM was reduced at all memory load levels. During encoding, activation in left ventrolateral prefrontal cortex (VLPFC) and extrastriate visual cortex, which in controls positively correlated with the amount of stored information, was reduced in patients. Additionally, patients showed disturbed functional connectivity between prefrontal and visual areas. During retrieval, right inferior VLPFC hyperactivation was correlated with hypoactivation of left VLPFC in patients during encoding. Visual WM encoding is disturbed by a failure to adequately engage a visual-prefrontal network critical for the transfer of perceptual information into WM. Prefrontal hyperactivation appears to be a secondary consequence of this primary deficit. Isolating the component processes of WM can lead to more specific neurophysiological markers for translational efforts seeking to improve the treatment of cognitive dysfunction in schizophrenia. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Schizophrenia Spectrum Disorders in Later Life: Prevalence and Distribution of Age at Onset and Sex in a Dutch Catchment Area

NARCIS (Netherlands)

Meesters, Paul D.; de Haan, Lieuwe; Comijs, Hannie C.; Stek, Max L.; Smeets-Janssen, Maureen M. J.; Weeda, Marjan R.; Eikelenboom, Piet; Smit, Johannes H.; Beekman, Aartjan T. F.

2012-01-01

Objectives: The prevalence of schizophrenia in later life is affected by both outflow of early onset patients, due to recovery and excess mortality, and inflow of patients with a later age at onset, making it likely that characteristics of older patients differ markedly from younger patients. We

Early treatment resistance in a Latin-American cohort of patients with schizophrenia.

Science.gov (United States)

Mena, Cristian; Gonzalez-Valderrama, Alfonso; Iruretagoyena, Barbara; Undurraga, Juan; Crossley, Nicolas A

2018-03-08

Failure to respond to antipsychotic medication in schizophrenia is a common clinical scenario with significant morbidity. Recent studies have highlighted that many patients present treatment-resistance from disease onset. We here present an analysis of clozapine prescription patterns, used as a real-world proxy marker for treatment-resistance, in a cohort of 1195 patients with schizophrenia from a Latin-American cohort, to explore the timing of emergence of treatment resistance and possible subgroup differences. Survival analysis from national databases of clozapine monitoring system, national disease notification registers, and discharges from an early intervention ward. Echoing previous studies, we found that around 1 in 5 patients diagnosed with schizophrenia were eventually prescribed clozapine, with an over-representation of males and those with a younger onset of psychosis. The annual probability of being prescribed clozapine was highest within the first year (probability of 0.11, 95% confidence interval of 0.093-0.13), compared to 0.018 (0.012-0.024) between years 1 and 5, and 0.006 (0-0.019) after 5years. Age at psychosis onset, gender, dose of clozapine used, and compliance with hematological monitoring at 12months, was not related to the onset of treatment resistance. A similar pattern was observed in a subgroup of 230 patients discharged from an early intervention ward with a diagnosis of non-affective first episode of psychosis. Our results highlight that treatment resistance is frequently present from the onset of psychosis. Future studies will shed light on the possible different clinical and neurobiological characteristics of this subtype of psychosis. Copyright © 2018. Published by Elsevier B.V.

Predicting severity of paranoid schizophrenia

OpenAIRE

Kolesnichenko Elena Vladimirovna

2015-01-01

Clinical symptoms, course and outcomes of paranoid schizophrenia are polymorphic. 206 cases of paranoid schizophrenia were investigated. Clinical predictors were collected from hospital records and interviews. Quantitative assessment of the severity of schizophrenia as special indexes was used. Schizoid, epileptoid, psychasthenic and conformal accentuation of personality in the premorbid, early onset of psychosis, paranoid and hallucinatory-paranoid variants of onset predicted more expressed ...

Emotional Modulation of Cognition in Recent Onset Schizophrenia

NARCIS (Netherlands)

S. Dieleman (Sieds)

2014-01-01

markdownabstract__Abstract__ The current thesis describes a number of important findings on the interaction between emotion and cognition in male recent onset schizophrenia patients. In healthy controls a general effect of emotional expressions on sustained attention is that it

Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

DEFF Research Database (Denmark)

Rasmussen, Henrik Berg; Timm, Sally; Wang, August G

2006-01-01

OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

Schizophrenia/first episode psychosis in children and adolescents

African Journals Online (AJOL)

Childhood onset schizophrenia (COS) is diagnosed before the age of 13 years, and early onset schizophrenia (EOS) is diagnosed before the age of 18 years. EOS is considered extremely rare and its prevalence in comparison to the worldwide prevalence of schizophrenia (1%) has not adequately been studied. Patients ...

Symptom dimensions and subgroups in childhood-onset schizophrenia.

Science.gov (United States)

Craddock, Kirsten E S; Zhou, Xueping; Liu, Siyuan; Gochman, Peter; Dickinson, Dwight; Rapoport, Judith L

2017-11-13

This study investigated symptom dimensions and subgroups in the National Institute of Mental Health (NIMH) childhood-onset schizophrenia (COS) cohort and their similarities to adult-onset schizophrenia (AOS) literature. Scores from the Scales for the Assessment of Positive and Negative Symptoms (SAPS & SANS) from 125 COS patients were assessed for fit with previously established symptom dimensions from AOS literature using confirmatory factor analysis (CFA). K-means cluster analysis of each individual's scores on the best fitting set of dimensions was used to form patient clusters, which were then compared using demographic and clinical data. CFA showed the SAPS & SANS data was well suited to a 2-dimension solution, including positive and negative dimensions, out of five well established models. Cluster analysis identified three patient groups characterized by different dimension scores: (1) low scores on both dimensions, (2) high negative, low positive scores, and (3) high scores on both dimensions. These groups had different Full scale IQ, Children's Global Assessment Scale (CGAS) scores, ages of onset, and prevalence of some co-morbid behavior disorders (all psymptom-based subgroups within the NIMH COS cohort using an established AOS symptom structure. These findings confirm the heterogeneity of COS and were generally consistent with AOS literature. Published by Elsevier B.V.

Clinical characteristics and premorbid variables in childhood-onset schizophrenia: a descriptive study of twelve cases from a schizophrenia founder population.

Science.gov (United States)

Maydell, R J; van der Walt, C; Roos, J L; Scribante, L; Ladikos, A

2009-05-01

To analyze clinical and demographic data of childhood-onset (12 years and younger) schizophrenia patients collected for a genetic study in schizophrenia, undertaken nationally in South Africa, using multiple parameters. Patients with an onset of schizophrenia at 12 years or younger, were included. From the Diagnostic Interview for Genetic Studies (DIGS), patients' information and summary report data was tabulated and analyzed. Specific subgroups were further compared. This sub-population of 12 subjects was further compared with a group of the adult sample. Of the 12 patients recruited, prominent results were: male to female ratio of 1:1; all had insidious onset of psychosis; a third had all 3 multidimensional impairment (MDI) symptoms; all patients that received ADHD treatment had ADHD treatment failure; two thirds had milestone delay; 58% had birth complications; a third were predominantly bottle fed; 42% had family history of schizophrenia; a third had family history of other major psychiatric conditions; all patients had at least one non-psychotic deviant behaviour (NPDB); no patient used cannabis; all delusions were paranoid; 92% had school achievement difficulty and a third had treatment resistance. Gender comparison included: earlier onset of psychosis in females; all females had aggression versus a third of males; more females had school achievement difficulty than males; males had more treatment resistance. Patients with MDI, compared to the sample average had: earlier onset of non-psychotic deviant behaviour; lower school drop-out rate; less social difficulty and no treatment resistance. The results compare well to previous research on this topic. The new concepts introduced by the present study require further investigation.

Detection of early psychotic symptoms: Validation of the Spanish version of the "Symptom Onset in Schizophrenia (SOS) inventory".

Science.gov (United States)

Mezquida, Gisela; Cabrera, Bibiana; Martínez-Arán, Anabel; Vieta, Eduard; Bernardo, Miguel

2018-03-01

The period of subclinical signs that precedes the onset of psychosis is referred to as the prodrome or high-risk mental state. The "Symptom Onset in Schizophrenia (SOS) inventory" is an instrument to characterize and date the initial symptoms of a psychotic illness. The present study aims to provide reliability and validity data for clinical and research use of the Spanish version of the SOS. Thirty-six participants with a first-episode of psychosis meeting DSM-IV criteria for schizophrenia/schizoaffective/schizophreniform disorder were administered the translated SOS and other clinical assessments. The internal validity, intrarater and interrater reliability were studied. We found strong interrater reliability. To detect the presence/absence of prodromal symptoms, Kappa coefficients ranged between 0.8 and 0.7. Similarly, the raters obtained an excellent level of agreement regarding the onset of each symptom and the duration of symptoms until first treatment (intraclass correlation coefficients between 0.9 and 1.0). Cronbach's alpha was 0.9-1.0 for all the items. The interrater reliability and concurrent validity were also excellent in both cases. This study provides robust psychometric properties of the Spanish version of the SOS. The translated version is adequate in terms of good internal validity, intrarater and interrater reliability, and is as time-efficient as the original version. Copyright © 2017 Elsevier B.V. All rights reserved.

Early detection of the first episode of schizophrenia and suicidal behavior

DEFF Research Database (Denmark)

Melle, Ingrid; Johannesen, Jan Olav; Friis, Svein

2006-01-01

The suicide rate in schizophrenia is high, with the risk being highest early in the course. The rate of suicide attempts before treatment onset is also high and is often the event leading up to first treatment contact. A previous report showed that the duration of untreated psychosis can be reduced...... through an early detection program, and that the reduction was associated with lower symptom levels at treatment initiation. Treatment programs that bring first-episode patients into treatment at lower symptom levels can have the potential to reduce risk for suicide attempts....

Long term functioning in early onset psychosis: Two years prospective follow-up study

Directory of Open Access Journals (Sweden)

Taha Ghada RA

2011-07-01

Full Text Available Abstract Background There were few studies on the outcome of schizophrenia in developing countries. Whether the outcome is similar to or different from developed world is still a point for research. The main aim of the current study was to know if patients with early onset non affective psychosis can behave and function properly after few years from start of the illness or not. Other aims included investigation of possible predictors and associated factors with remission and outcome. Method The study prospectively investigated a group of 56 patients with onset of psychosis during childhood or adolescence. Diagnosis made according to DSM-IV criteria and included; schizophrenia, psychotic disorder not otherwise specified and acute psychosis. Severity of psychosis was measured by PANSS. Measures of the outcome included; remission criteria of Andreasen et al 2005, the children's global assessment scale and educational level. Results Analysis of data was done for only 37 patients. Thirty patients diagnosed as schizophrenia and 7 with Psychotic disorder not otherwise specified. Mean duration of follow up was 38.4 +/- 16.9 months. At the end of the study, 6 patients (16.2% had one episode, 23(62.1% had multiple episodes and 8 (21.6% continuous course. Nineteen patients (51.4% achieved full remission, and only 11(29.7% achieved their average educational level for their age. Twenty seven percent of the sample had good outcome and 24.3% had poor outcome. Factors associated with non remission and poor outcome included gradual onset, low IQ, poor premorbid adjustment, negative symptoms at onset of the illness and poor adherence to drugs. Moreover, there was tendency of negative symptoms at illness start to predict poor outcome. Conclusion Some patients with early onset non affective psychosis can behave and function properly after few years from the start of the illness. Although remission is a difficult target in childhood psychosis, it is still achievable.

Theory of Mind differences in older patients with early-onset and late-onset paranoid schizophrenia

NARCIS (Netherlands)

Smeets-Janssen, M. M. J.; Meesters, P. D.; Comijs, H. C.; Eikelenboom, P.; Smit, J. H.; de Haan, L.; Beekman, A. T. F.; Stek, M. L.

2013-01-01

Theory of Mind (ToM) is considered an essential element of social cognition. In younger schizophrenia patients, ToM impairments have extensively been demonstrated. It is not clear whether similar impairments can be found in older schizophrenia patients and if these impairments differ between older

Theory of mind differences in older patients with early-onset and late-onset paranoid schizophrenia

NARCIS (Netherlands)

Smeets-Janssen, M.M.J.; Meesters, P.D.; Comijs, H.C.; Eikelenboom, P.; Smit, J.H.; de Haan, L.; Beekman, A.T.F.; Stek, M.L.

2013-01-01

Objective: Theory of Mind (ToM) is considered an essential element of social cognition. In younger schizophrenia patients, ToM impairments have extensively been demonstrated. It is not clear whether similar impairments can be found in older schizophrenia patients and if these impairments differ

Facial emotion perception in schizophrenia: Does sex matter?

Science.gov (United States)

Mote, Jasmine; Kring, Ann M

2016-06-22

To review the literature on sex differences in facial emotion perception (FEP) across the schizophrenia spectrum. We conducted a systematic review of empirical articles that were included in five separate meta-analyses of FEP across the schizophrenia spectrum, including meta-analyses that predominantly examined adults with chronic schizophrenia, people with early (onset prior to age 18) or recent-onset (experiencing their first or second psychotic episode or illness duration less than 2 years) schizophrenia, and unaffected first-degree relatives of people with schizophrenia. We also examined articles written in English (from November 2011 through June 2015) that were not included in the aforementioned meta-analyses through a literature search in the PubMed database. All relevant articles were accessed in full text. We examined all studies to determine the sample sizes, diagnostic characteristics, demographic information, methodologies, results, and whether each individual study reported on sex differences. The results from the meta-analyses themselves as well as the individual studies are reported in tables and text. We retrieved 134 articles included in five separate meta-analyses and the PubMed database that examined FEP across the schizophrenia spectrum. Of these articles, 38 examined sex differences in FEP. Thirty of these studies did not find sex differences in FEP in either chronically ill adults with schizophrenia, early-onset or recently diagnosed people with schizophrenia, or first-degree relatives of people with schizophrenia. Of the eight studies that found sex differences in FEP, three found that chronically ill women outperformed men, one study found that girls with early-onset schizophrenia outperformed boys, and two studies found that women (including first-degree relatives, adults with schizophrenia, and the healthy control group) outperformed men on FEP tasks. In total, six of the eight studies that examined sex differences in FEP found that women

Treating schizophrenia during menopause.

Science.gov (United States)

Brzezinski, Amnon; Brzezinski-Sinai, Noa A; Seeman, Mary V

2017-05-01

The aim of this review is to examine three questions: What are the risks and benefits of treating women with schizophrenia with hormone therapy (HT) at menopause? Should the antipsychotic regimen be changed at menopause? Do early- and late-onset women with schizophrenia respond differently to HT at menopause? MEDLINE databases for the years 1990 to 2016 were searched using the following interactive terms: schizophrenia, gender, menopause, estrogen, and hormones. The selected articles (62 out of 800 abstracts) were chosen on the basis of their applicability to the objectives of this targeted narrative review. HT during the perimenopause in women with schizophrenia ameliorates psychotic and cognitive symptoms, and may also help affective symptoms. Vasomotor, genitourinary, and sleep symptoms are also reduced. Depending on the woman's age and personal risk factors and antipsychotic side effects, the risk of breast cancer and cardiovascular disease may be increased. Antipsychotic types and doses may need to be adjusted at menopause, as may be the mode of administration. Both HT and changes in antipsychotic management should be considered for women with schizophrenia at menopause. The question about differences in response between early- and late-onset women cannot yet be answered.

Modifying the risk of atypical antipsychotics in the treatment of juvenile-onset schizophrenia.

Science.gov (United States)

Townsend, Lisa; Findling, Robert L

2010-02-01

This review summarizes the evidence for use of typical and atypical antipsychotic medications for the treatment of juvenile-onset schizophrenia. We highlight the risks and benefits of antipsychotic agents for youth with this disorder, paying special attention to weight gain and metabolic effects, an area of specific concern within child and adolescent psychiatry. We describe the seriousness of juvenile-onset schizophrenia and its impact on long-term functioning, noting that pharmacological treatment remains the standard of care for this disorder. We focus on weight gain and metabolic effects associated with atypical agents and review strategies to modify risks associated with these agents. We summarize strategies for attenuating the risk of weight gain for youth on atypical antipsychotics, including what is known about nutritional counseling and exercise programs as well as pharmacotherapy with adjunctive weight loss agents. Given the negative consequences associated with untreated schizophrenia, it appears that the most effective way to improve the risk:benefit ratio in the treatment of adolescents with schizophrenia is to reduce the risks associated with pharmacological treatment.

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

Science.gov (United States)

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

2017-07-12

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

Neurocognitive Functioning in Schizophrenia and during the Early Phases of Psychosis: Targeting Cognitive Remediation Interventions

Directory of Open Access Journals (Sweden)

Yulia Zaytseva

2013-01-01

Full Text Available Recent interest in the early course of schizophrenia accentuated altered cognition prior to the onset. Ultrahigh risk (UHR individuals with attenuated positive symptoms and transient psychotic episodes demonstrate neurocognitive deficits across multiple domains such as memory, executive functioning, and processing speed which are consistent with similar disturbances identified in patients with a first episode of schizophrenia. Cognitive remediation (CR approaches representing a broad set of activities are aimed to restore or improve cognitive functioning. CR proved to be effective in modulating the cognitive dysfunction in schizophrenia but is rarely used in ultrahigh risk individuals. From the clinical prospective, a better understanding of cognitive functioning in at-risk states is essential for the development of optimal early intervention models. In the review, we highlight the intervention targets, notably the specific cognitive deficits in at risk individuals which preceed the transition to psychosis and emphasize the need of the additional studies using CR approaches in UHR group aiming to enhance cognition and therefore mediate functional improvement.

Schizophrenia Delays and Alters Maturation of the Brain in Adolescence

Science.gov (United States)

Douaud, Gwenaelle; Mackay, Clare; Andersson, Jesper; James, Susan; Quested, Digby; Ray, Manaan Kar; Connell, Julie; Roberts, Neil; Crow, Timothy J.; Matthews, Paul M.; Smith, Stephen; James, Anthony

2009-01-01

Early-onset schizophrenia appears to be clinically more severe than the adult-onset form of the disease. In a previous study, we showed that anatomically related grey and white matter abnormalities found in adolescents patients were larger and more widespread than what had been reported in the literature on adult schizophrenia. Particularly, we…

Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

DEFF Research Database (Denmark)

Rasmussen, H.B.; Timm, S.; Wang, A.G.

2006-01-01

OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... to a psychiatric hospital department served as a measure of disease onset. RESULTS: Patients and comparison subjects differed marginally in their genotype distribution, with a slightly higher frequency of the deletion allele seen in the patients. The authors found the deletion allele to be associated with higher......-onset schizophrenia) and healthy subjects differed significantly. This was reflected in an increased frequency of the deletion allele in the patient subgroup. Patients with ages at first admission below and above 40 years significantly differed in distribution of genotypes and alleles, with an overrepresentation...

Do schizophrenia patients age early?

Science.gov (United States)

Shivakumar, Venkataram; Kalmady, Sunil V; Venkatasubramanian, Ganesan; Ravi, Vasanthapuram; Gangadhar, Bangalore N

2014-08-01

The etiopathogenesis of schizophrenia is poorly understood. Within the proposed "neurodegeneration paradigm", observations have been put forth for "accelerated aging" in this disorder. This proposition is largely based on the neuroscience research that demonstrates progressive changes in brain as well as other systemic abnormalities supportive of faster aging process in patients with this disorder. In this review, we have summarized the literature related to the concept of early aging in schizophrenia. These studies include P300 abnormalities & visual motion discrimination, neuroimaging findings, telomere dynamics as well as neuropathology of related brain regions. We also propose a role of vitamin D, neuroimmunological changes and elevated oxidative stress as well as mitochondrial dysfunction in addition to the above factors with 'vitamin-D deficiency' as the central paradox. Put together, the evidence supporting early aging in schizophrenia is compelling and this requires further systematic studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Early- versus Late-Onset Dysthymia

Science.gov (United States)

Sansone, Lori A.

2009-01-01

In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared to those with late-onset dysthymia, early-onset patients are more likely to harbor psychiatric comorbidity both on Axis I and II, exhibit less psychological resilience, and have more prominent family loadings for mood disorders. These findings suggest that this distinction is meaningful and that the early-onset subtype of dysthymia is more difficult to effectively treat. PMID:20049145

Early onset type 2 diabetes

DEFF Research Database (Denmark)

Bo, A; Thomsen, R W; Nielsen, J S

2018-01-01

was more frequent and meeting physical activity recommendations less likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age-gradient, with increasing prevalence of clinical and behavioural risk factors the younger the onset age of type 2 DM. Younger persons with early-onset type 2......AIM: To examine the association between early onset of type 2 diabetes (DM) and clinical and behavioural risk factors for later diabetes complications. METHODS: We conducted a cross-sectional study of 5115 persons with incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic...... Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis among those diagnosed at ≤45 years (early-onset) with diagnosis age 46-55, 56-65 (average-onset = reference), 66-75, and >75 years (late-onset). Prevalence ratios (PRs) were computed using Poisson regression. RESULTS: Poor...

Family motivational intervention for reducing cannabis use in recent-onset schizophrenia

NARCIS (Netherlands)

Smeerdijk, A.M.

2015-01-01

Cannabis use in highly prevalent among young adults with recent-onset schizophrenia and has been associated with an adverse course of the illness. Despite these association, the evidence for effective interventions for treating cannabis use in patients with psychosis is limited. This thesis focuses

Factor analysis of symptom profile in early onset and late onset OCD.

Science.gov (United States)

Grover, Sandeep; Sarkar, Siddharth; Gupta, Gourav; Kate, Natasha; Ghosh, Abhishek; Chakrabarti, Subho; Avasthi, Ajit

2018-04-01

This study aimed to assess the factor structure of early and late onset OCD. Additionally, cluster analysis was conducted in the same sample to assess the applicability of the factors. 345 participants were assessed with Yale Brown Obsessive Compulsive Scale symptom checklist. Patients were classified as early onset (onset of symptoms at age ≤ 18 years) and late onset (onset at age > 18 years) OCD depending upon the age of onset of the symptoms. Factor analysis and cluster analysis of early-onset and late-onset OCD was conducted. The study sample comprised of 91 early onset and 245 late onset OCD subjects. Males were more common in the early onset group. Differences in the frequency of phenomenology related to contamination related, checking, repeating, counting and ordering/arranging compulsions were present across the early and late onset groups. Factor analysis of YBOCS revealed a 3 factor solution for both the groups, which largely concurred with each other. These factors were named as hoarding and symmetry (factor-1), contamination (factor-2) and aggressive, sexual and religious factor (factor-3). To conclude this study shows that factor structure of symptoms of OCD seems to be similar between early-onset and late-onset OCD. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-adherence to antipsychotic medication, relapse and rehospitalisation in recent-onset schizophrenia

Directory of Open Access Journals (Sweden)

Widen Jan H

2008-04-01

Full Text Available Abstract Background The aims of this study were to describe outcome with respect to persistent psychotic symptoms, relapse of positive symptoms, hospital admissions, and application of treatment by coercion among patients with recent onset schizophrenia being adherent and non-adherent to anti-psychotic medication. Materials and methods The study included 50 patients with recent onset schizophrenia, schizoaffective or schizophreniform disorders. The patients were clinically stable at study entry and had less than 2 years duration of psychotic symptoms. Good adherence to antipsychotic medication was defined as less than one month without medication. Outcomes for poor and good adherence were compared over a 24-month follow-up period. Results The Odds Ratio (OR of having a psychotic relapse was 10.27 and the OR of being admitted to hospital was 4.00 among non-adherent patients. Use of depot-antipsychotics were associated with relapses (OR = 6.44. Conclusion Non-adherence was associated with relapse, hospital admission and having persistent psychotic symptoms. Interventions to increase adherence are needed. Trial registration Current Controlled Trials NCT00184509. Key words: Adherence, schizophrenia, antipsychotic medication, admittances, relapse.

Neuroimaging characteristics of very-late-onset schizophrenia-like psychosis

International Nuclear Information System (INIS)

Okuyama, Yu; Suzuki, Mitsuru; Okudera, Toshio; Matoh, Koichi

2006-01-01

The pathogenesis of delusion and hallucination among the elderly remains unclear. Biological markers have become required for proper diagnosis of the mental state. We aimed to identify the area and severity of both white and gray matter changes of very-late-onset schizophrenia-like psychosis (VLOSLP) by means of magnetic resonance images. Twenty-one non-demented patients who were International Statistical Classification of Disease (ICD)-10 diagnosed as schizophrenia or delusional disorder with onset after the age of 60, and those of 21 age- and gender-matched psychiatrically healthy controls were compared. Although both periventricular hyperintensites and deep and subcortical white matter hyperintensities were found both in the VLOSLP subjects and in the controls, significant difference of the white matter changes were not detected between them, except for more prominent lacuna infarctions and perivascular space at mainly bilateral frontal areas in the subjects. Regarding cortical lesions, the subjects had a significantly greater degree of bilateral frontal and temporal cortical atrophies than the controls. These structural changes suggest neuronal and vascular pathogenesis of VLOSLP. Front-temporal cortical atrophy and age-related white matter changes may be a predictive finding of VLOSLP; however, prospective and long-term follow-up neuroimaging studies are essential to integrate etiological diagnostics of VLOSLP. (author)

Demographic features and premorbid personality disorder traits in relation to age of onset and sex in paranoid schizophrenia.

Science.gov (United States)

Skokou, Maria; Gourzis, Philippos

2014-03-30

Personality disorders in the premorbid period of schizophrenia and particularly in relation to age of onset and sex, seem to be a rather under-researched area. In the present study, 88 patients with paranoid schizophrenia were examined, regarding demographic characteristics and premorbid personality disorder traits, in order to investigate for differences in the premorbid period of the disease, in relation to age of onset and sex. Age cutoff points were set at personality disorder traits were retrospectively assessed by using the Structured Clinical Interview for DSM-IV-Patient Edition for Axis II disorders (SCID-II). Comparisons were performed by applying the two-tailed Wilcoxon rank-sum and the χ(2) statistical tests. Young onset patients were characterized by significantly higher proportion of urban birth, single status, more avoidant premorbid personality disorder traits, and less passive-aggressive premorbid personality disorder traits, than late onset counterparts. Differences were more prominently shown in men. Earlier age of onset seems to be associated to increased social inhibition and worse psychosocial adaptation in the premorbid period of paranoid schizophrenia. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Neurological abnormalities in recent-onset schizophrenia and Asperger-Syndrome

Directory of Open Access Journals (Sweden)

Dusan eHirjak

2014-08-01

Full Text Available Background: Neurological abnormalities including a variety of subtle deficits such as discrete impairments in sensory integration, motor coordination, and sequencing of complex motor acts are frequently found in patients with schizophrenia and commonly referred to as neurological soft signs (NSS. Asperger-Syndrome (AS is characterized by sensory-motor difficulties as well. However, the question whether the two disorders share a common or a disease-specific pattern of NSS remains unresolved. Method: A total of 78 age- and education-matched participants (26 patients with recent-onset schizophrenia, 26 individuals with AS, and 26 healthy controls were recruited for the study. Analyses of covariance (ANCOVAs, with age, years of education and medication included as covariates, were used to examine group differences on total NSS and the five subscale scores. Discriminant analyses were employed to identify the NSS subscales that maximally discriminate between the three groups. Results: Significant differences among the three groups were found in NSS total score and on the five NSS subscales. The two clinical groups differed significantly in the NSS subscale „motor coordination. The correct discriminant rate between patients with schizophrenia and individuals with AS was 61.5%. The correct discriminant rate was 92.3% between individuals with AS and healthy controls, and 80.8% between schizophrenia patients and healthy controls, respectively. Conclusions: Our findings provide new evidence for the presence of NSS in AS and lend further support to previously reported difficulties in movement control in this disorder. According to the present results, schizophrenia and AS seem to be characterized by a different pattern of NSS.

Antipsychotic treatment for children and adolescents with schizophrenia spectrum disorders

DEFF Research Database (Denmark)

Pagsberg, Anne Katrine; Tarp, Simon; Glintborg, D

2014-01-01

INTRODUCTION: Antipsychotic treatment in early-onset schizophrenia (EOS) lacks a rich evidence base, and efforts to rank different drugs concerning their efficacy have not proven any particular drug superior. In contrast to the literature regarding adult-onset schizophrenia (AOS), comparative...... allocate children and adolescents presenting with schizophrenia or a related non-affective psychotic condition to an intervention group or to a control group. Two reviewers will-independently and in duplicate-screen titles and abstracts, complete full text reviews to determine eligibility, and subsequently...

Excess Early Mortality in Schizophrenia

DEFF Research Database (Denmark)

Laursen, Thomas Munk; Nordentoft, Merete; Mortensen, Preben Bo

2014-01-01

Schizophrenia is often referred to as one of the most severe mental disorders, primarily because of the very high mortality rates of those with the disorder. This article reviews the literature on excess early mortality in persons with schizophrenia and suggests reasons for the high mortality...... as well as possible ways to reduce it. Persons with schizophrenia have an exceptionally short life expectancy. High mortality is found in all age groups, resulting in a life expectancy of approximately 20 years below that of the general population. Evidence suggests that persons with schizophrenia may...... not have seen the same improvement in life expectancy as the general population during the past decades. Thus, the mortality gap not only persists but may actually have increased. The most urgent research agenda concerns primary candidates for modifiable risk factors contributing to this excess mortality...

Metabolic profiling of CSF: evidence that early intervention may impact on disease progression and outcome in schizophrenia.

Directory of Open Access Journals (Sweden)

Elaine Holmes

2006-08-01

Full Text Available The identification of schizophrenia biomarkers is a crucial step towards improving current diagnosis, developing new presymptomatic treatments, identifying high-risk individuals and disease subgroups, and assessing the efficacy of preventative interventions at a rate that is not currently possible.(1H nuclear magnetic resonance spectroscopy in conjunction with computerized pattern recognition analysis were employed to investigate metabolic profiles of a total of 152 cerebrospinal fluid (CSF samples from drug-naïve or minimally treated patients with first-onset paranoid schizophrenia (referred to as "schizophrenia" in the following text and healthy controls. Partial least square discriminant analysis showed a highly significant separation of patients with first-onset schizophrenia away from healthy controls. Short-term treatment with antipsychotic medication resulted in a normalization of the disease signature in over half the patients, well before overt clinical improvement. No normalization was observed in patients in which treatment had not been initiated at first presentation, providing the first molecular evidence for the importance of early intervention for psychotic disorders. Furthermore, the alterations identified in drug-naïve patients could be validated in a test sample set achieving a sensitivity and specificity of 82% and 85%, respectively.Our findings suggest brain-specific alterations in glucoregulatory processes in the CSF of drug-naïve patients with first-onset schizophrenia, implying that these abnormalities are intrinsic to the disease, rather than a side effect of antipsychotic medication. Short-term treatment with atypical antipsychotic medication resulted in a normalization of the CSF disease signature in half the patients well before a clinical improvement would be expected. Furthermore, our results suggest that the initiation of antipsychotic treatment during a first psychotic episode may influence treatment response

Clozapine and obsessions in patients with recent-onset schizophrenia and other psychotic disorders

NARCIS (Netherlands)

de Haan, L.; Linszen, D. H.; Gorsira, R.

1999-01-01

BACKGROUND: The increase or emergence of obsessions was compared in young patients with recent-onset schizophrenia or other psychotic disorders taking clozapine and other antipsychotic drugs. METHOD: We conducted a retrospective cohort study. Subjects were 121 consecutively admitted patients

Symptom assessment in early psychosis: The use of well-established rating scales in clinical high-risk and recent-onset populations

OpenAIRE

Fulford, Daniel; Pearson, Rahel; Stuart, Barbara K.; Fisher, Melissa; Mathalon, Daniel H.; Vinogradov, Sophia; Loewy, Rachel L.

2014-01-01

Symptom assessment in early psychosis research typically relies on scales validated in chronic schizophrenia samples. Our goal was to inform investigators who are selecting symptom scales for early psychosis research. We described measure characteristics, baseline scores, and scale inter-relationships in clinical high-risk (CHR) and recent-onset psychotic disorder (RO) samples using the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Scale for the Assessment of Positive ...

Antipsychotic medication for early episode schizophrenia

Science.gov (United States)

Bola, John; Kao, Dennis; Soydan, Haluk; Adams, Clive E

2014-01-01

Background Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment. Objectives To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders. Search methods We searched the Cochrane Schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data. Selection criteria Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment. Data collection and analysis Working independently, we critically appraised records from 681 studies, of which five studies met inclusion criteria. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results Five studies (combined total n=998) met inclusion criteria. Four studies (n=724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs n=353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT n=240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT n=236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT n=94, RR 0.96 CI 0.3 to 3.6). Two studies contributed data to assessment of adverse effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications

Age of Onset in Schizophrenia Spectrum Disorders: Complex Interactions between Genetic and Environmental Factors.

Science.gov (United States)

Mandelli, Laura; Toscano, Elena; Porcelli, Stefano; Fabbri, Chiara; Serretti, Alessandro

2016-03-01

In this study we evaluated the role of a candidate gene for major psychosis, Sialyltransferase (ST8SIA2), in the risk to develop a schizophrenia spectrum disorders, taking into account exposure to stressful life events (SLEs). Eight polymorphisms (SNPs) were tested in 94 Schizophreniainpatients and 176 healthy controls. Schizophrenia patients were also evaluated for SLEs in different life periods. None of the SNPs showed association with schizophrenia. Nevertheless, when crossing genetic variants with childhood SLEs, we could observe trends of interaction with age of onset. Though several limitations, our results support a protective role of ST8SIA2 in individuals exposed to moderate childhood stress.

Functioning in early and late stages of schizophrenia

Directory of Open Access Journals (Sweden)

Leonardo Gazzi Costa

2014-12-01

Full Text Available INTRODUCTION: Schizophrenia is frequently associated with a debilitating course and prominent impairment in social and occupational functioning. Although the criteria for classification into stages have not been defined in the literature, illness duration and functioning seem to be good candidates.OBJECTIVE:To compare functioning of patients with schizophrenia at different stages of the disease (early vs. late and healthy sex- and age-matched controls.METHODS: This double-blinded, case-controlled study included 79 individuals: 23 patients with schizophrenia diagnosed up to 5 years earlier; 19 patients with schizophrenia diagnosed at least 20 years earlier; and healthy matched controls. Diagnoses were established using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV Axis I Disorder. Functioning was assessed using the Functioning Assessment Short Test (FAST.RESULTS: Patients in the early stage had significantly higher scores than healthy controls in total FAST and in autonomy, occupational functioning, cognitive functioning and interpersonal relationships. Individuals in the late stage had significantly poorer functioning than controls in all domains. The comparison of functioning between the two groups of patients revealed no significant differences, except in occupational functioning, in which late stage patients had a poorer performance.CONCLUSION: Functioning impairment in schizophrenia tends to remain stable despite illness duration. Therefore, functioning should be effectively assessed at an early stage, as illness duration alone may not be the most reliable criterion to stage patients with schizophrenia.

Fragmented Perception : Slower Space-Based but Faster Object-Based Attention in Recent-Onset Psychosis with and without Schizophrenia

NARCIS (Netherlands)

Smid, Henderikus G. O. M.; Bruggeman, Richard; Martens, Sander

2013-01-01

Background: Schizophrenia is associated with impairments of the perception of objects, but how this affects higher cognitive functions, whether this impairment is already present after recent onset of psychosis, and whether it is specific for schizophrenia related psychosis, is not clear. We

Premorbid adjustment and neuropsychological performance in schizophrenia.

Science.gov (United States)

Silverstein, Marshall L; Mavrolefteros, George; Close, David

2002-01-01

To examine the relationship between premorbid adjustment and neuropsychological deficit in schizophrenia, this report examined retrospective ratings of social and school adjustment during three age epochs (childhood, early adolescence, and late adolescence) as predictors of neurocognitive performance in 61 clinically and pharmacologically stabilized schizophrenia outpatients. Results indicated greater cognitive deficits when premorbid adjustment was unfavorable, particularly for measures of attention and executive functions. Premorbid number and quality of peer relationships and psychosocial adaptation to the school environment were more closely related to neuropsychological performance during adulthood than were premorbid withdrawal and premorbid academic performance. Early onset of poor premorbid adjustment rather than deterioration from childhood to adolescence was associated with greater neuropsychological disturbance in adulthood. It is suggested that childhood onset of premorbid deficits in selective areas of social and academic adjustment appears to influence the cognitive performance seen in adult schizophrenia. This study is consistent with findings from other related reports; it extends these findings to a larger and clinically stabilized sample.

Prenatal and Early Life Risk Factors of Schizophrenia

Science.gov (United States)

Lattari, Fallon; Dragowski, Eliza A.

2011-01-01

Childhood-onset schizophrenia is an exceedingly rare mental illness whose complex, multifaceted behavioral presentation can disrupt child development and raise diagnostic and treatment difficulties for attending clinicians. The disorder, affecting one in 30,000 children, shares the same diagnostic criteria and symptoms as its adult counterpart,…

Parietal Lobe Volume Deficits in Adolescents with Schizophrenia and Adolescents with Cannabis Use Disorders

Science.gov (United States)

Kumra, Sanjiv; Robinson, Paul; Tambyraja, Rabindra; Jensen, Daniel; Schimunek, Caroline; Houri, Alaa; Reis, Tiffany; Lim, Kelvin

2012-01-01

Objective: In early-onset schizophrenia (EOS), the earliest structural brain volumetric abnormalities appear in the parietal cortices. Early exposure to cannabis may represent an environmental risk factor for developing schizophrenia. This study characterized cerebral cortical gray matter structure in adolescents in regions of interest (ROIs) that…

Isochromosome 13 in a patient with childhood-onset schizophrenia, ADHD, and motor tic disorder

Directory of Open Access Journals (Sweden)

Graw Sharon L

2012-01-01

Full Text Available Abstract Background A small percentage of all cases of schizophrenia have a childhood onset. The impact on the individual and family can be devastating. We report the results of genetic analyses from a patient with onset of visual hallucinations at 5 years, and a subsequent diagnosis at 9 years of schizophrenia, attention deficit hyperactivity disorder (ADHD with hyperactivity and impulsivity, and chronic motor tic disorder. Results Karyotypic analysis found 45,XX,i(13(q10 in all cells examined. Alpha satellite FISH of isochromosome 13 revealed a large unsplit centromeric region, interpreted as two centromeres separated by minimal or undetectable short-arm material or as a single monocentric centromere, indicating that the isochromosome likely formed post-zygotically by a short arm U-type or centromeric exchange. Characterization of chromosome 13 simple tandem repeats and Affymetrix whole-genome 6.0 SNP array hybridization found homozygosity for all markers, and the presence of only a single paternal allele in informative markers, consistent with an isodisomic isochromosome of paternal origin. Analysis of two chromosome 13 schizophrenia candidate genes, D-amino acid oxidase activator (DAOA and 5-hydroxytryptamine (serotonin receptor 2A (5-HTR2A, failed to identify non-synonymous coding mutations but did identify homozygous risk polymorphisms. Conclusions We report a female patient with childhood-onset schizophrenia, ADHD, and motor tic disorder associated with an isodisomic isochromosome 13 of paternal origin and a 45,XX,i(13(q10q10 karyotype. We examined two potential mechanisms to explain chromosome 13 involvement in the patient's pathology, including reduction to homozygosity of a paternal mutation and reduction to homozygosity of a paternal copy number variation, but were unable to identify any overtly pathogenic abnormality. Future studies may consider whether epigenetic mechanisms resulting from uniparental disomy (UPD and the lack of

Early- versus Late-Onset Systemic Sclerosis

Science.gov (United States)

Alba, Marco A.; Velasco, César; Simeón, Carmen Pilar; Fonollosa, Vicent; Trapiella, Luis; Egurbide, María Victoria; Sáez, Luis; Castillo, María Jesús; Callejas, José Luis; Camps, María Teresa; Tolosa, Carles; Ríos, Juan José; Freire, Mayka; Vargas, José Antonio; Espinosa, Gerard

2014-01-01

Abstract Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients. PMID:24646463

Hippocampus in schizophrenia, depression, and suicide: a postmortem stereological study of hippocampal volume and cell number

DEFF Research Database (Denmark)

Dorph-Petersen, Karl-Anton; Rosenberg, Raben; Nyengaard, Jens Randel

2015-01-01

Background: Robust data from studies of incidence rates in schizophrenia have yielded evidence for a peak in onset at age 22 years in both males and females. An early age of illness onset has been discussed as a more severe (Table Presented) subtype of schizophrenia, characterized by a worse illn...

Fragmented perception: slower space-based but faster object-based attention in recent-onset psychosis with and without Schizophrenia.

Directory of Open Access Journals (Sweden)

Henderikus G O M Smid

Full Text Available BACKGROUND: Schizophrenia is associated with impairments of the perception of objects, but how this affects higher cognitive functions, whether this impairment is already present after recent onset of psychosis, and whether it is specific for schizophrenia related psychosis, is not clear. We therefore tested the hypothesis that because schizophrenia is associated with impaired object perception, schizophrenia patients should differ in shifting attention between objects compared to healthy controls. To test this hypothesis, a task was used that allowed us to separately observe space-based and object-based covert orienting of attention. To examine whether impairment of object-based visual attention is related to higher order cognitive functions, standard neuropsychological tests were also administered. METHOD: Patients with recent onset psychosis and normal controls performed the attention task, in which space- and object-based attention shifts were induced by cue-target sequences that required reorienting of attention within an object, or reorienting attention between objects. RESULTS: Patients with and without schizophrenia showed slower than normal spatial attention shifts, but the object-based component of attention shifts in patients was smaller than normal. Schizophrenia was specifically associated with slowed right-to-left attention shifts. Reorienting speed was significantly correlated with verbal memory scores in controls, and with visual attention scores in patients, but not with speed-of-processing scores in either group. CONCLUSIONS: deficits of object-perception and spatial attention shifting are not only associated with schizophrenia, but are common to all psychosis patients. Schizophrenia patients only differed by having abnormally slow right-to-left visual field reorienting. Deficits of object-perception and spatial attention shifting are already present after recent onset of psychosis. Studies investigating visual spatial

Neuropsychological evidence for abnormal neurodevelopment associated with early-onset psychoses.

Science.gov (United States)

Bombin, I; Mayoral, M; Castro-Fornieles, J; Gonzalez-Pinto, A; de la Serna, E; Rapado-Castro, M; Barbeito, S; Parellada, M; Baeza, I; Graell, M; Payá, B; Arango, C

2013-04-01

The longitudinal neuropsychological study of first-episode early-onset psychosis (EOP) patients, whose brain maturation is still in progress at the time of illness onset, provides a unique opportunity to compare their cognitive development with that of healthy subjects, in search of specific patterns resulting from the interaction between neurodevelopmental processes and the presence of psychotic disorders. Method Seventy-five first-episode EOP patients (schizophrenia n = 35; bipolar disorder n = 17; other forms of psychosis n = 23) with a mean age of 15.53 years were assessed with a neuropsychological battery that included measures of attention, working memory, memory and executive functions within 6 months following the onset of the first psychotic symptom (baseline) and 2 years later. Psychotic symptoms were assessed at both times with the Positive and Negative Symptom Scale (PANSS). Seventy-nine healthy subjects matched for age and education served as controls. EOP patients showed significant cognitive impairment at both baseline and the 2-year follow-up, with no significant differences between diagnostic groups at either time. Both healthy controls and EOP patients improved in all cognitive measures, except for patient working memory. Improvement in patient attention lost significance after controlling for psychotic symptom reduction. No significant time/diagnosis interaction was found among patients (p > 0.405). Cognitive impairment in EOP is already present at the first episode, and cognitive development seems to be arrested early in EOP patients compared to their healthy peers, at least for some cognitive functions. These and previous similar results support the neurodevelopmental hypothesis of psychosis.

Role of 108 schizophrenia-associated loci in modulating psychopathological dimensions in schizophrenia and bipolar disorder.

Science.gov (United States)

Fabbri, Chiara; Serretti, Alessandro

2017-10-01

The Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC) identified 108 loci associated with schizophrenia, but their role in modulating specific psychopathological dimensions of the disease is unknown. This study investigated which symptom dimensions may be affected by these loci in schizophrenia, and bipolar disorder. Positive, negative and depressive symptoms, suicidal ideation, cognition, violent behaviors, quality of life, and early onset were investigated in schizophrenia and bipolar disorder using the clinical antipsychotic trials of intervention effectiveness (CATIE) and systematic treatment enhancement program for bipolar disorder (STEP-BD) studies. Individual loci were investigated, then genes within 50 Kbp from polymorphisms with p schizophrenia-associated variant (rs75059851) may modulate negative symptoms. Multi-locus models may provide interesting insights about the biological mechanisms that mediate psychopathological dimensions. © 2017 Wiley Periodicals, Inc.

Early onset depression: the relevance of anxiety.

Science.gov (United States)

Parker, G; Wilhelm, K; Asghari, A

1997-01-01

The aim of this study was to determine risk factors that may differentiate early onset from late onset depression. A non-clinical cohort that had been assessed from 1978 to 1993 at 5 yearly intervals and that had a high prevalence rate of lifetime depression took part in the study. We established an appropriate age cut-off to distinguish early onset (i.e. before 26 years) of major and of minor depression, and examined the relevance of a number of possible determinants of early onset depression assessed over the life of the study. Despite several dimensional measures of depression, self-esteem and personality being considered, they generally failed (when assessed early in the study) to discriminate subsequent early onset depression, with the exception of low masculinity scores being a weak predictor of major and/or minor depression. Early onset depression was strongly predicted, however, by a lifetime episode of a major anxiety disorder, with generalised anxiety being a somewhat stronger and more consistent predictor than panic disorder, agoraphobia and minor anxiety disorders (ie social phobia, simple phobia). The possibility that anxiety may act as a key predispositional factor to early onset depression and to a greater number of depressive episodes is important in that clinical assessment and treatment of any existing anxiety disorder may be a more efficient and useful strategy than focussing primarily on the depressive disorder.

Adverse Housing Conditions and Early-Onset Delinquency.

Science.gov (United States)

Jackson, Dylan B; Newsome, Jamie; Lynch, Kellie R

2017-09-01

Housing constitutes an important health resource for children. Research has revealed that, when housing conditions are unfavorable, they can interfere with child health, academic performance, and cognition. Little to no research, however, has considered whether adverse housing conditions and early-onset delinquency are significantly associated with one another. This study explores the associations between structural and non-structural housing conditions and delinquent involvement during childhood. Data from the Fragile Families and Child Wellbeing Study (FFCWS) were employed in this study. Each adverse housing condition was significantly associated with early-onset delinquency. Even so, disarray and deterioration were only significantly linked to early delinquent involvement in the presence of health/safety hazards. The predicted probability of early-onset delinquency among children exposed to housing risks in the presence of health/safety hazards was nearly three times as large as the predicted probability of early-onset delinquency among children exposed only to disarray and/or deterioration, and nearly four times as large as the predicted probability of early-onset delinquency among children exposed to none of the adverse housing conditions. The findings suggest that minimizing housing-related health/safety hazards among at-risk subsets of the population may help to alleviate other important public health concerns-particularly early-onset delinquency. Addressing household health/safety hazards may represent a fruitful avenue for public health programs aimed at the prevention of early-onset delinquency. © Society for Community Research and Action 2017.

Association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and age of onset in schizophrenia

DEFF Research Database (Denmark)

Vares, Maria; Saetre, Peter; Deng, Hong

2010-01-01

analysis. In an attempt to replicate the findings from the Scandinavian sample, the association between rs1801133 and age at onset was also analyzed in Chinese high-risk families, with two or more affected siblings (n = 243). Among the Scandinavian patients the functional MTHFR SNP rs1801133 (C677T...... 677T allele showed earlier age at onset than siblings being homozygous for the wild-type allele (P = 0.008). The MTHFR C677T polymorphism may play a role as a modifying factor for age of onset in schizophrenia....

Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset

NARCIS (Netherlands)

M.K. Chan (Man K.); M.-O. Krebs (M-O); D. Cox; P.C. Guest (Paul); R.H. Yolken; H. Rahmoune (Hassan); M. Rothermundt (Matthias); J. Steiner (Johann); F.M. Leweke (Marcus); N.J.M. van Beveren (Nico); D. Niebuhr (David); N. Weber (Natalya); D. Cowan (David); P. Suarez-Pinilla; B. Crespo-Facorro (Benedicto); C. Mam-Lam-Fook; J. Bourgin; R.J. Wenstrup (Richard); R.R. Kaldate; J.D. Cooper (Jason); S. Bahn (Sabine)

2015-01-01

markdownabstractRecent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker test for the identification of individuals at risk of developing schizophrenia based

X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations.

Science.gov (United States)

Shamim, Daniah; Alleyne, Karen

2017-01-01

Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10-13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease.

PRODROMAL PHASE IN THE DEVELOPMENT OF EARLY ONSET SCHIZOPHRENIC PSYCHOSIS - CASE REPORT

Directory of Open Access Journals (Sweden)

Jelena Kostić

2012-06-01

Full Text Available Schizophrenia and other mental disorders are often preceded by prodromal changes in behavior that can last from several days to several years, indicating the beginning of psychosis. If the disease starts at an earlier age, especially in adolescence, the prodromal phase is more non-specific and difficult to detect. There is a large number of operational instruments used for clinical assessment and quantification of prodromal symptoms and "at risk mental state", as well as the predictive potential for psychosis. This paper describes the prodromal phase in the development of early onset schizophrenic psychosis, with the emphasis on gradual, several-month psychopathological accumulation and evolution of nonspecific and subclinical, prodromal symptoms to florid schizophrenic symptoms.

Association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and age of onset in schizophrenia

DEFF Research Database (Denmark)

Vares, Maria; Saetre, Peter; Deng, Hong

2010-01-01

= 820) diagnosed with schizophrenia, schizoaffective disorder, and schizophreniform disorder were investigated. Two functional MTHFR single nucleotide polymorphisms (SNPs; rs1801131 and rs1801133) were genotyped and the effect of MTHFR polymorphisms on the age of onset was examined with survival...

Brain Age in Early Stages of Bipolar Disorders or Schizophrenia.

Science.gov (United States)

Hajek, Tomas; Franke, Katja; Kolenic, Marian; Capkova, Jana; Matejka, Martin; Propper, Lukas; Uher, Rudolf; Stopkova, Pavla; Novak, Tomas; Paus, Tomas; Kopecek, Miloslav; Spaniel, Filip; Alda, Martin

2017-12-20

The greater presence of neurodevelopmental antecedants may differentiate schizophrenia from bipolar disorders (BD). Machine learning/pattern recognition allows us to estimate the biological age of the brain from structural magnetic resonance imaging scans (MRI). The discrepancy between brain and chronological age could contribute to early detection and differentiation of BD and schizophrenia. We estimated brain age in 2 studies focusing on early stages of schizophrenia or BD. In the first study, we recruited 43 participants with first episode of schizophrenia-spectrum disorders (FES) and 43 controls. In the second study, we included 96 offspring of bipolar parents (48 unaffected, 48 affected) and 60 controls. We used relevance vector regression trained on an independent sample of 504 controls to estimate the brain age of study participants from structural MRI. We calculated the brain-age gap estimate (BrainAGE) score by subtracting the chronological age from the brain age. Participants with FES had higher BrainAGE scores than controls (F(1, 83) = 8.79, corrected P = .008, Cohen's d = 0.64). Their brain age was on average 2.64 ± 4.15 years greater than their chronological age (matched t(42) = 4.36, P stages of BD showed comparable BrainAGE scores to controls (F(2,149) = 1.04, corrected P = .70, η2 = 0.01) and comparable brain and chronological age. Early stages of schizophrenia, but not early stages of BD, were associated with advanced BrainAGE scores. Participants with FES showed neurostructural alterations, which made their brains appear 2.64 years older than their chronological age. BrainAGE scores could aid in early differential diagnosis between BD and schizophrenia. © The Author(s) 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

Neuropsychological functioning in early-onset first-episode psychosis: comparison of diagnostic subgroups.

Science.gov (United States)

Zabala, Arantzazu; Rapado, Marta; Arango, Celso; Robles, Olalla; de la Serna, Elena; González, Cristina; Rodríguez-Sánchez, José Manuel; Andrés, Patricia; Mayoral, María; Bombín, Igor

2010-04-01

The aims of this study were to examine the nature and extent of cognitive impairment in first-episode early-onset psychosis (FE-EOP) soon after their stabilisation and to search for potential differences according to specific diagnostic sub-groups of patients. As part of a Spanish multicentre longitudinal study, 107 FE-EOP patients and 98 healthy controls were assessed on the following cognitive domains: attention, working memory, executive functioning, and verbal learning and memory. Three diagnostic categories were established in the patient sample: schizophrenia (n = 36), bipolar disorder (n = 19), and other psychosis (n = 52). Patients performed significantly worse than controls in all cognitive domains. The three diagnostic sub-groups did not differ in terms of impaired/preserved cognitive functions or degree of impairment. FE-EOP patients show significant cognitive impairment that, during this early phase, seems to be non-specific to differential diagnosis.

Evidence for an agitated-aggressive syndrome in early-onset psychosis correlated with antisocial personality disorder, forensic history, and substance use disorder.

Science.gov (United States)

Huber, Christian G; Hochstrasser, Lisa; Meister, Klara; Schimmelmann, Benno G; Lambert, Martin

2016-08-01

Agitation, aggression, and violence are increased in psychotic disorders. Additionally, an earlier age at onset may be associated with aggressive behavior. However, the relationship of age at onset, an agitated-aggressive syndrome as measured with the Positive And Negative Syndrome Scale for Schizophrenia - Excited Component (PANSS-EC), and its potential correlates in first-episode psychosis (FEP) has not been studied. This study assessed the association between age at onset, an agitated-aggressive syndrome, and its potential correlates in a prospective sample of 52 FEP patients with early-onset and adult-onset followed up for 12months. Twenty-six patients conformed to the criteria of early-onset psychosis. Early age at onset was associated with antisocial personality disorder (p=0.004; φc=0.39), a history of legal involvement (p=0.005; φc=0.39), and higher rates of lifetime substance use disorder (SUD; p=0.002; φc=0.42). Early-onset patients had significantly higher PANSS-EC scores over the course of observation (F(1,44.4)=5.39; p=0.025; d=0.656), but no significant group differences emerged for the remaining PANSS subscores. PANSS-EC scores were correlated positively with antisocial personality disorder and forensic history at 6weeks, 3months, 6months, and 12months, and with lifetime substance use disorder at 3months and 6months. Patients with early onset psychosis may have increased levels of agitation/aggressiveness, and, more likely, antisocial personality disorder, forensic history, and lifetime substance use disorder. These variables were linked to suicidality, aggressiveness, and involuntary treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Ethics of the early intervention in the treatment of schizophrenia.

Science.gov (United States)

Filaković, Pavo; Degmecić, Dunja; Koić, Elvira; Benić, Domagoj

2007-09-01

When second generation antipsychotics were introduced in the mid 1990-s they offered the possibility of early psychopharmacological interventions in the treatment of schizophrenia. The idea applying antipsychotics in the prodromal phase of schizophrenia today is an realistic option. However ethical dilemmas about offering antipsychotics to the adolescents with at risk mental states, of whom only a few are real prodromes of schizophrenia remain for clinicians. In the literature about the ethics of the early interventions in psychiatry there are still many ethical questions which call for caution because of the low predictive value of at risk mental states, of which only 40% turn out to be a real prodrome of schizophrenia. These ethical questions can be addressed in three categories: - how to best identify who should receive early pharmacological intervention? - what this intervention should consist of? - how to evaluate treatment efficacy in the absence of illness base rates in the adolescents with a real prodrome of schizophrenia? Besides, arguing against the concept of early psychopharmacological interventions in the adolescent population are the fact of the unknown effect of antipsychotics on the developing brain as well as negative effects of stigma on those adolescents who receive them. The authors in the article analyse these ethical questions and take the side of those clinicians who think that caution and careful ethical judgment are needed before the prescribing of antipsychotics to adolescents with at risk mental states.

BDNF val66met polymorphism is associated with age at onset and intensity of symptoms of paranoid schizophrenia in a Polish population.

Science.gov (United States)

Suchanek, Renata; Owczarek, Aleksander; Paul-Samojedny, Monika; Kowalczyk, Małgorzata; Kucia, Krzysztof; Kowalski, Jan

2013-01-01

The brain-derived neurotrophic factor (BDNF) is one of the candidate genes for schizophrenia. There is evidence that val66met polymorphism may be involved in the pathophysiology of schizophrenia. The authors genotyped val66met (rs6265) polymorphism of the BDNF gene in 208 inpatients with paranoid schizophrenia and 254 control subjects in a Polish population. There was no association between val66met polymorphism and development of paranoid schizophrenia in either men or women. However, an association was found between this polymorphism and age at onset and psychopathology of paranoid schizophrenia. Men with the val/met genotype had an earlier age at onset, and the val/val genotype predisposed to more severe symptoms, particularly on the General Psychopathology Scale of the Positive and Negative Symptoms Scale (PANSS-G). The analysis of PANSS single items has shown that patients with the val/met genotype had higher scores on a hallucinatory behavior item than those with other genotypes.

The affective dimension of early-onset psychosis and its relationship with suicide.

Science.gov (United States)

Sanchez-Gistau, Vanessa; Baeza, Inmaculada; Arango, Celso; González-Pinto, Ana; de la Serna, Elena; Parellada, Mara; Graell, Montserrat; Paya, Beatriz; Llorente, Cloe; Castro-Fornieles, Josefina

2015-07-01

The affective dimension has scarcely been studied in early-onset psychosis. Our aims were to investigate the prevalence and type of affective symptoms in the prodromal and acute phases of early-onset psychosis and to examine their relationship with suicide. We also sought to establish whether the presence of premorbid antecedents or the presence of affective symptoms during the prodromal and acute phase might predict a later diagnosis of bipolar disorder (BP) or schizophrenia (SZ). Participants were 95 youths, aged 9-17 years, experiencing a first episode of a psychotic disorder (FEP) according to DSM-IV criteria. Prodromal affective symptoms in the year prior to the onset of full-blown psychosis were assessed by means of the K-SADS. Affective symptoms during the acute episode were evaluated using the Hamilton Depression Rating Scale and the Young Mania Rating Scale. Suicidality was assessed during the acute episode and at 6 and 12 months. Half of the patients experienced affective symptoms during the prodrome, with depressive symptoms being the most frequently reported. During the acute episode, 23.2% presented depressive, 41.4% mixed and 18.9% manic symptoms. After logistic regression analysis, only the presence of depressive symptoms was significantly associated with suicidality during the 12 months following the FEP. Neither early premorbid antecedents nor the prevalence or type of affective symptoms during the FEP predicted a diagnosis of BP or SZ at 12 months. However, both depressive and manic prodromal symptoms were associated with a later diagnosis of BP. The FEP of both SZ and BP is preceded by an identifiable prodromal phase. Early detection programs should target young people at clinical risk for the extended psychosis phenotype. The high prevalence of affective symptoms during the early phases of psychosis may encourage clinicians to identify and treat them in order to prevent suicide behaviour. © 2014 Association for Child and Adolescent Mental

Facial emotion identification in early-onset psychosis.

Science.gov (United States)

Barkl, Sophie J; Lah, Suncica; Starling, Jean; Hainsworth, Cassandra; Harris, Anthony W F; Williams, Leanne M

2014-12-01

Facial emotion identification (FEI) deficits are common in patients with chronic schizophrenia and are strongly related to impaired functioning. The objectives of this study were to determine whether FEI deficits are present and emotion specific in people experiencing early-onset psychosis (EOP), and related to current clinical symptoms and functioning. Patients with EOP (n=34, mean age=14.11, 53% female) and healthy controls (HC, n=42, mean age 13.80, 51% female) completed a task of FEI that measured accuracy, error pattern and response time. Relative to HC, patients with EOP (i) had lower accuracy for identifying facial expressions of emotions, especially fear, anger and disgust, (ii) were more likely to misattribute other emotional expressions as fear or disgust, and (iii) were slower at accurately identifying all facial expressions. FEI accuracy was not related to clinical symptoms or current functioning. Deficits in FEI (especially for fear, anger and disgust) are evident in EOP. Our findings suggest that while emotion identification deficits may reflect a trait susceptibility marker, functional deficits may represent a sequelae of illness. Copyright © 2014 Elsevier B.V. All rights reserved.

Early onset intellectual disability in chromosome 22q11.2 deletion syndrome.

Science.gov (United States)

Cascella, Marco; Muzio, Maria Rosaria

2015-01-01

Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Symptom response and side-effects of olanzapine and risperidone in young adults with recent onset schizophrenia

NARCIS (Netherlands)

van Bruggen, Johanna; Tijssen, Jans; Dingemans, Petrus; Gersons, Berthold; Linszen, Donald

2003-01-01

The symptom response and side-effects of olanzapine and risperidone were compared in patients with recent onset schizophrenia. Actively symptomatic patients n=44) randomly, received olanzapine 15 mg (median dose) or risperidone 4 mg (median dose). Symptom response and side-effects were measured

Regional brain activity during early visual perception in unaffected siblings of schizophrenia patients.

Science.gov (United States)

Lee, Junghee; Cohen, Mark S; Engel, Stephen A; Glahn, David; Nuechterlein, Keith H; Wynn, Jonathan K; Green, Michael F

2010-07-01

Visual masking paradigms assess the early part of visual information processing, which may reflect vulnerability measures for schizophrenia. We examined the neural substrates of visual backward performance in unaffected sibling of schizophrenia patients using functional magnetic resonance imaging (fMRI). Twenty-one unaffected siblings of schizophrenia patients and 19 healthy controls performed a backward masking task and three functional localizer tasks to identify three visual processing regions of interest (ROI): lateral occipital complex (LO), the motion-sensitive area, and retinotopic areas. In the masking task, we systematically manipulated stimulus onset asynchronies (SOAs). We analyzed fMRI data in two complementary ways: 1) an ROI approach for three visual areas, and 2) a whole-brain analysis. The groups did not differ in behavioral performance. For ROI analysis, both groups increased activation as SOAs increased in LO. Groups did not differ in activation levels of the three ROIs. For whole-brain analysis, controls increased activation as a function of SOAs, compared with siblings in several regions (i.e., anterior cingulate cortex, posterior cingulate cortex, inferior prefrontal cortex, inferior parietal lobule). The study found: 1) area LO showed sensitivity to the masking effect in both groups; 2) siblings did not differ from controls in activation of LO; and 3) groups differed significantly in several brain regions outside visual processing areas that have been related to attentional or re-entrant processes. These findings suggest that LO dysfunction may be a disease indicator rather than a risk indicator for schizophrenia. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Childhood onset diagnoses in a case series of teens at clinical high risk for psychosis.

Science.gov (United States)

Mazzoni, Paola; Kimhy, David; Khan, Shamir; Posner, Kelly; Maayan, Lawrence; Eilenberg, Mara; Messinger, Julie; Kestenbaum, Clarice; Corcoran, Cheryl

2009-12-01

REASONS: Schizophrenia is typically an adult neurodevelopmental disorder that has its antecedents in childhood and adolescence. Little is known about disorders "usually first diagnosed in infancy, childhood and adolescence" (e.g., childhood-onset disorders) in "prodromal" teens at heightened clinical risk for psychotic disorder. Childhood-onset disorders were prevalent in putatively prodromal teens, including anxiety and disruptive disorders, attention-deficit/hyperactivity disorder (ADHD), and, surprisingly, elimination disorders. These may reflect developmental antecedents in psychotic disorders such as schizophrenia. A case series of 9 teens (ages 13-17) identified as prodromal to psychosis were evaluated with the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL). Childhood-onset diagnoses commonly endorsed (threshold or subthreshold) included ADHD (5/9), oppositional defiant disorder (5/9), enuresis or encopresis (4/9), conduct disorder (2/9), separation anxiety (3/9), and transient tic disorder (2/9). Enuresis was identified in 3 of the 4 older teens (ages 15-17). An understanding of the childhood-onset disorders that occur in teens at risk for psychotic illnesses, such as schizophrenia, can shed light on the pathophysiology of schizophrenia and potentially inform early identification and intervention.

DNA methyl transferase (DNMT gene polymorphisms could be a primary event in epigenetic susceptibility to schizophrenia.

Directory of Open Access Journals (Sweden)

Koramannil Radha Saradalekshmi

Full Text Available DNA methylation has been implicated in the etiopathology of various complex disorders. DNA methyltransferases are involved in maintaining and establishing new methylation patterns. The aim of the present study was to investigate the inherent genetic variations within DNA methyltransferase genes in predisposing to susceptibility to schizophrenia. We screened for polymorphisms in DNA methyltransferases, DNMT1, DNMT3A, DNMT3B and DNMT3L in 330 schizophrenia patients and 302 healthy controls for association with Schizophrenia in south Indian population. These polymorphisms were also tested for subgroup analysis with patient's gender, age of onset and family history. DNMT1 rs2114724 (genotype P = .004, allele P = 0.022 and rs2228611 (genotype P = 0.004, allele P = 0.022 were found to be significantly associated at genotypic and allelic level with Schizophrenia in South Indian population. DNMT3B rs2424932 genotype (P = 0.023 and allele (P = 0.0063 increased the risk of developing schizophrenia in males but not in females. DNMT3B rs1569686 (genotype P = 0.027, allele P = 0.033 was found to be associated with early onset of schizophrenia and also with family history and early onset (genotype P = 0.009. DNMT3L rs2070565 (genotype P = 0.007, allele P = 0.0026 confers an increased risk of developing schizophrenia at an early age in individuals with family history. In-silico prediction indicated functional relevance of these SNPs in regulating the gene. These observations might be crucial in addressing and understanding the genetic control of methylation level differences from ethnic viewpoint. Functional significance of genotype variations within the DNMTs indeed suggest that the genetic nature of methyltransferases should be considered while addressing epigenetic events mediated by methylation in Schizophrenia.

Evidence for a genetic etiology of early-onset delinquency.

Science.gov (United States)

Taylor, J; Iacono, W G; McGue, M

2000-11-01

Age at onset of antisocial behavior discriminates persistent and transitory offenders. The authors proposed that early-onset delinquency has an underlying genetic influence that manifests in problems related to inhibition, whereas late-onset delinquency is more environmentally mediated. To test these notions, they selected 36 early starters, 86 late starters, and 25 nondelinquent controls from a large sample of 11-year-old twins and compared them on several measures related to inhibition and a peer group measure. As expected, early starters had more psychological, behavioral, and emotional problems related to inhibition than late starters and controls. A longitudinal analysis indicated an increase an antisocial behavior among peers of late starters shortly before their delinquency onset. Family history data and a twin analysis provided evidence of greater genetic influence on early-onset than late-onset delinquency.

Prenatal Ontogeny as a Susceptibility Period for Cortical GABA Neuron Disturbances in Schizophrenia

OpenAIRE

Volk, David W.; Lewis, David A.

2013-01-01

Cognitive deficits in schizophrenia have been linked to disturbances in GABA neurons in the prefrontal cortex. Furthermore, cognitive deficits in schizophrenia appear well before the onset of psychosis and have been reported to be present during early childhood and even during the first year of life. Taken together, these data raise the following question: Does the disease process that produces abnormalities in prefrontal GABA neurons in schizophrenia begin prenatally and disrupt the ontogeny...

Delayed early proprioceptive information processing in schizophrenia

DEFF Research Database (Denmark)

Arnfred, Sidse M; Hemmingsen, RP; Parnas, Josef

2006-01-01

. In the patients, the early contralateral parietal activity was delayed and later central activity had increased amplitude, but gating was unaffected. The results could be understood within the "deficiency of corollary discharge" model of schizophrenia but not within the "filtering" theory. Further studies...

Comparative study of clinical and neuropsychological characteristics between early-, late and very-late-onset schizophrenia-spectrum disorders.

Science.gov (United States)

Hanssen, Manon; van der Werf, Margriet; Verkaaik, Mike; Arts, Baer; Myin-Germeys, Inez; van Os, Jim; Verhey, Frans; Köhler, Sebastian

2015-08-01

To compare the clinical and neurocognitive profile of early-onset (EOP, neuropsychological tests from EOP and LOP when age is controlled for. This questions the idea that VLOP is the expression of underlying neurodegeneration. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Impaired early visual response modulations to spatial information in chronic schizophrenia

Science.gov (United States)

Knebel, Jean-François; Javitt, Daniel C.; Murray, Micah M.

2011-01-01

Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia. PMID:21764264

Emotion recognition deficits as predictors of transition in individuals at clinical high risk for schizophrenia: a neurodevelopmental perspective.

Science.gov (United States)

Corcoran, C M; Keilp, J G; Kayser, J; Klim, C; Butler, P D; Bruder, G E; Gur, R C; Javitt, D C

2015-10-01

Schizophrenia is characterized by profound and disabling deficits in the ability to recognize emotion in facial expression and tone of voice. Although these deficits are well documented in established schizophrenia using recently validated tasks, their predictive utility in at-risk populations has not been formally evaluated. The Penn Emotion Recognition and Discrimination tasks, and recently developed measures of auditory emotion recognition, were administered to 49 clinical high-risk subjects prospectively followed for 2 years for schizophrenia outcome, and 31 healthy controls, and a developmental cohort of 43 individuals aged 7-26 years. Deficit in emotion recognition in at-risk subjects was compared with deficit in established schizophrenia, and with normal neurocognitive growth curves from childhood to early adulthood. Deficits in emotion recognition significantly distinguished at-risk patients who transitioned to schizophrenia. By contrast, more general neurocognitive measures, such as attention vigilance or processing speed, were non-predictive. The best classification model for schizophrenia onset included both face emotion processing and negative symptoms, with accuracy of 96%, and area under the receiver-operating characteristic curve of 0.99. In a parallel developmental study, emotion recognition abilities were found to reach maturity prior to traditional age of risk for schizophrenia, suggesting they may serve as objective markers of early developmental insult. Profound deficits in emotion recognition exist in at-risk patients prior to schizophrenia onset. They may serve as an index of early developmental insult, and represent an effective target for early identification and remediation. Future studies investigating emotion recognition deficits at both mechanistic and predictive levels are strongly encouraged.

Acute Antipsychotic Treatment of Children and Adolescents With Schizophrenia-Spectrum Disorders

DEFF Research Database (Denmark)

Pagsberg, Anne Katrine; Tarp, Simon; Glintborg, Dorte

2017-01-01

. Serious adverse events, discontinuation of treatment, sedation, insomnia, or change in triglycerides did not differ among antipsychotics. CONCLUSION: This network meta-analysis showed comparable efficacy among antipsychotics for early-onset schizophrenia, except that efficacy appeared inferior...

Early-onset obsessive-compulsive disorder and personality disorders in adulthood.

Science.gov (United States)

Maina, Giuseppe; Albert, Umberto; Salvi, Virginio; Pessina, Enrico; Bogetto, Filippo

2008-03-15

Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset ( or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis.

Estrogen and early-onset Alzheimer's disease

NARCIS (Netherlands)

A.J.C. Slooter (Arjen); J.B. Bronzova (Juliana); A. Hofman (Albert); C. van Broeckhoven (Christine); C.M. van Duijn (Cornelia); J.C.M. Witteman (Jacqueline)

1999-01-01

textabstractEstrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5 years) and place of

Is there a degenerative process going on in the brain of people with schizophrenia?

Directory of Open Access Journals (Sweden)

Bjorn Rund

2009-10-01

Full Text Available Schizophrenia is a biological and behavioural disorder which manifests itself in neurocognitive dysfunctions. The question of whether these key characteristics of the disorder are due to schizophrenia being a degenerative disorder has been discussed for more than 100 years. Neuropsychological data indicate that neurocognitive functions are relatively stable over time after illness onset. Several studies show that there is a decline in neurocognitive functioning prior to and in connection with onset of illness. There is no convincing evidence, however, that there is a progressive neurodegenerative process after onset of illness. Morphological data, on the other hand, indicate a degenerative process. Several novel longitudinal studies indicate a rapid reduction of vital brain tissues after onset of illness. In this paper some ideas about compensatory reactions and Cognitive Reserve Theory is outlined as possible explanations of the recent MR studies that show structural changes in the brain after the onset of schizophrenia, at the same time as cognitive functioning does not become more impaired. Determining whether schizophrenia is a neurodegenerative illness with progressive structural changes in the brain after debut of the illness, or a neurodevelopmental disorder starting in early life, is of significant importance for understanding the pathophysiology of the illness and its treatments.

Baseline profiles of adolescent vs. adult-onset first-episode psychosis in an early detection program

DEFF Research Database (Denmark)

Joa, I; Johannessen, Jan Olav; Langeveld, J

2009-01-01

OBJECTIVE: Psychotic disorders often start in adolescence. We aim to investigate premorbid and baseline differences characterizing patients with an onset of psychosis in adolescence versus adulthood. METHOD: We compare first-episode, DSM-IV non-affective psychosis with onset before (n = 43) and a...... the description of what used to be labeled process (versus reactive) schizophrenia....

Social functioning and the course of early-onset schizophrenia: five-year follow-up of a psychosocial intervention

NARCIS (Netherlands)

Lenior, M. E.; Dingemans, P. M.; Linszen, D. H.; de Haan, L.; Schene, A. H.

2001-01-01

BACKGROUND: Schizophrenia implies severe social impairments. Since the treatment of patients with schizophrenia shifted from long-term hospital admissions to community services, research on social functioning has become increasingly important. AIMS: Follow-up assessment of social functioning in

Potential Value of Genomic Copy Number Variations in Schizophrenia

Directory of Open Access Journals (Sweden)

Chuanjun Zhuo

2017-06-01

Full Text Available Schizophrenia is a devastating neuropsychiatric disorder affecting approximately 1% of the global population, and the disease has imposed a considerable burden on families and society. Although, the exact cause of schizophrenia remains unknown, several lines of scientific evidence have revealed that genetic variants are strongly correlated with the development and early onset of the disease. In fact, the heritability among patients suffering from schizophrenia is as high as 80%. Genomic copy number variations (CNVs are one of the main forms of genomic variations, ubiquitously occurring in the human genome. An increasing number of studies have shown that CNVs account for population diversity and genetically related diseases, including schizophrenia. The last decade has witnessed rapid advances in the development of novel genomic technologies, which have led to the identification of schizophrenia-associated CNVs, insight into the roles of the affected genes in their intervals in schizophrenia, and successful manipulation of the target CNVs. In this review, we focus on the recent discoveries of important CNVs that are associated with schizophrenia and outline the potential values that the study of CNVs will bring to the areas of schizophrenia research, diagnosis, and therapy. Furthermore, with the help of the novel genetic tool known as the Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9 system, the pathogenic CNVs as genomic defects could be corrected. In conclusion, the recent novel findings of schizophrenia-associated CNVs offer an exciting opportunity for schizophrenia research to decipher the pathological mechanisms underlying the onset and development of schizophrenia as well as to provide potential clinical applications in genetic counseling, diagnosis, and therapy for this complex mental disease.

The effects of pre-natal-, early-life- and indirectly-initiated exposures to maximum adversities on the course of schizophrenia.

Science.gov (United States)

Levine, Stephen Z; Levav, Itzhak; Yoffe, Rinat; Pugachova, Inna

2014-09-01

The effects of pre-natal-, early-life- and indirectly-initiated exposures to protracted maximum adversity on the course of schizophrenia are unknown. To compare the aforementioned Holocaust directly exposed subgroups with an indirectly exposed subgroup on the course of schizophrenia. The study population were: Israeli Jews in-uterus or born in Nazi-occupied or dominated European nations by the end of the persecution of the Jews, who were alive in 1950, and who had a last discharge diagnosis of schizophrenia in the Israel National Psychiatric Case Registry by 2013 (N=4933). The population was disaggregated into subgroups who (1) migrated after WWII and who had (1a) pre-natal (n=584, 11.8%) and (1b) early-life (n=3709, 75.2%) initiated exposures to the maximum adversities of the Holocaust, and (2) indirectly exposed individuals to the Holocaust who migrated before the Nazi-era persecution begun (n=640, 13%). Recurrent event survival analyses were computed to examine the psychiatric re-hospitalization risk of the study subgroups, unadjusted and adjusted for age of onset of the disorder and sex. The pre-natal initiated exposure subgroup had a significantly (pPoland-born individuals, the years 1922 and 1935; and followed at least 10 years and to the year 2000. Pre-natal initiated exposure to the maximal adversity of the holocaust constitutes a consistent risk factor for a worse course of schizophrenia, a possible byproduct of neurodevelopment disruptions induced by maternal stress and/or famine and/or infections. Copyright © 2014 Elsevier B.V. All rights reserved.

Intrauterine growth restriction and placental gene expression in severe preeclampsia, comparing early-onset and late-onset forms.

Science.gov (United States)

Nevalainen, Jaana; Skarp, Sini; Savolainen, Eeva-Riitta; Ryynänen, Markku; Järvenpää, Jouko

2017-10-26

To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls. Chorionic villus sampling was conducted after cesarean section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups. Pathway analysis showed over-representation of gene ontology (GO) biological process terms related to inflammatory and immune response pathways, platelet development, vascular development, female pregnancy and reproduction in early-onset preeclampsia. Pathways related to immunity, complement and coagulation cascade were overrepresented in the hypergeometric test for the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Ten genes (ABI3BP, C7, HLA-G, IL2RB, KRBOX1, LRRC15, METTL7B, MPP5, RFLNB and SLC20A) had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to early controls. There were 362 genes that had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to late-onset preeclampsia group including ABI3BP, C7, HLA-G and IL2RB. There are significant differences in placental gene expression between severe early- and late-onset preeclampsia when both are associated with intrauterine growth restriction. ABI3BP, C7, HLA-G and IL2RB might contribute to the development of early form of severe preeclampsia.

Heterogeneity of schizophrenia: Genetic and symptomatic factors.

Science.gov (United States)

Takahashi, Sakae

2013-10-01

Schizophrenia may have etiological heterogeneity, and may reflect common symptomatology caused by many genetic and environmental factors. In this review, we show the potential existence of heterogeneity in schizophrenia based on the results of our previous studies. In our study of the NOTCH4 gene, there were no significant associations between any single nucleotide polymorphisms (SNPs) of NOTCH4 and schizophrenia. However, exploratory analyses suggested that the SNP, rs3134928 may be associated with early-onset schizophrenia, and that rs387071 may be associated with schizophrenia characterized by negative symptoms. In our highly familial schizophrenia study, the African-American cohort without environmental exposure showed a possible linkage at marker 8p23.1 in the dominant model and in the European-American cohort, a marker at 22q13.32 showed a probable linkage in the recessive model. In the less familial schizophrenia families, these linkages were not shown. Based on our eye movement study, a putative subtype of schizophrenia with severe symptoms related to excitement/hostility, negative symptoms and disorganization may be associated with chromosome 22q11. We consider that a sample stratification approach may clarify the heterogeneity of schizophrenia. Therefore, this approach may lead to a more straightforward way of identifying susceptibility genes of schizophrenia. © 2013 Wiley Periodicals, Inc.

Neurocognitive Deficits in Adolescents with Schizophrenia: Longitudinal Stability and Predictive Utility for Short-Term Functional Outcome

Science.gov (United States)

Cervellione, Kelly L.; Burdick, Katherine E.; Cottone, John G.; Rhinewine, Joseph P.; Kumra, Sanjiv

2007-01-01

Objective: Previous cross-sectional studies in adolescents with early-onset schizophrenia (EOS; onset of psychotic symptoms by 18 years of age) have reported patterns of generalized neurocognitive deficits as compared to healthy comparison subjects (HCSs). Here, the authors examined the longitudinal stability of neuropsychological deficits in…

Childhood body mass index and risk of schizophrenia in relation to childhood age, sex and age of first contact with schizophrenia.

Science.gov (United States)

Sørensen, H J; Gamborg, M; Sørensen, T I A; Baker, J L; Mortensen, E L

2016-04-01

Childhood leanness is associated with an increased risk of schizophrenia, but the effects of gender, age at anthropometric measurements and age at first diagnosis on this relationship are unclear. The present study aimed at elucidating these associations. Population-based cohort study with childhood anthropometric measures obtained annually from the age of 7 to 13 years in 253,353 Danes born 1930-1976 and followed to 31 December 2010. During this period, 4936 were registered with schizophrenia. The associations of childhood BMI with risk of schizophrenia were estimated with Cox regression models. Childhood BMI was significantly inversely associated with risk of schizophrenia, however with different patterns among boys and girls. In boys, childhood BMI had an inverse non-linear association with schizophrenia risk dependent on age at diagnosis; in particular, a surprisingly strong association was found between leanness and later onset of schizophrenia. In girls, the risk of schizophrenia decreased linearly with increasing BMI z-score (HR: 0.93; 95% CI: 0.88-0.98). In both boys and girls, birth weight was inversely associated with later risk. In girls, but not in boys, birth weight appeared to significantly modify the associations; there was a somewhat stronger inverse association in the lowest birth weight category. Birth weight as well as childhood BMI at ages 7 through 13 years is associated with risk of schizophrenia in both genders, but with a particular high risk of late-onset in lean boys irrespective of birth weight, and in lean girls with low birth weight. If replicated, these observations may inform preventive efforts build on schizophrenia trajectories rooted in early life. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Early course of schizophrenia in a representative Dutch incidence cohort

NARCIS (Netherlands)

Selten, Jean-Paul; Veen, Natalie D.; Hoek, Hans W.; Laan, Winfried; Schols, Diede; van der Tweel, Ingeborg; Feller, Wilma; Kahn, Rene S.

2007-01-01

Purpose: To describe the early course of psychotic disorders in general and to examine whether certain variables can predict the early course of schizophrenic disorders (DSM-IV: schizophrenia, schizophreniform or schizoaffective disorder), Subjects and method: Follow-up and re-diagnosis of a highly

Age at onset of DSM-IV pathological gambling in a non-treatment sample: Early- versus later-onset.

Science.gov (United States)

Black, Donald W; Shaw, Martha; Coryell, William; Crowe, Raymond; McCormick, Brett; Allen, Jeff

2015-07-01

Pathological gambling (PG) is a prevalent and impairing public health problem. In this study we assessed age at onset in men and women with PG and compared the demographic and clinical picture of early- vs. later-onset individuals. We also compared age at onset in PG subjects and their first-degree relatives with PG. Subjects with DSM-IV PG were recruited during the conduct of two non-treatment clinical studies. Subjects were evaluated with structured interviews and validated questionnaires. Early-onset was defined as PG starting prior to age 33years. Age at onset of PG in the 255 subjects ranged from 8 to 80years with a mean (SD) of 34.0 (15.3) years. Men had an earlier onset than women. 84% of all subjects with PG had developed the disorder by age 50years. Early-onset subjects were more likely to be male, to prefer action games, and to have substance use disorders, antisocial personality disorder, attention deficit/hyperactivity disorder, trait impulsiveness, and social anxiety disorder. Later-onset was more common in women and was associated with a preference for slots and a history of sexual abuse. Age at onset of PG is bimodal and differs for men and women. Early-onset PG and later-onset PG have important demographic and clinical differences. The implications of the findings are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Predisposing factors for early retirement in patients with schizophrenia in Germany.

Science.gov (United States)

Schnabel, Reinhard; Friedel, Heiko; Erfurth, Andreas; Angermayer, Matthias; Clouth, Johannes; Eichmann, Florian

2008-08-01

Although early retirement causes major changes in the life of schizophrenic patients and is among the major cost factors to be covered by payers, the causes leading to early retirement of schizophrenic patients have not been investigated in detail. Therefore, the objective of this retrospective non-interventional case-control study was to generate hypotheses on predisposing factors for early retirement in schizophrenia. Logistic regression was used to explore potential predisposing parameters with regard to their effect on the outcome early retirement. As the study results indicate, schizophrenia severity, assistance or care in the patient's everyday life, age and antipsychotic treatment with typical antipsychotics are linked to the occurrence of early retirement. Further research should be planned to confirm or refute the hypotheses determined in this retrospective analysis and to determine whether atypical antipsychotics could help to avoid early retirement and to improve the situation of schizophrenic patients.

Early-onset stargardt disease: phenotypic and genotypic characteristics

NARCIS (Netherlands)

Lambertus, S.; Huet, R.A.C. van; Bax, N.M.; Hoefsloot, L.H.; Cremers, F.P.M.; Boon, C.J.F.; Klevering, B.J.; Hoyng, C.B.

2015-01-01

OBJECTIVE: To describe the phenotype and genotype of patients with early-onset Stargardt disease. DESIGN: Retrospective cohort study. PARTICIPANTS: Fifty-one Stargardt patients with age at onset onset, medical history, initial

LORETA current source density for duration mismatch negativity and neuropsychological assessment in early schizophrenia.

Directory of Open Access Journals (Sweden)

Tomohiro Miyanishi

Full Text Available INTRODUCTION: Patients with schizophrenia elicit cognitive decline from the early phase of the illness. Mismatch negativity (MMN has been shown to be associated with cognitive function. We investigated the current source density of duration mismatch negativity (dMMN, by using low-resolution brain electromagnetic tomography (LORETA, and neuropsychological performance in subjects with early schizophrenia. METHODS: Data were obtained from 20 patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder, and 20 healthy control (HC subjects. An auditory odd-ball paradigm was used to measure dMMN. Neuropsychological performance was evaluated by the brief assessment of cognition in schizophrenia Japanese version (BACS-J. RESULTS: Patients showed smaller dMMN amplitudes than those in the HC subjects. LORETA current density for dMMN was significantly lower in patients compared to HC subjects, especially in the temporal lobes. dMMN current density in the frontal lobe was positively correlated with working memory performance in patients. CONCLUSIONS: This is the first study to identify brain regions showing smaller dMMN current density in early schizophrenia. Further, poor working memory was associated with decreased dMMN current density in patients. These results are likely to help understand the neural basis for cognitive impairment of schizophrenia.

[Clinical characteristics and renal uric acid excretion in early-onset gout patients].

Science.gov (United States)

Li, Q H; Liang, J J; Chen, L X; Mo, Y Q; Wei, X N; Zheng, D H; Dai, L

2018-03-01

Objective: To investigate clinical characteristics and renal uric acid excretion in early-onset gout patients. Methods: Consecutive inpatients with primary gout were recruited between 2013 and 2017. The patients with gout onset younger than 30 were defined as early-onset group while the others were enrolled as control group. Clinical characteristics and uric acid (UA) indicators were compared between two groups. Results: Among 202 recruited patients, the early-onset group included 36 patients (17.8%). Compared with control group, the early-onset group presented more patients with obesity [13 patients (36.1%) vs. 22 patients (13.3%), Pgout early onset. Conclusion: The gout patients with early-onset younger than 30 present high serum and glomerular load of uric acid which might be due to obesity and relative under-excretion of renal uric acid.

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.

Genetic and molecular risk factors within the newly identified primate-specific exon of the SAP97/DLG1 gene in the 3q29 schizophrenia-associated locus.

Science.gov (United States)

Uezato, Akihito; Yamamoto, Naoki; Jitoku, Daisuke; Haramo, Emiko; Hiraaki, Eri; Iwayama, Yoshimi; Toyota, Tomoko; Umino, Masakazu; Umino, Asami; Iwata, Yasuhide; Suzuki, Katsuaki; Kikuchi, Mitsuru; Hashimoto, Tasuku; Kanahara, Nobuhisa; Kurumaji, Akeo; Yoshikawa, Takeo; Nishikawa, Toru

2017-12-01

The synapse-associated protein 97/discs, large homolog 1 of Drosophila (DLG1) gene encodes synaptic scaffold PDZ proteins interacting with ionotropic glutamate receptors including the N-methyl-D-aspartate type glutamate receptor (NMDAR) that is presumed to be hypoactive in brains of patients with schizophrenia. The DLG1 gene resides in the chromosomal position 3q29, the microdeletion of which confers a 40-fold increase in the risk for schizophrenia. In the present study, we performed genetic association analyses for DLG1 gene using a Japanese cohort with 1808 schizophrenia patients and 2170 controls. We detected an association which remained significant after multiple comparison testing between schizophrenia and the single nucleotide polymorphism (SNP) rs3915512 that is located within the newly identified primate-specific exon (exon 3b) of the DLG1 gene and constitutes the exonic splicing enhancer sequence. When stratified by onset age, although it did not survive multiple comparisons, the association was observed in non-early onset schizophrenia, whose onset-age selectivity is consistent with our recent postmortem study demonstrating a decrease in the expression of the DLG1 variant in early-onset schizophrenia. Although the present study did not demonstrate the previously reported association of the SNP rs9843659 by itself, a meta-analysis revealed a significant association between DLG1 gene and schizophrenia. These findings provide a valuable clue for molecular mechanisms on how genetic variations in the primate-specific exon of the gene in the schizophrenia-associated 3q29 locus affect its regulation in the glutamate system and lead to the disease onset around a specific stage of brain development. © 2017 Wiley Periodicals, Inc.

Attention deficit hyperactivity disorder symptoms mediate early-onset smoking

NARCIS (Netherlands)

Huizink, A.C.; Van Lier, P.A.C.; Crijnen, A.A.M.

2009-01-01

Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized

Attention Deficit Hyperactivity Disorder Symptoms Mediate Early-Onset Smoking

NARCIS (Netherlands)

Huizink, A.C.; Lier, P.A.C. van; Crijnen, A.A.M.

2009-01-01

Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized

Attention deficit hyperactivity disorder symptoms mediate early-onset smoking

NARCIS (Netherlands)

A.C. Huizink (Anja); P.A.C. van Lier (Pol); A.A.M. Crijnen (Alfons)

2008-01-01

textabstractBackground/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based,

Exercise and Early-Onset Alzheimer’s Disease: Theoretical Considerations

Directory of Open Access Journals (Sweden)

Astrid M. Hooghiemstra

2012-04-01

Full Text Available Background/Aims: Although studies show a negative relationship between physical activity and the risk for cognitive impairment and late-onset Alzheimer’s disease, studies concerning early-onset Alzheimer’s disease (EOAD are lacking. This review aims to justify the value of exercise interventions in EOAD by providing theoretical considerations that include neurobiological processes. Methods: A literature search on key words related to early-onset dementia, exercise, imaging, neurobiological mechanisms, and cognitive reserve was performed. Results/Conclusion: Brain regions and neurobiological processes contributing to the positive effects of exercise are affected in EOAD and, thus, provide theoretical support for exercise interventions in EOAD. Finally, we present the design of a randomized controlled trial currently being conducted in early-onset dementia patients.

Variants of cognitive deficiency depending on the clinical characteristics of the disease in patients with paranoid schizophrenia

Directory of Open Access Journals (Sweden)

G. G. Lebedeva

2015-01-01

Full Text Available Pecific aspects of cognitive impairments in patients with paranoid schizophrenia depending on the clinical characteristics of the disease have been studied. One hundred and thirty patients were examined. A clinico-psychological, experimental psychological and statistical methods were used. Three main types of cognitive deficiency with paranoid schizophrenia, associated with the onset, disease duration, and severity of psychiatric symptomology : 1 long-term course of the disease accompanied by the average level of clinical symptomology associated with abnormal attention and visuospatial functions; 2 late onset of the disease and unexpressed clinical symptomology combined with memory impairments; 3 acute onset and early age combined with the absence of cognitive impairments.

Feasibility of teaching motivational interviewing to parents of young adults with recent-onset schizophrenia and co-occurring cannabis use

NARCIS (Netherlands)

Smeerdijk, Maarten; Keet, René; de Haan, Lieuwe; Barrowclough, Christine; Linszen, Don; Schippers, Gerard

2014-01-01

This study examined the feasibility of providing motivational interviewing (MI) training to parents of young adults with recent-onset schizophrenia and co-occurring cannabis use. The training was offered in a mental health care setting as part of a family motivational intervention (FMI).

Amotivation and functional outcomes in early schizophrenia.

Science.gov (United States)

Fervaha, Gagan; Foussias, George; Agid, Ofer; Remington, Gary

2013-12-15

Negative symptoms, particularly amotivation/apathy, are intimately tied to functional outcomes. In the present study, apathy strongly predicted psychosocial functioning in a sample of early course schizophrenia patients. This relationship remained robust even after controlling for other clinical variables. These data suggest amotivation is core to functioning across the disease course. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Early- versus Late-Onset Dysthymia: A Meaningful Clinical Distinction?

OpenAIRE

Sansone, Randy A.; Sansone, Lori A.

2009-01-01

In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared ...

Widespread disruption of functional brain organization in early-onset Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Sofie M Adriaanse

Full Text Available Early-onset Alzheimer's disease (AD patients present a different clinical profile than late-onset AD patients. This can be partially explained by cortical atrophy, although brain organization might provide more insight. The aim of this study was to examine functional connectivity in early-onset and late-onset AD patients. Resting-state fMRI scans of 20 early-onset (<65 years old, 28 late-onset (≥65 years old AD patients and 15 "young" (<65 years old and 31 "old" (≥65 years old age-matched controls were available. Resting-state network-masks were used to create subject-specific maps. Group differences were examined using a non-parametric permutation test, accounting for gray-matter. Performance on five cognitive domains were used in a correlation analysis with functional connectivity in AD patients. Functional connectivity was not different in any of the RSNs when comparing the two control groups (young vs. old controls, which implies that there is no general effect of aging on functional connectivity. Functional connectivity in early-onset AD was lower in all networks compared to age-matched controls, where late-onset AD showed lower functional connectivity in the default-mode network. Functional connectivity was lower in early-onset compared to late-onset AD in auditory-, sensory-motor, dorsal-visual systems and the default mode network. Across patients, an association of functional connectivity of the default mode network was found with visuoconstruction. Functional connectivity of the right dorsal visual system was associated with attention across patients. In late-onset AD patients alone, higher functional connectivity of the sensory-motor system was associated with poorer memory performance. Functional brain organization was more widely disrupted in early-onset AD when compared to late-onset AD. This could possibly explain different clinical profiles, although more research into the relationship of functional connectivity and cognitive

Abnormal externally guided movement preparation in recent-onset schizophrenia is associated with impaired selective attention to external input.

Science.gov (United States)

Smid, Henderikus G O M; Westenbroek, Joanna M; Bruggeman, Richard; Knegtering, Henderikus; Van den Bosch, Robert J

2009-11-30

Several theories propose that the primary cognitive impairment in schizophrenia concerns a deficit in the processing of external input information. There is also evidence, however, for impaired motor preparation in schizophrenia. This provokes the question whether the impaired motor preparation in schizophrenia is a secondary consequence of disturbed (selective) processing of the input needed for that preparation, or an independent primary deficit. The aim of the present study was to discriminate between these hypotheses, by investigating externally guided movement preparation in relation to selective stimulus processing. The sample comprised 16 recent-onset schizophrenia patients and 16 controls who performed a movement-precuing task. In this task, a precue delivered information about one, two or no parameters of a movement summoned by a subsequent stimulus. Performance measures and measures derived from the electroencephalogram showed that patients yielded smaller benefits from the precues and showed less cue-based preparatory activity in advance of the imperative stimulus than the controls, suggesting a response preparation deficit. However, patients also showed less activity reflecting selective attention to the precue. We therefore conclude that the existing evidence for an impairment of externally guided motor preparation in schizophrenia is most likely due to a deficit in selective attention to the external input, which lends support to theories proposing that the primary cognitive deficit in schizophrenia concerns the processing of input information.

Values in First-Episode Schizophrenia.

Science.gov (United States)

Agid, Ofer; Mcdonald, Krysta; Fervaha, Gagan; Littrell, Romie; Thoma, Jessica; Zipursky, Robert B; Foussias, George; Remington, Gary

2015-11-01

Functional impairment continues to represent a major challenge in schizophrenia. Surprisingly, patients with schizophrenia report a level of happiness comparable with control subjects, even in the face of the prominent functional deficits, a finding at odds with evidence indicating a positive relation between happiness and level of functioning. In attempting to reconcile these findings, we chose to examine the issue of values, defined as affectively infused criteria or motivational goals used to select and justify actions, people, and the self, as values are related to both happiness and functioning. Fifty-six first-episode patients in remission and 56 healthy control subjects completed happiness and values measures. Statistical analyses included correlations, analysis of variance, structural equation modelling, and smallest space analysis. Results indicated that patients with schizophrenia placed significantly greater priority on the value dimensions of Tradition (P = 0.02) and Power (P = 0.03), and significantly less priority on Self-direction (P = 0.007) and Stimulation, (P = 0.008). Essentially, people with schizophrenia place more emphasis on the customs and ideas that traditional culture or religion provide in conjunction with a decreased interest in change, which is at odds with the expectations of early adulthood. This value difference could be related to functional deficits. To this point, we have assumed that people hold to the same values that guided them before the illness' onset, but this may not be the case. Our study indicates that values differ in people with schizophrenia, compared with control subjects, even early in the illness and in the face of symptomatic remission.

[Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis].

Science.gov (United States)

Okada, Hiroshi; Shin, Takeshi; Kobori, Yoshitomo

2016-07-01

Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described.

Anti-social personality characteristics and psychotic symptoms: Two pathways associated with offending in schizophrenia.

Science.gov (United States)

Van Dongen, Josanne D M; Buck, Nicole M L; Barendregt, Marko; Van Beveren, Nico M; De Beurs, Edwin; Van Marle, Hjalmar J C

2015-07-01

Several research groups have shown that people with schizophrenia who offend do not form a homogenous group. A three-group model claimed by Hodgins proposes distinguishing between people who start offending before the onset of psychosis (early starters), after psychosis onset but at age 34 years or under (late starters) and after psychosis onset but at age 35 years or older (late first offenders). This study aimed to test the hypotheses (1) that the personality of early starters and non-psychotic offenders would be similar, but different from either late-starter group; (2) that the late-starter groups would be more likely to have positive psychotic symptoms than non-criminal patients with schizophrenia; and (3) that symptom types would differentiate the psychotic groups. A retrospective file study was conducted on cases of 97 early starters, 100 late starters and 26 late first offenders all drawn from the Netherlands Institute of Forensic Psychiatry and Psychology (NIFP) archives 1993-2008, 115 non-psychotic offenders from 2005-2008 NIFP archives and 129 patients with schizophrenia and no criminal history from one general service in Rotterdam. Early starters closely resembled the non-psychotic offenders in their premorbid anti-social personality characteristics. The two late-onset offending psychosis groups were more likely to have persecutory and/or grandiose delusions than non-offenders with psychosis, but so were the early starters. In a first study to compare subgroups of offenders with psychosis directly with non-psychotic offenders and non-offenders with psychosis, we found such additional support for a distinction between early and late starters with psychosis that different treatment strategies would seem indicated, focusing on personality and substance misuse for the former but psychotic symptoms for all. It remains to be seen whether the higher rate of alcohol misuse amongst late first offenders is a fundamental distinction or a function of age

Does Schizophrenia in Offspring Increase the Risk of Developing Alzheimer's Dementia

Directory of Open Access Journals (Sweden)

Christopher Rohde

2016-08-01

Full Text Available Background/Aims: Prior studies have consistently found a higher risk of dementia in individuals with schizophrenia, but whether this is due to a common etiology between the disorders remains obscure. We wanted to elucidate this association by investigating whether schizophrenia in offspring increases the risk of Alzheimer's dementia. Methods: All individuals born between 1930 and 1953 were identified through national registers and followed from their 50th birthday until the date of Alzheimer's dementia, death or end of the study. Regressions were performed to evaluate the association between offspring with schizophrenia and Alzheimer's dementia. Results: Individuals with offspring with schizophrenia did not have an increased risk of Alzheimer's dementia [incidence rate ratio (IRR, 0.97; 95% CI, 0.88-1.07] compared to individuals with offspring without psychiatric contact. This finding remained stable when evaluating early-onset (IRR, 1.10; 95% CI, 0.91-1.31 and late-onset Alzheimer's dementia (IRR, 0.92; 95% CI, 0.88-1.07. Similar findings were made for vascular and unspecified dementia. Conclusion: The finding of no familial coaggregation between schizophrenia and Alzheimer's dementia may suggest that no common etiology between the disorders exists. This may indicate that the excess risk of dementia in individuals with schizophrenia is a by-product of the higher rates of somatic comorbidity and adverse health risk factors among these individuals.

Ziprasidone vs olanzapine in recent-onset schizophrenia and schizoaffective disorder: results of an 8-week double-blind randomized controlled trial

NARCIS (Netherlands)

Grootens, K.P.; Veelen, N.M. van; Peuskens, J.; Sabbe, B.G.C.; Thys, E.; Buitelaar, J.K.; Verkes, R.J.; Kahn, R.S.

2011-01-01

INTRODUCTION: Head-to-head comparisons of antipsychotics have predominantly included patients with chronic conditions. The aim of the present study was to compare the efficacy and tolerability of ziprasidone and olanzapine in patients with recent-onset schizophrenia. METHODS: The study was an

Ziprasidone Vs Olanzapine in Recent-Onset Schizophrenia and Schizoaffective Disorder : Results of an 8-Week Double-Blind Randomized Controlled Trial

NARCIS (Netherlands)

Grootens, K. P.; van Veelen, N. M. J.; Peuskens, J.; Sabbe, B. G. C.; Thys, E.; Buitelaar, J. K.; Verkes, R. J.; Kahn, R. S.

Introduction: Head-to-head comparisons of antipsychotics have predominantly included patients with chronic conditions. The aim of the present study was to compare the efficacy and tolerability of ziprasidone and olanzapine in patients with recent-onset schizophrenia. Methods: The study was an

Early onset facioscapulohumeral dystrophy - a systematic review using individual patient data.

Science.gov (United States)

Goselink, Rianne J M; Voermans, Nicol C; Okkersen, Kees; Brouwer, Oebele F; Padberg, George W; Nikolic, Ana; Tupler, Rossella; Dorobek, Malgorzata; Mah, Jean K; van Engelen, Baziel G M; Schreuder, Tim H A; Erasmus, Corrie E

2017-12-01

Infantile or early onset is estimated to occur in around 10% of all facioscapulohumeral dystrophy (FSHD) patients. Although small series of early onset FSHD patients have been reported, comprehensive data on the clinical phenotype is missing. We performed a systematic literature search on the clinical features of early onset FSHD comprising a total of 43 articles with individual data on 227 patients. Additional data from four cohorts was provided by the authors. Mean age at reporting was 18.8 years, and 40% of patients were wheelchair-dependent at that age. Half of the patients had systemic features, including hearing loss (40%), retinal abnormalities (37%) and developmental delay (8%). We found an inverse correlation between repeat size and disease severity, similar to adult-onset FSHD. De novo FSHD1 mutations were more prevalent than in adult-onset FSHD. Compared to adult FSHD, our findings indicate that early onset FSHD is overall characterized by a more severe muscle phenotype and a higher prevalence of systemic features. However, similar as in adults, a significant clinical heterogeneity was observed. Based on this, we consider early onset FSHD to be on the severe end of the FSHD disease spectrum. We found natural history studies and treatment studies to be very scarce in early onset FSHD, therefore longitudinal studies are needed to improve prognostication, clinical management and trial-readiness. Copyright © 2017 Elsevier B.V. All rights reserved.

Intraspinal anomalies in early-onset idiopathic scoliosis.

Science.gov (United States)

Pereira, E A C; Oxenham, M; Lam, K S

2017-06-01

In the United Kingdom, lower incidences of intraspinal abnormalities in patients with early onset idiopathic scoliosis have been observed than in studies in other countries. We aimed to determine the rates of these abnormalities in United Kingdom patients diagnosed with idiopathic scoliosis before the age of 11 years. This retrospective study of patients attending an urban scoliosis clinic identified 71 patients satisfying a criteria of: clinical diagnosis of idiopathic scoliosis; age of onset ten years and 11 months or less; MRI screening for intraspinal abnormalities. United Kingdom census data combined with patient referral data was used to calculate incidence. Mean age at diagnosis was six years with 39 right-sided and 32 left-sided curves. Four patients (5.6%) were found to have intraspinal abnormalities on MRI. These consisted of: two combined Arnold-Chiari type 1 malformations with syrinx; one syrinx with a low lying conus; and one isolated syrinx. Overall annual incidence of early onset idiopathic scoliosis was one out of 182 000 (0.0006%). This study reports the lowest rates to date of intraspinal anomalies in patients with early onset idiopathic scoliosis, adding to knowledge regarding current incidences of these abnormalities as well as any geographical variation in the nature of the disease. Cite this article: Bone Joint J 2017;99-B:829-33. ©2017 The British Editorial Society of Bone & Joint Surgery.

Genetics Home Reference: early-onset glaucoma

Science.gov (United States)

... called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma. Other individuals experience early onset of primary open-angle glaucoma, the most ...

Does early-onset multiple sclerosis differ from adult-onset form in Iranian people

Directory of Open Access Journals (Sweden)

Fereshteh Ashtari

2010-01-01

Full Text Available Background: Few studies have attempted to delineate the clinical profile of multiple Sclerosis (MS among people of Asia. This study sought to identify the characteristics of early-onset Multiple Sclerosis (EOMS comparison to adult-onset form (AOMS in Isfahan, IRAN. Methods: This prospective study was conducted on 104 youths with multiple sclerosis beginning before the age of 16 years and 123 patients with adult-onset multiple sclerosis. Patients were observed for a mean period of 5 years. The common presenting symptoms, MRI finding, course of disease and disability score were compared between the two groups. Results: The mean onset age of disease in youths and adults were 14 ± 1.9 and 27.7 ± 8.06 years, respectively. Female/male ratio was 4.47:1 in EOMS and 3.92:1 in AOMS, this ratio was 7:1 in early childhood MS (≤ 10 year. The most common presenting symptom was optic neuritis in the EOMS group and paresthesia in AOMS. Optic neuritis was common in AOMS too, but brainstem/cerebellar signs were more common in EOMS than AOMS. Seizure occurred more frequently in EOMS than in the AOMS group (12.6% vs. 1.6%, respectively, p < 0.001. MRI showed that brainstem plaques were more prevalent in the EOMS compared with the AOMS group. Conclusions: It was concluded that early-onset MS does not significantly differ from adult form in terms of major clinical manifestation and course of disease, however Seizure is more common in EOMS, and brainstem and cerebellar symptoms as presenting symptom are more common.

Early onset obsessive-compulsive disorder with and without tics.

Science.gov (United States)

de Mathis, Maria Alice; Diniz, Juliana B; Shavitt, Roseli G; Torres, Albina R; Ferrão, Ygor A; Fossaluza, Victor; Pereira, Carlos; Miguel, Eurípedes; do Rosario, Maria Conceicão

2009-07-01

Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations. The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated. Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the "early onset" group (EOG): before 11 years of age, 75 patients had an "intermediate onset" (IOG), and 95 patients were from the "late onset" group (LOG): after 18 years of age. From the 160 EOG, 60 had comorbidity with tic disorders. The diagnostic instruments used were: the Yale-Brown Obsessive Compulsive Scale and the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS), Yale Global Tics Severity Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition. Statistical tests used were: Mann-Whitney, full Bayesian significance test, and logistic regression. The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the "aggression/violence" and "miscellaneous" dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the "contamination/cleaning" dimension. The current results disentangle some of the clinical overlap between early onset OCD with and without tics.

Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis.

Science.gov (United States)

Lee, Hyejoo; Malaspina, Dolores; Ahn, Hongshik; Perrin, Mary; Opler, Mark G; Kleinhaus, Karine; Harlap, Susan; Goetz, Raymond; Antonius, Daniel

2011-05-01

Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia. We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers' age at birth ≥ 35 years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale-Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS. Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early. These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

Early onset marijuana use is associated with learning inefficiencies.

Science.gov (United States)

Schuster, Randi Melissa; Hoeppner, Susanne S; Evins, A Eden; Gilman, Jodi M

2016-05-01

Verbal memory difficulties are the most widely reported and persistent cognitive deficit associated with early onset marijuana use. Yet, it is not known what memory stages are most impaired in those with early marijuana use. Forty-eight young adults, aged 18-25, who used marijuana at least once per week and 48 matched nonusing controls (CON) completed the California Verbal Learning Test, Second Edition (CVLT-II). Marijuana users were stratified by age of initial use: early onset users (EMJ), who started using marijuana at or before age 16 (n = 27), and late onset marijuana user group (LMJ), who started using marijuana after age 16 (n = 21). Outcome variables included trial immediate recall, total learning, clustering strategies (semantic clustering, serial clustering, ratio of semantic to serial clustering, and total number of strategies used), delayed recall, and percent retention. Learning improved with repetition, with no group effect on the learning slope. EMJ learned fewer words overall than LMJ or CON. There was no difference between LMJ and CON in total number of words learned. Reduced overall learning mediated the effect on reduced delayed recall among EMJ, but not CON or LMJ. Learning improved with greater use of semantic versus serial encoding, but this did not vary between groups. EMJ was not related to delayed recall after adjusting for encoding. Young adults reporting early onset marijuana use had learning weaknesses, which accounted for the association between early onset marijuana use and delayed recall. No amnestic effect of marijuana use was observed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Premorbid childhood ocular alignment abnormalities and adult schizophrenia-spectrum disorder

DEFF Research Database (Denmark)

Schiffman, Jason; Maeda, Justin A; Hayashi, Kentaro

2005-01-01

with no parental diagnoses (N=82). In 1992, adult psychiatric outcome data were obtained for 242 of the original subjects. It was found that children who later developed a schizophrenia-spectrum disorder had significantly higher eye exam scale and strabismus scale scores compared to children who developed other...... offspring of parents with other non-psychotic disorder and no mental illness), although the results failed to reach statistical significance. Results from this study suggest a premorbid relation between ocular deficits and schizophrenia-spectrum disorders in childhood prior to onset of psychopathology...... in adulthood. Strabismus may serve as a premorbid marker for spectrum disorders and may have implications for the understanding of early aberrant neurological development related to later schizophrenia-spectrum disorders....

Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

Science.gov (United States)

2017-05-11

Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

Early environmental exposures influence schizophrenia expression even in the presence of strong genetic predisposition.

Science.gov (United States)

Husted, Janice A; Ahmed, Rashid; Chow, Eva W C; Brzustowicz, Linda M; Bassett, Anne S

2012-05-01

There are few studies of environmental factors in familial forms of schizophrenia. We investigated whether childhood adversity or environmental factors were associated with schizophrenia in a familial sample where schizophrenia is associated with the NOSA1P gene. We found that a cumulative adversity index including childhood illness, family instability and cannabis use was significantly associated with narrow schizophrenia, independent of NOSA1P risk genotype, previously measured childhood trauma, covariates and familial clustering (adjusted odds ratio (95% confidence interval)=1.55 (1.01, 2.38)). The results provide further support that early environmental exposures influence schizophrenia expression even in the presence of strong genetic predisposition. Copyright © 2012 Elsevier B.V. All rights reserved.

Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

NARCIS (Netherlands)

Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12

Clinical correlates of first episode early onset psychosis in KwaZulu ...

African Journals Online (AJOL)

Background: The study of first episode early onset psychosis can yield many clues to understanding the early development of psychosis and guide interventions to decrease psychosis risk and improve outcome. The aim of the study was to investigate the socio-demographic profile and clinical correlates in early onset ...

Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

NARCIS (Netherlands)

Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

2006-01-01

Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12

Modeling Deficits From Early Auditory Information Processing to Psychosocial Functioning in Schizophrenia.

Science.gov (United States)

Thomas, Michael L; Green, Michael F; Hellemann, Gerhard; Sugar, Catherine A; Tarasenko, Melissa; Calkins, Monica E; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Nuechterlein, Keith H; Radant, Allen D; Seidman, Larry J; Shiluk, Alexandra L; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Stone, William S; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L; Light, Gregory A

2017-01-01

Neurophysiologic measures of early auditory information processing (EAP) are used as endophenotypes in genomic studies and biomarkers in clinical intervention studies. Research in schizophrenia has established correlations among measures of EAP, cognition, clinical symptoms, and functional outcome. Clarifying these associations by determining the pathways through which deficits in EAP affect functioning would suggest when and where to therapeutically intervene. To characterize the pathways from EAP to outcome and to estimate the extent to which enhancement of basic information processing might improve cognition and psychosocial functioning in schizophrenia. Cross-sectional data were analyzed using structural equation modeling to examine the associations among EAP, cognition, negative symptoms, and functional outcome. Participants were recruited from the community at 5 geographically distributed laboratories as part of the Consortium on the Genetics of Schizophrenia 2 from July 1, 2010, through January 31, 2014. This well-characterized cohort of 1415 patients with schizophrenia underwent EAP, cognitive, and thorough clinical and functional assessment. Mismatch negativity, P3a, and reorienting negativity were used to measure EAP. Cognition was measured by the Letter Number Span test and scales from the California Verbal Learning Test-Second Edition, the Wechsler Memory Scale-Third Edition, and the Penn Computerized Neurocognitive Battery. Negative symptoms were measured by the Scale for the Assessment of Negative Symptoms. Functional outcome was measured by the Role Functioning Scale. Participants included 1415 unrelated outpatients diagnosed with schizophrenia or schizoaffective disorder (mean [SD] age, 46 [11] years; 979 males [69.2%] and 619 white [43.7%]). Early auditory information processing had a direct effect on cognition (β = 0.37, P model in which EAP deficits lead to poor functional outcome via impaired cognition and increased negative symptoms

Early-onset childhood sarcoidosis: a case report

Directory of Open Access Journals (Sweden)

Lai-San Wong

2011-12-01

Full Text Available Sarcoidosis is a multisystemic granulomatous disease of unknown etiology and it most commonly affects young adults. Childhood sarcoidosis is relatively rare; older children usually present a picture similar to that of adults, with frequent hilar lymphadenopathy and pulmonary infiltration. Early-onset (<4 years of age childhood sarcoidosis is a unique disease and has a different presentation. It is characterized by arthritis, uveitis, and cutaneous involvement. The prognosis of early-onset childhood sarcoidosis varies in different studies due to the rarity of the disease. The treatment of choice in systemic involvement of childhood sarcoidosis is corticosteroids. Methotrexate can also be considered in the long-term treatment due to its safety, effectiveness, and steroid-sparing effect in children.

Adjuvant low-frequency rTMS in treating auditory hallucinations in recent-onset schizophrenia: a randomized controlled study investigating the effect of high-frequency priming stimulation.

Science.gov (United States)

Ray, Prasenjit; Sinha, Vinod Kumar; Tikka, Sai Krishna

2015-01-01

Repetitive transcranial magnetic stimulation (rTMS) has been found to be effective in reducing frequency and duration of auditory verbal hallucinations (AVH). Priming stimulation, which involves high-frequency rTMS stimulation followed by low-frequency rTMS, has been shown to markedly enhance the neural response to the low-frequency stimulation train. However, this technique has not been investigated in recent onset schizophrenia patients. The aim of this randomized controlled study was to investigate whether the effects of rTMS on AVH can be enhanced with priming rTMS in recent onset schizophrenia patients. Forty recent onset schizophrenia patients completed the study. Patients were randomized over two groups: one receiving low-frequency rTMS preceded by priming and another receiving low-frequency rTMS without priming. Both treatments were directed at the left temporo-parietal region. The severity of AVH and other psychotic symptoms were assessed with the auditory hallucination subscale (AHRS) of the Psychotic Symptom Rating Scales (PSYRATS), the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression (CGI). We found that all the scores of these ratings significantly reduced over time (i.e. baseline through 1, 2, 4 and 6 weeks) in both the treatment groups. We found no difference between the two groups on all measures, except for significantly greater improvement on loudness of AVH in the group with priming stimulation during the follow-ups (F = 2.72; p low-frequency rTMS alone and high-frequency priming of low-frequency rTMS do not elicit significant differences in treatment of overall psychopathology, particularly AVH when given in recent onset schizophrenia patients. Add on priming however, seems to be particularly better in faster reduction in loudness of AVH.

Late- versus early-onset geriatric depression in a memory research center

Directory of Open Access Journals (Sweden)

Carol Dillon

2009-10-01

Full Text Available Carol Dillon1, Ricardo F Allegri2, Cecilia M Serrano1, Mónica Iturry1, Pablo Salgado1, Frank B Glaser1, Fernando E Taragano21Memory Research Center, Department of Neurology, Hospital General Abel Zubizarreta, GCBA Buenos Aires, Argentina; 2Department of Neuropsychology (SIREN, CEMIC University, Buenos Aires, ArgentinaObjective: To contrast early-onset (<60 years and late-onset (>60 years depression in geriatric patients by evaluating differences in cognition, vascular comorbidity and sociological risk factors. Both patient groups were compared with normal subjects.Materials and methods: We recruited 76 patients with depressive symptoms (37 late onset and 39 early onset and 17 normal controls matched by age and educational level. All subjects were assessed using a semistructured neuropsychiatric interview and an extensive neuropsychological battery. Vascular and sociological risk factors were also evaluated.Results: We found a significant variation in performance between depressive patients and normal controls in most cognitive functions, especially memory (P < 0.0001, semantic fluency (P < 0.0001, verbal fluency, and digit-symbol (P < 0.0001. Late-onset depression patients scored lower and exhibited more severe impairment in memory domains than early-onset depression patients (P < 0.05. Cholesterol levels and marital status were significantly (P < 0.05 different between the depressive groups. Both depressed groups (early- and lateonset were more inactive than controls (P < 0.05; odds ratio: 6.02.Conclusion: Geriatric depression may be a manifestation of brain degeneration, and the initial symptom of a dementia. It is important to consider this in the treatment of patients that exhibit late-onset depressive symptoms.Keywords: early- and late-onset depression, geriatrics, cognition

Suicide in later life : A comparison between cases with early-onset and late-onset depression

NARCIS (Netherlands)

Voshaar, Richard C. Oude; Kapur, Nay; Bickley, Harriet; Williams, Alyson; Purandare, Nitin

Background: Suicide rates are high in elderly people with depressive disorder. We compared behavioural, clinical and care characteristics of depressed elderly patients, aged 60 years and over at the time of death by suicide, with an early-onset depression (EOD, onset before 60 years) with those

Genetic Determinism of Primary Early-Onset Osteoarthritis.

Science.gov (United States)

Aury-Landas, Juliette; Marcelli, Christian; Leclercq, Sylvain; Boumédiene, Karim; Baugé, Catherine

2016-01-01

Osteoarthritis (OA) is the most common joint disease worldwide. A minority of cases correspond to familial presentation characterized by early-onset forms which are genetically heterogeneous. This review brings a new point of view on the molecular basis of OA by focusing on gene mutations causing early-onset OA (EO-OA). Recently, thanks to whole-exome sequencing, a gain-of-function mutation in the TNFRSF11B gene was identified in two distant family members with EO-OA, opening new therapeutic perspectives for OA. Indeed, unraveling the molecular basis of rare Mendelian OA forms will improve our understanding of molecular processes involved in OA pathogenesis and will contribute to better patient diagnosis, management, and therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cognitive correlates of neuroimaging abnormalities in the onset of schizophrenia: A case report

OpenAIRE

Grassi, Silvia; Orsenigo, Giulia; Serati, Marta; Caletti, Elisabetta; Altamura, Alfredo Carlo; Buoli, Massimiliano

2017-01-01

Increasing evidence shows that cognitive impairment and brain abnormalities can appear early in the first episodes of schizophrenia, but it is currently debated how brain changes can correlate with clinical presentation of schizophrenic patients. Of note, this report describes the case of a young schizophrenic male presenting parietal magnetic resonance/positron emission tomography abnormalities and cognitive impairment, documented by specific neuropsychological tests. In our knowledge only f...

Association between GABA-A receptor alpha 5 subunit gene locus and schizophrenia of a later age of onset.

Science.gov (United States)

Papadimitriou, G; Dikeos, D; Daskalopoulou, E; Karadima, G; Avramopoulos, D; Contis, C; Stefanis, C

2001-01-01

Heritability is considered to be a major etiologic factor for schizophrenia. Among the genes considered as candidates for the disease, are those related to GABAergic neurotransmission. Our aim was to test for a genetic association between GABA-A receptor alpha 5 subunit gene locus (GABRA(5)) and schizophrenia. Genotyping of the GABRA(5) locus was performed by the use of a dinucleotide (CA) repeat marker in 46 schizophrenic patients and 50 healthy individuals, all unrelated Greeks. Eight alleles were identified, 276-290 bp long. A nonsignificant excess of the 282-bp allele, which was found in a previous study in a Greek population to be associated with bipolar affective disorder, was observed in schizophrenic patients (33.8 vs. 23.9% in the controls). The frequency of this allele was 43.3% among patients with a later age of onset (over 25 years), differing at a statistically significant level from the controls (p < 0.05). These results suggest that common pathophysiological mechanisms may possibly underlie affective disorders and schizophrenia, at least in a subgroup of patients. Copyright 2001 S. Karger AG, Basel

Abnormal asymmetry of white matter tracts between ventral posterior cingulate cortex and middle temporal gyrus in recent-onset schizophrenia.

Science.gov (United States)

Joo, Sung Woo; Chon, Myong-Wuk; Rathi, Yogesh; Shenton, Martha E; Kubicki, Marek; Lee, Jungsun

2018-02-01

Previous studies have reported abnormalities in the ventral posterior cingulate cortex (vPCC) and middle temporal gyrus (MTG) in schizophrenia patients. However, it remains unclear whether the white matter tracts connecting these structures are impaired in schizophrenia. Our study investigated the integrity of these white matter tracts (vPCC-MTG tract) and their asymmetry (left versus right side) in patients with recent onset schizophrenia. Forty-seven patients and 24 age-and sex-matched healthy controls were enrolled in this study. We extracted left and right vPCC-MTG tract on each side from T1W and diffusion MRI (dMRI) at 3T. We then calculated the asymmetry index of diffusion measures of vPCC-MTG tracts as well as volume and thickness of vPCC and MTG using the formula: 2×(right-left)/(right+left). We compared asymmetry indices between patients and controls and evaluated their correlations with the severity of psychiatric symptoms and cognition in patients using the Positive and Negative Syndrome Scale (PANSS), video-based social cognition scale (VISC) and the Wechsler Adult Intelligence Scale (WAIS-III). Asymmetry of fractional anisotropy (FA) and radial diffusivity (RD) in the vPCC-MTG tract, while present in healthy controls, was not evident in schizophrenia patients. Also, we observed that patients, not healthy controls, had a significant FA decrease and RD increase in the left vPCC-MTG tract. There was no significant association between the asymmetry indices of dMRI measures and IQ, VISC, or PANSS scores in schizophrenia. Disruption of asymmetry of the vPCC-MTG tract in schizophrenia may contribute to the pathophysiology of schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

Schizophrenia: do men and women suffer from the same disease?

Directory of Open Access Journals (Sweden)

Heinz Häfner

2002-01-01

onset - determined by their higher age at onset - and from their socially more adaptive behaviour. The illness behaviour of young men showed a significant excess of socially negative behaviours with an unfavourable impact on their early illness course. In contrast, older men were socially better adjusted. With genetic and morphological findings considered the subtypes of schizophrenia did not differ between men and women. Gender differences in symptomatology and course of schizophrenia obviously are not explained by differences in the disease process. They seem to be determined by a complex pattern of interaction between disease variables, hormonal and behavioural differences and their consequences for age at onset and illness course.

Decision making and executive function in male adolescents with early-onset or adolescence-onset conduct disorder and control subjects.

Science.gov (United States)

Fairchild, Graeme; van Goozen, Stephanie H M; Stollery, Sarah J; Aitken, Michael R F; Savage, Justin; Moore, Simon C; Goodyer, Ian M

2009-07-15

Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD. Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress. Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance. Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

Inflexible Minds : Impaired Attention Switching in Recent-Onset Schizophrenia

NARCIS (Netherlands)

Smid, Henderikus G. O. M.; Martens, Sander; de Witte, Marc R.; Bruggeman, Richard

2013-01-01

Impairment of sustained attention is assumed to be a core cognitive abnormality in schizophrenia. However, this seems inconsistent with a recent hypothesis that in schizophrenia the implementation of selection (i.e., sustained attention) is intact but the control of selection (i.e., switching the

Predictors of suicide attempt in early-onset, first-episode psychoses: a longitudinal 24-month follow-up study.

Science.gov (United States)

Sanchez-Gistau, Vanessa; Baeza, Inmaculada; Arango, Celso; González-Pinto, Ana; de la Serna, Elena; Parellada, Mara; Graell, Motserrat; Paya, Beatriz; Llorente, Cloe; Castro-Fornieles, Josefina

2013-01-01

To study the prevalence of suicide attempts and factors associated with risk for suicide during the first episode of psychosis, and to identify early predictors of suicide attempts over a 24-month follow-up period in an early-onset, first-episode psychosis cohort. 110 subjects in their first episode of psychosis aged between 9 and 17 years were assessed by using the DSM-IV diagnostic interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and a battery of clinical instruments at baseline and at 12 and 24 months. Patients were enrolled in the study from March 2003 through November 2005. Suicide attempts and level of suicidality at each assessment were evaluated by using the Clinical Global Impression for Severity of Suicidality and the Hamilton Depression Rating Scale. Subjects were classified as being at high, low, or no risk of suicide, depending on their scores on certain items of these scales. Clinical associations between the outcome measures high risk for suicide during acute episode and suicide attempts during follow-up were investigated by 2 sets of logistic regression analyses. The 24-month prevalence of suicide attempters was 12.4%. History of suicide attempts prior to psychotic episode (OR = 20.13; 95% CI, 1.83-220.55; P = .01), severe depressive symptoms (OR = 8.78; 95% CI, 1.15-67.11; P = .003), and antidepressant treatment (OR = 15.56; 95% CI, 2.66-90.86; P = .002) were associated with being classified as high suicide risk at baseline. The categorization of high suicide risk at baseline predicted suicide attempts during follow-up (OR = 81.66; 95% CI, 11.61-574.35; P = .000). Suicide is a major concern in early-onset first-episode psychosis. Suicidal behavior and depressive symptoms at psychosis onset are important signs to be aware of to prevent suicide attempts during the early period after first-episode psychosis. © Copyright 2013 Physicians Postgraduate Press, Inc.

Risk Factors for Early-Onset Peritonitis in Southern Chinese Peritoneal Dialysis Patients.

Science.gov (United States)

Wu, Haishan; Huang, Rong; Yi, Chunyan; Wu, Juan; Guo, Qunying; Zhou, Qian; Yu, Xueqing; Yang, Xiao

♦ BACKGROUND: Early peritonitis was confirmed to be associated with a higher risk of early technique failure. However, literature concerning peritonitis within the first 3 months of peritoneal dialysis (PD) initiation is scarce. The present study was to investigate risk factors associated with early-onset peritonitis in PD patients. ♦ METHODS: In this retrospective observational cohort study, all incident PD patients from January 1, 2006, to December 31, 2013, were recruited and followed up until December 31, 2014. According to time-to-first episode of peritonitis, patients were divided into early-onset (≤ 3 months) peritonitis and late-onset (> 3 months) peritonitis. Baseline demographic, clinical, and laboratory data, as well as episodes of peritonitis, were collected. Risk factors associated with early-onset peritonitis were evaluated using logistic regression model. ♦ RESULTS: Of 1,690 patients on PD, 503 (29.8%) developed at least 1 episode of peritonitis and 118 (7.0%) patients presented the first episodes of peritonitis within the first 3 months. A multivariate logistic analysis showed that higher body mass index (BMI) (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01 - 1.15, p = 0.034), hypoalbuminemia (OR 1.75, 95% CI 1.11 - 2.78, p = 0.017), and catheter exit-site infection (OR 4.14, 95% CI 2.45 - 7.00, p peritonitis. Compared to those with late-onset, patients with early-onset peritonitis had a higher overall peritonitis rate (0.76 vs 0.38 per patient-year, p 0.05). ♦ CONCLUSIONS: Higher BMI, hypoalbuminemia, and catheter exit-site infection were the risk factors associated with early-onset peritonitis in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

Early detection and intervention in first-episode schizophrenia

DEFF Research Database (Denmark)

Larsen, Tor Ketil; Friis, Svein; Haahr, U

2001-01-01

OBJECTIVE: To review the literature on early intervention in psychosis and to evaluate relevant studies. METHOD: Early intervention was defined as intervention in the prodromal phase (primary prevention) and intervention after the onset of psychosis, i.e. shortening of duration of untreated psych...

Different Profile of Serum Leptin between Early Onset and Late Onset Preeclampsia

Directory of Open Access Journals (Sweden)

Saeedeh Salimi

2014-01-01

Full Text Available Aim. This study was designed to clarify the role of leptin and adiponectin in preeclampsia (PE pathogenesis and different subtypes of preeclampsia. Method. This case control study was performed in 45 PE patients and 45 healthy controls matched for age, BMI, and ethnicity. Serum leptin and adiponectin levels were determined by enzyme linked immunosorbent assay (ELISA. Results. Maternal serum leptin and adiponectin were significantly higher in PE women than controls. Serum leptin was elevated in early onset preeclampsia (EOPE and late onset preeclampsia (LOPE compared to controls. Among PE patients, serum leptin was higher in EOPE than LOPE women. However, serum adiponectin was not different between EOPE and LOPE women. The serum leptin was significantly higher in severe PE than mild PE. The serum adiponectin was significantly elevated in severe PE compared to controls. Significant positive correlation was observed between leptin and adiponectin and also between leptin and BMI in controls. Moreover significant positive correlation was observed between adiponectin and BMI in PE patients and controls. Conclusion. The present study showed that serum leptin level may play a significant role as a biomarker to differentiate early and late onset PE and also its relation to BMI and severity of disease.

Cortical morphology of adolescents with bipolar disorder and with schizophrenia.

Science.gov (United States)

Janssen, Joost; Alemán-Gómez, Yasser; Schnack, Hugo; Balaban, Evan; Pina-Camacho, Laura; Alfaro-Almagro, Fidel; Castro-Fornieles, Josefina; Otero, Soraya; Baeza, Inmaculada; Moreno, Dolores; Bargalló, Nuria; Parellada, Mara; Arango, Celso; Desco, Manuel

2014-09-01

Recent evidence points to overlapping decreases in cortical thickness and gyrification in the frontal lobe of patients with adult-onset schizophrenia and bipolar disorder with psychotic symptoms, but it is not clear if these findings generalize to patients with a disease onset during adolescence and what may be the mechanisms underlying a decrease in gyrification. This study analyzed cortical morphology using surface-based morphometry in 92 subjects (age range 11-18 years, 52 healthy controls and 40 adolescents with early-onset first-episode psychosis diagnosed with schizophrenia (n=20) or bipolar disorder with psychotic symptoms (n=20) based on a two year clinical follow up). Average lobar cortical thickness, surface area, gyrification index (GI) and sulcal width were compared between groups, and the relationship between the GI and sulcal width was assessed in the patient group. Both patients groups showed decreased cortical thickness and increased sulcal width in the frontal cortex when compared to healthy controls. The schizophrenia subgroup also had increased sulcal width in all other lobes. In the frontal cortex of the combined patient group sulcal width was negatively correlated (r=-0.58, padolescents with schizophrenia and bipolar disorder with psychotic symptoms there is cortical thinning, decreased GI and increased sulcal width of the frontal cortex present at the time of the first psychotic episode. Decreased frontal GI is associated with the widening of the frontal sulci which may reduce sulcal surface area. These results suggest that abnormal growth (or more pronounced shrinkage during adolescence) of the frontal cortex represents a shared endophenotype for psychosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Early-onset Coronary Artery Disease: Clinical and Hereditary Aspects

DEFF Research Database (Denmark)

Christiansen, Morten Krogh

2017-01-01

), and to characterize and quantify subclinical atherosclerosis in their relatives. Furthermore, the aim was to explore the impact of common genetic risk variants on the age of onset, familial clustering and disease severity. In study I, 143 patients with early-onset CAD were recruited from the Western Denmark Heart...

Genome-wide association scan for variants associated with early-onset prostate cancer.

Directory of Open Access Journals (Sweden)

Ethan M Lange

Full Text Available Prostate cancer is the most common non-skin cancer and the second leading cause of cancer related mortality for men in the United States. There is strong empirical and epidemiological evidence supporting a stronger role of genetics in early-onset prostate cancer. We performed a genome-wide association scan for early-onset prostate cancer. Novel aspects of this study include the focus on early-onset disease (defined as men with prostate cancer diagnosed before age 56 years and use of publically available control genotype data from previous genome-wide association studies. We found genome-wide significant (p<5×10(-8 evidence for variants at 8q24 and 11p15 and strong supportive evidence for a number of previously reported loci. We found little evidence for individual or systematic inflated association findings resulting from using public controls, demonstrating the utility of using public control data in large-scale genetic association studies of common variants. Taken together, these results demonstrate the importance of established common genetic variants for early-onset prostate cancer and the power of including early-onset prostate cancer cases in genetic association studies.

Key goals and indicators for successful aging of adults with early-onset disability.

Science.gov (United States)

LaPlante, Mitchell P

2014-01-01

Substantial improvements have occurred in the longevity of several groups of individuals with early-onset disabilities, with many now surviving to advanced ages. This paper estimates the population of adults aging with early-onset disabilities at 12-15 million persons. Key goals for the successful aging of adults with early-onset disabilities are discussed, emphasizing reduction in risks for aging-related chronic disease and secondary conditions, while promoting social participation and independence. However, indicators suggest that elevated risk factors for aging-related chronic diseases, including smoking, obesity, and inactivity, as well as barriers to prevention and the diminished social and economic situation of adults with disabilities are continuing impediments to successful aging that must be addressed. Increased provider awareness that people with early-onset disabilities are aging and can age successfully and the integration of disability and aging services systems are transformative steps that will help adults with early-onset disability to age more successfully. Copyright © 2014 Elsevier Inc. All rights reserved.

Mutations of maturity-onset diabetes of the young (MODY) genes in Thais with early-onset type 2 diabetes mellitus.

Science.gov (United States)

Plengvidhya, Nattachet; Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapaporn; Sriussadaporn, Sutin; Vannaseang, Sathit; Banchuin, Napatawn; Yenchitsomanus, Pa-thai

2009-06-01

Six known genes responsible for maturity-onset diabetes of the young (MODY) were analysed to evaluate the prevalence of their mutations in Thai patients with MODY and early-onset type 2 diabetes. Fifty-one unrelated probands with early-onset type 2 diabetes, 21 of them fitted into classic MODY criteria, were analysed for nucleotide variations in promoters, exons, and exon-intron boundaries of six known MODY genes, including HNF-4alpha, GCK, HNF-1alpha, IPF-1, HNF-1beta, and NeuroD1/beta2, by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method followed by direct DNA sequencing. Missense mutations or mutations located in regulatory region, which were absent in 130 chromosomes of non-diabetic controls, were classified as potentially pathogenic mutations. We found that mutations of the six known MODY genes account for a small proportion of classic MODY (19%) and early-onset type 2 diabetes (10%) in Thais. Five of these mutations are novel including GCK R327H, HNF-1alpha P475L, HNF-1alphaG554fsX556, NeuroD1-1972 G > A and NeuroD1 A322N. Mutations of IPF-1 and HNF-1beta were not identified in the studied probands. Mutations of the six known MODY genes may not be a major cause of MODY and early-onset type 2 diabetes in Thais. Therefore, unidentified genes await discovery in a majority of Thai patients with MODY and early-onset type 2 diabetes.

Genomes of early onset prostate cancer

DEFF Research Database (Denmark)

Weischenfeldt, Joachim; Korbel, Jan O.

2017-01-01

Purpose of review Prostate cancer is a disease of the elderly but a clinically relevant subset occurs early in life. In the current review, we discuss recent findings and the current understanding of the molecular underpinnings associated with early-onset prostate cancer (PCa) and the evidence...... supporting age-specific differences in the cancer genomes. Recent findings Recent surveys of PCa patient cohorts have provided novel age-dependent links between germline and somatic aberrations which points to differences in the molecular cause and treatment options. Summary Identifying the earliest...... receptor pathway....

Auditory change detection in schizophrenia: sources of activity, related neuropsychological function and symptoms in patients with a first episode in adolescence, and patients 14 years after an adolescent illness-onset.

Science.gov (United States)

Oades, Robert D; Wild-Wall, Nele; Juran, Stephanie A; Sachsse, Jan; Oknina, Ljubov B; Röpcke, Bernd

2006-02-08

The event-related brain response mismatch negativity (MMN) registers changes in auditory stimulation with temporal lobe sources reflecting short-term echoic memory and frontal sources a deviance-induced switch in processing. Impairment, controversially present at the onset of schizophrenia, develops rapidly and can remain independent of clinical improvement. We examined the characteristics of the scalp-recorded MMN and related these to tests of short-term memory and set-shifting. We assessed whether the equivalent dipole sources are affected already at illness-onset in adolescence and how these features differ after a 14-year course following an adolescent onset. The strength, latency, orientation and location of frontal and temporal lobe sources of MMN activity early and late in the course of adolescent-onset schizophrenia are analysed and illustrated. MMN, a measure of auditory change-detection, was elicited by short deviant tones in a 3-tone oddball-presentation and recorded from 32 scalp electrodes. Four dipole sources were placed following hypothesis-led calculations using brain electrical source analysis on brain atlas and MR-images. A short neuropsychological test battery was administered. We compared 28 adolescent patients with a first episode of schizophrenia and 18 patients 14 years after diagnosis in adolescence with two age-matched control groups from the community (n = 22 and 18, respectively). MMN peaked earlier in the younger than the older subjects. The amplitude was reduced in patients, especially the younger group, and was here associated with negative symptoms and slow set-shifting. In first-episode patients the temporal lobe sources were more ventral than in controls, while the left cingular and right inferior-mid frontal sources were more caudal. In the older patients the left temporal locus remained ventral (developmental stasis), the right temporal locus extended more antero-laterally (illness progression), and the right frontal source moved

Predictive value of cognition for different domains of outcome in recent-onset schizophrenia.

Science.gov (United States)

Holthausen, Esther A E; Wiersma, Durk; Cahn, Wiepke; Kahn, René S; Dingemans, Peter M; Schene, Aart H; van den Bosch, Robert J

2007-01-15

The aim of this study was to see whether and how cognition predicts outcome in recent-onset schizophrenia in a large range of domains such as course of illness, self-care, interpersonal functioning, vocational functioning and need for care. At inclusion, 115 recent-onset patients were tested on a cognitive battery and 103 patients participated in the follow-up 2 years after inclusion. Differences in outcome between cognitively normal and cognitively impaired patients were also analysed. Cognitive measures at inclusion did not predict number of relapses, activities of daily living and interpersonal functioning. Time in psychosis or in full remission, as well as need for care, were partly predicted by specific cognitive measures. Although statistically significant, the predictive value of cognition with regard to clinical outcome was limited. There was a significant difference between patients with and without cognitive deficits in competitive employment status and vocational functioning. The predictive value of cognition for different social outcome domains varies. It seems that cognition most strongly predicts work performance, where having a cognitive deficit, regardless of the nature of the deficit, acts as a rate-limiting factor.

Correlates and prevalence of hypogonadism in patients with early- and late-onset type 2 diabetes.

Science.gov (United States)

Li, Y; Zhang, M; Liu, X; Cui, W; Rampersad, S; Li, F; Lin, Z; Yang, P; Li, H; Sheng, C; Cheng, X; Qu, S

2017-07-01

This study aims to compare the prevalence of hypogonadism between male patients with early-onset type 2 diabetes mellitus (T2DM) and late-onset type 2 diabetes. A total of 122 male patients with early-onset T2DM (diagnosis age ≤40 years) and 100 male patients with late-onset T2DM (diagnosis age >40 years) were recruited from our in-patient department between 1 January 2013 and 28 December 2015. Serum FSH, LH, testosterone, lipid profile, uric acid, HbA1c, and beta-cell function were determined in blood samples. The diagnosis of hypogonadism was based on the levels of LH, FSH, and total testosterone. The mean onset age was 29.86 ± 6.31 and 54.47 ± 9.97 years old in the early-onset group and late-onset group, respectively. Compared with late-onset T2DM, those with early-onset T2DM had a higher proportion of new-onset diabetes, were more likely to be obese, and had worse glycemic control, lipid control, and lower sex hormone-binding globulin (SHBG). The prevalence of hypogonadism was much higher in the early-onset group than in the late-onset group (48.0% vs. 26.7%, p hypogonadism in the early-onset group and late-onset group were 44.3% and 25.0%, respectively (p hypogonadism was higher in the patients with early-onset T2DM than that of late-onset T2DM. This prevalence might be attributable to greater obesity, worse lipid control, and lower SHBG levels in those patients. © 2017 American Society of Andrology and European Academy of Andrology.

CDKL5 and ARX mutations in males with early-onset epilepsy.

Science.gov (United States)

Mirzaa, Ghayda M; Paciorkowski, Alex R; Marsh, Eric D; Berry-Kravis, Elizabeth M; Medne, Livija; Alkhateeb, Asem; Grix, Art; Wirrell, Elaine C; Powell, Berkley R; Nickels, Katherine C; Burton, Barbara; Paras, Andrea; Kim, Katherine; Chung, Wendy; Dobyns, William B; Das, Soma

2013-05-01

Mutations in CDKL5 and ARX are known causes of early-onset epilepsy and severe developmental delay in males and females. Although numerous males with ARX mutations associated with various phenotypes have been reported in the literature, the majority of CDKL5 mutations have been identified in females with a phenotype characterized by early-onset epilepsy, severe global developmental delay, absent speech, and stereotypic hand movements. To date, only 10 males with CDKL5 mutations have been reported. Our retrospective study reports on the clinical, neuroimaging, and molecular findings of 18 males with early-onset epilepsy caused by either CDKL5 or ARX mutations. These 18 patients include eight new males with CDKL5 mutations and 10 with ARX mutations identified through sequence analysis of 266 and 346 males, respectively, at our molecular diagnostic laboratory. Our large dataset therefore expands on the number of reported males with CDKL5 mutations and highlights that aberrations of CDKL5 and ARX combined are an important consideration in the genetic forms of early-onset epilepsy in boys. Copyright © 2013 Elsevier Inc. All rights reserved.

Identifying aspects of neighbourhood deprivation associated with increased incidence of schizophrenia.

Science.gov (United States)

Bhavsar, Vishal; Boydell, Jane; Murray, Robin; Power, Paddy

2014-06-01

Several studies have found an association between area deprivation and incidence of schizophrenia. However, not all studies have concurred and definitions of deprivation have varied between studies. Relative deprivation and inequality seem to be particularly important, but which aspects of deprivation or how this effect might operate is not known. The Lambeth Early Onset case register is a database of all cases of first episode psychosis aged 16 to 35years from the London Borough of Lambeth, a highly urban area. We identified 405 people with first onset schizophrenia who presented between 2000 and 2007. We calculated the overall incidence of first onset schizophrenia and tested for an association with area-level deprivation, using a multi-domain index of deprivation (IMD 2004). Specific analyses into associations with individual sub-domains of deprivation were then undertaken. Incidence rates, directly standardized for age and gender, were calculated for Lambeth at two geographical levels (small and large neighbourhood level). The Poisson regression model predicting incidence rate ratios for schizophrenia using overall deprivation score was statistically significant at both levels after adjusting for ethnicity, ethnic density, population density and population turnover. The incidence rate ratio for electoral ward deprivation was 1.03 (95% CI=1.004-1.04) and for the super output area deprivation was 1.04 (95% CI=1.02-1.06). The individual domains of crime, employment deprivation and educational deprivation were statistically significant predictors of incidence but, after adjusting for the other domains as well as age, gender, ethnicity and population density, only crime and educational deprivation, remained statistically significant. Low income, poor housing and deprived living environment did not predict incidence. In a highly urban area, an association was found between area-level deprivation and incidence of schizophrenia, after controlling for age, gender

Differences between early and late onset adult depression

DEFF Research Database (Denmark)

Drachmann Bukh, Jens; Bock, Camilla; Vinberg, Maj

2011-01-01

episode depression were systematically recruited. Characteristics including psychiatric co-morbidity, personality disorders and traits, stressful life events prior to onset, family history, and treatment outcome were assessed by structured interviews and compared by chi-square tests for categorical data...... prevalence of co-morbid personality disorders, higher levels of neuroticism, and a lower prevalence of stressful life events preceding onset compared to patients with later age-of-onset. There were no differences in severity of the depressive episode, treatment outcome or family loading of psychiatric......, t-tests for continuous parametric data and Mann-Whitney U-test for continuous nonparametric data. Logistic and multiple regression analyses were used to adjust the analyses for potentially confounding variables. Results: Patients with early onset of depression were characterised by a higher...

Symptom assessment in early psychosis: the use of well-established rating scales in clinical high-risk and recent-onset populations.

Science.gov (United States)

Fulford, Daniel; Pearson, Rahel; Stuart, Barbara K; Fisher, Melissa; Mathalon, Daniel H; Vinogradov, Sophia; Loewy, Rachel L

2014-12-30

Symptom assessment in early psychosis research typically relies on scales validated in chronic schizophrenia samples. Our goal was to inform investigators who are selecting symptom scales for early psychosis research. We described measure characteristics, baseline scores, and scale inter-relationships in clinical-high-risk (CHR) and recent-onset psychotic disorder (RO) samples using the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Scale for the Assessment of Positive Symptoms, and Scale for the Assessment of Negative Symptoms; for the CHR group only, we included the Scale of Prodromal Symptoms. For investigators selecting symptom measures in intervention or longitudinal studies, we also examined the relationship of symptom scales with psychosocial functioning. In both samples, symptom subscales in the same domain, across measures, were moderately to highly intercorrelated. Within all measures, positive symptoms were not correlated with negative symptoms, but disorganized symptoms overlapped with both positive and negative symptoms. Functioning was significantly related to negative and disorganized, but not positive, symptoms in both samples on most measures. Findings suggest strong overlap in symptom severity ratings among the most common scales. In recent-onset samples, each has strengths and weaknesses. In CHR samples, they appear to add little information above and beyond the SOPS. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

Science.gov (United States)

Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer R; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A

2015-09-01

Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Early-Onset Dementia

DEFF Research Database (Denmark)

Konijnenberg, Elles; Fereshtehnejad, Seyed-Mohammad; Kate, Mara Ten

2017-01-01

BACKGROUND: Early-onset dementia (EOD) is a rare condition, with an often atypical clinical presentation, and it may therefore be challenging to diagnose. Specialized memory clinics vary in the type of patients seen, diagnostic procedures applied, and the pharmacological treatment given. The aim...... of this study was to investigate quality-of-care indicators in subjects with EOD from 3 tertiary memory clinics in 3 European countries. METHODS: We included 1325 newly diagnosed EOD patients, ages 65 years or younger, between January 1, 2007 and December 31, 2013, from the Danish Dementia Registry...... (Rigshospitalet, Copenhagen), the Swedish Dementia Registry ("SveDem", Karolinska University Hospital, Stockholm), and the Amsterdam Dementia Cohort (VU University Medical Center). RESULTS: The frequency of EOD among all dementia patients was significantly lower in Copenhagen (410, 20%) and Stockholm (284, 21...

Early and sustained dynamic intervention in schizophrenia

DEFF Research Database (Denmark)

Rosenbaum, Bent; Rosenbaum, Bent

2009-01-01

This paper is based on the Danish National Schizophrenia Project manual for psychodynamic individual psychotherapy with persons in states of schizophrenia. The methods for engaging with and treating a patient with schizophrenia in a supportive, psychodynamic way are described....

Gender differences in first onset Schizophrenia spectrum psychoses.

Science.gov (United States)

Talonen, Sanni; Väänänen, Juha; Kaltiala-Heino, Riittakerttu

2017-02-01

Mental health profiles differ between boys and girls from puberty onwards. It is not known whether differences also extend to symptom presentation in schizophrenia spectrum disorders. It may be that girls and boys are not treated entirely equally by the professionals. To study gender differences in symptom profiles, family adversities, pathway to care, and characteristics of inpatient treatment at the first episode of diagnosed schizophrenia spectrum disorder (F20-29) among adolescents aged 13-17. A retrospective chart review of all (n = 106) consecutive adolescents diagnosed for the first time with schizophrenia spectrum disorder (F20-29) in a specified catchment area. Girls and boys were compared with regard to sociodemographics, pathways to care, living arrangements, symptom profiles, and treatment received. During the study period more adolescent girls (n = 70, 66%) than boys (n = 36, 34%) were diagnosed with schizophrenia spectrum (F20-29) psychoses, most commonly F29. Girls were moreover younger (mean age = 15.46) than boys (mean age = 16.62) at admission. Girls more often displayed mood symptoms and boys aggressive behaviours, alcohol abuse problems, and isolation. Family adversities recorded as current stressors were more numerous among girls. Girls were more likely to be referred to specialized after-care than boys. The gender differences observed in symptoms presentation are reminiscent of differences encountered in the general adolescent population. Prior to transition to psychosis, girls and boys are equally in contact with psychiatric services due to other (possibly prodromal) symptoms/disorders. Family adversities may be more stressful for girls vulnerable to psychosis than to boys.

Early-onset preeclampsia is associated with perinatal mortality and severe neonatal morbidity

NARCIS (Netherlands)

Esch, J.J.A. van; Heijst, A.F. van; Haan, A.F.J. de; Heijden, O.W.H. van der

2017-01-01

OBJECTIVE: To evaluate neonatal outcomes of pregnancies complicated by early-onset preeclampsia (PE) and compare these outcomes to those of gestational age matched neonates born to mothers whose pregnancy was not complicated by early-onset PE. METHODS: We analyzed the outcome in 97 neonates born to

A family affair: brain abnormalities in siblings of patients with schizophrenia

Science.gov (United States)

Hulshoff Pol, Hilleke; Gogtay, Nitin

2013-01-01

Schizophrenia is a severe mental disorder that has a strong genetic basis. Converging evidence suggests that schizophrenia is a progressive neurodevelopmental disorder, with earlier onset cases resulting in more profound brain abnormalities. Siblings of patients with schizophrenia provide an invaluable resource for differentiating between trait and state markers, thus highlighting possible endophenotypes for ongoing research. However, findings from sibling studies have not been systematically put together in a coherent story across the broader age span. We review here the cortical grey matter abnormalities in siblings of patients with schizophrenia from childhood to adulthood, by reviewing sibling studies from both childhood-onset schizophrenia, and the more common adult-onset schizophrenia. When reviewed together, studies suggest that siblings of patients with schizophrenia display significant brain abnormalities that highlight both similarities and differences between the adult and childhood populations, with shared developmental risk patterns, and segregating trajectories. Based on current research it appears that the cortical grey matter abnormalities in siblings are likely to be an age-dependent endophenotype, which normalize by the typical age of onset of schizophrenia unless there has been more genetic or symptom burdening. With increased genetic burdening (e.g. discordant twins of patients) the grey matter abnormalities in (twin) siblings are progressive in adulthood. This synthesis of the literature clarifies the importance of brain plasticity in the pathophysiology of the illness, indicating that probands may lack protective factors critical for healthy development. PMID:23698280

Early Onset Malignancies - Genomic Study of Cancer Disparities

Science.gov (United States)

The Early Onset Malignancies Initiative studies the genomic basis of six cancers that develop at an earlier age, occur in higher rates, and are typically more aggressive in certain minority populations.

[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

Predictors of admission to a high-security hospital of people with intellectual disability with and without schizophrenia.

Science.gov (United States)

Doody, G A; Thomson, L D; Miller, P; Johnstone, E C

2000-04-01

reduction in the number of admissions to high-security hospitals in the UK. In people with comorbid intellectual disability and schizophrenia, males with an early age of onset and no known family history are more likely to require care and treatment in a secure psychiatric setting. Such comorbid subjects may be suffering from a particular malignant form of schizophrenia, manifesting in childhood as cognitive impairment prior to the early onset of psychosis in teenage years.

Cerebellar ataxia of early onset

International Nuclear Information System (INIS)

Yamashita, Sumimasa; Miyake, Shota; Yamada, Michiko; Iwamoto, Hiroko; Yamada, Kazuhiko.

1989-01-01

Eight cases of childhood cerebellar ataxia were reported. All these cases showed chronic cerebellar ataxia with early onset, and the other diseases of cerebellum such as infections, neoplasms and storage diseases were excluded by clinical symptoms and laboratory findings including blood counts, blood chemistry, lactate, pyruvate, ceruloplasmine, urinalysis, serum immunoglobulins, amino acid analysis in blood and urine, CSF analysis, leukocyte lysosomal enzymes, MCV, EMG, EEG and brain X-CT. Two pairs of siblings were included in this study. The clinical diagnosis were cerebellar type (5), spinocerebellar type (1), one Marinesco-Sjoegren syndrome and undetermined type (1). The age of onset was 1 to 5 years. The chief complaint was motor developmental delay in 6 cases; among them 5 patients could walk alone at the ages of 2 to 3 years'. Mental retardation was observed in 7 cases and epilepsy in 2. TRH was effective in 5 cases. The MRI study revealed that the area of medial sagittal slice of the cerebellum was reduced significantly in all cases and also that of pons was reduced in 5 cases. Different from typical adult onset spinocerebellar degenerations, most of the present cases have achieved slow developmental milestones and the clinical course was not progressive. Genetic factors are suspected in the pathogenesis of this disease in some cases. (author)

Trajectories of premorbid childhood and adolescent functioning in schizophrenia-spectrum psychoses: A first-episode study.

Science.gov (United States)

Horton, Leslie E; Tarbox, Sarah I; Olino, Thomas M; Haas, Gretchen L

2015-06-30

Evidence of social and behavioral problems preceding the onset of schizophrenia-spectrum psychoses is consistent with a neurodevelopmental model of these disorders. Here we predict that individuals with a first episode of schizophrenia-spectrum psychoses will evidence one of three patterns of premorbid adjustment: an early deficit, a deteriorating pattern, or adequate or good social adjustment. Participants were 164 (38% female; 31% black) individuals ages 15-50 with a first episode of schizophrenia-spectrum psychoses. Premorbid adjustment was assessed using the Cannon-Spoor Premorbid Adjustment Scale. We compared the fit of a series of growth mixture models to examine premorbid adjustment trajectories, and found the following 3-class model provided the best fit with: a "stable-poor" adjustment class (54%), a "stable-good" adjustment class (39%), and a "deteriorating" adjustment class (7%). Relative to the "stable-good" class, the "stable-poor" class experienced worse negative symptoms at 1-year follow-up, particularly in the social amotivation domain. This represents the first known growth mixture modeling study to examine premorbid functioning patterns in first-episode schizophrenia-spectrum psychoses. Given that the stable-poor adjustment pattern was most prevalent, detection of social and academic maladjustment as early as childhood may help identify people at increased risk for schizophrenia-spectrum psychoses, potentially increasing feasibility of early interventions. Published by Elsevier Ireland Ltd.

Schizophrenia.

Science.gov (United States)

Kahn, René S; Sommer, Iris E; Murray, Robin M; Meyer-Lindenberg, Andreas; Weinberger, Daniel R; Cannon, Tyrone D; O'Donovan, Michael; Correll, Christoph U; Kane, John M; van Os, Jim; Insel, Thomas R

2015-11-12

Schizophrenia is a chronic psychiatric disorder with a heterogeneous genetic and neurobiological background that influences early brain development, and is expressed as a combination of psychotic symptoms - such as hallucinations, delusions and disorganization - and motivational and cognitive dysfunctions. The mean lifetime prevalence of the disorder is just below 1%, but large regional differences in prevalence rates are evident owing to disparities in urbanicity and patterns of immigration. Although gross brain pathology is not a characteristic of schizophrenia, the disorder involves subtle pathological changes in specific neural cell populations and in cell-cell communication. Schizophrenia, as a cognitive and behavioural disorder, is ultimately about how the brain processes information. Indeed, neuroimaging studies have shown that information processing is functionally abnormal in patients with first-episode and chronic schizophrenia. Although pharmacological treatments for schizophrenia can relieve psychotic symptoms, such drugs generally do not lead to substantial improvements in social, cognitive and occupational functioning. Psychosocial interventions such as cognitive-behavioural therapy, cognitive remediation and supported education and employment have added treatment value, but are inconsistently applied. Given that schizophrenia starts many years before a diagnosis is typically made, the identification of individuals at risk and those in the early phases of the disorder, and the exploration of preventive approaches are crucial.

Awareness of early warning signs and help-seeking behaviours among patients with schizophrenia who utilize social rehabilitation facilities in Japan.

Science.gov (United States)

Koichi, R; Miyamoto, Y; Akiyama, M; Takamura, S

2009-10-01

The purpose of this study was to examine the relationship between early warning signs (EWS) and early help-seeking behaviours (HSB) and to identify the characteristics of patients with schizophrenia who sought early help. A cross-sectional study was carried out in 2004 using a self-reported questionnaire. Participants were recruited from social rehabilitation facilities for the mentally ill; 224 subjects participated, 170 of whom had schizophrenia. The survey included questions about demographic characteristics, self-care behaviours (HSB, recognition of EWS and others) and current service utilization and satisfaction. Fisher's exact test and Student's t-test were used to compare the characteristics of study participants. Logistic regression analyses were used to examine the association between recognition of EWS and early HSB.We found that 96 (56.5%) of 170 patients with schizophrenia reported at least one occasion of early HSB during their deterioration. Early HSB were related to the following factors: recognition of EWS, consultation with non-professional and professional support persons during deterioration, consulting with public mental health workers and living with family. Care and support should be offered to patients with schizophrenia to enable them to recognize their own mental deterioration.

Effects of the family schizophrenia psychoeducation program for individuals with recent onset schizophrenia in Viet Nam.

Science.gov (United States)

Ngoc, T N; Weiss, B; Trung, L T

2016-08-01

Although psychoeducation has been found effective for improving the life functioning of patients with schizophrenia in high income countries, there have been relatively few studies of schizophrenia psychoeducation adapted for low and middle-income countries (LMIC), particularly in Southeast Asia. The present study assessed effects of the Family Schizophrenia Psychoeducation Program (FSPP) among Vietnamese patients and their families on the patients' (1) quality of life and (2) medication non-compliance, and the family and patients' (3) stigma towards schizophrenia, and (4) consumer satisfaction. This intervention study involved 59 patients, and their families, from the Da Nang Psychiatric Hospital, randomly assigned to treatment (n=30) or control (n=29) conditions. Control subjects received services as usual (antipsychotic medication); treatment group subjects received the FSPP as well. Blind-rater assessments were conducted at T1 immediately after project enrollment (prior to participating in the FSPP) and at T2 six months later. There were significant treatment effects on: (1) quality of life, (2) stigma, (3) medication compliance, and (4) consumer satisfaction, with all effects favoring the treatment group. Effect sizes were moderate to large. This psychoeducation program appears to reduce stigma, improve quality of life and medication compliance, and increase consumer satisfaction of Vietnamese patients with schizophrenia and their families, beyond the effects of antipsychotic medication. It involves relatively little cost, and it may be useful for it or equivalent programs to be implemented in other hospitals in Viet Nam, and potentially other low-income Asian countries to improve the lives of patients with schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Using virtual reality to assess theory of mind subprocesses and error types in early and chronic schizophrenia.

Science.gov (United States)

Canty, Allana L; Neumann, David L; Shum, David H K

2017-12-01

Individuals with schizophrenia often demonstrate theory of mind (ToM) impairment relative to healthy adults. However, the exact nature of this impairment (first- vs. second-order ToM and cognitive vs. affective ToM) and the extent to which ToM abilities deteriorate with illness chronicity is unclear. Furthermore, little is known about the relationships between clinical symptoms and ToM error types (overmentalising, reduced mentalising and no ToM) in early and chronic schizophrenia. This study examined the nature and types of ToM impairment in individuals with early ( n  = 26) and chronic schizophrenia ( n  = 32) using a novel virtual reality task. Clinical participants and demographically-matched controls were administered the Virtual Assessment of Mentalising Ability, which provides indices of first- and second-order cognitive and affective ToM, and quantifies three different types of mentalising errors (viz., overmentalising, reduced mentalising, and no ToM). Individuals with early schizophrenia performed significantly poorer than healthy controls on first-order affective and second-order cognitive and affective ToM, but significantly higher than individuals with chronic schizophrenia on all ToM subscales. Whereas a lack of mental state concept was associated with negative symptoms, overmentalising was associated with positive symptoms. These findings suggest that ToM abilities selectively deteriorate with illness chronicity and error types are related to these individuals' presenting symptomology. An implication of the findings is that social-cognitive interventions for schizophrenia need to consider the nature, time course and symptomatology of the presenting patient.

Toxoplasma gondii as a Risk Factor for Early-Onset Schizophrenia: Analysis of Filter Paper Blood Samples Obtained at Birth

DEFF Research Database (Denmark)

Mortensen, Preben Bo; Nørgaard-Pedersen, Bent; Waltoft, Berit Lindum

2007-01-01

BACKGROUND: Infections during fetal life or neonatal period, including infections with Toxoplasma gondii, may be associated with a risk for schizophrenia and other mental disorders. The objectives of this study were to study the association between serological markers for maternal and neonatal....... Patients included persons born in Denmark in 1981 or later followed up through 1999 with respect to inpatient or outpatient treatment for schizophrenia or related disorders (ICD-10 F2) or affective disorders (ICD-10 F3). RESULTS: Toxoplasma gondii immunoglobulin G (IgG) levels corresponding to the upper...

Toxoplasma gondii as a Risk Factor for Early-Onset Schizophrenia: Analysis of Filter Paper Blood Samples Obtained at Birth

DEFF Research Database (Denmark)

Mortensen, Preben Bo; Nørgaard-Pedersen, Bent; Waltoft, Berit Lindum

2006-01-01

BACKGROUND: Infections during fetal life or neonatal period, including infections with Toxoplasma gondii, may be associated with a risk for schizophrenia and other mental disorders. The objectives of this study were to study the association between serological markers for maternal and neonatal....... Patients included persons born in Denmark in 1981 or later followed up through 1999 with respect to inpatient or outpatient treatment for schizophrenia or related disorders (ICD-10 F2) or affective disorders (ICD-10 F3). RESULTS: Toxoplasma gondii immunoglobulin G (IgG) levels corresponding to the upper...

Risk factors for development of schizophrenia

OpenAIRE

Dunglová, Eva

2013-01-01

Schizophrenia is a severe disease. There is a complicity of genetic and environmental factors in schizophrenia onset. Factors with probable influence on development of schizophrenia are rate of urbanization, geographic location, migration, month of birth, maternal nutrition during pregnancy and birth complications, stress during pregnancy, length of lactation period, prenatal and postnatal infection exposure, exposure to a cat during childhood or cannabis abuse. Until now the information on t...

Common variants at five new loci associated with early-onset inflammatory bowel disease.

Science.gov (United States)

Imielinski, Marcin; Baldassano, Robert N; Griffiths, Anne; Russell, Richard K; Annese, Vito; Dubinsky, Marla; Kugathasan, Subra; Bradfield, Jonathan P; Walters, Thomas D; Sleiman, Patrick; Kim, Cecilia E; Muise, Aleixo; Wang, Kai; Glessner, Joseph T; Saeed, Shehzad; Zhang, Haitao; Frackelton, Edward C; Hou, Cuiping; Flory, James H; Otieno, George; Chiavacci, Rosetta M; Grundmeier, Robert; Castro, Massimo; Latiano, Anna; Dallapiccola, Bruno; Stempak, Joanne; Abrams, Debra J; Taylor, Kent; McGovern, Dermot; Silber, Gary; Wrobel, Iwona; Quiros, Antonio; Barrett, Jeffrey C; Hansoul, Sarah; Nicolae, Dan L; Cho, Judy H; Duerr, Richard H; Rioux, John D; Brant, Steven R; Silverberg, Mark S; Taylor, Kent D; Barmuda, M Michael; Bitton, Alain; Dassopoulos, Themistocles; Datta, Lisa Wu; Green, Todd; Griffiths, Anne M; Kistner, Emily O; Murtha, Michael T; Regueiro, Miguel D; Rotter, Jerome I; Schumm, L Philip; Steinhart, A Hillary; Targan, Stephen R; Xavier, Ramnik J; Libioulle, Cécile; Sandor, Cynthia; Lathrop, Mark; Belaiche, Jacques; Dewit, Olivier; Gut, Ivo; Heath, Simon; Laukens, Debby; Mni, Myriam; Rutgeerts, Paul; Van Gossum, André; Zelenika, Diana; Franchimont, Denis; Hugot, J P; de Vos, Martine; Vermeire, Severine; Louis, Edouard; Cardon, Lon R; Anderson, Carl A; Drummond, Hazel; Nimmo, Elaine; Ahmad, Tariq; Prescott, Natalie J; Onnie, Clive M; Fisher, Sheila A; Marchini, Jonathan; Ghori, Jilur; Bumpstead, Suzannah; Gwillam, Rhian; Tremelling, Mark; Delukas, Panos; Mansfield, John; Jewell, Derek; Satsangi, Jack; Mathew, Christopher G; Parkes, Miles; Georges, Michel; Daly, Mark J; Heyman, Melvin B; Ferry, George D; Kirschner, Barbara; Lee, Jessica; Essers, Jonah; Grand, Richard; Stephens, Michael; Levine, Arie; Piccoli, David; Van Limbergen, John; Cucchiara, Salvatore; Monos, Dimitri S; Guthery, Stephen L; Denson, Lee; Wilson, David C; Grant, Straun F A; Daly, Mark; Silverberg, Mark S; Satsangi, Jack; Hakonarson, Hakon

2009-12-01

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

Verbal and Academic Skills in Children with Early-Onset Type 1 Diabetes

Science.gov (United States)

Hannonen, Riitta; Komulainen, Jorma; Eklund, Kenneth; Tolvanen, Asko; Riikonen, Raili; Ahonen, Timo

2010-01-01

Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

Recent advances in understanding schizophrenia.

Science.gov (United States)

Haller, Chiara S; Padmanabhan, Jaya L; Lizano, Paulo; Torous, John; Keshavan, Matcheri

2014-01-01

Schizophrenia is a highly disabling disorder whose causes remain to be better understood, and treatments have to be improved. However, several recent advances have been made in diagnosis, etiopathology, and treatment. Whereas reliability of diagnosis has improved with operational criteria, including Diagnostic and Statistical Manual of Mental Disorders, (DSM) Fifth Edition, validity of the disease boundaries remains unclear because of substantive overlaps with other psychotic disorders. Recent emphasis on dimensional approaches and translational bio-behavioral research domain criteria may eventually help move toward a neuroscience-based definition of schizophrenia. The etiology of schizophrenia is now thought to be multifactorial, with multiple small-effect and fewer large-effect susceptibility genes interacting with several environmental factors. These factors may lead to developmentally mediated alterations in neuroplasticity, manifesting in a cascade of neurotransmitter and circuit dysfunctions and impaired connectivity with an onset around early adolescence. Such etiopathological understanding has motivated a renewed search for novel pharmacological as well as psychotherapeutic targets. Addressing the core features of the illness, such as cognitive deficits and negative symptoms, and developing hypothesis-driven early interventions and preventive strategies are high-priority goals for the field. Schizophrenia is a severe, chronic mental disorder and is among the most disabling disorders in all of medicine. It is estimated by the National Institute of Mental Health (NIMH) that 2.4 million people over the age of 18 in the US suffer from schizophrenia. This illness typically begins in adolescence and derails the formative goals of school, family, and work, leading to considerable suffering and disability and reduced life expectancy by about 20 years. Treatment outcomes are variable, and some people are successfully treated and reintegrated (i.e. go back to work

Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia.

Science.gov (United States)

Kesby, James P; Cui, Xiaoying; Burne, Thomas H J; Eyles, Darryl W

2013-01-01

Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesized that abnormal DA signaling in the adult patient may result from altered DA signaling during fetal brain development. Environmental and genetic risk factors can be modeled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the etiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD) deficiency. DVD-deficient adult rats display an altered behavioral profile in response to DA releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters DA metabolism in the developing brain. We speculate such alterations in fetal brain development may change the trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in DA ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia

Directory of Open Access Journals (Sweden)

James P. Kesby

2013-07-01

Full Text Available Schizophrenia is a heterogeneous group of disorders with unknown aetiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesised that abnormal dopamine signalling in the adult patient may result from altered dopamine signalling during foetal brain development. Environmental and genetic risk factors can be modelled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the aetiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD deficiency. DVD-deficient adult rats display an altered behavioural profile in response to dopamine releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters dopamine metabolism in the developing brain. We speculate such alterations in foetal brain development may change the trajectory of dopamine neuron ontogeny to induce the behavioural abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in dopamine ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

Validation study of the early onset schizophrenia diagnosis in the Danish Psychiatric Central Research Register

DEFF Research Database (Denmark)

Vernal, Ditte Lammers; Stenstrøm, Anne Dorte; Staal, Nina

2018-01-01

on classification. Compared to diagnoses made in outpatient settings, EOS diagnoses during hospitalizations were more likely to be valid and had fewer registration errors. Diagnosed in inpatient settings, EOS diagnoses are reliable and valid for register-based research. Schizophrenia diagnosed in children...... and adolescents in outpatient settings were found to have a high number of false-positives, both due to registration errors and diagnostic practice. Utilizing this knowledge, it is possible to reduce the number of false-positives in register-based research of EOS....

Neuropsychological dysfunction in adults with early-onset obsessive-compulsive disorder: the search for a cognitive endophenotype

Directory of Open Access Journals (Sweden)

Jie Zhang

2015-06-01

Full Text Available Objective:Evidence suggests that early-onset obsessive-compulsive disorder (OCD is an etiologically distinct subtype of OCD. The objective of the present work was to search for neurocognitive endophenotypes of early-onset OCD based on assessments of attention, memory, and executive function in patients with the disorder and their unaffected siblings.Methods:We compared the performance of 40 adult patients with early-onset OCD, 40 of their unaffected siblings, and 40 unrelated healthy controls on a neuropsychological battery designed for this study. We searched for associations among test performance, demographic variables (age, sex and years of education and clinical symptoms of early-onset OCD.Results:Patients performed significantly worse than healthy controls on the Tower of Hanoi, and the Stroop and Wisconsin tests, indicating impairments in planning, mental flexibility and inhibitory control. The performance of the unaffected first-degree siblings of patients with early-onset OCD on the Stroop and Wisconsin tests also differed from that of healthy controls. Symptom severity in early-onset OCD was strongly correlated with performance on the Tower of Hanoi.Conclusions:Our findings support the existence of specific executive function deficits in patients with early-onset OCD. Relatives presented an intermediate phenotype between patients and controls, suggesting that executive functions such as mental flexibility and response inhibition may be considered candidate endophenotypes of early-onset OCD.

How genes and environmental factors determine the different neurodevelopmental trajectories of schizophrenia and bipolar disorder.

Science.gov (United States)

Demjaha, Arsime; MacCabe, James H; Murray, Robin M

2012-03-01

The debate endures as to whether schizophrenia and bipolar disorder are separate entities or different manifestations of a single underlying pathological process. Here, we argue that this sterile argument obscures the fact that the truth lies somewhere in between. Thus, recent studies support a model whereby, on a background of some shared genetic liability for both disorders, patients with schizophrenia have been subject to additional genetic and/or environmental factors that impair neurodevelopment; for example, copy number variants and obstetric complications are associated with schizophrenia but not with bipolar disorder. As a result, children destined to develop schizophrenia show an excess of neuromotor delays and cognitive difficulties while those who later develop bipolar disorder perform at least as well as the general population. In keeping with this model, cognitive impairments and brain structural abnormalities are present at first onset of schizophrenia but not in the early stages of bipolar disorder. However, with repeated episodes of illness, cognitive and brain structural abnormalities accumulate in both schizophrenia and bipolar disorder, thus clouding the picture.

Auditory change detection in schizophrenia: sources of activity, related neuropsychological function and symptoms in patients with a first episode in adolescence, and patients 14 years after an adolescent illness-onset

Directory of Open Access Journals (Sweden)

Sachsse Jan

2006-02-01

Full Text Available Abstract Background The event-related brain response mismatch negativity (MMN registers changes in auditory stimulation with temporal lobe sources reflecting short-term echoic memory and frontal sources a deviance-induced switch in processing. Impairment, controversially present at the onset of schizophrenia, develops rapidly and can remain independent of clinical improvement. We examined the characteristics of the scalp-recorded MMN and related these to tests of short-term memory and set-shifting. We assessed whether the equivalent dipole sources are affected already at illness-onset in adolescence and how these features differ after a 14-year course following an adolescent onset. The strength, latency, orientation and location of frontal and temporal lobe sources of MMN activity early and late in the course of adolescent-onset schizophrenia are analysed and illustrated. Methods MMN, a measure of auditory change-detection, was elicited by short deviant tones in a 3-tone oddball-presentation and recorded from 32 scalp electrodes. Four dipole sources were placed following hypothesis-led calculations using brain electrical source analysis on brain atlas and MR-images. A short neuropsychological test battery was administered. We compared 28 adolescent patients with a first episode of schizophrenia and 18 patients 14 years after diagnosis in adolescence with two age-matched control groups from the community (n = 22 and 18, respectively. Results MMN peaked earlier in the younger than the older subjects. The amplitude was reduced in patients, especially the younger group, and was here associated with negative symptoms and slow set-shifting. In first-episode patients the temporal lobe sources were more ventral than in controls, while the left cingular and right inferior-mid frontal sources were more caudal. In the older patients the left temporal locus remained ventral (developmental stasis, the right temporal locus extended more antero

Adult-onset offenders: Is a tailored theory warranted?

Science.gov (United States)

Beckley, Amber L.; Caspi, Avshalom; Harrington, Honalee; Houts, Renate M.; Mcgee, Tara Renae; Morgan, Nick; Schroeder, Felix; Ramrakha, Sandhya; Poulton, Richie; Moffitt, Terrie E.

2016-01-01

Purpose To describe official adult-onset offenders, investigate their antisocial histories and test hypotheses about their origins. Methods We defined adult-onset offenders among 931 Dunedin Study members followed to age 38, using criminal-court conviction records. Results Official adult-onset offenders were 14% of men, and 32% of convicted men, but accounted for only 15% of convictions. As anticipated by developmental theories emphasizing early-life influences on crime, adult-onset offenders’ histories of antisocial behavior spanned back to childhood. Relative to juvenile-offenders, during adolescence they had fewer delinquent peers and were more socially inhibited, which may have protected them from conviction. As anticipated by theories emphasizing the importance of situational influences on offending, adult-onset offenders, relative to non-offenders, during adulthood more often had schizophrenia, bipolar disorder, and alcohol-dependence, had weaker social bonds, anticipated fewer informal sanctions, and self-reported more offenses. Contrary to some expectations, adult-onset offenders did not have high IQ or high socioeconomic-status families protecting them from juvenile conviction. Conclusions A tailored theory for adult-onset offenders is unwarranted because few people begin crime de novo as adults. Official adult-onset offenders fall on a continuum of crime and its correlates, between official non-offenders and official juvenile-onset offenders. Existing theories can accommodate adult-onset offenders. PMID:27134318

Genetics Home Reference: inclusion body myopathy with early-onset Paget disease and frontotemporal dementia

Science.gov (United States)

... Share: Email Facebook Twitter Home Health Conditions IBMPFD Inclusion body myopathy with early-onset Paget disease and ... Javascript to view the expand/collapse boxes. Description Inclusion body myopathy with early-onset Paget disease and ...

Early-Onset Physical Frailty in Adults with Diabesity and Peripheral Neuropathy.

Science.gov (United States)

Tuttle, Lori J; Bittel, Daniel C; Bittel, Adam J; Sinacore, David R

2017-12-07

Diabesity (obesity and diabetes mellitus) has been identified as a potential contributor to early-onset frailty. Impairments contributing to early onset of physical frailty in this population are not well understood, and there is little evidence of the impact of peripheral neuropathy on frailty. The purpose of this study was to determine impairments that contribute to early-onset physical frailty in individuals with diabesity and peripheral neuropathy. We studied 105 participants, 82 with diabesity and peripheral neuropathy (57 years of age, body mass index [BMI] 31 kg/m 2 ); 13 with diabesity only (53 years of age, BMI 34 kg/m 2 ) and 10 obese controls (67 years of age, BMI 32 kg/m 2 ). Peripheral neuropathy was determined using Semmes Weinstein monofilaments; physical frailty was classified using the 9-item, modified Physical Performance Test; and knee extension and ankle plantarflexion peak torques were measured using isokinetic dynamometry. Participants with diabesity and peripheral neuropathy were 7.4 times more likely to be classified as physically frail. Impairments in lower-extremity function were associated with classification of frailty. Individuals with diabesity and peripheral neuropathy are particularly likely to be classified as frail. Earlier identification and interventions aimed at improving lower-extremity function may be important to mitigate the early-onset functional decline. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Risk for schizophrenia and schizophrenia-like psychosis among patients with epilepsy: population based cohort study

DEFF Research Database (Denmark)

Qin, Ping; Xu, Huylan; Laursen, Thomas Munk

2005-01-01

.20) in people with a history of epilepsy. The effect of epilepsy was the same in men and in women and increased with age. Family history of psychosis and a family history of epilepsy were significant risk factors for schizophrenia and schizophrenia-like psychosis, and the effect of epilepsy, both in cases......OBJECTIVES: To investigate whether age at onset of epilepsy, type of epilepsy, family history of psychosis, or family history of epilepsy affect the risk of schizophrenia or schizophrenia-like psychosis among patients with epilepsy. DESIGN: Comparison of population based data. SETTING: Danish...... and families, was greater among people with no family history of psychosis. In addition, the increased risk for schizophrenia or schizophrenia-like psychosis did not differ by type of epilepsy but increased with increasing number of admissions to hospital and, particularly, was significantly greater for people...

Early-onset Hirayama disease in a female

Directory of Open Access Journals (Sweden)

Matthias Baumann

2017-01-01

Full Text Available Objectives: Hirayama disease is a rare myelopathy, occurring predominantly in males with onset in the teens. Methods and results: Here, we report a young female patient who developed the first signs of Hirayama disease at 10.5 years of age. Prior to onset, she had experienced a growth spurt and grew about 8 cm. The disease progressed over 3 years and the typical clinical, electrophysiological, and neuroimaging signs of Hirayama disease were found. After this period and achievement of her final height, no further progression was noticed. Conclusions: This case highlights that pediatric neurologists should be aware of Hirayama disease, which can also occur in girls in early adolescence.

Neonatal stress-induced affective changes in adolescent Wistar rats: early signs of schizophrenia-like behavior

Directory of Open Access Journals (Sweden)

Carlos Eduardo Neves Girardi

2014-09-01

Full Text Available Psychiatric disorders are multifactorial diseases with etiology that may involve genetic factors, early life environment and stressful life events. The neurodevelopmental hypothesis of schizophrenia is based on a wealth of data on increased vulnerability in individuals exposed to insults during the perinatal period. Maternal deprivation disinhibits the adrenocortical response to stress in neonatal rats and has been used as an animal model of schizophrenia. To test if long-term affective consequences of early life stress were influenced by maternal presence, we submitted 10-day old rats, either deprived (for 22 h or not from their dams, to a stress challenge (i.p. saline injection. Corticosterone plasma levels were measured 2 h after the challenge, whereas another subgroup was assessed for behavior in the open field, elevated plus maze, social investigation and the negative contrast sucrose consumption test in adolescence (postnatal day 45. Maternally deprived rats exhibited increased plasma corticosterone levels which were higher in maternally deprived and stress challenged pups. Social investigation was impaired in maternally deprived rats only, while saline injection, independently of maternal deprivation, was associated with increased anxiety-like behavior in the elevated plus maze and an impaired intake decrement in the negative sucrose contrast. In the open field, center exploration was reduced in all maternally-deprived adolescents and in control rats challenged with saline injection. The most striking finding was that exposure to a stressful stimulus per se, regardless of maternal deprivation, was linked to differential emotional consequences. We therefore propose that besides being a well-known and validated model of schizophrenia in adult rats, the maternal deprivation paradigm could be extended to model early signs of psychiatric dysfunction, and would particularly be a useful tool to detect early signs that resemble schizophrenia.

GRIN1 Mutations in Early-Onset Epileptic Encephalopathy

Directory of Open Access Journals (Sweden)

Wenjuan Chen

2015-06-01

Full Text Available Investigators from Yokohama City University and other medical centers in Israel and Japan reported mutations on N-methyl-D-aspartate (NMDA receptors subunit GRIN1 (GluN1 identified in patients with nonsyndromic intellectual disability and early-onset epileptic encephalopathy.

Motivational deficits in early schizophrenia: prevalent, persistent, and key determinants of functional outcome.

Science.gov (United States)

Fervaha, Gagan; Foussias, George; Agid, Ofer; Remington, Gary

2015-08-01

Negative symptoms, in particular motivational deficits, are reported as impediments to functional recovery in patients with schizophrenia. This study examined the prevalence of motivational deficits in patients early in the illness, and the impact these deficits have on community functioning. Patients with schizophrenia between the ages of 18 and 35years, and within 5years of initiating antipsychotic treatment were included in the present investigation (N=166). The impact of motivation and cognition on concurrent and longitudinal functioning was evaluated. Motivational impairments were found in more than 75% of participants, and were not associated with receipt of social support. These deficits served as the most robust and reliable predictor of functional outcome, while neurocognition demonstrated significantly weaker associations with outcome. When considered together, motivational deficits demonstrated a reliable link with concurrent and longitudinal functioning, with cognition not offering any independent predictive value. Moreover, motivation was found to mediate the relationship between cognition and outcome. Changes in motivation were linked to changes in functioning; however, this was not the case for changes in cognitive performance. Motivation emerged as a significant predictor of functioning even after selected demographic and clinical characteristics (e.g., positive symptoms) were accounted for. These data indicate that motivational deficits are prevalent in patients with schizophrenia, even in the early stages of the illness, and these deficits stand as one of the most robust barriers to people with schizophrenia achieving functional recovery. Greater understanding of the mechanisms underlying these deficits is critical to effective treatment innovation. Copyright © 2015 Elsevier B.V. All rights reserved.

Early- versus Late-Onset Alzheimer’s Disease—Differences in Functional Impairment.

OpenAIRE

Wattmo, Carina; Wallin, Åsa

2016-01-01

Background: Persons with clinical onset of Alzheimer’s disease (AD) before 65 years of age are diagnosed with early-onset AD (EOAD). The prevalence of EOAD is low, but varies among studies from 6% to 16%. Most individuals with EOAD are still working, have an active social life, and might have children living at home. Therefore, the consequences of being diagnosed early with a disease that implies progressive deterioration of cognitive performance and activities of daily living (ADL), and pers...

Screening and Treatment for Early-Onset Gestational Diabetes Mellitus: a Systematic Review and Meta-analysis.

Science.gov (United States)

Immanuel, Jincy; Simmons, David

2017-10-02

We conducted a systematic review to evaluate the current evidence for screening and treatment for early-onset gestational diabetes mellitus (GDM) RECENT FINDINGS: Many of the women with early GDM in the first trimester do not have evidence of hyperglycemia at 24-28 weeks' gestation. A high proportion (15-70%) of women with GDM can be detected early in pregnancy depending on the setting, criteria used and screening strategy. However, there remains no good evidence for any of the diagnostic criteria for early-onset GDM. In a meta-analysis of 13 cohort studies, perinatal mortality (relative risk (RR) 3.58 [1.91, 6.71]), neonatal hypoglycemia (RR 1.61 [1.02, 2.55]), and insulin use (RR 1.71 [1.45, 2.03]) were greater among early-onset GDM women compared to late-onset GDM women, despite treatment. Considering the high likelihood of benefit from treatment, there is an urgent need for randomized controlled trials that investigate any benefits and possible harms of treatment of early-onset GDM.

Mothers' experience of caring for a child with early onset scoliosis: A qualitative descriptive study.

Science.gov (United States)

Lauder, Bonnie; Sinclair, Peter M; Maguire, Jane

2018-04-01

This study aimed to identify and describe the experience of parents of children diagnosed with early onset scoliosis living in Australia. Chronic childhood disease has a major impact on health-related quality of life. Caring for a child with a chronic illness is well documented but the specific experiences of parents who care for children with early onset scoliosis, a rare but devastating illness, has not been explored. Numerous studies have described the interrelated psychological, financial, social, physical and logistical factors that impact the experience of the caregiver role with various diseases, but in the case of early onset scoliosis, limited studies have been conducted about the parental experience. A qualitative descriptive design was used. A snowball sampling technique assisted in the recruitment. Parents invited to the study included mothers, fathers and guardians. Data were collected through semistructured interviews and transcribed verbatim. Transcripts were analysed thematically. Data collection complied with the Consolidated criteria for reporting qualitative research guidelines. Twelve mothers of children with early onset scoliosis were interviewed, as only mothers consented to participate. Four major themes emerged: emotional rollercoaster ride, a lack of resources, money talks and pervasive burden. Factors that impacted on the participants' ability to confront, manage and endure caring for a child with early onset scoliosis emerged from the data. The findings suggest there are multiple factors that influence the experience of mothers' caring for a child with early onset scoliosis. The recognition and appropriate management of these factors by healthcare professionals have the potential to improve the quality of life of parents who care for a child with early onset scoliosis. Healthcare professionals have first-line contact with parents of children with early onset scoliosis and are well placed to provide parents with evidence-based education

Imaging Frontostriatal Function in Ultra-High-Risk, Early, and Chronic Schizophrenia During Executive Processing

Science.gov (United States)

Morey, Rajendra A.; Inan, Seniha; Mitchell, Teresa V.; Perkins, Diana O.; Lieberman, Jeffrey A.; Belger, Aysenil

2009-01-01

Context Individuals experiencing prodromal symptoms of schizophrenia (ultra-high-risk group) demonstrate impaired performance on tasks of executive function, attention, and working memory. The neurobiological underpinnings of such executive deficits in ultra-high-risk individuals remains unclear. Objective We assessed frontal and striatal functions during a visual oddball continuous performance task, in ultra-high-risk, early, and chronic schizophrenic patients with the use of functional magnetic resonance imaging. Design Cross-sectional case-control design. Setting Community; outpatient clinic. Patients Fifty-two individuals (control, n = 16; ultra-high risk, n = 10; early, n = 15; chronic, n = 11) from a referred clinical sample and age- and sex-matched control volunteers underwent scanning. Main Outcome Measures Percentage of active voxels and percentage signal change calculated for the anterior cingulate gyrus (ACG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), basal ganglia, and thalamus. Performance on the visual oddball task was measured with percentage of hits and d′ (a measure based on the hit rate and the false-alarm rate). Results The ultra-high-risk group showed significantly smaller differential activation between task-relevant and task-irrelevant stimuli in the frontal regions (ACG, IFG, MFG) than the control group. Frontostriatal activation associated with target stimuli in the early and chronic groups was significantly lower than the control group, while the ultra-high-risk group showed a trend toward the early group. Conclusions Our findings suggest that prefrontal function begins to decline before the onset of syndromally defined illness and hence may represent a vulnerability marker in assessing the risk of developing psychotic disorders among ultra-high-risk individuals. PMID:15753238

Estrogen use and early onset Alzheimer's disease: a population-based study

NARCIS (Netherlands)

A.J.C. Slooter (Arjen); J.B. Bronzova (Juliana); J.C.M. Witteman (Jacqueline); C.M. van Duijn (Cornelia); C. van Broeckhoven (Christine); A. Hofman (Albert)

1999-01-01

textabstractEstrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5

Risk of early-onset prostate cancer associated with occupation in the Nordic countries

DEFF Research Database (Denmark)

Hughes Barry, Kathryn; Martinsen, Jan Ivar; Alavanja, Michael C. R.

2017-01-01

-49 and those aged 50 or older. We also conducted separate analyses by period of follow-up, 1961-1985 and 1986-2005, corresponding to pre- and post-prostate-specific antigen (PSA) screening. RESULTS: For early-onset prostate cancer (n = 1521), we observed the highest SIRs for public safety workers (e......BACKGROUND: Early-onset prostate cancer is often more aggressive and may have a different aetiology than later-onset prostate cancer, but has been relatively little studied to date. We evaluated occupation in relation to early- and later-onset prostate cancer in a large pooled study. METHODS: We...... used occupational information from census data in five Nordic countries from 1960 to 1990. We identified prostate cancer cases diagnosed from 1961 to 2005 by linkage of census information to national cancer registries and calculated standardised incidence ratios (SIRs) separately for men aged 30...

Sex/gender differences in the brain and cognition in schizophrenia.

Science.gov (United States)

Mendrek, Adrianna; Mancini-Marïe, Adham

2016-08-01

The early conceptualizations of schizophrenia have noted some sex/gender differences in epidemiology and clinical expression of the disorder. Over the past few decades, the interest in differences between male and female patients has expanded to encompass brain morphology and neurocognitive function. Despite some variability and methodological shortcomings, a few patterns emerge from the available literature. Most studies of gross neuroanatomy show more enlarged ventricles and smaller frontal lobes in men than in women with schizophrenia; finding reflecting normal sexual dimorphism. In comparison, studies of brain asymmetry and specific corticolimbic structures, suggest a disturbance in normal sexual dimorphism. The neurocognitive findings are somewhat consistent with this picture. Studies of cognitive functions mediated by the lateral frontal network tend to show sex differences in patients which are in the same direction as those observed in the general population, whereas studies of processes mediated by the corticolimbic system more frequently reveal reversal of normal sexual dimorphisms. These trends are faint and future research would need to delineate neurocognitive differences between men and women with various subtypes of schizophrenia (e.g., early versus late onset), while taking into consideration hormonal status and gender of tested participants. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Multilevel Functional Study of a SNAP25 At-Risk Variant for Bipolar Disorder and Schizophrenia.

Science.gov (United States)

Houenou, Josselin; Boisgontier, Jennifer; Henrion, Annabelle; d'Albis, Marc-Antoine; Dumaine, Anne; Linke, Julia; Wessa, Michèle; Daban, Claire; Hamdani, Nora; Delavest, Marine; Llorca, Pierre-Michel; Lançon, Christophe; Schürhoff, Franck; Szöke, Andrei; Le Corvoisier, Philippe; Barau, Caroline; Poupon, Cyril; Etain, Bruno; Leboyer, Marion; Jamain, Stéphane

2017-10-25

The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant in SNAP25 , rs6039769 , that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combined in vitro and in vivo approaches in humans to understand the functional impact of the at-risk allele. Thus, we showed in vitro that the rs6039769 C allele was sufficient to increase the SNAP25 transcription level. In a postmortem expression analysis of 33 individuals affected with schizophrenia and 30 unaffected control subjects, we showed that the SNAP25b / SNAP25a ratio was increased in schizophrenic patients carrying the rs6039769 at-risk allele. Last, using genetics imaging in a cohort of 71 subjects, we showed that male risk carriers had an increased amygdala-ventromedial prefrontal cortex functional connectivity and a larger amygdala than non-risk carriers. The latter association has been replicated in an independent cohort of 121 independent subjects. Altogether, results from these multilevel functional studies are bringing strong evidence for the functional consequences of this allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal-limbic network, which therefore may increase the vulnerability to both early-onset bipolar disorder and schizophrenia. SIGNIFICANCE STATEMENT Functional characterization of disease-associated variants is a key challenge in understanding neuropsychiatric disorders and will open an avenue in the development of personalized treatments. Recent studies have accumulated evidence that the SNARE complex, and more specifically

Health-related quality of life, adiposity, and sedentary behavior in patients with early schizophrenia: preliminary study

Directory of Open Access Journals (Sweden)

Strassnig M

2012-10-01

Full Text Available Martin Strassnig,1 Jaspreet S Brar,2 Rohan Ganguli31Department of Psychiatry, Miller School of Medicine, University of Miami, Miami, FL, USA; 2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; 3Department of Psychiatry, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, CanadaObjective: To examine adiposity and sedentary behavior in relation to health-related quality of life (QoL in patients with early schizophrenia.Methods: A cross-sectional study was used to assess adiposity by dual-energy X-ray absorptiometry scans, habitual physical activity and idle sitting time by the Short Form International Physical Activity Questionnaire, and health-related QoL by the RAND Medical Outcomes Study SF-36. QoL scores were compared with age-adjusted Canadian normative population data.Results: There were 36 participants with early schizophrenia, average age 25.1 (±3.6. Twenty-nine (72.5% were males. Mean illness duration was 30 (±18 months, and mean body mass index was 28.3 (±5. Females had higher body fat content than males (30.8 ± 6.9 vs 24.7 ± 10.6; t = −2.6, df = 34; P = 0.015. Total body fat (F = 14; P = 0.001, lean body mass (F = 10.2; P = 0.001, and sedentary behavior (F = 5; P = 0.013 significantly increased across body mass index categories. Total body fat was correlated with sedentary behavior (r = 0.62; P = 0.001, and total lean body mass was negatively correlated with sedentary behavior (r = 0.39; P = 0.03. Based on SF-36 scores, participants had significantly lower physical functioning (P = 0.0034, role physical (P = 0.0003, general health (P < 0.0001, vitality (P = 0.03, and physical component scores (P = 0.003 than Canadian population comparisons. Habitual sedentary behavior, more than activity or adiposity levels, was associated with health-related QoL in early schizophrenia.Conclusion: Health-related QoL is lower in early schizophrenia and is predominantly experienced in the physical

Overlapping and disease specific trait, response, and reflection impulsivity in adolescents with first-episode schizophrenia spectrum disorders or attention-deficit/hyperactivity disorder

DEFF Research Database (Denmark)

Jepsen, J. R.M.; Rydkjaer, J.; Fagerlund, B.

2018-01-01

and Schizophrenia for School-aged Children – Present and Lifetime Version. Subjects with early-onset, first-episode schizophrenia spectrum disorders (EOS) (N = 29) or ADHD (N = 29) and healthy controls (N = 45) were compared on two performance measures (Information Sampling Task, Stop Signal Task) and a subjective......Background: Schizophrenia and attention-deficit/hyperactivity disorder (ADHD) are developmental disorders with shared clinical characteristics such as cognitive impairments and impulsivity. Impulsivity is a core feature of ADHD and an important factor in aggression, violence, and substance use...... in schizophrenia. Based on the hypothesis that schizophrenia and ADHD represent a continuum of neurodevelopmental impairments, the aim was to identify overlapping and disease specific forms of impulsivity. Methods: Adolescents between 12 and 17 years of age were assessed with the Schedule for Affective Disorders...

Association of interleukin 2 (IL-2), interleukin 6 (IL-6), and TNF-alpha (TNFα) gene polymorphisms with paranoid schizophrenia in a Polish population.

Science.gov (United States)

Paul-Samojedny, Monika; Owczarek, Aleksander; Kowalczyk, Małgorzata; Suchanek, Renata; Palacz, Marta; Kucia, Krzysztof; Fila-Daniłow, Anna; Borkowska, Paulina; Kowalski, Jan

2013-01-01

Numerous reports have brought attention to the potential role of cytokines in schizophrenia. The aim of the study was to determine whether polymorphisms of IL-2, IL-6, and TNFα genes are risk factors for development of paranoid schizophrenia in a Polish population. Promoter polymorphisms of IL-6 (rs1800795), TNFα (rs1800629), and IL-2 (rs2069762) genes in patients (N=115) and controls (N=135) were genotyped by PCR-RFLP and AS-PCR methods, respectively. Genotype TT and allele T for IL-2 polymorphism, and genotype AA and allele A for TNFα polymorphism were found to be significantly associated with paranoid schizophrenia. Similarly, haplotypes CTA and GTA increased the risk (4.4 times and 5.9 times, respectively) of schizophrenia. To reveal associations between Positive and Negative Symptom Scale subscales and age at onset of schizophrenia, the authors used a novel method called Grade Correspondence Analysis. This analysis revealed that patients with early age at onset have higher scores on the Negative and General subscales of PANSS, and, in that group of patients, haplotype CTA was the most represented. As far as is known, this analysis was used for the first time with reference to genetic data.

Neonatal disruption of serine racemase causes schizophrenia-like behavioral abnormalities in adulthood: clinical rescue by d-serine.

Directory of Open Access Journals (Sweden)

Hiroko Hagiwara

Full Text Available D-Serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA receptor, is synthesized from L-serine by serine racemase (SRR. Given the role of D-serine in both neurodevelopment and the pathophysiology of schizophrenia, we examined whether neonatal disruption of D-serine synthesis by SRR inhibition could induce behavioral abnormalities relevant to schizophrenia, in later life.Neonatal mice (7-9 days were injected with vehicle or phenazine methosulfate (Met-Phen: 3 mg/kg/day, an SRR inhibitor. Behavioral evaluations, such as spontaneous locomotion, novel object recognition test (NORT, and prepulse inhibition (PPI were performed at juvenile (5-6 weeks old and adult (10-12 weeks old stages. In addition, we tested the effects of D-serine on PPI deficits in adult mice after neonatal Met-Phen exposure. Finally, we assessed whether D-serine could prevent the onset of schizophrenia-like behavior in these mice. Neonatal Met-Phen treatment reduced D-serine levels in the brain, 24 hours after the final dose. Additionally, this treatment caused behavioral abnormalities relevant to prodromal symptoms in juveniles and to schizophrenia in adults. A single dose of D-serine improved PPI deficits in adult mice. Interestingly, chronic administration of D-serine (900 mg/kg/day from P35 to P70 significantly prevented the onset of PPI deficits after neonatal Met-Phen exposure.This study shows that disruption of D-serine synthesis during developmental stages leads to behavioral abnormalities relevant to prodromal symptoms and schizophrenia, in later life. Furthermore, early pharmacological intervention with D-serine may prevent the onset of psychosis in adult.

Management of Very Early-onset Fetal Growth Restriction: Results from 92 Consecutive Cases.

Science.gov (United States)

Hoellen, Friederike; Beckmann, Annika; Banz-Jansen, Constanze; Weichert, Jan; Rody, Achim; Bohlmann, Michael K

2016-01-01

To evaluate management of early-onset intrauterine growth restriction (IUGR) and to define outcome according to obstetric setting. During an 11-year period (2000-2011), data of patients presenting with IUGR and preterm delivery of less than 30 weeks of gestation at a tertiary perinatal center were retrospectively reviewed. A total of 92 pregnancies were investigated. Delivery was indicated for fetal reasons in 38 out of 92 patients. Sixteen children of our cohort died within one year post partum, out of which eight had suffered from severe early-onset IUGR causing iatrogenic preterm delivery. Concerning the fetal outcome, gestational age at delivery and antenatal exposure to corticosteroids were found to be crucial. In some cases, respiratory distress syndrome prophylaxis and a "wait and see" approach to management in favor of a prolongation of the pregnancy might be favorable. Randomized prospective trials in early-onset IUGR with threatened preterm deliveries are needed in order to define guidelines for an individually tailored management of early-onset preterm infants. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Alterations of white matter integrity related to the season of birth in schizophrenia: a DTI study.

Directory of Open Access Journals (Sweden)

Stéphanie Giezendanner

Full Text Available In schizophrenia there is a consistent epidemiological finding of a birth excess in winter and spring. Season of birth is thought to act as a proxy indicator for harmful environmental factors during foetal maturation. There is evidence that prenatal exposure to harmful environmental factors may trigger pathologic processes in the neurodevelopment, which subsequently increase the risk of schizophrenia. Since brain white matter alterations have repeatedly been found in schizophrenia, the objective of this study was to investigate whether white matter integrity was related to the season of birth in patients with schizophrenia. Thirty-four patients with schizophrenia and 33 healthy controls underwent diffusion tensor imaging. Differences in the fractional anisotropy maps of schizophrenia patients and healthy controls born in different seasons were analysed with tract-based spatial statistics. A significant main effect of season of birth and an interaction of group and season of birth showed that patients born in summer had significantly lower fractional anisotropy in widespread white matter regions than those born in the remainder of the year. Additionally, later age of schizophrenia onset was found in patients born in winter months. The current findings indicate a relationship of season of birth and white matter alterations in schizophrenia and consequently support the neurodevelopmental hypothesis of early pathological mechanisms in schizophrenia.

Genetics Home Reference: early-onset myopathy with fatal cardiomyopathy

Science.gov (United States)

... in childhood, people with EOMFC may also develop joint deformities called contractures that restrict the movement of ... Home Edition for Patients and Caregivers: Dilated Cardiomyopathy Neuromuscular Disease Center, Washington University Orphanet: Early-onset myopathy ...

Comparison of peripheral and central schizophrenia biomarker profiles.

Directory of Open Access Journals (Sweden)

Laura W Harris

Full Text Available We have recently shown that a molecular biomarker signature comprised of inflammatory, hormonal and growth factors occurs in the blood serum from first onset schizophrenia patients. Here, we use the same platform to investigate post mortem brain tissue (Brodmann area 10 from schizophrenia patients who were mainly chronically ill and drug treated. Twenty-one analytes are differentially expressed in post-mortem brain tissue. Comparison with our previous mRNA profiling studies of the same patient samples in another frontal cortical area showed that 9 of these molecules were also altered at the transcriptional level. Furthermore, 9 of the molecules were also altered in serum from living first onset schizophrenia patients compared to controls. We propose a model in which the brain and periphery are coordinated through hormones and other regulatory molecules released into the blood via the diffuse neuroendocrine system. These findings provide further evidence for the systemic nature of schizophrenia and give added validity to the concept that schizophrenia can be investigated through studies of blood-based biomarkers.

Genetics of Early-Onset Alzheimer Dementia

Directory of Open Access Journals (Sweden)

Rosa Rademakers

2003-01-01

Full Text Available Alzheimer�s dementia (AD is the most common degenerative disorder of the central nervous system. Although the onset of dementia is above 65 years of age in the majority of the patients (late-onset AD, LOAD, a small subgroup of patients develops AD before 65 years of age (early-onset AD, EOAD. To date 3 genes responsible for EOAD have been identified: the amyloid precursor protein gene (APP, presenilin 1 (PSEN1 and presenilin 2 (PSEN2. PSEN1 is the most frequently mutated EOAD gene with a mutation frequency of 18 to 50% in autosomal dominant EOAD. In addition, the e4 allele of the gene encoding apolipoprotein E (APOE was identified as a risk factor for both LOAD and EOAD. Many studies reported other susceptibility genes, but the APOE?4 alelle has been the only risk factor that was consistently replicated in all AD populations. Extensive cell biology research in the past ten years led to the hypothesis that the 4 EOAD genes lead to AD through a common biological pathway resulting in abnormal APP processing by subtle different mechanisms. Now, transgenic mice are produced to study the influence of EOAD mutations in vivo, eventually leading to the development of novel therapeutic strategies.

Diagnostic specificity of poor premorbid adjustment: comparison of schizophrenia, schizoaffective disorder, and mood disorder with psychotic features.

Science.gov (United States)

Tarbox, Sarah I; Brown, Leslie H; Haas, Gretchen L

2012-10-01

Individuals with schizophrenia have significant deficits in premorbid social and academic adjustment compared to individuals with non-psychotic diagnoses. However, it is unclear how severity and developmental trajectory of premorbid maladjustment compare across psychotic disorders. This study examined the association between premorbid functioning (in childhood, early adolescence, and late adolescence) and psychotic disorder diagnosis in a first-episode sample of 105 individuals: schizophrenia (n=68), schizoaffective disorder (n=22), and mood disorder with psychotic features (n=15). Social and academic maladjustment was assessed using the Cannon-Spoor Premorbid Adjustment Scale. Worse social functioning in late adolescence was associated with higher odds of schizophrenia compared to odds of either schizoaffective disorder or mood disorder with psychotic features, independently of child and early adolescent maladjustment. Greater social dysfunction in childhood was associated with higher odds of schizoaffective disorder compared to odds of schizophrenia. Premorbid decline in academic adjustment was observed for all groups, but did not predict diagnosis at any stage of development. Results suggest that social functioning is disrupted in the premorbid phase of both schizophrenia and schizoaffective disorder, but remains fairly stable in mood disorders with psychotic features. Disparities in the onset and time course of social dysfunction suggest important developmental differences between schizophrenia and schizoaffective disorder. Copyright © 2012 Elsevier B.V. All rights reserved.

Epidemiological study of schizophrenia in the Chernobyl exclusion zone personnel

International Nuclear Information System (INIS)

Loganovsky, K.N.; Nyagu, A.I.

1997-01-01

Nakane and Ohta (1986) revealed very high (6 %) prevalence rate of schizophrenia in A-bomb survivors. The goal of this study was the epidemiological investigation of schizophrenia in the Chernobyl exclusion zone personnel on the base of 10-years follow up study and analysis of the psychiatric archives (1986-1996). As a result the register of schizophrenia spectrum disorders has been created, including 65 staff members. According to both ICD-9 and ICD-10 criteria there were 48 patients with schizophrenia. It has been revealed a statistically significant increase of the schizophrenia percentage amongst all psychoses in the Chernobyl exclusion zone personnel in comparison with the general Ukrainian population. It has been established that among 48 cases of schizophrenia there were 39 (81.2 %) of schizophrenia onset occurred in the zone. Since 1990 a significant increase (more than 4 times: 5.4 per 10,000 in the zone and 1.1 per 10,000 in Ukraine) in schizophrenia incidence has been taking place among the irradiated population of the exclusion zone in comparison with the general population. Our data testify to possibility of radiation-induced schizophrenia onset, which seem to be like stochastic effects of ionizing radiation. The mechanisms of these effects realization are the subject of further investigations. (author)

Neutrophil CD64 in early-onset neonatal sepsis

African Journals Online (AJOL)

EL-HAKIM

of 3.5 to 8 cases per 1,000 live births; and mortality rate 16 to 30%. Cytokines, produced by ... 40 weeks with a picture of early onset neonatal sepsis within 48 hours of life admitted to neonatal ..... Infect Dis J 2000;19 (9):879-87. 5. Gonzalez BE ...

Diagnostic agreement of schizophrenia spectrum disorders among chronic patients with functional psychoses

DEFF Research Database (Denmark)

Jakobsen, K D; Frederiksen, J N; Parnas, J

2006-01-01

of 100 individuals (35 women and 65 men) were randomly sampled and assessed using the Operational Criteria Checklist for Psychotic Illness and Affective Illness (OPCRIT). Based on the OPCRIT diagnoses the subjects suffering from schizophrenia and schizophrenia spectrum disorders according to seven...... function previous to the onset of illness. Similarly high pairwise CR were observed for schizophrenia spectrum disorders across all diagnostic systems. CONCLUSIONS: This study demonstrates that diagnostic agreement is higher among chronic patients than that observed in subjects with a recent onset...... serious epistemological consequences, thus underlining the conventional nature of the present schizophrenia diagnoses and the need for biologically founded diagnostic criteria....

ASSESSMENT OF OXIDATIVE STRESS IN EARLY AND LATE ONSET PRE-ECLAMPSIA AMONG GHANAIAN WOMEN.

Science.gov (United States)

Tetteh, P W; Adu-Bonsaffoh, K; Antwi-Boasiako, C; Antwi, D A; Gyan, B; Obed, S A

2015-01-01

Pre-eclampsia is a multisystem pregnancy-related disorder with multiple theories regarding its aetiology resulting in lack of reliable screening tests and well-established measures for primary prevention. However, oxidative stress is increasingly being implicated in the pathogenesi of pre-eclampsia although conflicting findings have been reported. To determine and compare the levels of oxidative stress in early and late onset pre-eclampsia by measuring urinary excretion of isoprostane and total antioxidant power (TAP) in a cohort of pre-eclamptic women at Korle Bu Teaching Hospital. This was a cross-sectional study conducted at Korle-Bu Teaching Hospital, Accra, Ghana involving pre-eclamptic women between the ages 18 and 45 years who gave written informed consent. Urinary isoprostane levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit whereas the Total Anti-oxidant Power in urine samples was determined using Total Antioxidant Power Colorimetric Microplate Assay kit. The data obtained were analyzed using MEGASTAT statistical software package. We included 102 pre-eclamptic women comprising 68 (66.7%) and 34 (33.3%) with early-onset and late-onset pre-eclampsia respectively. There were no statistically significant differences between the mean maternal age, haematological indices, serum ALT, AST, ALT, albumin, urea, creatinine uric acid and total protein at the time of diagnosis. The mean gestational age at diagnosis of early and late onset pre-eclampsia were 31.65 ± 0.41 and 38.03 ± 0.21 respectively (p ˂ 0.001). Also, there were statistically significant differences between the diastolic blood pressure (BP), systolic BP and mean arterial pressure (MAP) at diagnosis of pre-eclampsia in the two categories. The mean urinary Isoprostane excretion was significantly higher in the early onset pre-eclamptic group (3.04 ± 0.34 ng/mg Cr) compared to that of the late onset pre-eclamptic group (2.36 ± 0.45 ng/mg Cr), (p=0.019). Urinary total

INFLAMMATORY BOWEL DISEASE WITH A VERY EARLY ONSET

Directory of Open Access Journals (Sweden)

E. A. Kornienko

2016-01-01

Full Text Available Inflammatory bowel disease (Crohn's disease and ulcerative colitis has a tendency to manifest at earlier age. In childhood (< 6 years of age it has an especially severe course and is characterized by high grade inflammation, predominantly in the colon, by complication and extra-intestinal autoimmune injury. At younger age, Crohn's disease and ulcerative colitis require more aggressive treatment with frequently poor results. From genetic point of view, monogenic mutations controlling the immune response are characteristic for these diseases with an early onset; therefore, they are frequently associated with primary immunodeficiency. This implies various immunologic deficits, such as breakdown of the epithelial barrier, phagocytic dysfunction and dysfunction of Т and В lymphocytes and regulatory Т cells. Depending on this, a number of primary immunodeficiencies are identified associated with monogenic mutations of more than 50 genes. There some age-related specific features at manifestation. Thus, defects in interleukin 10 and FOXP3 manifest in the first months of life, whereas severe combined immunodeficiencies and phagocytosis defects become evident somewhat later. Virtually all 24 children with very early onset of inflammatory bowel disease, whom we examined, had immunologic defects and one child had a XIAP gene mutation. After identification of a specific immunologic defect, one can understand the mechanism of the disease and suspect one or another genetic defect with subsequent reasonable assessment of mutations in candidate genes. Detection of immunologic and genetic defects in children with a very early onset of inflammatory bowel disease allows for choosing an adequate strategy of non-conventional treatment that may differ depending on the mechanism of the disease.

Abnormal immune system development and function in schizophrenia helps reconcile diverse findings and suggests new treatment and prevention strategies.

Science.gov (United States)

Anders, Sherry; Kinney, Dennis K

2015-08-18

Extensive research implicates disturbed immune function and development in the etiology and pathology of schizophrenia. In addition to reviewing evidence for immunological factors in schizophrenia, this paper discusses how an emerging model of atypical immune function and development helps explain a wide variety of well-established - but puzzling - findings about schizophrenia. A number of theorists have presented hypotheses that early immune system programming, disrupted by pre- and perinatal adversity, often combines with abnormal brain development to produce schizophrenia. The present paper focuses on the hypothesis that disruption of early immune system development produces a latent immune vulnerability that manifests more fully after puberty, when changes in immune function and the thymus leave individuals more susceptible to infections and immune dysfunctions that contribute to schizophrenia. Complementing neurodevelopmental models, this hypothesis integrates findings on many contributing factors to schizophrenia, including prenatal adversity, genes, climate, migration, infections, and stress, among others. It helps explain, for example, why (a) schizophrenia onset is typically delayed until years after prenatal adversity, (b) individual risk factors alone often do not lead to schizophrenia, and (c) schizophrenia prevalence rates actually tend to be higher in economically advantaged countries. Here we discuss how the hypothesis explains 10 key findings, and suggests new, potentially highly cost-effective, strategies for treatment and prevention of schizophrenia. Moreover, while most human research linking immune factors to schizophrenia has been correlational, these strategies provide ethical ways to experimentally test in humans theories about immune function and schizophrenia. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Early and phasic cortical metabolic changes in vestibular neuritis onset.

Directory of Open Access Journals (Sweden)

Marco Alessandrini

Full Text Available Functional brain activation studies described the presence of separate cortical areas responsible for central processing of peripheral vestibular information and reported their activation and interactions with other sensory modalities and the changes of this network associated to strategic peripheral or central vestibular lesions. It is already known that cortical changes induced by acute unilateral vestibular failure (UVF are various and undergo variations over time, revealing different cortical involved areas at the onset and recovery from symptoms. The present study aimed at reporting the earliest change in cortical metabolic activity during a paradigmatic form of UVF such as vestibular neuritis (VN, that is, a purely peripheral lesion of the vestibular system, that offers the opportunity to study the cortical response to altered vestibular processing. This research reports [(18F]fluorodeoxyglucose positron emission tomography brain scan data concerning the early cortical metabolic activity associated to symptoms onset in a group of eight patients suffering from VN. VN patients' cortical metabolic activity during the first two days from symptoms onset was compared to that recorded one month later and to a control healthy group. Beside the known cortical response in the sensorimotor network associated to vestibular deafferentation, we show for the first time the involvement of Entorhinal (BAs 28, 34 and Temporal (BA 38 cortices in early phases of symptomatology onset. We interpret these findings as the cortical counterparts of the attempt to reorient oneself in space counteracting the vertigo symptom (Bas 28, 34 and of the emotional response to the new pathologic condition (BA 38 respectively. These interpretations were further supported by changes in patients' subjective ratings in balance, anxiety, and depersonalization/derealization scores when tested at illness onset and one month later. The present findings contribute in expanding

Schizophrenia and the neurodevelopmental continuum:evidence from genomics.

Science.gov (United States)

Owen, Michael J; O'Donovan, Michael C

2017-10-01

The idea that disturbances occurring early in brain development contribute to the pathogenesis of schizophrenia, often referred to as the neurodevelopmental hypothesis, has become widely accepted. Despite this, the disorder is viewed as being distinct nosologically, and by implication pathophysiologically and clinically, from syndromes such as autism spectrum disorders, attention-deficit/hyperactivity disorder (ADHD) and intellectual disability, which typically present in childhood and are grouped together as "neurodevelopmental disorders". An alternative view is that neurodevelopmental disorders, including schizophrenia, rather than being etiologically discrete entities, are better conceptualized as lying on an etiological and neurodevelopmental continuum, with the major clinical syndromes reflecting the severity, timing and predominant pattern of abnormal brain development and resulting functional abnormalities. It has also been suggested that, within the neurodevelopmental continuum, severe mental illnesses occupy a gradient of decreasing neurodevelopmental impairment as follows: intellectual disability, autism spectrum disorders, ADHD, schizophrenia and bipolar disorder. Recent genomic studies have identified large numbers of specific risk DNA changes and offer a direct and robust test of the predictions of the neurodevelopmental continuum model and gradient hypothesis. These findings are reviewed in detail. They not only support the view that schizophrenia is a disorder whose origins lie in disturbances of brain development, but also that it shares genetic risk and pathogenic mechanisms with the early onset neurodevelopmental disorders (intellectual disability, autism spectrum disorders and ADHD). They also support the idea that these disorders lie on a gradient of severity, implying that they differ to some extent quantitatively as well as qualitatively. These findings have important implications for nosology, clinical practice and research. © 2017 World

Early onset diabetes-genetic and hormonal analysis in pakistan population

International Nuclear Information System (INIS)

Wahid, M.; Kamran, M.

2016-01-01

Background: Mitochondrial DNA mutation and hormonal imbalance is involved in the pathogenesis of early onset diabetes but data is lacking in Pakistani population. The study was planned to delineate the clinical presentation of early onset diabetes with possible hormonal and genetic etiological factors and aascertain the possible etiological role of insulin and glucagon in these patients either on oral hypoglycaemic or subcutaneous insulin therapy. Methods: Retrospective, analytical case control study with conventional sampling technique carried at Centre for Research in Experimental and Applied Medicine (CREAM) affiliated with the department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi from Dec 2006 to July 2011. Study included the patients (20-35 years of age) with early onset diabetes on oral hypoglycemic (n=240), insulin therapy (n=280), and compared with non-diabetic healthy controls (n=150). A fragment surrounding tRNALeu (UUR) gene was amplified by AmpliTaq from mtDNA which was extracted from peripheral blood leucocytes. Then it was subjected to restriction endonucleases, ApaI for A3242G mutation and HaeIII for G3316A mutation detection. Plasma glucose, glycosylated Hb, osmolality, insulin and glucagon levels along with ABGs analysis was also done. Results: Non diabetic controls comprised of 51% males and 49% females, diabetics on oral hypoglycemic 60% males and 40 % females and on insulin therapy 54% males and 46% females. Insulin dependent diabetics had statistically significant hyperglucagonemia, acidemia and bicarbonate deficit. MtDNA A3242G and G3316A mutations were not detected. Conclusion: relative hyperglucagonemia and acidemia in Insulin dependent diabetics was a potent threat leading to DKA. The absence of two mtDNA mutations in ND1 gene rules out the possibility of involvement of these mutations in early onset diabetes in Pakistani population. (author)

IKs Gain- and Loss-of-Function In Early-Onset Lone Atrial Fibrillation

DEFF Research Database (Denmark)

Steffensen, Annette Buur; Refsgaard, Lena; Andersen, Martin Nybo

2015-01-01

INTRODUCTION: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. The potassium current IKs is essential for cardiac repolarization. Gain-of-function mutation in KCNQ1, the gene encoding the pore-forming α-subunit of the IKs channel (KV 7.1), was the first ion channel dysfunction...... to be associated with familial AF. We hypothesized that early-onset lone AF is associated with a high prevalence of mutations in KCNQ1. METHODS AND RESULTS: We bidirectionally sequenced the entire coding sequence of KCNQ1 in 209 unrelated patients with early-onset lone AF (...-of-function phenotype. CONCLUSIONS: Mutations in the IKs channel leading to gain-of-function have previously been described in familial AF, yet this is the first time a loss-of-function mutation in KCNQ1 is associated with early-onset lone AF. These findings suggest that both gain-of function and loss...

Early Onset Squamous Cell Carcinoma In A Case Of Lichen Planus

Directory of Open Access Journals (Sweden)

Singh Shri Nath

1998-01-01

Full Text Available Lichen planus, which is a very common condition, is being presented. However, the uncommon feature in this cases is its early onset and equally early development of squamous cell carcinoma on a lesion on the right thigh.

Variants of early-onset restrictive eating disturbances in middle childhood.

Science.gov (United States)

Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja

2016-01-01

This study sought to determine the factor structure of the newly developed self-report screening questionnaire Eating Disturbances in Youth-Questionnaire (EDY-Q) as well as to report the distribution of variants of early-onset restrictive eating disturbances characteristic of avoidant/restrictive food intake disorder (ARFID) in a middle childhood population sample. Using the EDY-Q, a total of 1,444 children aged 8-13 years were screened in elementary schools in Switzerland via self-report. The factor analysis of the 12 items covering ARFID related symptoms was performed using a principal component analysis (PCA). The PCA showed a four factor solution, with clear allocation to the scales covering three variants of early-onset restrictive eating disturbances and weight problems. Inadequate overall food intake was reported by 19.3% of the children, a limited accepted amount of food by 26.1%, and food avoidance based on a specific underlying fear by 5.0%. The postulated factor structure of the EDY-Q was confirmed, further supporting the existence of distinct variants of early-onset restrictive eating disturbances. Avoidant/restrictive eating behavior seems to be a common experience in middle childhood, but results have to be confirmed using validated interviews. © 2015 Wiley Periodicals, Inc.

CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy.

Science.gov (United States)

Elia, M; Falco, M; Ferri, R; Spalletta, A; Bottitta, M; Calabrese, G; Carotenuto, M; Musumeci, S A; Lo Giudice, M; Fichera, M

2008-09-23

To search for CDKL5 gene mutations in boys presenting with severe early-onset encephalopathy and intractable epilepsy, a clinical picture very similar to that already described in girls with CDKL5 mutations. Eight boys (age range 3-16 years, mean age 8.5 years, SD 4.38) with severe or profound mental retardation and early-onset intractable seizures were selected for CDKL5 gene mutation screening by denaturing high-performance liquid chromatography analysis. We found three unrelated boys carrying three different missense mutations of the CDKL5 gene: c.872G>A (p.C291Y), c.863C>T (p.T288I), and c.533G>C (p.R178P). They presented early-onset, polymorphous, and drug-resistant seizures, mostly myoclonic and tonic or spasms. EEG showed epileptiform abnormalities which were multifocal during wakefulness, and pseudoperiodic bisynchronous during sleep. This study describes three boys carrying CDKL5 missense mutations and their detailed clinical and EEG data, and indicates that CDKL5 gene mutations may represent a cause of severe or profound mental retardation and early-onset intractable seizures, also in boys. Screening for CDKL5 mutations is strongly recommended in individuals with these clinical features.

Conversion (dissociative) symptoms as a presenting feature in early onset bipolar disorder: a case series

OpenAIRE

Ghosal, Malay Kumar; Guha, Prathama; Sinha, Mausumi; Majumdar, Debabrata; Sengupta, Payel

2009-01-01

We present three cases of early onset bipolar disorder where dissociative (conversion) symptoms preceded the onset of mania. This case series underscores the significance of dissociative/conversion symptoms as an early atypical presentation in juvenile bipolar disorder.

Canadian Guidelines for the Pharmacological Treatment of Schizophrenia Spectrum and Other Psychotic Disorders in Children and Youth.

Science.gov (United States)

Abidi, Sabina; Mian, Irfan; Garcia-Ortega, Iliana; Lecomte, Tania; Raedler, Thomas; Jackson, Kevin; Jackson, Kim; Pringsheim, Tamara; Addington, Donald

2017-09-01

Schizophrenia spectrum and other psychotic disorders often have their onset in adolescence. The sequelae of these illnesses can negatively alter the trajectory of emotional, cognitive, and social development in children and youth if left untreated. Early and appropriate interventions can improve outcomes. This article aims to identify best practices in the pharmacotherapy management of children and youth with schizophrenia spectrum disorders. A systematic search was conducted for published guidelines for schizophrenia and schizophrenia spectrum disorders in children and youth (under age 18 years). Recommendations were drawn from the National Institute for Health and Care Excellence guidelines on psychosis and schizophrenia in children and youth (2013 and 2015 updates). Current guidelines were adopted using the ADAPTE process, which includes consensus ratings by a panel of experts. Recommendations identified covered a range of issues in the pharmacotherapy management of children and youth with schizophrenia spectrum disorders. Further work in this area is warranted as we continue to further understand their presentation in the developing brain. Canadian guidelines for the pharmacotherapy management of children and youth with schizophrenia spectrum disorders are essential to assist clinicians in treating this vulnerable population. Ongoing work in this area is recommended.

Dysbindin (DTNBP1, 6p22.3) is Associated with Childhood-Onset Psychosis and Endophenotypes Measured by the Premorbid Adjustment Scale (PAS)

Science.gov (United States)

Gornick, M. C.; Addington, A. M.; Sporn, A.; Gogtay, N.; Greenstein, D.; Lenane, M.; Gochman, P.; Ordonez, A.; Balkissoon, R.; Vakkalanka, R.; Weinberger, D. R.; Rapoport, J. L.; Straub, R. E.

2005-01-01

Straub "et al." ("2002") recently identified the 6p22.3 gene dysbindin (DTNBP1) through positional cloning as a schizophrenia susceptibility gene. We studied a rare cohort of 102 children with onset of psychosis before age 13. Standardized ratings of early development, medication response, neuropsychological and cognitive performance, premorbid…

Predictors of neonatal outcome in early-onset placental dysfunction

NARCIS (Netherlands)

Baschat, Ahmet A.; Cosmi, Erich; Bilardo, Catarina M.; Wolf, Hans; Berg, Christoph; Rigano, Serena; Germer, Ute; Moyano, Dolores; Turan, Sifa; Hartung, John; Bhide, Amarnath; Müller, Thomas; Bower, Sarah; Nicolaides, Kypros H.; Thilaganathan, Baskaran; Gembruch, Ulrich; Ferrazzi, Enrico; Hecher, Kurt; Galan, Henry L.; Harman, Chris R.

2007-01-01

To identify specific estimates and predictors of neonatal morbidity and mortality in early onset fetal growth restriction due to placental dysfunction. Prospective multicenter study of prenatally diagnosed growth-restricted liveborn neonates of less than 33 weeks of gestational age. Relationships

Review of risperidone for the treatment of pediatric and adolescent bipolar disorder and schizophrenia

Directory of Open Access Journals (Sweden)

Jeffrey R Bishop

2008-03-01

Full Text Available Jeffrey R Bishop1,2, Mani N Pavuluri21Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA; 2Department of Psychiatry, Pediatric Mood Disorders Program and Center for Cognitive Medicine, University of Illinois at Chicago College of Medicine, Chicago, IL, USAAbstract: Risperidone is a commonly used medication for the treatment of bipolar disorder and schizophrenia in children and adolescents. It has been studied as a monotherapy treatment in early onset schizophrenia and as both monotherapy and combination therapy for pediatric bipolar disorder. Studies to date indicate that risperidone is an effective treatment for positive and negative symptoms of schizophrenia and mania symptoms of bipolar disorder. In young patient populations, side effects such as weight gain, extrapyramidal side effects, and prolactin elevation require consideration when evaluating the risk benefit ratio for individual patients. Here we review published studies of risperidone for the treatment of bipolar disorder and schizophrenia in children and adolescents to provide practitioners with an overview of published data on the efficacy and safety of risperidone in these patient populations.Keywords: risperidone, bipolar disorder, schizophrenia, children, adolescents

An extended cost-effectiveness analysis of schizophrenia treatment in India under universal public finance.

Science.gov (United States)

Raykar, Neha; Nigam, Aditi; Chisholm, Dan

2016-01-01

Schizophrenia remains a priority condition in mental health policy and service development because of its early onset, severity and consequences for affected individuals and households. This paper reports on an 'extended' cost-effectiveness analysis (ECEA) for schizophrenia treatment in India, which seeks to evaluate through a modeling approach not only the costs and health effects of intervention but also the consequences of a policy of universal public finance (UPF) on health and financial outcomes across income quintiles. Using plausible values for input parameters, we conclude that health gains from UPF are concentrated among the poorest, whereas the non-health gains in the form of out-of-pocket private expenditures averted due to UPF are concentrated among the richest income quintiles. Value of insurance is the highest for the poorest quintile and declines with income. Universal public finance can play a crucial role in ameliorating the adverse economic and social consequences of schizophrenia and its treatment in resource-constrained settings where health insurance coverage is generally poor. This paper shows the potential distributional and financial risk protection effects of treating schizophrenia.

Associations of personal and family preeclampsia history with the risk of early-, intermediate- and late-onset preeclampsia.

Science.gov (United States)

Boyd, Heather A; Tahir, Hassaan; Wohlfahrt, Jan; Melbye, Mads

2013-12-01

Preeclampsia encompasses multiple conditions of varying severity. We examined the recurrence and familial aggregation of preeclampsia by timing of onset, which is a marker for severity. We ascertained personal and family histories of preeclampsia for women who delivered live singletons in Denmark in 1978-2008 (almost 1.4 million pregnancies). Using log-linear binomial regression, we estimated risk ratios for the associations between personal and family histories of preeclampsia and the risk of early-onset (before 34 weeks of gestation, which is typically the most severe), intermediate-onset (at 34-36 weeks of gestation), and late-onset (after 36 weeks of gestation) preeclampsia. Previous early-, intermediate-, or late-onset preeclampsia increased the risk of recurrent preeclampsia with the same timing of onset 25.2 times (95% confidence interval (CI): 21.8, 29.1), 19.7 times (95% CI: 17.0, 22.8), and 10.3 times (95% CI: 9.85, 10.9), respectively, compared with having no such history. Preeclampsia in a woman's family was associated with a 24%-163% increase in preeclampsia risk, with the strongest associations for early- and intermediate-onset preeclampsia in female relatives. Preeclampsia in the man's family did not affect a woman's risk of early-onset preeclampsia and was only weakly associated with her risks of intermediate- and late-onset preeclampsia. Early-onset preeclampsia appears to have the largest genetic component, whereas environmental factors likely contribute most to late-onset preeclampsia. The role of paternal genes in the etiology of preeclampsia appears to be limited.

Breastfeeding and risk of schizophrenia in the Copenhagen Perinatal Cohort

DEFF Research Database (Denmark)

Sørensen, Holger Jelling; Mortensen, Erik Lykke; Reinisch, J M

2005-01-01

) and 5170 (76%) had been breastfed longer. Maternal schizophrenia, parental social status, single mother status and gender were included as covariates in a multiple regression analysis of the effect of early weaning on the risk of hospitalization with schizophrenia. RESULTS: The sample comprised 93 cases......OBJECTIVE: The aim was to study whether early weaning from breastfeeding may be associated with increased risk of schizophrenia. METHOD: The current sample comprises 6841 individuals from the Copenhagen Perinatal Cohort of whom 1671 (24%) had been breastfed for 2 weeks or less (early weaning...... of schizophrenia (1.4%). Maternal schizophrenia was the strongest risk factor and a significant association between single mother status and elevated offspring risk of schizophrenia was also observed. Early weaning was significantly related to later schizophrenia in both unadjusted and adjusted analyses (adjusted...

Is lead exposure in early life an environmental risk factor for Schizophrenia? Neurobiological connections and testable hypotheses.

Science.gov (United States)

Guilarte, Tomás R; Opler, Mark; Pletnikov, Mikhail

2012-06-01

Schizophrenia is a devastating neuropsychiatric disorder of unknown etiology. There is general agreement in the scientific community that schizophrenia is a disorder of neurodevelopmental origin in which both genes and environmental factors come together to produce a schizophrenia phenotype later in life. The challenging questions have been which genes and what environmental factors? Although there is evidence that different chromosome loci and several genes impart susceptibility for schizophrenia; and epidemiological studies point to broad aspects of the environment, only recently there has been an interest in studying gene × environment interactions. Recent evidence of a potential association between prenatal lead (Pb(2+)) exposure and schizophrenia precipitated the search for plausible neurobiological connections. The most promising connection is that in schizophrenia and in developmental Pb(2+) exposure there is strong evidence for hypoactivity of the N-methyl-d-aspartate (NMDA) subtype of excitatory amino acid receptors as an underlying neurobiological mechanism in both conditions. A hypofunction of the NMDA receptor (NMDAR) complex during critical periods of development may alter neurobiological processes that are essential for brain growth and wiring, synaptic plasticity and cognitive and behavioral outcomes associated with schizophrenia. We also describe on-going proof of concept gene-environment interaction studies of early life Pb(2+) exposure in mice expressing the human mutant form of the disrupted in schizophrenia 1 (DISC-1) gene, a gene that is strongly associated with schizophrenia and allied mental disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Is Lead Exposure in Early Life An Environmental Risk Factor for Schizophrenia? Neurobiological Connections and Testable Hypotheses

Science.gov (United States)

Guilarte, Tomás R.; Opler, Mark; Pletnikov, Mikhail

2013-01-01

Schizophrenia is a devastating neuropsychiatric disorder of unknown etiology. There is general agreement in the scientific community that schizophrenia is a disorder of neurodevelopmental origin in which both genes and environmental factors come together to produce a schizophrenia phenotype later in life. The challenging questions have been which genes and what environmental factors? Although there is evidence that different chromosome loci and several genes impart susceptibility for schizophrenia; and epidemiological studies point to broad aspects of the environment, only recently there has been an interest in studying gene × environment interactions. Recent evidence of a potential association between prenatal lead (Pb2+) exposure and schizophrenia precipitated the search for plausible neurobiological connections. The most promising connection is that in schizophrenia and in developmental Pb2+ exposure there is strong evidence for hypoactivity of the N-methyl-d-aspartate (NMDA) subtype of excitatory amino acid receptors as an underlying neurobiological mechanism in both conditions. A hypofunction of the NMDA receptor (NMDAR) complex during critical periods of development may alter neurobiological processes that are essential for brain growth and wiring, synaptic plasticity and cognitive and behavioral outcomes associated with schizophrenia. We also describe on-going proof of concept gene-environment interaction studies of early life Pb2+ exposure in mice expressing the human mutant form of the disrupted in schizophrenia 1 (DISC-1) gene, a gene that is strongly associated with schizophrenia and allied mental disorders. PMID:22178136

Convergence of genetic and environmental factors on parvalbumin-positive interneurons in schizophrenia

Directory of Open Access Journals (Sweden)

Zhihong eJiang

2013-09-01

Full Text Available Schizophrenia etiology is thought to involve an interaction between genetic and environmental factors during postnatal brain development. However, there is a fundamental gap in our understanding of the molecular mechanisms by which environmental factors interact with genetic susceptibility to trigger symptom onset and disease progression. In this review, we summarize the most recent findings implicating oxidative stress as one mechanism by which environmental insults, especially early life social stress, impact the development of schizophrenia. Based on a review of the literature and the results of our own animal model, we suggest that environmental stressors such as social isolation render parvalbumin-positive interneurons vulnerable to oxidative stress. We previously reported that social isolation stress exacerbates many of the schizophrenia-like phenotypes seen in a conditional genetic mouse model of schizophrenia in which NMDARs are selectively ablated in half of cortical and hippocampal interneurons during early postnatal development (Belforte et al., 2010. We have since revealed that this social isolation-induced effect is caused by impairments in the antioxidant defense capacity in the parvalbumin-positive interneurons in which NMDARs are ablated. We propose that this effect is mediated by the down-regulation of PGC-1α, a master regulator of mitochondrial energy metabolism and anti-oxidant defense, following the deletion of NMDARs (Jiang et al, 2013. Other potential molecular mechanisms underlying redox dysfunction upon gene and environmental interaction will be discussed, with a focus on the unique properties of parvalbumin-positive interneurons.

The impact of initiation: Early onset marijuana smokers demonstrate altered Stroop performance and brain activation

Directory of Open Access Journals (Sweden)

K.A. Sagar

2015-12-01

Full Text Available Marijuana (MJ use is on the rise, particularly among teens and emerging adults. This poses serious public health concern, given the potential deleterious effects of MJ on the developing brain. We examined 50 chronic MJ smokers divided into early onset (regular MJ use prior to age 16; n = 24 and late onset (age 16 or later; n = 26, and 34 healthy control participants (HCs. All completed a modified Stroop Color Word Test during fMRI. Results demonstrated that MJ smokers exhibited significantly poorer performance on the Interference subtest of the Stroop, as well as altered patterns of activation in the cingulate cortex relative to HCs. Further, early onset MJ smokers exhibited significantly poorer performance relative to both HCs and late onset smokers. Additionally, earlier age of MJ onset as well as increased frequency and magnitude (grams/week of MJ use were predictive of poorer Stroop performance. fMRI results revealed that while late onset smokers demonstrated a more similar pattern of activation to the control group, a different pattern was evident in the early onset group. These findings underscore the importance of assessing age of onset and patterns of MJ use and support the need for widespread education and intervention efforts among youth.

The rationale for early intervention in schizophrenia and related disorders

DEFF Research Database (Denmark)

Nordentoft, Merete; Jeppesen, Pia; Petersen, Lone

2009-01-01

and this relationship holds even after controlling for the potential confounding variable of premorbid functioning. In Norway, the early Treatment and Intervention in PSychosis study demonstrated that duration of untreated psychosis is amenable to intervention with the combination of educational campaigns...... and the initiation of treatment. The average duration of untreated psychosis is around 1–2 years. During this period, brain function may continue to deteriorate and social networks can be irreversibly damaged. Studies have consistently linked longer duration of untreated psychosis with poorer outcomes......, adherence to treatment, comorbid drug abuse, relapse and readmission. Some benefits persist after cessation of the intervention. Conclusions: Early intervention in schizophrenia is justified to reduce the negative personal and social impact of prolonged periods of untreated symptoms. Furthermore, phase...

A significant causal association between C-reactive protein levels and schizophrenia

OpenAIRE

Inoshita, Masatoshi; Numata, Shusuke; Tajima, Atsushi; Kinoshita, Makoto; Umehara, Hidehiro; Nakataki, Masahito; Ikeda, Masashi; Maruyama, Souichiro; Yamamori, Hidenaga; Kanazawa, Tetsufumi; Shimodera, Shinji; Hashimoto, Ryota; Imoto, Issei; Yoneda, Hiroshi; Iwata, Nakao

2016-01-01

Many observational studies have shown elevated blood CRP levels in schizophrenia compared with controls, and one population-based prospective study has reported that elevated plasma CRP levels were associated with late- and very-late-onset schizophrenia. Furthermore, several clinical studies have reported the efficacy of anti-inflammatory drugs on the symptoms in patients with schizophrenia. However, whether elevated CRP levels are causally related to schizophrenia is not still established be...

Cognitive and Neuroplasticity Mechanisms by Which Congenital or Early Blindness May Confer a Protective Effect Against Schizophrenia

Science.gov (United States)

Silverstein, Steven M.; Wang, Yushi; Keane, Brian P.

2013-01-01

Several authors have noted that there are no reported cases of people with schizophrenia who were born blind or who developed blindness shortly after birth, suggesting that congenital or early (C/E) blindness may serve as a protective factor against schizophrenia. By what mechanisms might this effect operate? Here, we hypothesize that C/E blindness offers protection by strengthening cognitive functions whose impairment characterizes schizophrenia, and by constraining cognitive processes that exhibit excessive flexibility in schizophrenia. After briefly summarizing evidence that schizophrenia is fundamentally a cognitive disorder, we review areas of perceptual and cognitive function that are both impaired in the illness and augmented in C/E blindness, as compared to healthy sighted individuals. We next discuss: (1) the role of neuroplasticity in driving these cognitive changes in C/E blindness; (2) evidence that C/E blindness does not confer protective effects against other mental disorders; and (3) evidence that other forms of C/E sensory loss (e.g., deafness) do not reduce the risk of schizophrenia. We conclude by discussing implications of these data for designing cognitive training interventions to reduce schizophrenia-related cognitive impairment, and perhaps to reduce the likelihood of the development of the disorder itself. PMID:23349646

Cognitive and Neuroplasticity Mechanisms By Which Congenital or Early Blindness May Confer a Protective Effect Against Schizophrenia

Directory of Open Access Journals (Sweden)

Steven eSilverstein

2013-01-01

Full Text Available Several authors have noted that there are no reported cases of people with schizophrenia who were born blind or who developed blindness shortly after birth, suggesting that congenital or early (C/E blindness may serve as a protective factor against schizophrenia. By what mechanisms might this effect operate? Here, we hypothesize that C/E blindness offers protection by strengthening cognitive functions whose impairment characterizes schizophrenia, and by constraining cognitive processes that exhibit excessive flexibility in schizophrenia. After briefly summarizing evidence that schizophrenia is fundamentally a cognitive disorder, we review areas of perceptual and cognitive function that are both impaired in the illness and augmented in C/E blindness, as compared to healthy sighted individuals. We next discuss: 1 the role of neuroplasticity in driving these cognitive changes in C/E blindness; 2 evidence that C/E blindness does not confer protective effects against other mental disorders; and 3 evidence that other forms of C/E sensory loss (e.g., deafness do not reduce the risk of schizophrenia. We conclude by discussing implications of these data for designing cognitive training interventions to reduce schizophrenia-related cognitive impairment, and perhaps to reduce the likelihood of the development of the disorder itself.

Early-Onset Bipolar Disorder: Characteristics and Outcomes in the Clinic.

Science.gov (United States)

Connor, Daniel F; Ford, Julian D; Pearson, Geraldine S; Scranton, Victoria L; Dusad, Asha

2017-12-01

To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially

F247. INTERNALIZED STIGMA HAS A STRONGER RELATIONSHIP WITH INTRINSIC MOTIVATION COMPARED TO AMOTIVATION IN EARLY PHASE AND PROLONGED SCHIZOPHRENIA

Science.gov (United States)

Firmin, Ruth; Luther, Lauren; Lysaker, Paul; Vohs, Jennifer

2018-01-01

Abstract Background Motivation deficits predict decreased functioning in schizophrenia. Recent work suggests deficits reflect challenges in separate domains: intrinsic motivation (one’s internal drive to engage in a behavior out of enjoyment or interest) and amotivation (one’s broader decrease in motivated behavior linked to avolition and anhedonia). Internalized stigma is another determinant of functioning for people with schizophrenia that may impact motivation. However, little is known about these relationships, including which aspects of motivation it may impact nor when these links emerge. Identifying the link between these constructs may help to identify whether internalized stigma may be a novel treatment target to facilitate improvements in motivation. Methods Forty adults with early phase schizophrenia and 66 adults with prolonged schizophrenia completed measures of internalized stigma, intrinsic motivation, and amotivation. Pearson’s correlations were examined followed by Fischer’s r-to-z transformations to compare differences in the magnitude of associations between internalized stigma and intrinsic motivation and internalized stigma and amotivation among the first episode and prolonged samples. Next, we conducted stepwise regressions to examine whether internalized stigma was associated with intrinsic motivation above and beyond associations with amotivation in each sample. Results In the early phase sample, the association between internalized stigma was greater with intrinsic motivation (r=-0.48, p=.00) compared to amotivation (r=0.27, p=0.10). Associations with internalized stigma in the prolonged sample were also greater with intrinsic motivation (r=-0.30, p=0.02) versus amotivation (r=0.19, p=0.12). The magnitude of the associations between internalized stigma and intrinsic motivation (z=1.03, p=0.15) and between internalized stigma and amotivation (z=0.41, p = 0.34) did not significantly differ when comparing phase of illness. Regression

Early-Onset Creutzfeldt-Jakob Disease Mimicking Immune-Mediated Encephalitis

Directory of Open Access Journals (Sweden)

Wietse A. Wiels

2018-04-01

Full Text Available ObjectivesThe objective of this study is to explore the clinical, radiological, and pathological manifestations of a rare subtype of prion disease and their implication for differential diagnosis in case of an early onset neuropsychiatric deterioration.MethodsWe discuss a patients’ clinical history, as well as the string of investigations and symptomatological evolution that finally led to a pathological diagnosis.ResultsOur patient had the extremely rare VV1 type sporadic Creutzfeldt-Jakob disease (sCJD. We explain the differential diagnosis of progressive encephalomyelitis with rigidity and myoclonus and its implications for treatment.ConclusionsCJD, especially the VV1 subtype, can present at an early age with an insidious psychiatric onset. Classical findings of prion disease—14-3-3 protein, PSWC on electroencephalography, and magnetic resonance imaging patterns—are not always present. The presence of neural autoantibodies does not always implicate pathogenicity in the presence of other neurological/neurodegenerative conditions.

Somatic Diseases and Conditions Before the First Diagnosis of Schizophrenia

DEFF Research Database (Denmark)

Sørensen, Holger J; Nielsen, Philip Finn Rising; Benros, Michael E

2015-01-01

OBJECTIVE: Schizophrenia is associated with excess physical comorbidity. Yet, to our knowledge, large studies are lacking on the associations with somatic diseases before the onset of schizophrenia. The authors conducted a nationwide study of the full spectrum of treated somatic diseases before t...

Is schizophrenia developmental adaptation to environmental menaces?

Science.gov (United States)

Goto, Yukiori; Lee, Young-A

2011-11-01

Schizophrenia is a devastating mental disorder, with its symptoms typically emerging during late adolescence to young adulthood. In contrast, accumulating evidence suggests that schizophrenia is a developmental disorder in which brain abnormalities may occur even before birth. This has brought the major challenge to explain such discrepancy of brain deficits occurring during prenatal period and emergence of symptoms during adulthood. A number of ideas have been proposed to explain delayed emergence of symptoms at adulthood in relation to maturational processes of various brain systems during adolescence. However, these still lack clear relationship to prenatal deficits. Thus, a key to better understand the pathology of schizophrenia is to unveil a theory or model that can explain the relationship between prenatal deficits and post-pubertal onset of symptoms. Here we propose a novel hypothesis, along with discussion of several lines of evidences supporting it, that schizophrenia may not be a disorder in a strict sense, but rather be understood as the biological state occurring as consequence of adaptation to severe environmental conditions during the prenatal periods, which explains the relationship between prenatal developmental deficits and the postnatal maturational process for onset of symptoms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genetic evidence for the association between the early growth response 3 (EGR3 gene and schizophrenia.

Directory of Open Access Journals (Sweden)

Rui Zhang

Full Text Available Recently, two genome scan meta-analysis studies have found strong evidence for the association of loci on chromosome 8p with schizophrenia. The early growth response 3 (EGR3 gene located in chromosome 8p21.3 was also found to be involved in the etiology of schizophrenia. However, subsequent studies failed to replicate this finding. To investigate the genetic role of EGR3 in Chinese patients, we genotyped four SNPs (average interval ∼2.3 kb in the chromosome region of EGR3 in 470 Chinese schizophrenia patients and 480 healthy control subjects. The SNP rs35201266 (located in intron 1 of EGR3 showed significant differences between cases and controls in both genotype frequency distribution (P = 0.016 and allele frequency distribution (P = 0.009. Analysis of the haplotype rs35201266-rs3750192 provided significant evidence for association with schizophrenia (P = 0.0012; a significant difference was found for the common haplotype AG (P = 0.0005. Furthermore, significant associations were also found in several other two-, and three-SNP tests of haplotype analyses. The meta-analysis revealed a statistically significant association between rs35201266 and schizophrenia (P = 0.0001. In summary, our study supports the association of EGR3 with schizophrenia in our Han Chinese sample, and further functional exploration of the EGR3 gene will contribute to the molecular basis for the complex network underlying schizophrenia pathogenesis.

Olanzapine approved for the acute treatment of schizophrenia or manic/mixed episodes associated with bipolar I disorder in adolescent patients

Directory of Open Access Journals (Sweden)

Ann E Maloney

2010-11-01

Full Text Available Ann E Maloney1,2, Linmarie Sikich31Maine Medical Center Research Institute, Scarborough, ME, USA; 2Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA; 3Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USABackground: Severe and persistent mental illnesses in children and adolescents, such as early-onset schizophrenia spectrum (EOSS disorders and pediatric bipolar disorder (pedBP, are increasingly recognized. Few treatments have demonstrated efficacy in rigorous clinical trials. Enduring response to current medications appears limited. Recently, olanzapine was approved for the treatment of adolescents with schizophrenia or acute manic/mixed episodes in pedBP.Methods: PubMed searches were conducted for olanzapine combined with pharmacology, schizophrenia, or bipolar disorder. Searches related to schizophrenia and bipolar disorder were limited to children and adolescents. The bibliographies of the retrieved articles were hand-checked for additional relevant studies. The epidemiology, phenomenology, and treatment of EOSS and pedBP, and olanzapine’s pharmacology are reviewed. Studies of olanzapine treatment in youth with EOSS and pedBP are examined.Results: Olanzapine is efficacious for EOSS and pedBP. However, olanzapine is not more efficacious than risperidone, molindone, or haloperidol in EOSS and is less efficacious than clozapine in treatment-resistant EOSS. No comparative trials have been done in pedBP. Olanzapine is associated with weight gain, dyslipidemia, and transaminase elevations in youth. Extrapyramidal symptoms, neuroleptic malignant syndrome, and blood dyscrasias have also been reported but appear rare.Conclusions: The authors conclude that olanzapine should be considered a second-line agent in EOSS and pedBP due to its risks for significant weight gain and lipid dysregulation. Awareness of the consistent weight and metabolic changes observed in olanzapine

Parental and Child Characteristics Related to Early-Onset Disordered Eating: A Systematic Review.

Science.gov (United States)

Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia; Andersen, Anne-Marie Nybo

2015-01-01

After participating in this activity, learners should be better able to: Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. Eating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full-blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating

Deficient multisensory integration in schizophrenia: an event-related potential study.

Science.gov (United States)

Stekelenburg, Jeroen J; Maes, Jan Pieter; Van Gool, Arthur R; Sitskoorn, Margriet; Vroomen, Jean

2013-07-01

In many natural audiovisual events (e.g., the sight of a face articulating the syllable /ba/), the visual signal precedes the sound and thus allows observers to predict the onset and the content of the sound. In healthy adults, the N1 component of the event-related brain potential (ERP), reflecting neural activity associated with basic sound processing, is suppressed if a sound is accompanied by a video that reliably predicts sound onset. If the sound does not match the content of the video (e.g., hearing /ba/ while lipreading /fu/), the later occurring P2 component is affected. Here, we examined whether these visual information sources affect auditory processing in patients with schizophrenia. The electroencephalography (EEG) was recorded in 18 patients with schizophrenia and compared with that of 18 healthy volunteers. As stimuli we used video recordings of natural actions in which visual information preceded and predicted the onset of the sound that was either congruent or incongruent with the video. For the healthy control group, visual information reduced the auditory-evoked N1 if compared to a sound-only condition, and stimulus-congruency affected the P2. This reduction in N1 was absent in patients with schizophrenia, and the congruency effect on the P2 was diminished. Distributed source estimations revealed deficits in the network subserving audiovisual integration in patients with schizophrenia. The results show a deficit in multisensory processing in patients with schizophrenia and suggest that multisensory integration dysfunction may be an important and, to date, under-researched aspect of schizophrenia. Copyright © 2013. Published by Elsevier B.V.

STAT4 polymorphism is associated with early-onset type 1 diabetes, but not with late-onset type 1 diabetes.

Science.gov (United States)

Lee, Hye-Soon; Park, Hyewon; Yang, Seiwon; Kim, Dukhee; Park, Yongsoo

2008-12-01

In an effort to discover non-HLA genes affecting susceptibility to type 1 diabetes (T1D), we have investigated the association of polymorphisms in STAT4, an important signaling molecule of IL-12, gammaIFN, and IL-23, in a sample of 389 T1D patients and 152 nondiabetic controls in Korea. Four SNPs on chromosome 2q, which were recently found to be associated with rheumatoid arthritis, were examined for association and linkage disequilibrium. We found that neither alleles or genotypes among all four SNPs nor reconstructed haplotypes of the three SNPs within the same LD block (rs7574865, rs8179673, and rs10181656) were associated with susceptibility to T1D. When we stratified T1D patients into early-onset and late-onset subgroups on the basis of fewer or more than 7.8 years of age at diagnosis, however, the minor alleles of three SNPs (rs7574865, rs8179673, and rs10181656) showed a significant association with susceptibility to T1D in the early-onset subgroup (i.e., rs7574865, OR = 1.44 [1.03-2.01], P rs7574865, rs8179673, and rs10181656) showed very comparable degrees of risk for T1D. The age at diagnosis is lowest in the patients carrying the homozygotes of a minor allele, middle in the heterozygotes, and highest in the homozygotes of a major allele, suggesting the dosage effects of risk alleles on the age of onset of disease. Recognizing that only the early-onset cases might represent the true autoimmune T1D in Asian populations, we see that STAT4 alleles and haplotype might influence cytokine signaling and, therefore, development of T1D.

Cognitive reserve as a predictor of two year neuropsychological performance in early onset first-episode schizophrenia.

Science.gov (United States)

de la Serna, Elena; Andrés-Perpiñá, Susana; Puig, Olga; Baeza, Inmaculada; Bombin, Igor; Bartrés-Faz, David; Arango, Celso; Gonzalez-Pinto, Ana; Parellada, Mara; Mayoral, María; Graell, Montserrat; Otero, Soraya; Guardia, Joan; Castro-Fornieles, Josefina

2013-01-01

The concept of cognitive reserve (CR) has been defined as individual differences in the efficient utilization of brain networks which allow some people to cope better than others with brain pathology. CR has been developed mainly in the field of aging and dementia after it was observed that there appears to be no direct relationship between the degree of brain pathology and the severity of clinical manifestations of this damage. The present study applies the concept of CR to a sample of children and adolescents with a first episode of schizophrenia, aiming to assess the possible influence of CR on neuropsychological performance after two year follow-up, controlling for the influence of clinical psychopathology. 35 patients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder (SSD) and 98 healthy controls (HC) matched for age and gender were included. CR was assessed at baseline, taking into account premorbid IQ, educational-occupational level and leisure activities. Clinical and neuropsychological assessments were completed by all patients at two year follow-up. The CR proxy was able to predict working memory and attention at two year follow-up. Verbal memory and cognitive flexibility were not predicted by any of the variables included in the regression model. The SSD group obtained lower scores than HC on CR. CR measures correctly classified 79.8% of the sample as being SSD or HC. Lower scores on CR were observed in SSD than in HC and the CR measure correctly classified a high percentage of the sample into the two groups. CR may predict SSD performance on working memory and attention tasks. Copyright © 2012 Elsevier B.V. All rights reserved.

Stigma toward psychosis and its formulation process: prejudice and discrimination against early stages of schizophrenia.

Science.gov (United States)

Baba, Yoko; Nemoto, Takahiro; Tsujino, Naohisa; Yamaguchi, Taiju; Katagiri, Naoyuki; Mizuno, Masafumi

2017-02-01

Stigma toward psychosis can prevent social attendance and help-seeking behavior. Early detection and intervention has been shown to improve patient outcome in schizophrenia. The aim of this study was to reveal the characteristics and formulation process of stigma toward each clinical stage of schizophrenia, taking people's backgrounds into consideration. The participants consisted of three groups: general public, patients with mental illness, and psychiatric professionals. We performed a survey examining stigmas toward people with psychotic-like-experiences (PLE), at-risk mental state for psychosis (ARMS), schizophrenia, or depression. Prejudice was measured using a 21-item questionnaire, and discrimination was measured using the Social Distance Scale. The participants consisted of 149 people from the general public, 97 patients, and 119 psychiatric professionals. Generally, a similar pattern was observed among the groups in which prejudice and discrimination against PLE was mildest, followed by that against ARMS and depression, and finally schizophrenia. When the stigma of the general public was compared with that of psychiatric professionals, the prejudice and discrimination against PLE of the general public were both lower than those of the psychiatric professionals. However, the prejudice of the general public was stronger than that of the professionals for ARMS. Furthermore, the discrimination of the general public was stronger than that of the professionals for schizophrenia. The stigmas of mental illness differed according to the clinical stage, although the pattern of severity was similar among the three groups. A formulation process is suggested in which stigma toward schizophrenia develops from an attitudinal property (prejudice) against ARMS and a behavioral property (discrimination) against schizophrenia. Copyright © 2016 Elsevier Inc. All rights reserved.

Deficits in Facial Expression Recognition in Male Adolescents with Early-Onset or Adolescence-Onset Conduct Disorder

Science.gov (United States)

Fairchild, Graeme; Van Goozen, Stephanie H. M.; Calder, Andrew J.; Stollery, Sarah J.; Goodyer, Ian M.

2009-01-01

Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that…

Changes in the pattern of substance abuse after the onset of psychosis.

Science.gov (United States)

Kaiser, Roland; Löhrer, Frank; Morgan, Vera; Hambrecht, Martin

2005-06-01

The aim of this study was to examine early signs of psychosis in patients suffering from both drug dependence and schizophrenia, compared to a control group of drug-addicted patients without a comorbid psychotic disorder, and to assess whether the presence of these signs was related to changes in the pattern of substance abuse. In a rehabilitation hospital for young addicts, 32 patients with a comorbid diagnosis of schizophrenia and 30 patients without the diagnosis of a psychotic disorder, were assessed using the Interview for the Retrospective Assessment of the Onset of Schizophrenia. Information relating to 64 signs of early psychosis was collected from every patient. From the 64 signs, five groups of symptoms were defined: non-specific and precursor symptoms; non-specific and depressive symptoms; negative symptoms; positive symptoms; and impaired social adjustment. The semiquantitative pattern of substance abuse for each 1-year interval over the previous 10 years was investigated using the categories of chapter F1 of ICD-10 and including an additional category "biological drugs". The relationship between the pattern of substance abuse and the presence of early signs was assessed using anova and non-parametric statistical methods. The results indicate that the defined pathological symptomatology greatly influences the pattern of consumption of psychoactive substances in both the psychosis group and the control group. The group factor exerted the greatest influence within the categories "biological drugs" and "other stimulants", where the "psychosis and addiction group" consumed significantly more than the control group. There is a subgroup of non-psychotic addicted patients whose pattern of psychoactive substance abuse is similar to that found in addicted patients suffering from schizophrenia. It may be helpful to systematically identify this subgroup with regard to possible therapeutic implications, particularly with regard to possible pharmacological treatment

Conflict-related anterior cingulate functional connectivity is associated with past suicidal ideation and behavior in recent-onset schizophrenia.

Science.gov (United States)

Minzenberg, Michael J; Lesh, Tyler; Niendam, Tara; Yoon, Jong H; Cheng, Yaoan; Rhoades, Remy; Carter, Cameron S

2015-06-01

Suicide is highly prevalent in schizophrenia (SZ), yet it remains unclear how suicide risk factors such as past suicidal ideation or behavior relate to brain function. Circuits modulated by the prefrontal cortex (PFC) are altered in SZ, including in dorsal anterior cingulate cortex (dACC) during conflict-monitoring (an important component of cognitive control), and dACC changes are observed in post-mortem studies of heterogeneous suicide victims. We tested whether conflict-related dACC functional connectivity is associated with past suicidal ideation and behavior in SZ. 32 patients with recent-onset of DSM-IV-TR-defined SZ were evaluated with the Columbia Suicide Severity Rating Scale and functional MRI during cognitive control (AX-CPT) task performance. Group-level regression models relating past history of suicidal ideation or behavior to dACC-seeded functional connectivity during conflict-monitoring controlled for severity of depression, psychosis and impulsivity. Past suicidal ideation was associated with relatively higher functional connectivity of the dACC with the precuneus during conflict-monitoring. Intensity of worst-point past suicidal ideation was associated with relatively higher dACC functional connectivity in medial parietal lobe and striato-thalamic nuclei. In contrast, among those with past suicidal ideation (n = 17), past suicidal behavior was associated with lower conflict-related dACC connectivity with multiple lateral and medial PFC regions, parietal and temporal cortical regions. This study provides unique evidence that recent-onset schizophrenia patients with past suicidal ideation or behavior show altered dACC-based circuit function during conflict-monitoring. Suicidal ideation and suicidal behavior have divergent patterns of associated dACC functional connectivity, suggesting a differing pattern of conflict-related brain dysfunction with these two distinct features of suicide phenomenology. Published by Elsevier Ltd.

[Analysis of gene mutation of early onset epileptic spasm with unknown reason].

Science.gov (United States)

Yang, X; Pan, G; Li, W H; Zhang, L M; Wu, B B; Wang, H J; Zhang, P; Zhou, S Z

2017-11-02

Objective: To summarize the gene mutation of early onset epileptic spasm with unknown reason. Method: In this prospective study, data of patients with early onset epileptic spasm with unknown reason were collected from neurological department of Children's Hospital of Fudan University between March 2016 and December 2016. Patients with known disorders such as infection, metabolic, structural, immunological problems and known genetic mutations were excluded. Patients with genetic disease that can be diagnosed by clinical manifestations and phenotypic characteristics were also excluded. Genetic research methods included nervous system panel containing 1 427 epilepsy genes, whole exome sequencing (WES), analysis of copy number variation (CNV) and karyotype analysis of chromosome. The basic information, phenotypes, genetic results and the antiepileptic treatment of patients were analyzed. Result: Nine of the 17 cases with early onset epileptic spasm were boys and eight were girls. Patients' age at first seizure onset ranged from 1 day after birth to 8 months (median age of 3 months). The first hospital visit age ranged from 1 month to 2 years (median age of 4.5 months). The time of following-up ranged from 8 months to 3 years and 10 months. All the 17 patients had early onset epileptic spasm. Video electroencephalogram was used to monitor the spasm seizure. Five patients had Ohtahara syndrome, 10 had West syndrome, two had unclear classification. In 17 cases, 10 of them had detected pathogenic genes. Nine cases had point mutations, involving SCN2A, ARX, UNC80, KCNQ2, and GABRB3. Except one case of mutations in GABRB3 gene have been reported, all the other cases had new mutations. One patient had deletion mutation in CDKL5 gene. One CNV case had 6q 22.31 5.5MB repeats. Ten cases out of 17 were using 2-3 antiepileptic drugs (AEDs) and the drugs had no effect. Seven cases used adrenocorticotropic hormone (ACTH) and prednisone besides AEDs (a total course for 8 weeks

Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

Science.gov (United States)

Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

2016-12-01

Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

Disease and genetic contributions toward local tissue volume disturbances in schizophrenia: a tensor-based morphometry study.

Science.gov (United States)

Yang, Yaling; Nuechterlein, Keith H; Phillips, Owen R; Gutman, Boris; Kurth, Florian; Dinov, Ivo; Thompson, Paul M; Asarnow, Robert F; Toga, Arthur W; Narr, Katherine L

2012-09-01

Structural brain deficits, especially frontotemporal volume reduction and ventricular enlargement, have been repeatedly reported in patients with schizophrenia. However, it remains unclear whether brain structural deformations may be attributable to disease-related or genetic factors. In this study, the structural magnetic resonance imaging data of 48 adult-onset schizophrenia patients, 65 first-degree nonpsychotic relatives of schizophrenia patients, 27 community comparison (CC) probands, and 73 CC relatives were examined using tensor-based morphometry (TBM) to isolate global and localized differences in tissue volume across the entire brain between groups. We found brain tissue contractions most prominently in frontal and temporal regions and expansions in the putamen/pallidum, and lateral and third ventricles in schizophrenia patients when compared with unrelated CC probands. Results were similar, though less prominent when patients were compared with their nonpsychotic relatives. Structural deformations observed in unaffected patient relatives compared to age-similar CC relatives were suggestive of schizophrenia-related genetic liability and were pronounced in the putamen/pallidum and medial temporal regions. Schizophrenia and genetic liability effects for the putamen/pallidum were confirmed by regions-of-interest analysis. In conclusion, TBM findings complement reports of frontal, temporal, and ventricular dysmorphology in schizophrenia and further indicate that putamen/pallidum enlargements, originally linked mainly with medication exposure in early studies, also reflect a genetic predisposition for schizophrenia. Thus, brain deformation profiles revealed in this study may help to clarify the role of specific genetic or environmental risk factors toward altered brain morphology in schizophrenia.

RELATIONSHIP BETWEEN TOBACCO DEPENDENCE AND SCHIZOPHRENIA

Directory of Open Access Journals (Sweden)

Wayan Widhidewi

2014-02-01

Full Text Available Tobacco dependence in schizophrenia patients is a problem that got more concern, withfew treatment options. Peoples with schizophrenia have a prevalence rate of cigarettesmoking two until four times higher than the general population. Consequently, patientsalso have a lower smoking quit rate than the general population. Tobacco dependence inthis population may complicate symptoms and also has adverse physiological effects onpatients. Besides that, patients with schizophrenia tend to smoke more heavily thansmokers in general population. This can increased smoking-related morbidity andmortality and impose a significant financial burden on patients. Recent studiesdemonstrated that patients with schizophrenia smoke before the onset of the illness andalso start smoking earlier than the average population. Patients become psychotic earlierthan patients who do not smoke, and require higher dose of anti-psychotic medications.

CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis

NARCIS (Netherlands)

Ozen, Ahmet; Comrie, William A; Ardy, Rico C; Domínguez Conde, Cecilia; Dalgic, Buket; Beser, Ömer F; Morawski, Aaron R; Karakoc-Aydiner, Elif; Tutar, Engin; Baris, Safa; Ozcay, Figen; Serwas, Nina K; Zhang, Yu; Matthews, Helen F; Pittaluga, Stefania; Folio, Les R; Unlusoy Aksu, Aysel; McElwee, Joshua J; Krolo, Ana; Kiykim, Ayca; Baris, Zeren; Gulsan, Meltem; Ogulur, Ismail; Snapper, Scott B; Houwen, Roderick H J; Leavis, Helen L; Ertem, Deniz; Kain, Renate; Sari, Sinan; Erkan, Tülay; Su, Helen C; Boztug, Kaan; Lenardo, Michael J

2017-01-01

BACKGROUND: Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies. METHODS: We studied 11 patients with abdominal pain and diarrhea caused by early-onset protein-losing enteropathy with primary

First impression at stroke onset plays an important role in early hospital arrival.

Science.gov (United States)

Iguchi, Yasuyuki; Wada, Kuniyasu; Shibazaki, Kensaku; Inoue, Takeshi; Ueno, Yuji; Yamashita, Shinji; Kimura, Kazumi

2006-01-01

Treatment for acute ischemic stroke should be administered as soon as possible after symptom onset. The aim of this study was to investigate whether or not the patient's and bystander's first impression at stroke onset was associated with hospital arrival time. To investigate the factors influencing the prehospital delay, we prospectively interviewed consecutive stroke patients and bystanders about their first impression at the stroke onset and assessed the methods of transportation, and clinical characteristics. Early arrival was defined as a hospital arrival of within 2 h from stroke onset. One hundred thirty patients were enrolled: 82% were ischemic stroke and 18% were cerebral hemorrhage. The median interval between symptom onset and the hospital arrival was 7.5 h and 30% of patients presented within 2 h of stroke onset. First impression of stroke (odds ratios [OR] 4.56, 95% confidence interval [CI] 1.54-13.5, p=0.006), presence of consciousness disturbance (OR 4.29, CI 1.39-13.3, p=0.011), arrival through other facilities (OR 0.25, CI 0.08-0.76, p=0.015), a history of diabetes (OR 0.23, CI 0.06-0.80, p=0.028) and nocturnal onset (OR 0.19, CI 0.04-0.88, p=0.042) independently contributed to the early arrival. The first impression of patients and bystanders at stroke onset is important in order to reach hospital earlier in Japan. Public educational systems such as those, which advertise stroke warning signs, are necessary.

The Constellation of Macrovascular Risk Factors in Early Onset T2DM: A Cross-Sectional Study in Xinjiang Province, China

Directory of Open Access Journals (Sweden)

Mingchen Zhang

2018-01-01

Full Text Available Background. Despite a rapid popular of early onset type 2 diabetes (defined as diagnosis at <40 years old recently, there is a lack of studies on this population in economically undeveloped area. We aimed to investigate the risk factors of macrovascular complications in the early onset T2DM patients in Xinjiang, China. Methods. A cross-sectional survey of 1736 consecutive patients with T2DM was conducted. Macrovascular complications and risk factors were documented. Another nondiabetic population matched with age and sex was as a control group. Logistic regression analysis was performed to obtain odds ratios (OR for macrovascular complications in early and late onset T2DM, respectively. Results. The final analysis consisted of 1036 late onset and 219 early onset T2DM patients. The mean HbA1c in the early onset group was higher than that in the late onset group (9.1 ± 2.4% versus 8.3 ± 2.2%, P=0.039 despite a higher proportion of patients in the early onset group receiving insulin treatment (73.1% versus 58.7%, P<0.001. Compared to the control, early onset patients had higher blood pressure and worse lipid profiles (all P<0.01. More than half of the early onset T2DM patients already had macro- and microvascular complications, despite of their young age (39.5 ± 10.8 and short DM duration (6.6 ± 8.0. In the early onset group, women had a ~3-fold hazard of atherosclerotic plaques compared with men (OR 3.22, 95% CI 1.53–6.78. Conclusions. Patients with early onset T2DM have worse glycemic control and higher burden of atherogenic risk factors. The prevalence of macro- and microvascular complications is astonishingly high in these young adults with T2DM. Moreover, young women with T2DM are more susceptible to cardiovascular complications than their male counterpart.

Maternal left ventricular hypertrophy and diastolic dysfunction and brain natriuretic peptide concentration in early- and late-onset pre-eclampsia.

Science.gov (United States)

Borges, V T M; Zanati, S G; Peraçoli, M T S; Poiati, J R; Romão-Veiga, M; Peraçoli, J C; Thilaganathan, B

2018-04-01

Pre-eclampsia (PE) is associated with maternal cardiac remodeling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and levels of brain natriuretic peptide (BNP) in women with early-onset (< 34 weeks' gestation) vs those with late-onset (≥ 34 weeks' gestation) PE. This was a prospective, cross-sectional, observational study of 30 women with early-onset PE, 32 with late-onset PE and 23 normotensive controls. Maternal cardiac structure and diastolic function were assessed by echocardiography and plasma levels of BNP were measured by enzyme immunoassay. Early- and late-onset PE were associated with increased left ventricular mass index and relative wall thickness compared with normotensive controls. In women with early-onset PE, the prevalence of concentric hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher (both P < 0.05) compared with women with late-onset PE (16% for both). Maternal serum BNP levels were significantly higher (P < 0.05) in women with early-onset PE and correlated with relative wall thickness and left ventricular mass index. Early-onset PE is associated with more severe cardiac impairment than is late-onset PE, as evidenced by an increased prevalence of concentric hypertrophy, diastolic dysfunction and higher levels of BNP. These findings suggest that early-onset PE causes greater myocardial damage, increasing the risk of both peripartum and postpartum cardiovascular morbidity. Although these cardiovascular effects are easily identified by echocardiographic parameters and measuring BNP, further studies are needed to assess their clinical utility. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Early Onset Marfan Syndrome: Atypical Clinical Presentation of Two Cases

Directory of Open Access Journals (Sweden)

Ozyurt Abdullah

2015-06-01

Full Text Available Early onset Marfan Syndrome (eoMFS is a rare, severe form of Marfan Syndrome (MFS. The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system.

Early-onset Major Depressive Disorder in men is associated with childlessness.

Science.gov (United States)

Yates, William R; Meller, William H; Lund, Brian C; Thurber, Steve; Grambsch, Patricia L

2010-07-01

The self-reported number of children was compared for men and women from the National Epidemiologic Survey of Alcoholism and Related Conditions Survey (NESARC). Subjects with a diagnosis of major depressive disorder or bipolar disorder were compared to those without an axis I disorder. The effect of age, gender, marriage and diagnostic status on number of children was completed using multivariate analyses. Men with a history of major depressive disorder but not bipolar disorder reported higher rates of childlessness and lower mean number of children. This reduced number of children was related to an early age of onset of MDD. Thirty percent of men with an age of onset of MDD before 22 were childless compared to only 18.9% of men without an axis I disorder (Odds ratio=1.82, 95% CI=1.45-2.27). No effect of mood disorder on number of children was found in women with major depression or bipolar disorder. This study suggests that an early age of onset of major depressive disorder contributes to childlessness in men.

Early Onset Childhood Obesity and Risk of Metabolic Syndrome

Centers for Disease Control (CDC) Podcasts

This podcast features Lorena Pacheco, a doctoral student at the University of California San Diego and one of the winners of PCD's 2017 Student Research Paper Contest. Lorena answers questions about her winning research, which focuses on the relationship between early onset obesity as a risk factor for increased metabolic syndrome in Chilean children.

Early Onset Substance Use in Adolescents with Depressive, Conduct, and Comorbid Symptoms

Science.gov (United States)

Stone, Andrea L.; Vander Stoep, Ann; McCauley, Elizabeth

2016-01-01

This study investigates whether co-occurring depressive and conduct symptoms in early adolescence are associated with an elevated occurrence of early onset substance. Five hundred twenty-one sixth graders were assessed for depressive symptoms and conduct problems and underwent five substance use assessments during middle school. Logistic…

Factors associated with early response to olanzapine and clinical and functional outcomes of early responders treated for schizophrenia in the People’s Republic of China

Directory of Open Access Journals (Sweden)

Ye W

2014-05-01

Full Text Available Wenyu Ye,1 William Montgomery,2 Zbigniew Kadziola,3 Li Liu,4 Haibo Xue,4 Michael D Stensland,5 Tamas Treuer61Real World Analytics, Eli Lilly and Company, Indianapolis, IN, USA; 2Global Patient Outcomes and Real World Evidence, Eli Lilly Australia Pty Ltd, West Ryde, Australia; 3Real World Analytics Capabilities, Eli Lilly GmbH, Vienna, Austria; 4Lilly Suzhou Pharmaceutical Co, Ltd, Shanghai Branch, People’s Republic of China; 5Agile Outcomes Research, Inc., Rochester, MN, USA; 6Neuroscience Research, Eli Lilly and Company, Budapest, HungaryBackground: The aims of this analysis were to identify factors associated with early response (at 4 weeks to olanzapine treatment and to assess whether early response is associated with better longer-term outcomes for patients with schizophrenia in the People’s Republic of China.Methods: A post hoc analysis of a multi-country, 6-month, prospective, observational study of outpatients with schizophrenia or bipolar mania who initiated or switched to treatment with oral olanzapine was conducted using data from the Chinese schizophrenia subgroup (n=330. Factors associated with early response were identified using a stepwise logistic regression with baseline clinical characteristics, baseline participation in a weight control program, and adherence with antipsychotics during the first 4 weeks of treatment. Mixed models for repeated measures with baseline covariates were used to compare outcomes over time between early responders and early nonresponders to olanzapine.Results: One hundred and thirty patients (40% achieved an early response. Early response was independently predicted by higher baseline Clinical Global Impressions-Severity score (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.15–1.97, fewer years since first diagnosis (OR 0.94, CI 0.90–0.98, a greater number of social activities (OR 1.22, CI 1.05–1.40, participation in a weight control program (OR 1.81, CI 1.04–3.15, and high adherence

Analysis of early-onset bloodstream infection due to Escherichia coli infection in premature babies

OpenAIRE

Chen, I-Lun; Huang, Hsin-Chun; Wu, Chih-Te; Ou-Yang, Mei-Chen; Chung, Mei-Yung; Chen, Chih-Cheng; Suen, Jau-Ling; Hung, Chih-Hsing

2017-01-01

Abstract In early-onset bacteremia among preterm neonates, Escherichia coli (E. coli) is the main pathogen and can cause a high mortality rate. Thus, the predictive factors of mortality and extended-spectrum ?-lactamase (ESBL)-producing E. coli in preterm babies with E. coli early-onset bacteremia were reported. We retrospectively reviewed preterm neonates who had E. coli bacteremia occurring within 3 days after birth between 2004 and 2015. Maternal and perinatal information were collected fr...

Association between age at onset of psychosis and age at onset of cannabis use in non-affective psychosis.

Science.gov (United States)

Galvez-Buccollini, Juan A; Proal, Ashley C; Tomaselli, Veronica; Trachtenberg, Melissa; Coconcea, Cristinel; Chun, Jinsoo; Manschreck, Theo; Fleming, Jerry; Delisi, Lynn E

2012-08-01

Several studies have associated cannabis use with the development of schizophrenia. However, it has been difficult to disentangle the effects of cannabis from that of other illicit drugs, as previous studies have not evaluated pure cannabis users. To test whether the onset of cannabis use had an effect on the initiation of psychosis, we examined the time relationship between onset of use and onset of psychosis, restricting our analysis to a cohort of individuals who only used cannabis and no other street drugs. Fifty-seven subjects with non-affective psychoses who used cannabis prior to developing a psychosis were interviewed using the Diagnostic Interview for Genetic Studies (DIGS). The Family Interview for Genetic Studies (FIGS) was also used to interview a family informant about psychiatric illness in the patient and the entire family. Multiple linear regression techniques were used to estimate the association between variables. After adjusting for potential confounding factors such as sex, age, lifetime diagnosis of alcohol abuse or dependence, and family history of schizophrenia, the age at onset of cannabis was significantly associated with age at onset of psychosis (β=0.4, 95% CI=0.1-0.7, p=0.004) and age at first hospitalization (β=0.4, 95% CI=0.1-0.8, p=0.008). The mean time between beginning to use cannabis and onset of psychosis was 7.0±4.3. Age at onset of alcohol use was not associated with age at onset of psychosis or age at first hospitalization. Age at onset of cannabis is directly associated with age at onset of psychosis and age at first hospitalization. These associations remain significant after adjusting for potential confounding factors and are consistent with the hypothesis that cannabis could cause or precipitate the onset of psychosis after a prolonged period of time. Published by Elsevier B.V.

Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis.

Directory of Open Access Journals (Sweden)

Svati H Shah

2009-01-01

Full Text Available Neuropeptide Y (NPY is a strong candidate gene for coronary artery disease (CAD. We have previously identified genetic linkage to familial CAD in the genomic region of NPY. We performed follow-up genetic, biostatistical, and functional analysis of NPY in early-onset CAD. In familial CAD (GENECARD, N = 420 families, we found increased microsatellite linkage to chromosome 7p14 (OSA LOD = 4.2, p = 0.004 in 97 earliest age-of-onset families. Tagged NPY SNPs demonstrated linkage to CAD of a 6-SNP block (LOD = 1.58-2.72, family-based association of this block with CAD (p = 0.02, and stronger linkage to CAD in the earliest age-of-onset families. Association of this 6-SNP block with CAD was validated in: (a 556 non-familial early-onset CAD cases and 256 controls (OR 1.46-1.65, p = 0.01-0.05, showing stronger association in youngest cases (OR 1.84-2.20, p = 0.0004-0.09; and (b GENECARD probands versus non-familial controls (OR 1.79-2.06, p = 0.003-0.02. A promoter SNP (rs16147 within this 6-SNP block was associated with higher plasma NPY levels (p = 0.04. To assess a causal role of NPY in atherosclerosis, we applied the NPY1-receptor-antagonist BIBP-3226 adventitially to endothelium-denuded carotid arteries of apolipoprotein E-deficient mice; treatment reduced atherosclerotic neointimal area by 50% (p = 0.03. Thus, NPY variants associate with atherosclerosis in two independent datasets (with strong age-of-onset effects and show allele-specific expression with NPY levels, while NPY receptor antagonism reduces atherosclerosis in mice. We conclude that NPY contributes to atherosclerosis pathogenesis.

Maternal serum copeptin concentrations in early- and late-onset pre-eclampsia

Directory of Open Access Journals (Sweden)

Abdullah Tuten

2015-08-01

Conclusion: Our results suggest that copeptin levels might be useful in the evaluation of the severity of pre-eclampsia. However, copeptin might be involved in early- rather than late-onset pre-eclampsia.

Cannabis use and cognition in schizophrenia

Directory of Open Access Journals (Sweden)

Else-Marie Løberg

2009-11-01

Full Text Available People with schizophrenia frequently report cannabis use, and cannabis may be a risk factor for schizophrenia, mediated through effects on brain function and biochemistry. Thus, it is conceivable that cannabis may also influence cognitive functioning in this patients group. We report data from our own laboratory on the use of cannabis by schizophrenia patients, and review the existing literature on the effects of cannabis on cognition in schizophrenia and related psychosis. Of the 23 studies that were found, 14 reported that the cannabis users had better cognitive performance than the schizophrenia non-users. Eight studies reported no or minimal differences in cognitive performance in the two groups, but only one study reported better cognitive performance in the schizophrenia non-user group. Our own results confirm the overall impression from the literature review of better cognitive performance in the cannabis user group. These paradoxical findings may have several explanations, which are discussed. We suggest that cannabis causes a transient cognitive breakdown enabling the development of psychosis, imitating the typical cognitive vulnerability seen in schizophrenia. This is further supported by an earlier age of onset and fewer neurological soft signs in the cannabis-related schizophrenia group, suggesting an alternative pathway to psychosis.

The association of with severe early-onset pre-eclampsia

African Journals Online (AJOL)

however also found no differences in APA levels between patients with severe early-onset pre-eclampsia and controls."lO Further, Kilpatrick et a/.'°state that even Branch et a/. 6 found ACAs in only 16% of their patients. In the present study, both ACA and LAC levels were assayed, and all 4 patients had significantly raised ...

Psychosocial and psychoeducational group program for main caregiver of mentally sick in early phase of schizophrenia

Directory of Open Access Journals (Sweden)

Estíbaliz Amaro Martín

2012-03-01

Full Text Available Deinstitutionalization processes in recent times have led to a new age in relations between family and mental health professionals. Care professionals were replaced, after the psychiatric reform, for care carried out by the family without the knowledge, information and skills to assume these functions. This is the situation of many families of patients with schizophrenia.Disabling features of schizophrenia usually cause depends on their families, who take care with the consequent impact on their lives. Psychosocial interventions assessing their work and want to build an alliance with them by giving them skills and coping mechanisms to reduce adverse family atmosphere, anticipate and solve problems and reduce the expressions of anger and guilt keeping appropiate expectations. However, these actions must be enforced by providing main caregivers with the skills that enable them to gain control, this is the main target of psychoeducational programs.Today there are many people in favour of such interventions in the early stages of schizophrenia. However, it is no clear how far development of these programs is supported by evidence of effectiveness. So it has proposed a psychosocial and psychoeducational program aimed at main caregivers of patients with schizophrenia in early stages. This program will be led by a psychiatric nurse in collaboration with other professionals in the interdisciplinary team; psychiatrist, clinical psychologist and social worker. It has developed clinical trial with a control group who will receive the gide for families, caregivers and people affected, "Cómo afrontar la esquizofrenia," and an experimental group will receive, in addition to the guide, the group intervention sessions.

Suicide in the Early Stage of Schizophrenia

OpenAIRE

Ventriglio, Antonio; Gentile, Alessandro; Bonfitto, Iris; Stella, Eleonora; Mari, Massimo; Steardo, Luca; Bellomo, Antonello

2016-01-01

Suicide is a relevant leading cause of death among patients affected by schizophrenia. Even if suicidal ideation may be present in different stages of disease, some differences have been described between the risk of suicide in patients experiencing first episode of psychosis and those with long-term schizophrenia. It is particularly higher during the first year of illness and reaches a steady decline over the following years. Suicidal ideation and attempts may also be common among subjects w...

Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

Science.gov (United States)

Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

2011-01-01

Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

Early-onset alopecia and amyotrophic lateral sclerosis: a cohort study.

Science.gov (United States)

Fondell, Elinor; Fitzgerald, Kathryn C; Falcone, Guido J; O'Reilly, Eilis J; Ascherio, Alberto

2013-10-01

A recent meta-analysis of 7 genome-wide association studies on early balding (alopecia) revealed single nucleotide polymorphism variants in the region of the amyotrophic lateral sclerosis (ALS) gene TAR DNA-binding protein 43 (TARDBP/TDP-43). We therefore explored the association of early-onset alopecia and ALS in the Health Professionals Follow-up Study, a large cohort of 51,529 US men. In 1992, the participants (then aged 46-81 years) were asked to report their hair line pattern at age 45 years. During the follow-up period (1992-2008), 42 men were diagnosed with ALS. Of those, 13 had reported no alopecia, 18 had reported moderate alopecia, and 11 had reported extensive alopecia at age 45 years. Those who reported extensive alopecia had an almost 3-fold increased risk of ALS compared with those who reported no alopecia (relative risk = 2.74, 95% confidence interval: 1.23, 6.13). Furthermore, we observed a linear trend of increased risk of ALS with increasing level of balding at age 45 years (Ptrend = 0.02). In conclusion, men with early-onset alopecia seem to have a higher risk of ALS. The mechanisms underlying this association deserve further investigation.

Schizophrenia and Suicide

Directory of Open Access Journals (Sweden)

Ozlem Cetin

2011-12-01

Full Text Available Suicide is one of the major causes of premature death among patients with schizophrenia. Follow-up studies have estimated that 4-5% of these patients die by suicide. Reducing the high rates of suicide in schizophrenia is possible with understanding of predictive risk factors. Various studies have identified risk factors for suicide in schizophrenia patients. Clinical risk factors include previous suicide attempts, comorbid depression, feelings of hopelessness, concept of insight and substance abuse. Biopsychosocial factors, such as a high intelligence quotient and high level of premorbid functioning, have also been associated with an increased risk of suicide in patients with schizophrenia. The risk of suicide is considered to be highest in the early course of illness. Antipsychotic drugs, in particular clozapine and antidepressants may be helpful in reducing the risk of suicide in schizophrenia.

Disorganization at the stage of schizophrenia clinical outcome: Clinical-biological study.

Science.gov (United States)

Nestsiarovich, A; Obyedkov, V; Kandratsenka, H; Siniauskaya, M; Goloenko, I; Waszkiewicz, N

2017-05-01

According to the multidimensional model of schizophrenia, three basic psychopathological dimensions constitute its clinical structure: positive symptoms, negative symptoms and disorganization. The latter one is the newest and the least studied. Our aim was to discriminate disorganization in schizophrenia clinical picture and to identify its distinctive biological and socio-psychological particularities and associated genetic and environmental factors. We used SAPS/SANS psychometrical scales, scales for the assessment of patient's compliance, insight, social functioning, life quality. Neuropsychological tests included Wisconsin Card Sorting Test (WCST), Stroop Color-Word test. Neurophysiological examination included registration of P300 wave of the evoked cognitive auditory potentials. Environmental factors related to patient's education, family, surrounding and nicotine use, as well as subjectively significant traumatic events in childhood and adolescence were assessed. Using PCR we detected SNP of genes related to the systems of neurotransmission (COMT, SLC6A4 and DRD2), inflammatory response (IL6, TNF), cellular detoxification (GSTM1, GSTT1), DNA methylation (MTHFR, DNMT3b, DNMT1). Disorganization is associated with early schizophrenia onset and history of psychosis in family, low level of insight and compliance, high risk of committing delicts, distraction errors in WCST, lengthened P300 latency of evoked cognitive auditory potentials, low-functional alleles of genes MTHFR (rs1801133) and DNMT3b (rs2424913), high level of urbanicity and psychotraumatic events at early age. Severe disorganization at the stage of schizophrenia clinical outcome is associated with the set of specific biological and social-psychological characteristics that indicate its epigenetic nature and maladaptive social significance. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts

Directory of Open Access Journals (Sweden)

Rafaela Torres Portugal Leite

2015-01-01

Full Text Available Introduction. Bipolar disorder (BD implies risk of suicide. The age at onset (AAO of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words “bipolar disorder,” “suicide attempts,” “cannabis,” “marijuana,” “early age at onset,” and “early onset.” Results. The following percentages in bipolar patients were found: suicide attempts 3.6–42%; suicide attempts and substance use 5–60%; suicide attempts and cannabis use 15–42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear.

Feasibility of PRIME: A Cognitive Neuroscience-Informed Mobile App Intervention to Enhance Motivated Behavior and Improve Quality of Life in Recent Onset Schizophrenia.

Science.gov (United States)

Schlosser, Danielle; Campellone, Timothy; Kim, Daniel; Truong, Brandy; Vergani, Silvia; Ward, Charlie; Vinogradov, Sophia

2016-04-28

Despite improvements in treating psychosis, schizophrenia remains a chronic and debilitating disorder that affects approximately 1% of the US population and costs society more than depression, dementia, and other medical illnesses across most of the lifespan. Improving functioning early in the course of illness could have significant implications for long-term outcome of individuals with schizophrenia. Yet, current gold-standard treatments do not lead to clinically meaningful improvements in outcome, partly due to the inherent challenges of treating a population with significant cognitive and motivational impairments. The rise of technology presents an opportunity to develop novel treatments that may circumvent the motivational and cognitive challenges observed in schizophrenia. The purpose of this study was two-fold: (1) to evaluate the feasibility and acceptability of implementing a Personalized Real-Time Intervention for Motivation Enhancement (PRIME), a mobile app intervention designed to target reward-processing impairments, enhance motivation, and thereby improve quality of life in recent onset schizophrenia, and (2) evaluate the empirical benefits of using an iterative, user-centered design (UCD) process. We conducted two design workshops with 15 key stakeholders, followed by a series of in-depth interviews in collaboration with IDEO, a design and innovation firm. The UCD approach ultimately resulted in the first iteration of PRIME, which was evaluated by 10 RO participants. Results from the Stage 1 participants were then used to guide the next iteration that is currently being evaluated in an ongoing RCT. Participants in both phases were encouraged to use the app daily with a minimum frequency of 1/week over a 12-week period. The UCD process resulted in the following feature set: (1) delivery of text message (short message service, SMS)-based motivational coaching from trained therapists, (2) individualized goal setting in prognostically important

EARLY ONSET OF DELINQUENCY AND THE TRAJECTORY OF ALCOHOL-IMPAIRED DRIVING AMONG YOUNG MALES*

Science.gov (United States)

Zhang, Lening; Wieczorek, William F.; Welte, John W.

2011-01-01

Building upon the literature in developmental and life-course criminology, the present study assesses the possible association of age onset of delinquency with the trajectory of alcohol-impaired driving using data collected from the three waves of the Buffalo Longitudinal Survey of Young Men (BLSYM). It is argued that as a unique form of delinquency, alcohol-impaired driving among adolescents may be better understood in a broad context of adolescent delinquency involvement. The study adopts the general approach for the analysis of early onset of delinquency and criminal careers in developmental and life-course criminology and hypothesizes that early onset of delinquency is associated with a higher growth of alcohol-impaired driving over time among adolescents when age onsets of alcohol-impaired driving, drinking, and drug use are controlled. Our analysis with the HLM growth modeling method provides support for the hypothesis. Respondents who had an early start in delinquency were likely to have a faster growth of alcohol-impaired driving over the three waves of BLSYM, which implies that these respondents were likely to have a longer path of alcohol-impaired driving in their transition to adulthood. The implication of this finding is discussed. PMID:21831528

Precuneus atrophy in early-onset Alzheimer's disease: a morphometric structural MRI study

International Nuclear Information System (INIS)

Karas, Giorgos; Scheltens, Philip; Jones, Bethany; Rombouts, Serge; Schijndel, Ronald van; Klein, Martin; Flier, Wiesje van der; Vrenken, Hugo; Barkhof, Frederik

2007-01-01

Alzheimer's disease (AD) usually first presents in elderly patients, but may also develop at an earlier age. Patients with an early age at onset tend to present with complaints other than memory impairment, such as visuospatial problems or apraxia, which may reflect a different distribution of cortical involvement. In this study we set out to investigate whether age at onset in patients with AD determines the pattern of atrophy on cerebral MRI scans. We examined 55 patients with AD over a wide age range and analyzed their 3-D T1-weighted structural MRI scans in standard space using voxel-based morphometry (VBM). Regression analysis was performed to estimate loss of grey matter as a function of age, corrected for mini-mental state examination (MMSE) scores and sex. The VBM analyses identified multiple areas (including the temporal and parietal lobes), showing more atrophy with advancing age. By contrast, a younger age at onset was found to be associated with lower grey matter density in the precuneus. Regionalized volumetric analysis of this region confirmed the existence of disproportionate atrophy in the precuneus in patients with early-onset AD. Application of a multivariate model with precuneus grey matter density as input, showed that precuneal and hippocampal atrophy are independent from each other. Additionally, we found that a smaller precuneus is associated with impaired visuospatial functioning. Our findings support the notion that age at onset modulates the distribution of cortical involvement, and that disproportionate precuneus atrophy is more prominent in patients with a younger age of onset. (orig.)

Depression and quality of life in monogenic compared to idiopathic, early-onset Parkinson's disease

DEFF Research Database (Denmark)

Kasten, Meike; Kertelge, Lena; Tadic, Vera

2012-01-01

, and 44% of manifesting carriers of mutations in PD genes, but was rare in the nonmanifesting carriers (7%) and healthy controls (5%). Subjects with Parkinson-associated depression reported fewer feelings of guilt or self-doubt than treated controls, but the occurrence of suicidal ideation was associated......Quality of life (QoL) is decreased in PD and is linked with depression and anxiety. However, little is known about QoL in monogenic PD. Subjects with mutations in PD genes were recruited from ongoing family and genetic studies (manifesting carriers, n = 23; nonmanifesting carriers, n = 19......). For comparison purposes, we included patients with idiopathic PD (IPD; n = 128; early onset, n = 38; late onset, n = 90), healthy controls (n = 127), and data on depressive symptoms of 144 patients with major depression (treated controls). Depression affected 31% of early-onset PD cases, 21% of late-onset cases...

Structural neurobiological correlates of Mayer-Salovery-Caruso Emotional Intelligence Test performance in early course schizophrenia.

Science.gov (United States)

Wojtalik, Jessica A; Eack, Shaun M; Keshavan, Matcheri S

2013-01-10

The Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) is a key measure of social cognition in schizophrenia that has good psychometric properties and is recommended by the MATRICS committee. As a way to further investigate the validity of the MSCEIT, this study sought to examine the neurobiological correlates of MSCEIT performance in patients with early course schizophrenia. A total of 51 patients diagnosed with early course, stabilized schizophrenia or schizoaffective disorder completed structural magnetic resonance imaging (MRI) scans and the MSCEIT. Investigation of the associations between MSCEIT performance and gray matter morphology was examined by conducting voxel-based morphometry (VBM) analyses across hypothesized social-cognitive regions of interest using automated anatomical labeling in Statistical Parametric Mapping Software, version 5 (SPM5). All VBM analyses utilized general linear models examining gray matter density partitioned images, adjusting for demographic and illness-related confounds. VBM results were then followed up with confirmatory volumetric analyses. Patients with poorer overall and Facilitating, Understanding, and Managing Emotions subscale performances on the MSCEIT showed significantly reduced gray matter density in the left parahippocampal gyrus. Additionally, attenuated performance on the Facilitating and Managing Emotions subscales was significantly associated with reduced right posterior cingulate gray matter density. All associations observed between MSCEIT performance and gray matter density were supported with confirmatory gray matter volumetric analyses, with the exception of the association between the right posterior cingulate and the facilitation of emotions. These findings provide additional evidence for the MSCEIT as a valid social-cognitive measure by elucidating its correlates with neurobiological structures commonly implicated in emotion processing. These findings provide additional biological evidence

Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia.

Science.gov (United States)

Li, Tao; Wang, Qiang; Zhang, Jie; Rolls, Edmund T; Yang, Wei; Palaniyappan, Lena; Zhang, Lu; Cheng, Wei; Yao, Ye; Liu, Zhaowen; Gong, Xiaohong; Luo, Qiang; Tang, Yanqing; Crow, Timothy J; Broome, Matthew R; Xu, Ke; Li, Chunbo; Wang, Jijun; Liu, Zhening; Lu, Guangming; Wang, Fei; Feng, Jianfeng

2017-03-01

Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis. © The Author 2016. Published by

Early Onset Bipolar Spectrum Disorder: Psychopharmacological, Psychological, and Educational Management

Science.gov (United States)

McIntosh, David E.; Trotter, Jeffrey S.

2006-01-01

Although published research continues to advocate medication as the first line of treatment for early onset bipolar spectrum disorder (EOBSD; N. Lofthouse & M.A. Fristad, 2004), preliminary research demonstrating the utility of cognitive, cognitive-behavioral, and psychoeducational therapies is promising. It appears as if future treatment of EOBSD…

The temporal relationship between schizophrenia and crime

DEFF Research Database (Denmark)

Munkner, Runa; Haastrup, Soeren; Joergensen, Torben

2003-01-01

BACKGROUND: Little is known about the temporal relationship between illness onset and the possible beginning of a criminal career among people with schizophrenia, even though criminality, especially violent criminality, has been shown to be more common among people with schizophrenia than among...... people in general. AIM: The aim of this study was to analyse the temporal relationship between registered crime and contact to the psychiatric hospital system. METHOD: This is a register-based study merging data on the psychiatric career with criminal records. RESULTS: Among the males with schizophrenia......, 37% started a criminal career and 13% had committed first violent crime before first contact with the psychiatric hospital system. CONCLUSION: The criminality committed before first contact to the psychiatric hospital system is substantial, especially among males with schizophrenia....

Psychological differences between early- and late-onset psoriasis: a study of personality traits, anxiety and depression in psoriasis.

Science.gov (United States)

Remröd, C; Sjöström, K; Svensson, A

2013-08-01

Onset of psoriasis may occur at any age. Early negative experiences often influence personality development, and may lead to physical disease, anxiety and depression in adulthood. Knowledge about onset of psoriasis and psychopathology is limited. To examine whether patients with early-onset psoriasis differ psychologically from patients with late-onset psoriasis, regarding personality traits, anxiety and depression. A descriptive cross-sectional study was conducted among 101 consecutively recruited outpatients with psoriasis. A psychosocial interview was performed followed by self-assessment of validated questionnaires: Swedish Universities Scales of Personality (SSP), Spielberger State-Trait Anxiety Inventory and Beck Depression Inventory. Psoriasis severity was assessed by the Psoriasis Area and Severity Index. Patients with early-onset psoriasis (age personality traits: SSP-embitterment, -trait irritability, -mistrust and -verbal trait aggression. Our results indicate that early detection of psychological vulnerability when treating children and adolescents with psoriasis seems to be of great importance. Traits of psychological vulnerability and pessimistic personality traits were found to be significantly associated with the early onset of psoriasis, but not with disease duration in this study. These traits may be seen as a consequence of psoriasis, and/or as individual traits modulating and impairing clinical course and efforts to cope with psoriasis. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Early vs late age at onset frontotemporal dementia and frontotemporal lobar degeneration.

Science.gov (United States)

Seo, Sang Won; Thibodeau, Marie-Pierre; Perry, David C; Hua, Alice; Sidhu, Manu; Sible, Isabel; Vargas, Jose Norberto S; Gaus, Stephanie E; Rabinovici, Gil D; Rankin, Katherine D; Boxer, Adam L; Kramer, Joel H; Rosen, Howard J; Gorno-Tempini, Maria Luisa; Grinberg, Lea T; Huang, Eric J; DeArmond, Stephen J; Trojanowski, John Q; Miller, Bruce L; Seeley, William W

2018-03-20

To examine clinicopathologic correlations in early vs late age at onset frontotemporal dementia (FTD) and frontotemporal lobar degeneration (FTLD). All patients were clinically evaluated and prospectively diagnosed at the UCSF Memory and Aging Center. Two consecutive series were included: (1) patients with a clinically diagnosed FTD syndrome who underwent autopsy (cohort 1) and (2) patients with a primary pathologic diagnosis of FTLD, regardless of the clinical syndrome (cohort 2). These series were divided by age at symptom onset (cutoff 65 years). In cohort 1, 48 (25.3%) were 65 years or older at symptom onset. Pathologic causes of behavioral variant FTD (bvFTD) were similar in the early age at onset (EO) and late age at onset (LO) bvFTD groups. In corticobasal syndrome (CBS), however, the most common pathologic substrate differed according to age at onset: progressive supranuclear palsy (42.9%) in LO-CBS and Alzheimer disease (AD; 40.7%) in EO-CBS. In cohort 2, 57 (28.4%) were classified as LO-FTLD. Regarding FTLD major molecular classes, FTLD with transactive response DNA-binding protein of 43 kDa was most common in EO-FTLD (44.4%), whereas FTLD-tau (58.3%) was most common in LO-FTLD. Antemortem diagnosis of a non-FTD syndrome, usually AD-type dementia, was more frequent in LO-FTLD than EO-FTLD (19.3% vs 7.7%, p = 0.017). LO-FTLD was also associated with more prevalent comorbid pathologic changes. Of these, moderate to severe AD neuropathologic change and argyrophilic grain disease were overrepresented among patients who received an antemortem diagnosis of AD-type dementia. Patients with FTD and FTLD often develop symptoms after age 65, and age at onset represents an important consideration when making antemortem neuropathologic predictions. © 2018 American Academy of Neurology.

Early-onset restrictive eating disturbances in primary school boys and girls.

Science.gov (United States)

Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja

2015-07-01

This study sought to determine the distribution of early-onset restrictive eating disturbances characteristic of the new DSM-5 diagnosis, avoidant/restrictive food intake disorder (ARFID) in middle childhood, as well as to evaluate the screening instrument, Eating Disturbances in Youth-Questionnaire (EDY-Q). A total of 1,444 8- to 13-year-old children were screened in regular schools (3rd to 6th grade) in Switzerland using the self-report measure EDY-Q, consisting of 12 items based on the DSM-5 criteria for ARFID. 46 children (3.2%) reported features of ARFID in the self-rating. Group differences were found for body mass index, with underweight children reporting features of ARFID more often than normal and overweight children. The EDY-Q revealed good psychometric properties, including adequate discriminant and convergent validity. Early-onset restrictive eating disturbances are commonly reported in middle childhood. Because of possible negative short- and long-term impact, early detection is essential. Further studies with structured interviews and parent reports are needed to confirm this study's findings.

Model of Management (Mo.Ma) for the patient with schizophrenia: crisis control, maintenance, relapse prevention, and recovery with long-acting injectable antipsychotics (LAIs).

Science.gov (United States)

Brugnoli, Roberto; Rapinesi, Chiara; Kotzalidis, Georgios D; Marcellusi, Andrea; Mennini, Francesco S; De Filippis, Sergio; Carrus, Dario; Ballerini, Andrea; Francomano, Antonio; Ducci, Giuseppe; Del Casale, Antonio; Girardi, Paolo

2016-01-01

Schizophrenia is a severe mental disease that affects approximately 1% of the population with a relevant chronic impact on social and occupational functioning and daily activities. People with schizophrenia are 2-2.5 times more likely to die early than the general population. Non-adherence to antipsychotic medications, both in chronic and first episode schizophrenia, is one of the most important risk factors for relapse and hospitalization, that consequently contributes to increased costs due to psychiatric hospitalization. Atypical long-acting injectable (LAI) antipsychotics can improve treatment adherence and decrease re-hospitalization rates in patients with schizophrenia since its onset. The primary goals in the management of schizophrenia are directed not only at symptom reduction in the short and long term, but also at maintaining physical and mental functioning, improving quality of life, and promoting patient recovery. To propose a scientific evidence-based integrated model that provides an algorithm for recovery of patients with schizophrenia and to investigate the effectiveness and safety of antipsychotics LAI in the treatment, maintenance, relapse prevention, and recovery of schizophrenia. After an accurate literature review we identified, collected and analyzed the crucial points in taking care schizophrenia patients, through which we defined the steps described in the model of management and the choice of the better treatment option. Results. In the management model we propose, the choice of a second generation long acting antipsychotic, could allow from the earliest stages of illness better patient management, especially for young individuals with schizophrenia onset, a better recovery and significant reductions of relapse and health care costs. LAI formulations of antipsychotics are valuable, because they help patients to remain adherent to their medication through regular contact with healthcare professionals and to prevent covert non-adherence. The

Biological study in schizophrenia

International Nuclear Information System (INIS)

Kasai, Kiyoto; Yoshikawa, Akane; Natsubori, Takanobu; Koike, Shinsuke; Nagai, Tatsuya; Araki, Tsuyoshi; Nishimura, Yukika; Iwamoto, Kazuya

2012-01-01

Schizophrenia is associated with enormous morbidity, mortality, personal disability, and social cost. Although considerable research on schizophrenia has been performed, the etiology of this disease has not been fully elucidated. In recent years, imaging and genetic technologies have been developed dramatically. Disturbances in glutamate and gamma-aminobutyric acid (GABA)ergic neurotransmission may underlie the pathophysiology of schizophrenia. We attempted an integrative review, of studies pertaining to recent advances of schizophrenia research with a focus on neuroimaging and genetic studies. Additionally, we present the preliminary findings of the clinical research in our outpatient unit, specialized for early intervention, at the University of Tokyo Hospital. (author)

ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties.

Science.gov (United States)

St Pourcain, B; Robinson, E B; Anttila, V; Sullivan, B B; Maller, J; Golding, J; Skuse, D; Ring, S; Evans, D M; Zammit, S; Fisher, S E; Neale, B M; Anney, R J L; Ripke, S; Hollegaard, M V; Werge, T; Ronald, A; Grove, J; Hougaard, D M; Børglum, A D; Mortensen, P B; Daly, M J; Davey Smith, G

2018-02-01

Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, N⩽5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.

Three-dimensional brain growth abnormalities in childhood-onset schizophrenia visualized by using tensor-based morphometry.

Science.gov (United States)

Gogtay, Nitin; Lu, Allen; Leow, Alex D; Klunder, Andrea D; Lee, Agatha D; Chavez, Alex; Greenstein, Deanna; Giedd, Jay N; Toga, Arthur W; Rapoport, Judith L; Thompson, Paul M

2008-10-14

Earlier studies revealed progressive cortical gray matter (GM) loss in childhood-onset schizophrenia (COS) across both lateral and medial surfaces of the developing brain. Here, we use tensor-based morphometry to visualize white matter (WM) growth abnormalities in COS throughout the brain. Using high-dimensional elastic image registration, we compared 3D maps of local WM growth rates in COS patients and healthy children over a 5-year period, based on analyzing longitudinal brain MRIs from 12 COS patients and 12 healthy controls matched for age, gender, and scan interval. COS patients showed up to 2.2% slower growth rates per year than healthy controls in WM (P = 0.02, all P values corrected). The greatest differences were in the right hemisphere (P = 0.006). This asymmetry was attributable to a right slower than left hemisphere growth rate mapped in COS patients (P = 0.037) but not in healthy controls. WM growth rates reached 2.6% per year in healthy controls (P = 0.0002). COS patients showed only a 1.3% per year trend for growth in the left hemisphere (P = 0.066). In COS, WM growth rates were associated with improvement in the Children's Global Assessment Scale (R = 0.64, P = 0.029). Growth rates were reduced throughout the brain in COS, but this process appeared to progress in a front-to-back (frontal-parietal) fashion, and this effect was not attributable to lower IQ. Growth rates were correlated with functional prognosis and were visualized as detailed 3D maps. Finally, these findings also confirm that the progressive GM deficits seen in schizophrenia are not the result of WM overgrowth.

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia.

Science.gov (United States)

Nakagawa, Yutaka; Chiba, Kenji

2016-09-01

Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

[The relationship between accommodative accuracy at different near-work distances and early-onset myopia].

Science.gov (United States)

Yu, Q W; Zhang, P; Zhou, S B; Hu, Y; Ji, M X; Luo, Y C; You, H L; Yao, Z X

2016-07-01

To observe the accommodative accuracy of children with early-onset myopia at different near-work distances, and discuss the relationship between accommodative accuracy and early-onset myopia. This was a case-control study. Thirty-seven emmetropic children, 41 early-onset myopic children without correction, and 39 early-onset myopic children with spectacles, aged 7 to 13 years, were included. Measures of refractive errors and accommodative accuracy at four near-work distances, including 50 cm, 40 cm, 30 cm, and 20 cm, were made using the binocular fusion cross cylinder (FCC) of an automatic phoropter. Most candidates showed accommodative lags, including the children with emmetropia. The ratio of lags in all candidates at different near-work distances was 75.21% (50 cm), 87.18% (40 cm), 92.31% (30 cm), and 98.29% (20 cm), respectively. All accommodative accuracies became worse, and the accommodative lag ratio and values of FCC increased, along with the shortening of the distance. The difference in accommodative accuracy among groups was statistically significant at 30 cm (χ(2)=7.852, P= 0.020) and 20 cm (χ(2)=6.480, P=0.039). The values of FCC among groups were significantly different at 30 cm (F=3.626, P=0.030) and 20 cm (F=3.703, P=0.028), but not at 50 cm and 40 cm (P>0.05). In addition, the FCC values of 30 cm and 20 cm had a statistically significant difference between myopic children without correction [(1.25±0.44) D and (1.76±0.43) D] and emmetropic children [(0.95±0.52) D and (1.41±0.58) D] (P=0.012, 0.008). The correlation between diopters of myopia and accommodative accuracy at different nearwork distances was not statistically significant (P>0.05). However, the correlation between diopters of myopia and the accommodative lag value (FCC) at 20 cm was statistically significant (r=0.246, P=0.028). The closer the near-work distance is, the worse the accommodative accuracy is. This is more significant in early-onset myopia, especially myopia without

Immediate Early Genes Anchor a Biological Pathway of Proteins Required for Memory Formation, Long-Term Depression and Risk for Schizophrenia

Directory of Open Access Journals (Sweden)

Ketan K. Marballi

2018-02-01

Full Text Available While the causes of myriad medical and infectious illnesses have been identified, the etiologies of neuropsychiatric illnesses remain elusive. This is due to two major obstacles. First, the risk for neuropsychiatric disorders, such as schizophrenia, is determined by both genetic and environmental factors. Second, numerous genes influence susceptibility for these illnesses. Genome-wide association studies have identified at least 108 genomic loci for schizophrenia, and more are expected to be published shortly. In addition, numerous biological processes contribute to the neuropathology underlying schizophrenia. These include immune dysfunction, synaptic and myelination deficits, vascular abnormalities, growth factor disruption, and N-methyl-D-aspartate receptor (NMDAR hypofunction. However, the field of psychiatric genetics lacks a unifying model to explain how environment may interact with numerous genes to influence these various biological processes and cause schizophrenia. Here we describe a biological cascade of proteins that are activated in response to environmental stimuli such as stress, a schizophrenia risk factor. The central proteins in this pathway are critical mediators of memory formation and a particular form of hippocampal synaptic plasticity, long-term depression (LTD. Each of these proteins is also implicated in schizophrenia risk. In fact, the pathway includes four genes that map to the 108 loci associated with schizophrenia: GRIN2A, nuclear factor of activated T-cells (NFATc3, early growth response 1 (EGR1 and NGFI-A Binding Protein 2 (NAB2; each of which contains the “Index single nucleotide polymorphism (SNP” (most SNP at its respective locus. Environmental stimuli activate this biological pathway in neurons, resulting in induction of EGR immediate early genes: EGR1, EGR3 and NAB2. We hypothesize that dysfunction in any of the genes in this pathway disrupts the normal activation of Egrs in response to stress. This may

Immediate Early Genes Anchor a Biological Pathway of Proteins Required for Memory Formation, Long-Term Depression and Risk for Schizophrenia

Science.gov (United States)

Marballi, Ketan K.; Gallitano, Amelia L.

2018-01-01

While the causes of myriad medical and infectious illnesses have been identified, the etiologies of neuropsychiatric illnesses remain elusive. This is due to two major obstacles. First, the risk for neuropsychiatric disorders, such as schizophrenia, is determined by both genetic and environmental factors. Second, numerous genes influence susceptibility for these illnesses. Genome-wide association studies have identified at least 108 genomic loci for schizophrenia, and more are expected to be published shortly. In addition, numerous biological processes contribute to the neuropathology underlying schizophrenia. These include immune dysfunction, synaptic and myelination deficits, vascular abnormalities, growth factor disruption, and N-methyl-D-aspartate receptor (NMDAR) hypofunction. However, the field of psychiatric genetics lacks a unifying model to explain how environment may interact with numerous genes to influence these various biological processes and cause schizophrenia. Here we describe a biological cascade of proteins that are activated in response to environmental stimuli such as stress, a schizophrenia risk factor. The central proteins in this pathway are critical mediators of memory formation and a particular form of hippocampal synaptic plasticity, long-term depression (LTD). Each of these proteins is also implicated in schizophrenia risk. In fact, the pathway includes four genes that map to the 108 loci associated with schizophrenia: GRIN2A, nuclear factor of activated T-cells (NFATc3), early growth response 1 (EGR1) and NGFI-A Binding Protein 2 (NAB2); each of which contains the “Index single nucleotide polymorphism (SNP)” (most SNP) at its respective locus. Environmental stimuli activate this biological pathway in neurons, resulting in induction of EGR immediate early genes: EGR1, EGR3 and NAB2. We hypothesize that dysfunction in any of the genes in this pathway disrupts the normal activation of Egrs in response to stress. This may result in

Alcohol intake and early-onset basal cell carcinoma in a case-control study.

Science.gov (United States)

Zhang, Y; Ferrucci, L M; Cartmel, B; Molinaro, A M; Leffell, D J; Bale, A E; Mayne, S T

2014-12-01

Previous epidemiological studies of overall alcohol intake and basal cell carcinoma (BCC) are inconsistent, with some evidence for differences by type of alcoholic beverage. While alcohol may enhance the carcinogenicity of ultraviolet (UV) radiation, this has not been evaluated in existing epidemiological studies. To evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure. Basal cell carcinoma cases (n = 380) and controls with benign skin conditions (n = 390) under 40 years of age were identified through Yale Dermatopathology. Participants provided information on lifetime alcohol intake, including type of beverage, during an in-person interview. Self-reported data on indoor tanning and outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios (OR) and 95% confidence intervals (CIs) using unconditional multivariate logistic regression in the full sample and in women only. There was no statistically significant association between lifetime alcohol intake and early-onset BCC overall [above median intake vs. no regular alcohol intake (OR 1·10, 95% CI 0·69-1·73)] or in women only (OR 1·21, 95% CI 0·73-2·01). Similarly, intake of red wine, white wine, beer or spirits and mixed drinks was not associated with early-onset BCC. In exploratory analyses, we saw limited evidence for an interaction (P(interaction) = 0·003), with highest risk for high alcohol and high UV exposures, especially in women, but subgroup risk estimates had wide and overlapping CIs. Overall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC. © 2014 British Association of Dermatologists.

Two-Year Diagnostic Stability in Early-Onset First-Episode Psychosis

Science.gov (United States)

Castro-Fornieles, Josefina; Baeza, Immaculada; de la Serna, Elena; Gonzalez-Pinto, Ana; Parellada, Mara; Graell, Montserrat; Moreno, Dolores; Otero, Soraya; Arango, Celso

2011-01-01

Background: Only one study has used a prospective method to analyze the diagnostic stability of first psychotic episodes in children and adolescents. The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a 2-year, prospective longitudinal study of early-onset first episodes of psychosis (EO-FEP). Aim: To describe diagnostic stability…

A girl with early-onset epileptic encephalopathy associated with microdeletion involving CDKL5.

Science.gov (United States)

Saitsu, Hirotomo; Osaka, Hitoshi; Nishiyama, Kiyomi; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Matsumoto, Naomichi

2012-05-01

Recent studies have shown that aberrations of CDKL5 in female patients cause early-onset intractable seizures, severe developmental delay or regression, and Rett syndrome-like features. We report on a Japanese girl with early-onset epileptic encephalopathy, hypotonia, developmental regression, and Rett syndrome-like features. The patient showed generalized tonic seizures, and later, massive myoclonus induced by phone and light stimuli. Brain magnetic resonance imaging showed no structural brain anomalies but cerebral atrophy. Electroencephalogram showed frontal dominant diffuse poly spikes and waves. Through copy number analysis by genomic microarray, we found a microdeletion at Xp22.13. A de novo 137-kb deletion, involving exons 5-21 of CDKL5, RS1, and part of PPEF1 gene, was confirmed by quantitative PCR and breakpoint specific PCR analyses. Our report suggests that the clinical features associated with CDKL5 deletions could be implicated in Japanese patients, and that genetic testing of CDKL5, including both sequencing and deletion analyses, should be considered in girls with early-onset epileptic encephalopathy and RTT-like features. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Vasoactive agents for the prediction of early- and late-onset preeclampsia in a high-risk cohort

Science.gov (United States)

2013-01-01

Background To evaluate the soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio for the prediction of early- and late-onset preeclampsia in a high-risk cohort. Methods We studied serial serum samples collected prospectively at 12 + 0 - 14 + 0, 18 + 0 - 20 + 0, and 26 + 0 - 28 + 0 weeks + days of gestation in 6 women who developed early-onset preeclampsia (before 34 weeks of gestation) and in 21 women who developed late-onset preeclampsia (after 34 weeks of gestation) with automated ElecSys 2010 immunoanalyzer (Roche Diagnostics, Germany). Twenty-six high-risk women and 53 women without risk factors with normal pregnancies served as controls. Results Serum PlGF concentrations were lower at 18 + 0 to 20 + 0, and 26 + 0 to 28 + 0 weeks of gestation in women who developed early-onset preeclampsia compared to women who developed late-onset preeclampsia and to controls (p preeclampsia (AUC 100.0%, p = 0.0007, 95% CI 100–100). Amongst women with late-onset preeclampsia, those who developed severe form of the disease (N = 8) had significantly higher serum sFlt-1 concentrations at all three timepoints (p = 0.004, p = 0.006, and p = 0.003, respectively) compared to women with non-severe form (N = 13). Conclusions Low serum PlGF concentration predicts early-onset preeclampsia from the second trimester and elevated serum sFlt-1/PlGF ratio from 26 to 28 weeks of gestation. Elevated serum sFlt-1 concentration in the first trimester in women who later develop late-onset, severe preeclampsia may suggest different etiology compared to the late-onset non-severe form of the disease. PMID:23663420

The effect of implementation of an early detection team: A nationwide register-based study of characteristics and help-seeking behavior in first-episode schizophrenia in Denmark.

Science.gov (United States)

Hastrup, Lene Halling; Haahr, Ulrik Helt; Nordgaard, Julie; Simonsen, Erik

2018-04-26

In an effort to make people with signs of psychosis seek help as early as possible, Region Zealand launched in 2012 an early detection team project as the first and only in Denmark. The project consisted of a combination of easy access and an information campaign targeting the public. This nation-wide study examined characteristics and help-seeking behavior of patients with first-episode schizophrenia (FES) in the early detection region in comparison with other Danish regions. Data from the Danish National Schizophrenia register on all Danish patients diagnosed with first-episode schizophrenia during 2012 to 2015 were linked to demographic and health care data drawn from official national registers. Binary logistic regression analyses examined the difference between the early detection region and other regions controlling for demographic characteristics and utilization of mental health care services and contacts to general practitioner (GP). Patients in the early detection region were younger (OR = 0.51; CI: 0.42-0.62; p < 0.000) than in regions without early detection teams. Furthermore, they were more likely to be of Danish origin, and less likely to have contact with mental health services and GPs prior to FES. The study suggests that implementing an early detection team in combination with an information campaign contributed to detecting patients with first-episode schizophrenia earlier than in regions without the early detection team. The study gives an indication of different pathways among patients in the early detection region. Copyright © 2018. Published by Elsevier B.V.

Normal cognitive conflict resolution in psychosis patients with and without schizophrenia.

Science.gov (United States)

Smid, Henderikus G O M; Bruggeman, Richard; Martens, Sander

2016-01-01

Schizophrenia is thought to be associated with impairments of executive functions, among which conflict control functions play an important role. The available evidence, however, suggests that conflict control is intact in schizophrenia, despite being based on methods that have successfully unveiled conflict control problems in other disorders. Differences between schizophrenia patients and healthy controls in stimulus perception, selective attention, alertness, processing speed and reaction time variability may have been previously overlooked. By controlling for these potential confounders, the present experiments were aimed to be more rigorous tests of the hypothesis that psychosis and schizophrenia are associated with impairments of conflict control. To that end, 27 healthy controls and 53 recent-onset psychosis patients with (n = 27) and without schizophrenia (n = 26) with comparable age, intelligence, and education level, performed three iconic conflict control tasks: the Simon task, the Eriksen flanker task, and the Stroop task, all equipped with neutral trials, and analyzed for various potential confounders. They further performed a battery of standard neuropsychological tests. Schizophrenia patients showed no increased conflict effects in any of the 3 tasks for any alternative measures used. Nonschizophrenia patients only showed abnormally increased response competition in the Simon task. All patients nevertheless demonstrated impaired control of attention and verbal memory. These findings indicate that the type of conflict control engaged by conflict tasks is intact in recent-onset schizophrenia, suggesting that a major component of executive function is spared in schizophrenia. We discuss these findings in terms of proactive and reactive control. (c) 2016 APA, all rights reserved.

The Rest-Activity Rhythm and Physical Activity in Early-Onset Dementia

NARCIS (Netherlands)

Hooghiemstra, A.M.; Eggermont, L.H.P.; Scheltens, P.; van der Flier, W.M.; Scherder, E.J.A.

2015-01-01

Background: A substantial part of elderly persons with dementia show rest-activity rhythm disturbances. The rest-activity rhythm is important to study in people with early-onset dementia (EOD) for rest-activity rhythm disturbances are predictive of institutionalization, and caregivers of young

Early Onset of Drug and Polysubstance Use as Predictors of Injection Drug Use Among Adult Drug Users

Science.gov (United States)

Trenz, Rebecca C.; Scherer, Michael; Harrell, Paul; Zur, Julia; Sinha, Ashish; Latimer, William

2012-01-01

Early onset of alcohol, marijuana, and cigarette use is an indicator of later substance use problems in adulthood such as alcohol or other drug dependence. This paper seeks to address the association between early onset alcohol, marijuana, cigarette, and polysubstance use with injection drug use among recent illicit drug users. The current study used baseline data from the Baltimore site of the NEURO-HIV Epidemiologic Study, an investigation of neuropsychological and social-behavioral risk factors of HIV, hepatitis A, hepatitis B, and Hepatitis C among both injection and non-injection drug users in Baltimore Maryland. The present study used a subset (N = 651) of the larger parent study that identified as White or Black, and reported any drug use in the past 6 months. In the full sample slightly more than half (52.5%) of study participants were IDUs. IDUs differed from non-IDUs on age of initiation for cigarettes, marijuana, and alcohol, with IDUs initiating the use of all three substances significantly earlier than non-IDUs. IDUs also had significantly greater proportions of early onset of alcohol (χ2 = 19.71, p < .01), cigarette (χ2 = 11.05, p < .01), marijuana (χ2 = 10.83, p < .01), and polysubstance use (χ2 = 23.48, p < .01) than non-IDUs. After adjusting for age, gender, and race/ethnicity, only participants identified as early onset alcohol users (AOR = 1.47, 95% CI: 1.00-2.18) and early onset polysubstance users (AOR = 1.62, 95% CI: 1.10-2.38) were more likely to have IDU status than those who reported initiating substance use later. IDU status was then stratified by race/ethnicity. After controlling for age and gender, only early polysubstance use was a significant predictor of IDU status for Whites (AOR = 2.06, 95% CI: 1.07-3.93). Consistent with literature on early substance initiation and later illicit substance use, early onset alcohol and polysubstance use is an important risk factor for IDU in adulthood. PMID:22172686

The role of SLC2A1 in early onset and childhood absence epilepsies

DEFF Research Database (Denmark)

Muhle, Hiltrud; Helbig, Ingo; Frøslev, Tobias Guldberg

2013-01-01

Early Onset Absence Epilepsy constitutes an Idiopathic Generalized Epilepsy with absences starting before the age of four years. Mutations in SLC2A1, encoding the glucose transporter, account for approximately 10% of EOAE cases. The role of SLC2A1 mutations in absence epilepsies with a later onset...

Childhood laterality and adult schizophrenia spectrum disorders: a prospective investigation

DEFF Research Database (Denmark)

Schiffman, Jason; Pestle, Sarah; Mednick, Sara

2005-01-01

Left or mixed-handedness, footedness, and eye dominance are thought to indicate abnormalities in lateralization related to schizophrenia. Increased left or mixed-dominance in schizophrenia suggests possible hemispheric abnormalities associated with the disorder. A related body of research suggests...... that some indications of lateralization abnormalities may be evident prior to the onset of schizophrenia, suggesting that disruptions in lateralization are inherent to the developmental course of the disorder. We attempted to replicate and extend upon findings indicating differences in lateralization...... between children who later developed a schizophrenia spectrum disorder (n = 26) and those who did not develop a schizophrenia spectrum disorder (n = 216), among a high-risk and control, longitudinal sample. The rate of left or mixed-footedness, eye dominance, and any anomalous lateralization...

Differences in diagnostic subtypes among patients with late and early onset of a single depressive episode

DEFF Research Database (Denmark)

Kessing, Lars Vedel

2006-01-01

OBJECTIVE: It is unclear whether patients with late onset and patients with early onset present with different subtypes of depression. The aim of the study was to compare the prevalence of subtypes of ICD-10 single depressive episodes for patients with late onset (age >65 years) and patient...... with early onset (age single depressive episode in a period from 1994-2002 at the end of the first outpatient treatment or at the first discharge from...... psychiatric hospitalisation ever in Denmark were identified in a nationwide register. RESULTS: In total, 18.192 patients were given a diagnosis of a single depressive episode at the first outpatient contact and 8.396 patients were given a diagnosis of a single depressive episode at the first psychiatric...

A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer.

Directory of Open Access Journals (Sweden)

Marina Antelo

Full Text Available Early-onset colorectal cancer (CRC represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously.We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed ≤ 50 years old (n=188, a group of sporadic CRC >50 years (MSS n=89; MSI n=46, and a group of Lynch syndrome CRCs (n=20. Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated.Mean LINE-1 methylation levels (± SD in the five study groups were early-onset CRC, 56.6% (8.6; sporadic MSI, 67.1% (5.5; sporadic MSS, 65.1% (6.3; Lynch syndrome, 66.3% (4.5 and normal mucosa, 76.5% (1.5. Early-onset CRC had significantly lower LINE-1 methylation than any other group (p<0.0001. Compared to patients with <65% LINE-1 methylation in tumors, those with ≥ 65% LINE-1 methylation had significantly better overall survival (p=0.026, log rank test.LINE-1 hypomethylation constitutes a potentially important feature of early-onset CRC, and suggests a distinct molecular subtype. Further studies are needed to assess the potential of LINE-1 methylation status as a prognostic biomarker for young people with CRC.

IQ subgroups in relation to neurocognitive profiles, psychopathology and brain volume in first-episode schizophrenia

DEFF Research Database (Denmark)

Jensen, Maria Høj; Glenthøj, Birte Yding; Rostrup, Egill

. low) using the healthy controls as reference. The IQ subgroups were compared using psychopathology ratings (Positive and Negative Symptoms Scale), neuropsychological assessments (Brief Assessment of Cognition in schizophrenia and Cambridge Neuropsychological Test Automated Battery) and a combined 3T......Background and Aim: Approximately half of patients with schizophrenia experience a deterioration in IQ before or around illness onset and recent studies have found apositive association between IQ and brain volume in first episode schizophrenia. The aim of this study was to examine the combined...... impact of estimated IQ trajectory and IQ level at illness onset on psychopathology, neurocognitive profiles and brain volume. Materials and methods: The design is a cross-sectional, case-control study of 60 first-episode antipsychotic-naïve schizophrenia patients and 60 matched healthy controls...

Predicting risk and the emergence of schizophrenia.

LENUS (Irish Health Repository)

Clarke, Mary C

2012-09-01

This article gives an overview of genetic and environmental risk factors for schizophrenia. The presence of certain molecular, biological, and psychosocial factors at certain points in the life span, has been linked to later development of schizophrenia. All need to be considered in the context of schizophrenia as a lifelong brain disorder. Research interest in schizophrenia is shifting to late childhood\\/early adolescence for screening and preventative measures. This article discusses those environmental risk factors for schizophrenia for which there is the largest evidence base.

Childhood abuse and late-life depression: Mediating effects of psychosocial factors for early- and late-onset depression.

Science.gov (United States)

Wielaard, Ilse; Hoyer, Mathijs; Rhebergen, Didi; Stek, Max L; Comijs, Hannie C

2018-03-01

Childhood abuse makes people vulnerable to developing depression, even in late life. Psychosocial factors that are common in late life, such as loneliness or lack of a partner, may explain this association. Our aim was to investigate whether the association between childhood abuse and depression in older adults can be explained by psychosocial factors. Cross-sectional data were derived from the Netherlands Study of Depression in Older Persons (aged 60-93), including 132 without lifetime depression, 242 persons with an early-onset depression (Childhood abuse (yes/no) and a frequency-based childhood abuse index were included. Multinomial regression and multivariable mediation analyses were used to examine the association between childhood abuse and the onset of depression, and the influence of loneliness, social network, and partner status. Multinomial regression analyses showed a significant association between childhood abuse and the childhood abuse index with early- and late-onset depression. Multivariable mediation analyses showed that the association between childhood abuse and early-onset depression was partly mediated by social network size and loneliness. This was particularly present for emotional neglect and psychological abuse, but not for physical and sexual abuse. No psychosocial mediators were found for the association between childhood abuse and late-onset depression. A smaller social network and feelings of loneliness mediate the association between childhood abuse and early-onset depression in older adults. Our findings show the importance of detecting childhood abuse as well as the age at depression onset and mapping of relevant psychosocial factors in the treatment of late-life depression. Copyright © 2018 John Wiley & Sons, Ltd.

Apolipoprotein E Allelic Frequency Altered in Women with Early-onset Breast Cancer

Directory of Open Access Journals (Sweden)

Tirtsa Porrata-Doria

2010-01-01

Full Text Available Among women, the most prevalent type of cancer is breast cancer, affecting 1 out of every 8 women in the United States; in Puerto Rico, 70 out of every 100,000 will develop some type of breast cancer. Therefore, a better understanding of the potential risk factors for breast cancer could lead to the development of early detection tools. A gene that has been proposed as a risk factor in several populations around the world is Apolipoprotein E (apoE. ApoE functions as a mechanism of transport for lipoproteins and cholesterol throughout the body, with 3 main isoforms present in humans (apoE2, apoE3, and apoE4. Whether or not apoE4 is a risk factor for breast cancer remains controversial. Previous studies have either included test subjects of all ages (20–80 or have focused on late-onset (after age 50 breast cancer; none has concentrated specifically on early-onset (aged 50 and younger breast cancer. The objectives of this study was to examine (in a Puerto Rican population the differences in the relative frequency of occurrence of apoE4 in non-breast cancer versus breast cancer patients and to examine, as well, the potential differences of same in early- versus late-onset patients. We found an increased frequency of apoE4 (odds ratio 2.15 only in early-onset breast cancer survivors, which is similar to the findings of those studies that combined or adjusted for age as well as for an association between apoE4 and decreased tumor size. ApoE is also a potential risk factor for long-term cognitive effects after chemotherapy and affects response to hormone replacement. Our data supports the theory that knowing the apoE genotype of women who are at risk of developing breast cancer may be beneficial, as such knowledge would aid in the prediction of tumor size and the development of treatment regimens.

A Novel TTBK2 De Novo Mutation in a Danish Family with Early-Onset Spinocerebellar Ataxia

DEFF Research Database (Denmark)

Lindquist, Suzanne Granhøj; Møller, Lisbeth Birk; Dali, Christine I.

2017-01-01

Spinocerebellar ataxia type 11 (SCA11) is rare and has previously been described in four families worldwide. We report a Danish family with onset of symptoms in early childhood and affected family members in two generations. The proband, a Danish female born in 1968, and family members were...... examined. Exome sequencing was performed and a “movement disorders” gene panel consisting of approximately 200 genes was used for filtering, while Sanger sequencing was used for subsequent testing for the mutation in the family. Onset of symptoms in affected family members was in early childhood. A novel...... delineates the phenotypic spectrum of the rare SCA11 disease. In contrast to previously reported cases, onset of symptoms was in early childhood and the mutation was de novo in the proband....

Schizophrenia and Violence: Systematic Review and Meta-Analysis

OpenAIRE

Fazel, Seena; Gulati, Gautam; Linsell, Louise; Geddes, John R.; Grann, Martin

2009-01-01

Editors' Summary Background Schizophrenia is a lifelong, severe psychotic condition. One in 100 people will have at least one episode of schizophrenia during their lifetime. Symptoms include delusions (for example, patients believe that someone is plotting against them) and hallucinations (hearing or seeing things that are not there). In men, schizophrenia usually starts in the late teens or early 20s; women tend to develop schizophrenia a little later. The causes of schizophrenia include gen...

Advanced paternal age increases the risk of schizophrenia and obsessive-compulsive disorder in a Chinese Han population.

Science.gov (United States)

Wu, Yuejing; Liu, Xiang; Luo, Hongrong; Deng, Wei; Zhao, Gaofeng; Wang, Qiang; Zhang, Lan; Ma, Xiaohong; Liu, Xiehe; Murray, Robin A; Collier, David A; Li, Tao

2012-08-15

Using the Structured Clinical Interview for DSM-IV, patient and non-patient version (SCID-P/NP), this study investigated 351 patients with schizophrenia, 122 with obsessive-compulsive disorder (OCD), and 238 unrelated healthy volunteers in a Chinese Han population. The relative risks posed by advanced paternal age for schizophrenia and OCD in offspring were computed under logistic regression analyses and adjusted for the participant's sex, age and co-parent age at birth. Compared to the offspring with paternal age of 25-29 years old, the relative risks rose from 2.660 to 10.183 in the paternal age range of 30-34 and ≥35. The relative risks for OCD increased from 2.225 to 5.413 in 30-34 and ≥35. For offspring with paternal age of maternal age and risk for schizophrenia/OCD was not seen. Interaction analysis showed an interaction effect between paternal age and maternal age at birth. Such a tendency of risk affected by parental age for schizophrenia and OCD existed after splitting out the data of early onset patients. Sex-specific analyses found that the relative risks for schizophrenia with paternal age of 30-34 and ≥35 in male offspring were 2.407 and 10.893, and in female offspring were 3.080 and 9.659. The relative risks for OCD with paternal age of 30-34 and ≥35 in male offspring were 3.493 and 7.373, and in female offspring 2.005 and 4.404. The mean paternal age of schizophrenia/OCD patients born before the early 1980s was much greater than that of patients who were born after then. The findings illustrated that advanced paternal age is associated with increased risk for both schizophrenia and OCD in a Chinese Han population, prominently when paternal age is over 35. Biological and non-biological mechanisms may both be involved in the effects of advanced paternal age on schizophrenia and OCD. Copyright © 2012. Published by Elsevier Ireland Ltd.

Non-Therapeutic Risk Factors for Onset of Tardive Dyskinesia in Schizophrenia : A Meta-Analysis

NARCIS (Netherlands)

Tenback, Diederik E.; van Harten, Peter N.; van Os, Jim

2009-01-01

A meta-analysis of prospective studies with schizophrenia patients was conducted to examine whether the evidence exists for risk factors for the emergence of Tardive Dyskinesia (TD) in schizophrenia. A computer assisted Medline/PubMed and Embase search was' conducted in January 2008 for the years

Association of Early-Onset Spasticity and Risk for Cognitive Impairment With Mutations at Amino Acid 499 in SPAST.

Science.gov (United States)

Gillespie, Meredith K; Humphreys, Peter; McMillan, Hugh J; Boycott, Kym M

2018-04-01

Hereditary spastic paraplegia is a phenotypically and genetically heterogeneous group of neurodegenerative disorders characterized by lower extremity weakness and spasticity. Spastic paraplegia 4 (SPG4), caused by heterozygous mutations in the gene SPAST, typically causes a late-onset, uncomplicated form of hereditary spastic paraplegia in affected individuals. Additional clinical features in SPG4 have been reported on occasion, but no genotype-phenotype correlation has been established. Through targeted clinical testing, we identified 2 unrelated female patients with the same de novo p.Arg499His mutation in SPAST. Both patients presented with early-onset spasticity resulting in delayed motor milestones, which led to a diagnosis of cerebral palsy in one child and tethered cord in the other. Review of the literature identified several patients with mutations at amino acid 499 and early-onset symptoms associated with a risk of cognitive impairment. Early and accurate diagnosis of children with early-onset spasticity is important for informed prognosis and genetic counselling.

Clinical characteristics in schizophrenia patients with or without suicide attempts and non-suicidal self-harm--a cross-sectional study.

Science.gov (United States)

Mork, Erlend; Walby, Fredrik A; Harkavy-Friedman, Jill M; Barrett, Elizabeth A; Steen, Nils E; Lorentzen, Steinar; Andreassen, Ole A; Melle, Ingrid; Mehlum, Lars

2013-10-09

To investigate whether schizophrenia patients with both suicide attempts and non-suicidal self-harm have earlier age of onset of psychotic and depressive symptoms and higher levels of clinical symptoms compared to patients with only suicide attempts or without suicide attempt. Using a cross-sectional design, 251 patients (18-61 years old, 58% men) with schizophrenia treated at hospitals in Oslo and Innlandet Hospital Trust, Norway, were assessed with a comprehensive clinical research protocol and divided into three groups based on their history of suicide attempts and non-suicidal self-harm. Suicide attempts were present in 88 patients (35%); 52 had suicide attempts only (29%) and 36 had both suicide attempts and non-suicidal self-harm (14%). When compared with nonattempters and those with suicide attempts without non-suicidal self-harm, patients with both suicide attempts and non-suicidal self-harm were more frequently women, younger at the onset of psychotic symptoms, had longer duration of untreated psychosis, and had higher levels of current impulsivity/aggression and depression. Patients with both suicide attempts and non-suicidal self-harm were more likely to repeat suicide attempts than patients with suicide attempts only. Patients with both suicide attempts and non-suicidal self-harm had different illness history and clinical characteristics compared to patients with only suicide attempts or patients without suicidal behavior. Our study suggests that patients with both suicide attempts and non-suicidal self-harm represent a distinct subgroup among patients with schizophrenia and suicidal behavior with their early onset of psychotic symptoms, high rate of repeated suicidal behavior and significant treatment delay.

Accelerated Brain Aging in Schizophrenia: A Longitudinal Pattern Recognition Study.

Science.gov (United States)

Schnack, Hugo G; van Haren, Neeltje E M; Nieuwenhuis, Mireille; Hulshoff Pol, Hilleke E; Cahn, Wiepke; Kahn, René S

2016-06-01

Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used support vector regression, a supervised machine learning technique, to address this question. In a longitudinal sample of 341 schizophrenia patients and 386 healthy subjects with one or more structural MRI scans (1,197 in total), machine learning algorithms were used to build models to predict the age of the brain and the presence of schizophrenia ("schizophrenia score"), based on the gray matter density maps. Age at baseline ranged from 16 to 67 years, and follow-up scans were acquired between 1 and 13 years after the baseline scan. Differences between brain age and chronological age ("brain age gap") and between schizophrenia score and healthy reference score ("schizophrenia gap") were calculated. Accelerated brain aging was calculated from changes in brain age gap between two consecutive measurements. The age prediction model was validated in an independent sample. In schizophrenia patients, brain age was significantly greater than chronological age at baseline (+3.36 years) and progressively increased during follow-up (+1.24 years in addition to the baseline gap). The acceleration of brain aging was not constant: it decreased from 2.5 years/year just after illness onset to about the normal rate (1 year/year) approximately 5 years after illness onset. The schizophrenia gap also increased during follow-up, but more pronounced variability in brain abnormalities at follow-up rendered this increase nonsignificant. The progressive brain loss in schizophrenia appears to reflect two different processes: one relatively homogeneous, reflecting accelerated aging of the brain and related to various measures of outcome, and a more variable one, possibly reflecting individual variation and

Impaired contingent attentional capture predicts reduced working memory capacity in schizophrenia.

Directory of Open Access Journals (Sweden)

Jutta S Mayer

Full Text Available Although impairments in working memory (WM are well documented in schizophrenia, the specific factors that cause these deficits are poorly understood. In this study, we hypothesized that a heightened susceptibility to attentional capture at an early stage of visual processing would result in working memory encoding problems. 30 patients with schizophrenia and 28 demographically matched healthy participants were presented with a search array and asked to report the orientation of the target stimulus. In some of the trials, a flanker stimulus preceded the search array that either matched the color of the target (relevant-flanker capture or appeared in a different color (irrelevant-flanker capture. Working memory capacity was determined in each individual using the visual change detection paradigm. Patients needed considerably more time to find the target in the no-flanker condition. After adjusting the individual exposure time, both groups showed equivalent capture costs in the irrelevant-flanker condition. However, in the relevant-flanker condition, capture costs were increased in patients compared to controls when the stimulus onset asynchrony between the flanker and the search array was high. Moreover, the increase in relevant capture costs correlated negatively with working memory capacity. This study demonstrates preserved stimulus-driven attentional capture but impaired contingent attentional capture associated with low working memory capacity in schizophrenia. These findings suggest a selective impairment of top-down attentional control in schizophrenia, which may impair working memory encoding.

Impaired contingent attentional capture predicts reduced working memory capacity in schizophrenia.

Science.gov (United States)

Mayer, Jutta S; Fukuda, Keisuke; Vogel, Edward K; Park, Sohee

2012-01-01

Although impairments in working memory (WM) are well documented in schizophrenia, the specific factors that cause these deficits are poorly understood. In this study, we hypothesized that a heightened susceptibility to attentional capture at an early stage of visual processing would result in working memory encoding problems. 30 patients with schizophrenia and 28 demographically matched healthy participants were presented with a search array and asked to report the orientation of the target stimulus. In some of the trials, a flanker stimulus preceded the search array that either matched the color of the target (relevant-flanker capture) or appeared in a different color (irrelevant-flanker capture). Working memory capacity was determined in each individual using the visual change detection paradigm. Patients needed considerably more time to find the target in the no-flanker condition. After adjusting the individual exposure time, both groups showed equivalent capture costs in the irrelevant-flanker condition. However, in the relevant-flanker condition, capture costs were increased in patients compared to controls when the stimulus onset asynchrony between the flanker and the search array was high. Moreover, the increase in relevant capture costs correlated negatively with working memory capacity. This study demonstrates preserved stimulus-driven attentional capture but impaired contingent attentional capture associated with low working memory capacity in schizophrenia. These findings suggest a selective impairment of top-down attentional control in schizophrenia, which may impair working memory encoding.

Overlapping and disease specific aspects of impulsivity in children and adolescents with schizophrenia spectrum disorders or Attention-Deficit/Hyperactivity Disorder

DEFF Research Database (Denmark)

Jepsen, Jens Richardt Møllegaard; Rydkjær, Jacob; Fagerlund, Birgitte

Objectives: To identify disease specific and overlapping aspects of impulsivity in children and adolescents with early-onset schizophrenia spectrum disorders or ADHD. Methods: Motor impulsivity (Stop Signal Task), reflection impulsivity (Information Sampling Task), and trait impulsivity (Barratt ...... their decision making to gather more information in a condition with a conflict between reward and certainty. The reduced information sampling may also reflect an increased conviction in the decision at a point of relative uncertainty....

Inhibition of return is not impaired but masked by increased facilitation in schizophrenia patients.

Science.gov (United States)

Kalogeropoulou, Fenia; Woodruff, Peter W R; Vivas, Ana B

2015-01-01

When attention is attracted to an irrelevant location, performance on a subsequent target is hindered at that location in relation to novel, not previously attended, locations. This phenomenon is known as inhibition of return (IOR). Previous research has shown that IOR is not observed, or its onset is delayed, in schizophrenia patients. In the present study, the authors tested the hypothesis that IOR may be intact but masked by increased facilitation in schizophrenia patients. To test this hypothesis, they used a procedure that usually reduces or eliminates the early facilitation. In the first experiment, the authors used the typical single-cue IOR task in the group of healthy adults (N = 28) and in a group of schizophrenia patients (N = 32). In the second experiment, they manipulated cue-target discriminability by presenting spatially overlapping cues and targets where the cues were more intense than the targets. In Experiment 1, they did not find significant IOR effects in the group of schizophrenia patients, even with cue-target intervals as long as 3,200 ms. However, in Experiment 2, IOR effects were significant at the 350- and 450-ms cue-target intervals for healthy and patients, respectively. This is the first study that shows that schizophrenia patients can actually show inhibitory effects very similar to healthy controls, even when no help is provided to shift their attention away from the irrelevant location. The authors suggest that inhibition is intact in schizophrenia patients, but it is usually masked by increased facilitation. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Effects of comorbidity and early age of onset in young people with Bipolar Disorder on self harming behaviour and suicide attempts.

Science.gov (United States)

Moor, Stephanie; Crowe, Marie; Luty, Sue; Carter, Janet; Joyce, Peter R

2012-02-01

The age of the first episode of illness in Bipolar Disorder has been shown to be an important predictor of outcome with early onset, particularly onset before puberty, associated with greater comorbidity, a poorer quality of life and greatest impairment in functioning. Baseline data from a psychotherapy study was used to examine the prevalence of other comorbid psychiatric conditions and the impact of onset at an early age on both self harming behaviour and suicide attempts in young people with Bipolar Disorder. This study of 100 adolescents and young adults (aged 15-36 years) with Bipolar Disorder showed that comorbid conditions were very common, even at the start of their bipolar illness. Comorbidity increased as the age of onset decreased with very early onset (self harmed and attempted suicide with high lethal intent. Self harming behaviour was predicted by having a lifetime diagnoses of Borderline Personality Disorder and Panic Disorder along with an early age of onset of Bipolar Disorder. In contrast, previous suicide attempts were predicted by greater comorbidity and not by very early (<13 years) age of onset. Copyright © 2011 Elsevier B.V. All rights reserved.

Cognitive Remediation in Schizophrenia: Current Status and Future Perspectives

Science.gov (United States)

Deste, Giacomo; De Peri, Luca

2013-01-01

Objectives. This study is aimed to review the current scientific literature on cognitive remediation in schizophrenia. In particular, the main structured protocols of cognitive remediation developed for schizophrenia are presented and the main results reported in recent meta-analyses are summarized. Possible benefits of cognitive remediation in the early course of schizophrenia and in subjects at risk for psychosis are also discussed. Methods. Electronic search of the relevant studies which appeared in the PubMed database until April 2013 has been performed and all the meta-analyses and review articles on cognitive remediation in schizophrenia have been also taken into account. Results. Numerous intervention programs have been designed, applied, and evaluated, with the objective of improving cognition and social functioning in schizophrenia. Several quantitative reviews have established that cognitive remediation is effective in reducing cognitive deficits and in improving functional outcome of the disorder. Furthermore, the studies available support the usefulness of cognitive remediation when applied in the early course of schizophrenia and even in subjects at risk of the disease. Conclusions. Cognitive remediation is a promising approach to improve real-world functioning in schizophrenia and should be considered a key strategy for early intervention in the psychoses. PMID:24455253

Cognitive Deficits in Schizophrenia: Understanding the Biological Correlates and Remediation Strategies

Science.gov (United States)

Tripathi, Adarsh; Shukla, Rashmi

2018-01-01

Cognitive deficits are one of the core symptoms of schizophrenia that evolve during the course of schizophrenia, after being originated even before the onset of illness. Existing pharmacological and biological treatment modalities fall short to meet the needs to improve the cognitive symptoms; hence, various cognitive remediation strategies have been adopted to address these deficits. Research evidences suggest that cognitive remediation measures improve the functioning, limit disability bettering the quality of life. The functional outcomes of cognitive remediation in schizophrenia are resultant of neurobiological changes in specific brain areas. Recent years witnessed significant innovations in cognitive remediation strategies in schizophrenia. This comprehensive review highlights the biological correlates of cognitive deficits in schizophrenia and the remedial measures with evidence base. PMID:29397662

Polycystic ovary syndrome and early-onset preeclampsia: reproductive manifestations of increased cardiovascular risk.

Science.gov (United States)

Veltman-Verhulst, Susanne M; van Rijn, Bas B; Westerveld, H Egbertine; Franx, Arie; Bruinse, Hein W; Fauser, Bart C J M; Goverde, Angelique J

2010-01-01

Primary prevention of cardiovascular disease (CVD) in women is a major healthcare issue. Detection of premenopausal women with increased risk of CVD could enhance prevention strategies and reduce first event-related morbidity and mortality. In this study, we argue that an unfavorable metabolic constitution in women may present itself early in life as a reproductive complication, such as polycystic ovary syndrome (PCOS) and preeclampsia. We evaluated the cardiovascular risk of women with a history of early-onset preeclampsia and women with PCOS and assessed their need for implementation of early risk factor-reduction strategies. We performed a standardized evaluation of 240 women with a history of early-onset preeclampsia and 456 women diagnosed with PCOS for established major CVD risk factors. Metabolic syndrome characteristics were analyzed per body mass index category. Mean age was 30.6 and 29.0 years for women with preeclampsia and PCOS, respectively. High percentages of metabolic syndrome were found in both groups (preeclampsia group, 14.6%; and PCOS group, 18.4%), with an incidence of greater than 50% in both groups of women if body mass index was greater than 30 kg/m. Overall, more than 90% of the women qualified for either lifestyle or medical intervention according to the American Heart Association guideline for CVD prevention in women. Women with PCOS and early-onset preeclampsia already show an unfavorable cardiovascular risk profile with high need for lifestyle or medical intervention at a young age. We therefore recommend an active role of the gynecologist in routine screening and follow-up of women with reproductive conditions linked to future cardiovascular risk.

Novel CDKL5 Mutations in Czech Patients with Phenotypes of Atypical Rett Syndrome and Early-Onset Epileptic Encephalopathy.

Science.gov (United States)

Záhoráková, D; Langová, M; Brožová, K; Laštůvková, J; Kalina, Z; Rennerová, L; Martásek, P

2016-01-01

The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation- dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c.902_977+29del105, and c.1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases.

Early drinking onset: a study of prevalence and determinants among 13-year-old adolescents in Norway.

Science.gov (United States)

Adolfsen, Frode; Strøm, Henriette Kyrrestad; Martinussen, Monica; Natvig, Henrik; Eisemann, Martin; Handegård, Bjørn Helge; Koposov, Roman

2014-10-01

Early drinking onset is associated with different psychosocial adjustment problems among adolescents. The aim of this study was to assess determinants associated with early drinking and to identify factors predicting early drinking onset among adolescents. The study included 1,550 eighth-graders with a mean age of 13.5 years from 41 schools. A total of 24% (boys 29%, girls 19%) had ever drunk alcohol, while 14% had drunk some alcohol in the last 30 days. Further, early drinking was associated with gender, religion, school performance, smoking and bullying in the bivariate tests. Predictors of early drinking onset were identified by generalized linear mixed models with two multivariable models created. The first model included social and environmental variables. Entering intentions, expectancies, attitudes and norms into the multivariable analysis resulted in a significant improvement of the model fit constituting 86% in the second model. The percentage correctly classified those (56%) who had been drinking in the second model which was two times higher compared to the first model. Gender, religion and smoking emerged as significant predictors of drinking in both models. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Early-onset Alzheimer's disease: nonamnestic subtypes and type 2 AD.

Science.gov (United States)

Mendez, Mario F

2012-11-01

Patients with Alzheimer's disease (AD), the most prevalent neurodegenerative dementia, are usually elderly; however, ∼4-5% develop early-onset AD (EOAD) with onset before age 65. Most EOAD is sporadic, but about 5% of patients with EOAD have an autosomal dominant mutation such as Presenilin 1, Presenilin 2, or alterations in the Amyloid Precursor Protein gene. Although most Alzheimer's research has concentrated on older, late-onset AD (LOAD), there is much recent interest and research in EOAD. These recent studies indicate that EOAD is a heterogeneous disorder with significant differences from LOAD. From 22-64% of EOAD patients have a predominant nonamnestic syndrome presenting with deficits in language, visuospatial abilities, praxis, or other non-memory cognition. These nonamnestic patients may differ in several ways from the usual memory or amnestic patients. Patients with nonamnestic EOAD compared to typical amnestic AD have a more aggressive course, lack the apolipoprotein Eɛ4 (APOE ɛ4) susceptibility gene for AD, and have a focus and early involvement of non-hippocampal areas of brain, particularly parietal neocortex. These differences in the EOAD subtypes indicate differences in the underlying amyloid cascade, the prevailing pathophysiological theory for the development of AD. Together the results of recent studies suggest that nonamnestic subtypes of EOAD constitute a Type 2 AD distinct from the usual, typical disorder. In sum, the study of EOAD can reveal much about the clinical heterogeneity, predisposing factors, and neurobiology of this disease. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors

Science.gov (United States)

Tournier, Isabelle; Marlin, Régine; Walton, Kelly; Charbonnier, Françoise; Coutant, Sophie; Théry, Jean-Christophe; Charbonnier, Camille; Spurrell, Cailyn; Vezain, Myriam; Ippolito, Lorena; Bougeard, Gaëlle; Roman, Horace; Tinat, Julie; Sabourin, Jean-Christophe; Stoppa-Lyonnet, Dominique; Caron, Olivier; Bressac-de Paillerets, Brigitte; Vaur, Dominique; King, Mary-Claire; Harrison, Craig; Frebourg, Thierry

2014-01-01

To identify novel genetic bases of early-onset epithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the INHBA gene encoding the βA-subunit of inhibins/activins, which play a key role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a second patient with early-onset serous borderline papillary cystadenoma, we identified an unreported germline mutation (c.179G>T/p.Arg60Leu) of the INHA gene encoding the α-subunit, the partner of the βA-subunit. This mutation also alters the secreted activin/inhibin ratio, by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases, we detected an additional unreported germline mutation of the INHBA gene (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovarian tumors. PMID:24302632

New Predictive Model at 11+0 to 13+6 Gestational Weeks for Early-Onset Preeclampsia With Fetal Growth Restriction.

Science.gov (United States)

Chang, Ying; Chen, Xu; Cui, Hong-Yan; Li, Xing; Xu, Ya-Ling

2017-05-01

The aim of the present study was to determine a predictive model for early-onset preeclampsia with fetal growth restriction (FGR) to be used at 11 +0 to 13 +6 gestational weeks, by combining the maternal serum level of pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF), placental protein 13 (PP13), soluble endoglin (sEng), mean arterial pressure (MAP), and uterine artery Doppler. This was a retrospective cohort study of 4453 pregnant women. Uterine artery Doppler examination was conducted in the first trimester. Maternal serum PAPP-A, PLGF, PP13, and sEng were measured. Mean arterial pressure was obtained. Women were classified as with/without early-onset preeclampsia, and women with preeclampsia were classified as with/without FGR. Receiver operating characteristic analysis was performed to determine the value of the model. There were 30 and 32 pregnant women with early-onset preeclampsia with and without FGR. The diagnosis rate of early-onset preeclampsia with FGR was 67.4% using the predictive model when the false positive rate was set at 5% and 73.2% when the false positive rate was 10%. The predictive model (MAP, uterine artery Doppler measurements, and serum biomarkers) had some predictive value for the early diagnosis (11 +0 to 13 +6 gestational weeks) of early-onset preeclampsia with FGR.

Cerebrospinal Fluid Aβ43 Is Reduced in Early-Onset Compared to Late-Onset Alzheimer’s Disease, But Has Similar Diagnostic Accuracy to Aβ42

Directory of Open Access Journals (Sweden)

Camilla Lauridsen

2017-06-01

Full Text Available Background: Amyloid beta 1–43 (Aβ43 may be a useful additional biomarker for diagnosing Alzheimer’s disease (AD. We have investigated cerebrospinal fluid (CSF levels of Aβ43 in patients with early-onset AD in contrast to levels in late-onset AD. For comparison, in addition to the ‘core’ biomarkers, several other analytes were also determined [YKL-40, neurofilament light (NF-L, glial fibrillary acidic protein (GFAP, and progranulin].Material and Methods: Cerebrospinal fluid samples were obtained from patients with early-onset AD (age ≤ 62, n = 66, late-onset AD (age ≥ 68, n = 25, and groups of cognitively intact individuals (age ≤ 62, n = 41, age ≥ 68, n = 39. Core CSF AD biomarkers [amyloid beta 1–42 (Aβ42, total tau, phosphorylated tau] were analyzed, as well as levels of Aβ43 and other analytes, using commercially available enzyme-linked immunosorbent assays.Results: Cerebrospinal fluid Aβ43 was significantly reduced in early-onset AD compared to late-onset AD (14.8 ± 7.3 vs. 21.8 ± 9.4 pg/ml, respectively, whereas the levels of Aβ42 in the two AD groups were not significantly different (474.9 ± 142.0 vs. 539.6 ± 159.9 pg/ml, respectively. Aβ43 and all core biomarkers were significantly altered in patients with AD compared to corresponding controls. NF-L was significantly increased in early-onset AD compared to younger controls, an effect not found between the older groups. Relationships between the Aβ peptides and tau proteins, YKL-40, NF-L, GFAP and progranulin were also investigated without finding marked associations. However, age-associated increases in levels of tau proteins, YKL-40, NF-L and GFAP were found with respect to age in healthy controls. Results for these other analytes were similar to previously published data. Aβ43 did not improve diagnostic accuracy in either AD group compared to Aβ42. Discussion: Cerebrospinal fluid Aβ43, but not Aβ42 levels, varied significantly with age in patients with

Schizophrenia and psychotic symptoms in families of two American Indian tribes

Directory of Open Access Journals (Sweden)

Albaugh Bernard

2007-06-01

population isolates and in the general population. Vulnerabilities to early onset alcohol and drug use disorders do not lend convincing support to a diathesis-stressor model with these stressors, commonly reported with these tribes. Nearly one-fifth of the respondents reported experiencing psychotic-like symptoms, reaffirming the need to examine sociocultural factors actively before making positive diagnoses of psychosis or schizophrenia.

Premature adrenarche: novel lessons from early onset androgen excess.

Science.gov (United States)

Idkowiak, Jan; Lavery, Gareth G; Dhir, Vivek; Barrett, Timothy G; Stewart, Paul M; Krone, Nils; Arlt, Wiebke

2011-08-01

Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

Interaction between parental psychosis and early motor development and the risk of schizophrenia in a general population birth cohort.

Science.gov (United States)

Keskinen, E; Marttila, A; Marttila, R; Jones, P B; Murray, G K; Moilanen, K; Koivumaa-Honkanen, H; Mäki, P; Isohanni, M; Jääskeläinen, E; Miettunen, J

2015-09-01

Delayed motor development in infancy and family history of psychosis are both associated with increased risk of schizophrenia, but their interaction is largely unstudied. To investigate the association of the age of achieving motor milestones and parental psychosis and their interaction in respect to risk of schizophrenia. We used data from the general population-based prospective Northern Finland Birth Cohort 1966 (n=10,283). Developmental information of the cohort members was gathered during regular visits to Finnish child welfare clinics. Several registers were used to determine the diagnosis of schizophrenia among the cohort members and psychosis among the parents. Altogether 152 (1.5%) individuals had schizophrenia by the age of 46 years, with 23 (15.1%) of them having a parent with psychosis. Cox regression analysis was used in analyses. Parental psychosis was associated (Prisk for schizophrenia was increased if holding the head up (hazard ratio [HR]: 2.46; degrees of freedom [df]=1; 95% confidence interval [95% CI]: 1.07-5.66) and touching the thumb with the index finger (HR: 1.84; df=1; 95% CI: 1.11-3.06) was later. In the group without parental psychosis, a delay in the following milestones increased the risk of schizophrenia: standing without support and walking without support. Parental psychosis had an interaction with delayed touching thumb with index finger (HR: 1.87; df=1; 95% CI: 1.08-3.25) when risk of schizophrenia was investigated. Parental psychosis was associated with achieving motor milestones later in infancy, particularly the milestones that appear early in a child's life. Parental psychosis and touching the thumb with the index finger had a significant interaction on risk of schizophrenia. Genetic risk for psychosis may interact with delayed development to raise future risk of schizophrenia, or delayed development may be a marker of other risk processes that interact with genetic liability to cause later schizophrenia. Copyright © 2015

Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples

DEFF Research Database (Denmark)

den Hoed, M; Luan, J; Langenberg, C

2013-01-01

BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes. OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population-based sam......BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes. OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population......, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population....

Hopes and Expectations Regarding Genetic Testing for Schizophrenia Among Young Adults at Clinical High-Risk for Psychosis.

Science.gov (United States)

Friesen, Phoebe; Lawrence, Ryan E; Brucato, Gary; Girgis, Ragy R; Dixon, Lisa

2016-11-01

Genetic tests for schizophrenia could introduce both risks and benefits. Little is known about the hopes and expectations of young adults at clinical high-risk for psychosis concerning genetic testing for schizophrenia, despite the fact that these youth could be among those highly affected by such tests. We conducted semistructured interviews with 15 young adults at clinical high-risk for psychosis to ask about their interest, expectations, and hopes regarding genetic testing for schizophrenia. Most participants reported a high level of interest in genetic testing for schizophrenia, and the majority said they would take such a test immediately if it were available. Some expressed far-reaching expectations for a genetic test, such as predicting symptom severity and the timing of symptom onset. Several assumed that genetic testing would be accompanied by interventions to prevent schizophrenia. Participants anticipated mixed reactions on finding out they had a genetic risk for schizophrenia, suggesting that they might feel both a sense of relief and a sense of hopelessness. We suggest that genetic counseling could play an important role in counteracting a culture of genetic over-optimism and helping young adults at clinical high-risk for psychosis understand the limitations of genetic testing. Counseling sessions could also invite individuals to explore how receiving genetic risk information might impact their well-being, as early evidence suggests that some psychological factors help individuals cope, whereas others heighten distress related to genetic test results.

[On the front line: survey on shared responsibility. General practitioners and schizophrenia].

Science.gov (United States)

Stip, Emmanuel; Boyer, Richard; Sepehry, Amir Ali; Rodriguez, Jean Pierre; Umbricht, Daniel; Tempier, Adrien; Simon, Andor E

2007-01-01

General practitioners (GP) play a preponderant role in the treatment of patients suffering of schizophrenia. Discovering the number of patients with schizophrenia who are treated by GPs ; the needs and attitudes of GPs, their knowledge concerning diagnosis, and the treatment they provide. A postal survey was conducted with Quebec GPs who were randomly chosen. A total of 1003 GPs have participated in the survey. Among them, a small percentage have to treat an early onset schizophrenia and the GPs have expressed their wish to be more informed on the accessibility of specialized services. Results pertaining to questions on diagnoses and knowledge on treatments are inconsistent. The majority of GPs treat the first psychotic episodes with antipsychotic medication. Only a third of GPs surveyed propose maintaining the treatment after a first psychotic episode, in accordance with international recommendations and the recent Canadian guidelines on practices that recommends at least 6 to 12 months of treatment after a partial or complete clinical response. Time given by male GPs to a first contact varies between 10 and 20 minutes, while 80 % of female GPs spend at least 20 minutes. The adverse effects of antipsychotic medication that raise most concern is weight gain before neurological signs. some of this survey's data should be considered by various professional and governmental associations, in order to improve the place of GPs in a health plan destined to treat schizophrenia.

Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia.

Science.gov (United States)

Zhong, Xiao Yan; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Holzgreve, Wolfgang; Hahn, Sinuhe

2005-08-01

Elevations in circulatory DNA, as measured by real-time PCR, have been observed in pregnancies with manifest preeclampsia. Recent reports have indicated that circulatory nucleosome levels are elevated in the periphery of cancer patients. We have now examined whether circulatory nucleosome levels are similarly elevated in cases with preeclampsia. Maternal plasma samples were prepared from 17 cases with early onset preeclampsia (34 weeks gestation) with 10 matched normotensive controls. Levels of circulatory nucleosomes were quantified by commercial ELISA (enzyme-linked immunosorbant assay). The level of circulatory nucleosomes was significantly elevated in both study preeclampsia groups, compared to the matched normotensive control group (p = 0.000 and p = 0.001, respectively). Our data suggests that preeclampsia is associated with the elevated presence of circulatory nucleosomes, and that this phenomenon occurs in both early- and late-onset forms of the disorder. Copyright 2005 John Wiley & Sons, Ltd.

Altered brain arginine metabolism in schizophrenia.

Science.gov (United States)

Liu, P; Jing, Y; Collie, N D; Dean, B; Bilkey, D K; Zhang, H

2016-08-16

Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease.

Association study between BDNF C-281A polymorphism and paranoid schizophrenia in Polish population.

Science.gov (United States)

Suchanek, Renata; Owczarek, Aleksander; Kowalski, Jan

2012-01-01

Brain-derived neurotrophic factor (BDNF) is one of the candidate genes for schizophrenia. Polymorphism C-281A (rs28383487) in BDNF gene leads to the reduction of promoter activity in the hippocampal neurons in vitro. To our knowledge, this is the first study to examine the influence of alleles and genotypes of BDNF C-281A polymorphism on development, as well as the clinical course (age of onset, suicidal behaviour and psychopathology) of paranoid schizophrenia. The psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) as subscale scores and also single-item scores. We have also performed the haplotype analysis with val66met BDNF polymorphism, which is known to be involved in the pathogenesis of schizophrenia. We have not found significant differences in the distribution of genotypes and alleles between schizophrenic patients and controls in both the overall analysis, as well as sex stratified. Also, we have not shown statistically significant differences between genotype groups and PANSS scale. However, an association between C-281A polymorphism and time of the first episode of paranoid schizophrenia was revealed. Genotype C/A had been connected with later age of onset of paranoid schizophrenia in men but not in women (p schizophrenia group compared to the controls.

Serial elongation-derotation-flexion casting for children with early-onset scoliosis.

Science.gov (United States)

Canavese, Federico; Samba, Antoine; Dimeglio, Alain; Mansour, Mounira; Rousset, Marie

2015-12-18

Various early-onset spinal deformities, particularly infantile and juvenile scoliosis (JS), still pose challenges to pediatric orthopedic surgeons. The ideal treatment of these deformities has yet to emerge, as both clinicians and surgeons still face multiple challenges including preservation of thoracic motion, spine and cage, and protection of cardiac and lung growth and function. Elongation-derotation-flexion (EDF) casting is a technique that uses a custom-made thoracolumbar cast based on a three-dimensional correction concept. EDF can control progression of the deformity and - in some cases-coax the initially-curved spine to grow straighter by acting simultaneously in the frontal, sagittal and coronal planes. Here we provide a comprehensive review of how infantile and JS can affect normal spine and thorax and how serial EDF casting can be used to manage these spinal deformities. A fresh review of the literature helps fully understand the principles of the serial EDF casting technique and the effectiveness of conservative treatment in patients with early-onset spinal deformities, particularly infantile and juvenile scolisois.

Early-onset stroke with moyamoya-like syndrome and extraneurological signs: a first reported paediatric series

International Nuclear Information System (INIS)

Law-ye, Bruno; Saliou, Guillaume; Toulgoat, Frederique; Tardieu, Marc; Deiva, Kumaran; Adamsbaum, Catherine; Husson, Beatrice

2016-01-01

Moyamoya syndrome is characterised by an occlusion of the carotid terminations with the development of collateral vessels. Our objective is to describe a series of infants presenting early-onset moyamoya-like syndrome, which may constitute a distinct entity. From a cohort of children with rare cerebral vascular pathologies, we studied eight infants (28 days-1 year) with early-onset moyamoya-like syndrome demonstrated by angiography. We retrospectively analysed the patterns on MRI and MRA, as well as all other available data. Median age at diagnosis was 7 months (IQR: 6-8) with arterial ischaemic stroke in the middle cerebral artery territory. All of the children experienced severe stroke recurrence within a median time of 11 months (IQR: 10-12), and all showed extraneurological symptoms. The anterior cerebral circulation was involved in all cases and the posterior circulation was involved in six. Two children died and all of the other children suffered permanent neurological deficits. The presence of extraneurological signs in cases of early-onset moyamoya syndrome is suggestive of a newly described systemic vasculopathy with predominantly cerebrovascular expression. Given its rapid progression marked by severe recurrent strokes and poor clinical outcome, early diagnosis could help in the decision to institute aggressive therapy. (orig.)

Caregivers' perspectives on the pre-diagnostic period in early onset dementia: a long and winding road

NARCIS (Netherlands)

van Vliet, D.; de Vugt, M.E.; Bakker, C.; Koopmans, R.T.C.M.; Pijnenburg, Y.A.L.; Vernooij-Dassen, M.; Verhey, F.R.J.

2011-01-01

Background: Recognizing and diagnosing early onset dementia (EOD) can be complex and often takes longer than for late onset dementia. The objectives of this study are to investigate the barriers to diagnosis and to develop a typology of the diagnosis pathway for EOD caregivers. Methods:

Δ9-tetrahydrocannabinol (Δ9-THC) administration after neonatal exposure to phencyclidine potentiates schizophrenia-related behavioral phenotypes in mice.

Science.gov (United States)

Rodríguez, Guadalupe; Neugebauer, Nichole M; Yao, Katherine Lan; Meltzer, Herbert Y; Csernansky, John G; Dong, Hongxin

2017-08-01

The clinical onset of schizophrenia often coincides with cannabis use in adolescents and young adults. However, the neurobiological consequences of this co-morbidity are not well understood. In this study, we examined the effects of Δ9-THC exposure during early adulthood on schizophrenia-related behaviors using a developmental mouse model of schizophrenia. Phencyclidine (PCP) or saline was administered once in neonatal mice (at P7; 10mg/kg). In turn, Δ9-THC or saline was administered sub-acutely later in life to cohorts of animals who had received either PCP or saline (P55-80, 5mg/kg). Mice who were administered PCP alone displayed behavioral changes in the Morris water waze (MWM) and pre-pulse inhibition (PPI) task paradigm that were consistent with schizophrenia-related phenotypes, but not in the locomotor activity or novel object recognition (NOR) task paradigms. Mice who were administered PCP and then received Δ9-THC later in life displayed behavioral changes in the locomotor activity paradigm (pschizophrenia-related phenotype, as well as potentiated changes in the NOR (pschizophrenia-related behavioral phenotypes induced by neonatal exposure to PCP in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Source retrieval is not properly differentiated from object retrieval in early schizophrenia: An fMRI study using virtual reality

Directory of Open Access Journals (Sweden)

Colin Hawco

2015-01-01

Full Text Available Source memory, the ability to identify the context in which a memory occurred, is impaired in schizophrenia and has been related to clinical symptoms such as hallucinations. The neurobiological underpinnings of this deficit are not well understood. Twenty-five patients with recent onset schizophrenia (within the first 4.5 years of treatment and twenty-four healthy controls completed a source memory task. Participants navigated through a 3D virtual city, and had 20 encounters of an object with a person at a place. Functional magnetic resonance imaging was performed during a subsequent forced-choice recognition test. Two objects were presented and participants were asked to either identify which object was seen (new vs. old object recognition, or identify which of the two old objects was associated with either the person or the place being presented (source memory recognition. Source memory was examined by contrasting person or place with object. Both patients and controls demonstrated significant neural activity to source memory relative to object memory, though activity in controls was much more widespread. Group differences were observed in several regions, including the medial parietal and cingulate cortex, lateral frontal lobes and right superior temporal gyrus. Patients with schizophrenia did not differentiate between source and object memory in these regions. Positive correlations with hallucination proneness were observed in the left frontal and right middle temporal cortices and cerebellum. Patients with schizophrenia have a deficit in the neural circuits which facilitate source memory, which may underlie both the deficits in this domain and be related to auditory hallucinations.

Mismatch negativity in chronic schizophrenia and first-episode schizophrenia.

Science.gov (United States)

Salisbury, Dean F; Shenton, Martha E; Griggs, Carlye B; Bonner-Jackson, Aaron; McCarley, Robert W

2002-08-01

Mismatch negativity (MMN) is an event-related brain potential that is sensitive to stimulus deviation from a repetitive pattern. The MMN is thought primarily to reflect the activity of sensory memory, with, at most, moderate influences of higher-level cognitive processes, such as attention. The MMN is reported to be reduced in patients with chronic schizophrenia. However, it is unknown whether MMN is reduced in patients with first-episode schizophrenia (at first hospitalization). Subject groups comprised patients with chronic schizophrenia (n = 16) and older control subjects (n = 13), and patients with first-episode schizophrenia (n = 21) and younger control subjects (n = 27). The MMN was visualized by subtracting the averaged event-related brain potential to standard tones (1 kHz [95% of all tones]) from the event-related brain potential to pitch-deviant tones (1.2 kHz [5% of all tones]). The MMN voltage was the mean voltage from 100 to 200 milliseconds. Pitch-deviant MMN was reduced by approximately 47% in patients with chronic illness along the sagittal midline relative to controls. The MMN was not reduced in patients with first-episode schizophrenia. All 4 groups showed approximately 64% larger MMN to pitch-deviant tones over the right hemisphere compared with the left hemisphere. The pitch-deviant MMN reductions present in patients with chronic schizophrenia are not present at first hospitalization. The sensory, echoic memory functions indexed by MMN seem unaffected early in the schizophrenia disease process. Reductions in MMN amplitude may develop over time and index the progression of the disorder, although that can only be definitively determined by longitudinal assessments.

Early-onset baldness and the risk of aggressive prostate cancer: findings from a case-control study.

Science.gov (United States)

Papa, Nathan P; MacInnis, Robert J; English, Dallas R; Bolton, Damien; Davis, Ian D; Lawrentschuk, Nathan; Millar, Jeremy L; Severi, Gianluca; Hopper, John L; Giles, Graham G

2018-01-01

We aimed to evaluate the associations between androgenetic alopecia at a young age and subsequent development of aggressive prostate cancer (PC). Using a case-control design with self-administered questionnaire, we evaluated the association between aggressive PC and very early-onset balding at age 20, and early-onset balding at age 40 years in 1,941 men. Cases were men with high-grade and/or advanced stage cancer and controls were clinic based men who had undergone biopsy and were found to be histologically cancer negative. Additionally, for cases we assessed whether early-onset balding was associated with earlier onset of disease. Men with very early-onset balding at age 20 years were at increased risk for subsequent aggressive PC [odds ratio (OR) 1.51, 95% confidence interval (CI) 1.07-2.12] after adjustment for age at baseline, family history of PC, smoking status, alcohol intake, body shape, timing of growth spurt and ejaculatory frequency. Additionally, these men were diagnosed with PC approximately 16 months earlier than cases without the exposure. The effect was present particularly for men with advanced stage pT3+ disease (OR 1.68, 95% CI 1.14-2.47) while men with organ-confined high-grade (8-10) PC did not exhibit the same relationship. No significant associations were observed for men who were balding at age 40 years, given no balding at age 20. Men with androgenetic alopecia at age 20 years are at increased risk of advanced stage PC. This small subset of men are potentially candidates for earlier screening and urological follow-up.

The incidence of schizophrenia and schizophrenia spectrum disorders in Denmark in the period 2000-2012. A register-based study.

Science.gov (United States)

Kühl, Johanne Olivia Grønne; Laursen, Thomas Munk; Thorup, Anne; Nordentoft, Merete

2016-10-01

We aimed to examine changes over time in the incidence of broad and narrow schizophrenia spectrum disorders in Denmark from 2000 to 2012. Patients were classified as incident schizophrenia if registered with a first time in- or outpatient contact with relevant diagnostic codes in the Danish Psychiatric Central Register between 2000 and 2012. Their history of contacts was traced back to 1969. Broad schizophrenia included schizophrenia, schizotypal disorder, persistent delusional disorder, acute and transient psychotic disorders, schizoaffective disorders, and other nonorganic and unspecified psychotic disorders, (ICD 10 codes F20-F29). Narrow schizophrenia was defined with the ICD 10 codes F20.0-F20.9. Incidence rates (IR) and incidence rate ratios (IRR) were calculated using Poisson regression. The IRR for broad schizophrenia increased by 1.43 (CI 95% 1.34-1.52) for females and 1.26 (CI 95% 1.20-1.33) for males. IRR for narrow schizophrenia increased by 1.36 (CI 95% 1.24-1.48) for females and 1.20 (CI 95% 1.11-1.29) for males. There was a significantly increased incidence in patients up to 32years of age. This was mainly explained by a significant 2-3 fold increase in outpatient incidence. We found a significant decrease in IRR for patients with broad and narrow schizophrenia aged 33 or older for both in- and outpatients. The increased incidence of schizophrenia could partly be explained by better implementation of the diagnostic criteria for schizophrenia in child and adolescent psychiatry and improved access to early intervention services, but a true increase in incidence of schizophrenia cannot be excluded. The decrease of incidence in the older age group could indicate that the national Danish early intervention strategy was successful. Copyright © 2016 Elsevier B.V. All rights reserved.

Preliminary findings demonstrating latent effects of early adolescent marijuana use onset on cortical architecture

Directory of Open Access Journals (Sweden)

Francesca M. Filbey

2015-12-01

Conclusions: Divergent patterns between current MJ use and elements of cortical architecture were associated with early MJ use onset. Considering brain development in early adolescence, findings are consistent with disruptions in pruning. However, divergence with continued use for many years thereafter suggests altered trajectories of brain maturation during late adolescence and beyond.

Evaluation of a neurodevelopmental model of schizophrenia--early postnatal PCP treatment in attentional set-shifting

DEFF Research Database (Denmark)

Broberg, Brian Villumsen; Dias, Rebecca; Glenthøj, Birte Yding

2008-01-01

Phencyclidine (PCP) was administered to male and female Lister hooded rats on postnatal days (PND) 7, 9 and 11. All PCP animals tested in adulthood (PND 53-93) showed deficits in cognitive flexibility, specifically in their ability to shift attentional set, compared to controls. This novel finding...... is reminiscent of the impairment observed in schizophrenia patients, and supports the validity of the early postnatal PCP regimen as a disease-like model....

Identifying anomalously early spring onsets in the CESM large ensemble project

Science.gov (United States)

Labe, Zachary; Ault, Toby; Zurita-Milla, Raul

2017-06-01

Seasonal transitions from winter to spring impact a wide variety of ecological and physical systems. While the effects of early springs across North America are widely documented, changes in their frequency and likelihood under the combined influences of climate change and natural variability are poorly understood. Extremely early springs, such as March 2012, can lead to severe economical losses and agricultural damage when these are followed by hard freeze events. Here we use the new Community Earth System Model Large Ensemble project and Extended Spring Indices to simulate historical and future spring onsets across the United States and in the particular the Great Lakes region. We found a marked increase in the frequency of March 2012-like springs by midcentury in addition to an overall trend towards earlier spring onsets, which nearly doubles that of observational records. However, changes in the date of last freeze do not occur at the same rate, therefore, causing a potential increase in the threat of plant tissue damage. Although large-scale climate modes, such as the Pacific Decadal Oscillation, have previously dominated decadal to multidecadal spring onset trends, our results indicate a decreased role in natural climate variability and hence a greater forced response by the end of the century for modulating trends. Without a major reduction in greenhouse gas emissions, our study suggests that years like 2012 in the US could become normal by mid-century.

Early-onset acute kidney injury is a poor prognostic sign for allogeneic SCT recipients.

Science.gov (United States)

Shingai, N; Morito, T; Najima, Y; Kobayashi, T; Doki, N; Kakihana, K; Ohashi, K; Ando, M

2015-12-01

Acute kidney injury (AKI) following stem-cell transplantation (SCT) contributes to a poor prognosis, yet its impact may vary depending on the timing of AKI onset. A prospective cohort study was performed to understand the significance of the onset timing in 103 allogeneic SCT (allo-SCT) recipients. AKI prior to stem-cell engraftment was defined as early AKI and subsequently occurring AKI as late AKI. Propensity score (PS) for early AKI was calculated using a logistic regression model to reduce confounding effects related to differences in clinical background between the early and late AKI groups. The cumulative incidences of early and late AKI were 22.3% and 54.9%, respectively. Non-relapse mortality (NRM) was 39.1% and 7.0%, and overall survival (OS) was 56.5% and 90.9% in early and late AKI at 100 days after AKI, respectively (PSCT was 41.5% and 19.1% in early and late AKI, respectively (P=0.048). Logistic regression analysis adjusted for the PS showed that early AKI was significantly associated with OS (odds ratio (95% confidence interval); 4.63 (1.15-21.4), P=0.031) but with neither NRM (1.25 (0.28-5.33), P=0.766) nor CKD (1.85 (0.41-8.60), P=0.422). In conclusion, early AKI may portend a poor survival for allo-SCT recipients.

Early pubertal onset and its relationship with sexual risk taking, substance use and anti-social behaviour: a preliminary cross-sectional study

Directory of Open Access Journals (Sweden)

Bellis Mark A

2009-12-01

Full Text Available Abstract Background In many countries age at pubertal onset has declined substantially. Relatively little attention has been paid to how this decline may affect adolescent behaviours such as substance use, violence and unprotected sex and consequently impact on public health. Methods In the UK, two opportunistic samples (aged 16-45 years, paper-based (n = 976 and online (n = 1117, examined factors associated with earlier pubertal onset and whether earlier age of onset predicted sexual risk-taking, substance use and anti-social behaviours during early adolescence. Results Overall, 45.6% of females reported menarche ≤ 12 years and 53.3% of males were categorised as having pubertal onset ≤ 11 years. For both sexes earlier pubertal onset was associated with poorer parental socio-economic status. Other pre-pubertal predictors of early onset were being overweight, more childhood illnesses (females and younger age at time of survey (males. For both sexes earlier puberty predicted having drunk alcohol, been drunk, smoked and used drugs Conclusion Results provide sufficient evidence for changes in age of pubertal onset to be further explored as a potential influence on trends in adolescent risk behaviours. Further insight into the relationship between early puberty and both obesity and socio-economic status may help inform early interventions to tackle the development of risk behaviours and health inequalities during early adolescence.

High Prevalence of Long QT Syndrome Associated SCN5A Variants in Patients with Early-Onset Lone Atrial Fibrillation

DEFF Research Database (Denmark)

Olesen, Morten S; Yuan, Lei; Liang, Bo

2012-01-01

a mechanistic overlap between LQTS3 and early-onset lone AF. In 9 of 10 identified mutations and rare variants, we observed compromised biophysical properties affecting the transient peak current. CONCLUSIONS: In a cohort of patients with early-onset lone AF, we identified a high prevalence of SCN5A mutations...

Cerebral hemodynamic difference between early- and late-onset Alzheimer's disease by circumferential profile analysis with 123I-IMP brain SPECT

International Nuclear Information System (INIS)

Arai, Hisayuki; Hanyu, Haruo; Abe, Shinei; Asano, Tetsuichi; Takasaki, Masaru; Suzuki, Takanari; Abe, Kimihiko; Katsunuma, Hideyo.

1992-01-01

We conducted investigation to determine whether early- and late-onset Alzheimer's diseases differ pathophysiologically. Five patients with the early-onset (65 years and under) of the disease and 11 with the late-onset (65 years and over) of the disease were studied by single photon emission CT (SPECT) with N-isopropyl-p-[ 123 I]iodoamphetamine (IMP). Circumferential profile analysis (CPA) was performed to examine differences in the predominant hypoperfusion in the temporoparietal lobe, which is considered to be functionally damaged the most in Alzheimer's disease. The Xm values, calculated from gradients between the motorsensory or occipital cortices and temporoparietal cortex in the circumferential profile curve, were compared in both groups. The Xm values for patients with early- and late-onset Alzheimer's disease were 6.81±2.10 (counts/degree) and 3.28±1.58, respectively, the difference being significant. Our results suggest that functional abnormalities in the temporoparietal area severer in early- than late-onset Alzheimer's disease and that the application of CPA to IMP SPECT is useful to elucidate the pathophysiological difference between each of the disease. (author)

Early Onset Childhood Obesity and Risk of Metabolic Syndrome

Centers for Disease Control (CDC) Podcasts

2017-10-09

This podcast features Lorena Pacheco, a doctoral student at the University of California San Diego and one of the winners of PCD’s 2017 Student Research Paper Contest. Lorena answers questions about her winning research, which focuses on the relationship between early onset obesity as a risk factor for increased metabolic syndrome in Chilean children.  Created: 10/9/2017 by Preventing Chronic Disease (PCD), National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/9/2017.

Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.

Science.gov (United States)

Starčević, Mirta; Predojević, Maja; Butorac, Dražan; Tumbri, Jasna; Konjevoda, Paško; Kadić, Aida Salihagić

2016-02-01

To determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR. This cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT). 50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm). Adverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta. Copyright © 2015 Elsevier Ireland Ltd

High-Definition transcranial direct current stimulation in early onset epileptic encephalopathy: a case study.

Science.gov (United States)

Meiron, Oded; Gale, Rena; Namestnic, Julia; Bennet-Back, Odeya; David, Jonathan; Gebodh, Nigel; Adair, Devin; Esmaeilpour, Zeinab; Bikson, Marom

2018-01-01

Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy. HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study. These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy.

Science.gov (United States)

Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

2013-03-01

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.

Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes.

NARCIS (Netherlands)

Bonifati, V.; Rohe, C.F.; Breedveld, G.J.; Fabrizio, E.; Mari, M. De; Tassorelli, C.; Tavella, A.; Marconi, R.; Nicholl, D.; Chien, H.F.; Fincati, E.; Abbruzzese, G.; Marini, P.; Gaetano, A. De; Horstink, M.W.I.M.; Maat-Kievit, J.A.; Sampaio, C.; Antonini, A.; Stocchi, F.; Montagna, P.; Toni, V.; Guidi, M.; Dalla Libera, A.; Tinazzi, M.; Pandis, F. De; Goldwurm, S.; Klein, A. de; Barbosa, E.; Lopiano, L.; Martignoni, E.; Lamberti, P.; Vanacore, N.; Meco, G.; Oostra, B.A.

2005-01-01

OBJECTIVE: To assess the prevalence, nature, and associated phenotypes of PINK1 gene mutations in a large series of patients with early-onset (<50 years) parkinsonism. METHODS: The authors studied 134 patients (116 sporadic and 18 familial; 77% Italian) and 90 Italian controls. The whole PINK1

CDKL5 Mutations in Boys With Encephalopathy and Early-Onset Intractable Epilepsy

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2008-10-01

Full Text Available Clinical and EEG data of 3 Italian boys (ages 3, 9, and 13 years with severe early-onset encephalopathy, mental retardation, facial dysmorphisms, and intractable epilepsy were found to carry missense mutations in the CDKL5 gene, in a report from Troina, Italy.

Differences of neuroimaging between early-onset and late-onset alzheimer-type dementia

International Nuclear Information System (INIS)

Hanyu, Haruo; Nakano, Seigo; Abe, Shin'e; Arai, Hisayuki; Iwamoto, Toshihiko; Takasaki, Masaru

1995-01-01

Several studies have shown that the symptomatology and the neuropathological and neurochemical changes of early-onset Alzheimer's disease (EAD) differ from those of late-onset Alzheimer's disease (LAD). The aim of the present study is to examine differences in SPECT and MRI findings between EAD and LAD. Cerebral blood flow and patterns on SPECT, and deep white matter lesions and cerebral atrophy on MRI in 17 patients with EAD were compared with 30 patients with LAD without cerebrovascular risk factors. Temporoparietal activity ratio, divided by cerebellum, on SPECT imaging in patients with EAD was significantly lower than in patients with LAD. In a qualitative assessment of perfusion patterns, bilateral temporoparietal hypoperfusion, which is typical in AD, was seen more frequently in patients with EAD than in those with LAD. Among white matter changes in MRI, the score of white matter hyperintensity was significantly higher in LAD than in EAD patients. However, there was no significant difference between periventricular hyperintensity scores. Though ventricular enlargement did not differ significantly in EAD and LAD, cortical atrophy scores in LAD were significantly higher than in EAD. Cortical atrophy scores were significantly higher in patients with atypical perfusion patterns on SPECT (e.g. global hypoperfusion in addition to temporoparietal change) than in patients with typical perfusion pattern. These results indicate that functional and morphological imagings in LAD differ with those in EAD, probably due to less-prominent neuropathological degeneration combined with age-related alterations. (author)

Differences of neuroimaging between early-onset and late-onset alzheimer-type dementia

Energy Technology Data Exchange (ETDEWEB)

Hanyu, Haruo; Nakano, Seigo; Abe, Shin` e; Arai, Hisayuki; Iwamoto, Toshihiko; Takasaki, Masaru [Tokyo Medical Coll. (Japan)

1995-10-01

Several studies have shown that the symptomatology and the neuropathological and neurochemical changes of early-onset Alzheimer`s disease (EAD) differ from those of late-onset Alzheimer`s disease (LAD). The aim of the present study is to examine differences in SPECT and MRI findings between EAD and LAD. Cerebral blood flow and patterns on SPECT, and deep white matter lesions and cerebral atrophy on MRI in 17 patients with EAD were compared with 30 patients with LAD without cerebrovascular risk factors. Temporoparietal activity ratio, divided by cerebellum, on SPECT imaging in patients with EAD was significantly lower than in patients with LAD. In a qualitative assessment of perfusion patterns, bilateral temporoparietal hypoperfusion, which is typical in AD, was seen more frequently in patients with EAD than in those with LAD. Among white matter changes in MRI, the score of white matter hyperintensity was significantly higher in LAD than in EAD patients. However, there was no significant difference between periventricular hyperintensity scores. Though ventricular enlargement did not differ significantly in EAD and LAD, cortical atrophy scores in LAD were significantly higher than in EAD. Cortical atrophy scores were significantly higher in patients with atypical perfusion patterns on SPECT (e.g. global hypoperfusion in addition to temporoparietal change) than in patients with typical perfusion pattern. These results indicate that functional and morphological imagings in LAD differ with those in EAD, probably due to less-prominent neuropathological degeneration combined with age-related alterations. (author).

An interictal schizophrenia-like psychosis in an adult patient with 22q11.2 deletion syndrome

Directory of Open Access Journals (Sweden)

Yasutaka Tastuzawa

2015-01-01

Full Text Available In addition to causing polymalformative syndrome, 22q11.2 deletion can lead to various neuropsychiatric disorders including mental retardation, psychosis, and epilepsy. However, few reports regarding epilepsy-related psychosis in 22q11.2 deletion syndrome (22q11.2DS exist. We describe the clinical characteristics and course of 22q11.2DS in a Japanese patient with comorbid mild mental retardation, childhood-onset localization-related epilepsy, and adult-onset, interictal schizophrenia-like psychosis. From a diagnostic viewpoint, early detection of impaired intellectual functioning and hyperprolinemia in patients with epilepsy with 22q11.2DS may be helpful in predicting the developmental timing of interictal psychosis. From a therapeutic viewpoint, special attention needs to be paid to phenytoin-induced hypocalcemia in this syndrome.

Early onset neonatal sepsis in preterm premature rupture of membranes

International Nuclear Information System (INIS)

Ashraf, M.N.

2015-01-01

To determine the frequency of early onset neonatal sepsis in newborn with various duration of preterm premature rupture of membranes (PPROM). Study Design: Cross sectional study. Place and Duration of Study: Neonatal Intensive Care Unit Combined Military Hospital, Lahore from November 2009 to November 2010. Material and Methods: Neonates of singleton pregnancies complicated by preterm premature rupture of the membranes (PPROM) with delivery between 30 and 36 weeks gestation were included in the study. The overall frequency of neonatal sepsis was calculated on clinical and serological basis. Comparison of the frequency of sepsis among groups with varying duration of rupture of membranes was done. Results: Out of 164 babies, 84 (51.2%) were female and 80 (48.8%) were male. Mean maternal age was 23 years (range: 18-36 years). Mean gestational age was 33 weeks (range: 30-36 weeks). Sepsis was suspected in 41(25%) babies on clinical grounds. C-reactive protein was raised in 36 (22%) neonates. There was statistically insignificant difference between clinical versus serological diagnosis (p=0.515). Frequency of neonatal sepsis was significantly higher in mothers with longer duration of rupture of membrane (p < 0.001). Conclusion: Frequency of neonatal sepsis was observed to be 22%. PPROM is an important risk factor for early onset neonatal sepsis. (author)

Gene expression profiling reveals different molecular patterns in G-protein coupled receptor signaling pathways between early- and late-onset preeclampsia.

Science.gov (United States)

Liang, Mengmeng; Niu, Jianmin; Zhang, Liang; Deng, Hua; Ma, Jian; Zhou, Weiping; Duan, Dongmei; Zhou, Yuheng; Xu, Huikun; Chen, Longding

2016-04-01

Early-onset preeclampsia and late-onset preeclampsia have been regarded as two different phenotypes with heterogeneous manifestations; To gain insights into the pathogenesis of the two traits, we analyzed the gene expression profiles in preeclamptic placentas. A whole genome-wide microarray was used to determine the gene expression profiles in placental tissues from patients with early-onset (n = 7; 36 weeks) preeclampsia and their controls who delivered preterm (n = 5; 36 weeks). Genes were termed differentially expressed if they showed a fold-change ≥ 2 and q-value preeclampsia (177 genes were up-regulated and 450 were down-regulated). Gene ontology analysis identified significant alterations in several biological processes; the top two were immune response and cell surface receptor linked signal transduction. Among the cell surface receptor linked signal transduction-related, differentially expressed genes, those involved in the G-protein coupled receptor protein signaling pathway were significantly enriched. G-protein coupled receptor signaling pathway related genes, such as GPR124 and MRGPRF, were both found to be down-regulated in early-onset preeclampsia. The results were consistent with those of western blotting that the abundance of GPR124 was lower in early-onset compared with late-onset preeclampsia. The different gene expression profiles reflect the different levels of transcription regulation between the two conditions and supported the hypothesis that they are separate disease entities. Moreover, the G-protein coupled receptor signaling pathway related genes may contribute to the mechanism underlying early- and late-onset preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is early-onset microsatellite and chromosomally stable colorectal cancer a hallmark of a genetic susceptibility syndrome?

Science.gov (United States)

Kets, C M; van Krieken, J H J M; van Erp, P E J; Feuth, T; Jacobs, Y H A; Brunner, H G; Ligtenberg, M J L; Hoogerbrugge, N

2008-02-15

Most colorectal cancers show either microsatellite or chromosomal instability. A subset of colorectal cancers, especially those diagnosed at young age, is known to show neither of these forms of genetic instability and thus might have a distinct pathogenesis. Colorectal cancers diagnosed at young age are suggestive for hereditary predisposition. We investigate whether such early-onset microsatellite and chromosomally stable colorectal cancers are a hallmark of a genetic susceptibility syndrome. The ploidy status of microsatellite stable (familial) colorectal cancers of patients diagnosed before age 50 (n = 127) was analyzed in relation to the histopathological characteristics and family history. As a control the ploidy status of sporadic colorectal cancer, with normal staining of mismatch repair proteins, diagnosed at the age of 69 years or above (n = 70) was determined. A diploid DNA content was used as a marker for chromosomal stability. Within the group of patients with (familial) early onset microsatellite stable colorectal cancer the chromosomally stable tumors did not differ from chromosomally unstable tumors with respect to mean age at diagnosis, fulfillment of Amsterdam criteria or pathological characteristics. Segregation analysis did not reveal any family with microsatellite and chromosomally stable colorectal cancer in 2 relatives. The prevalence of microsatellite and chromosomally stable colorectal cancer was not significantly different for the early and late onset group (28 and 21%, respectively). We find no evidence that early-onset microsatellite and chromosomally stable colorectal cancer is a hallmark of a hereditary colorectal cancer syndrome. (c) 2007 Wiley-Liss, Inc.

Association between polymorphisms in cancer-related genes and early onset of esophageal adenocarcinoma.

Science.gov (United States)

Wu, I-Chen; Zhao, Yang; Zhai, Rihong; Liu, Geoffrey; Ter-Minassian, Monica; Asomaning, Kofi; Su, Li; Liu, Chen-Yu; Chen, Feng; Kulke, Matthew H; Heist, Rebecca S; Christiani, David C

2011-04-01

There is an increasing incidence of esophageal adenocarcinoma (EA) among younger people in the western populations. However, the association between genetic polymorphisms and the age of EA onset is unclear. In this study, 1330 functional/tagging single-nucleotide polymorphisms (SNPs) from 354 cancer-related genes were genotyped in 335 white EA patients. Twenty important SNPs that have the highest importance scores and lowest classification error rate were identified by the random forest algorithm to be associated with early onset of EA (age ≤ 55 years). Subsequent logistic regression analysis indicated that 10 SNPs (rs2070744 of NOS3, rs720321 of BCL2, rs17757541 of BCL2, rs11775256 of TNFRSF10A, rs1035142 of CASP8, rs2236302 of MMP14, rs4740363 of ABL1, rs696217 of GHRL, rs2445762 of CYP19A1, and rs11941492 of VEGFR2/KDR) were significantly associated with early onset of EA (≤55 vs >55 years, all P polymorphisms in cancer-related genes, especially those in the apoptotic pathway, play an important role in the development of younger-aged EA in a dose-response manner.

Epidemiology of Schizophrenia: Review of Findings and Myths

OpenAIRE

Messias, Erick; Chen, Chuan-Yu; Eaton, William W.

2007-01-01

By describing patterns of disease distribution within populations, identifying risk factors, and finding associations, epidemiological studies have contributed to our current understanding of schizophrenia. Advanced paternal age and the association with auto-immune diseases are some of the newly described epidemiological finding in schizophrenia epidemiology, shaping our current definition of schizophrenia. Though early intervention strategies have gained momentum, primary prevention of schiz...

Genome-wide identification of blood DNA methylation patterns associated with early-onset hepatocellular carcinoma development in hepatitis B carriers.

Science.gov (United States)

Kao, Wei-Yi; Yang, Shu-Han; Liu, Wen-Jie; Yeh, Meng-Yin; Lin, Chih-Lin; Liu, Chun-Jen; Huang, Chi-Jung; Lin, Shi-Ming; Lee, Shou-Dong; Chen, Pei-Jer; Yu, Ming-Whei

2017-02-01

The etiology of early-onset hepatocellular carcinoma (HCC) among hepatitis B virus (HBV) carriers remains unclear. DNA methylation levels in peripheral leukocytes have been associated with different environmental exposures and immune or inflammatory response. We aimed to identify methylation signatures of peripheral leukocytes that could track hepatitis B progression to HCC, especially for early-onset HCC. We first performed an epigenome-wide association analysis on 48 matched case-control pairs in a nested case-control study within a 22-yr follow-up cohort of HBV carriers. Through this analysis we found that progression to early-onset HCC involved methylation variable positions across the genome, in which a substantial proportion displayed significant variation due to HBV viral load, chronic hepatitis status, and/or leukocyte subtype composition, and these associations were significantly enriched among genes in immune pathways. Methylation at probes cg00300879, cg06872964, and cg07080864, that are located within the proximal promoter of CNKSR1, IFI44L, and PENK, respectively, was validated by bisulfite pyrosequencing and findings were replicated in a case-sibling study of early-onset HCC (134 cases vs. 174 sibling controls). Furthermore, a high methylation score, constructed using the three probes, was predictive for the risk of early-onset HCC in two datasets (adjusted-odds ratios = 0.21-0.32, P ≤ 0.0206). This association was also observed for late-onset HCC (adjusted-odds ratio = 0.42-0.47, P ≤ 0.0194) in a nested case-control study (120 cases vs. 178 controls). In prospective analysis, change in the score was detected 5-9 yr before HCC onset. Blood-based methylation profiling provides new insights into the complexity of virus-host interaction underlying HBV-related HCC, holding promise for the disease risk management. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Utility of Washington Early Recognition Center (WERC Self-Report Screening Questionnaires in the Assessment of Patients with Schizophrenia and Bipolar Disorder

Directory of Open Access Journals (Sweden)

Christina Jen-Chia Hsieh

2016-08-01

Full Text Available Early identification and treatment are associated with improved outcomes in bipolar disorder and schizophrenia. Screening for the presence of these disorders usually involves time-intensive interviews that may not be practical in settings where mental health providers are limited. Thus, individuals at earlier stages of illness are often not identified. The Washington Early Recognition Center Affectivity and Psychosis (WERCAP Screen is a self-report questionnaire originally developed to identify clinical risk for developing bipolar or psychotic disorders. The goal of the current study was to investigate the utility of the WERCAP Screen and two complementary questionnaires, the WERC Stress Screen and the WERC Substance Screen, in identifying individuals with established schizophrenia or bipolar disorder. Participants consisted of 35 bipolar disorder (BPD and 34 schizophrenia (SCZ patients, as well as 32 controls (CON, aged 18-30 years. Univariate analyses were used to test for score differences between groups. Logistic regression and ROC curves were used to identify diagnostic predictors. Significant group differences were found for the psychosis section of the WERCAP (pWERCAP; p 20 (AUC: 0.87; sensitivity: 0.91; specificity: 1.0; while that for the pWERCAP to identify schizophrenia was a score of >13 (AUC: 0.89; sensitivity: 0.88; specificity: 0.88. These results indicate that the WERCAP Screen may be useful in screening individuals for bipolar disorder and schizophrenia, and that identifying stress and substance use severity can be rapidly done using self-report questionnaires. Larger studies in undiagnosed individuals will be needed to test the WERCAP Screen’s ability to identify mania or psychosis in the community.

The BRCA1 and BRCA2 Genes in Early-Onset Breast Cancer Patients.

Science.gov (United States)

Saleem, Mohamed; Ghazali, Mohd Bazli; Wahab, Md Azlan Mohamed Abdul; Yusoff, Narazah Mohd; Mahsin, Hakimah; Seng, Ch'ng Ewe; Khalid, Imran Abdul; Rahman, Mohd Nor Gohar; Yahaya, Badrul Hisham

2018-04-24

Approximately 5-10% of breast cancers are attributable to genetic susceptibility. Mutations in the BRCA1 and BRCA2 genes are the best known genetic factors to date. The goal of this study was to determine the structure and distribution of haplotypes of the BRCA1 and BRCA2 genes in early-onset breast cancer patients. We enrolled 70 patients diagnosed with early-onset breast cancer. A total of 21 SNPs (11 on BRCA1 and 10 on BRCA2) and 1 dinucleotide deletion on BRCA1 were genotyped using nested allele-specific PCR methods. Linkage disequilibrium (LD) analysis was conducted, and haplotypes were deduced from the genotype data. Two tightly linked LD blocks were observed on each of the BRCA1 and BRCA2 genes. Variant-free haplotypes (TAT-AG for BRCA1 and ATA-AAT for BRCA2) were observed at a frequency of more than 50% on each gene along with variable frequencies of derived haplotypes. The variant 3'-subhaplotype CGC displayed strong LD with 5'-subhaplotypes GA, AA, and GG on BRCA1 gene. Haplotypes ATA-AGT, ATC-AAT, and ATA-AAC were the variant haplotypes frequent on BRCA2 gene. Although the clinical significance of these derived haplotypes has not yet been established, it is expected that some of these haplotypes, especially the less frequent subhaplotypes, eventually will be shown to be indicative of a predisposition to early-onset breast cancer.

Structural connectivity in schizophrenia and its impact on the dynamics of spontaneous functional networks

International Nuclear Information System (INIS)

Cabral, Joana; Fernandes, Henrique M.; Van Hartevelt, Tim J.; Kringelbach, Morten L.; James, Anthony C.; Deco, Gustavo

2013-01-01

The neuropathology of schizophrenia remains unclear. Some insight has come from modern neuroimaging techniques, which offer an unparalleled opportunity to explore in vivo the structure and function of the brain. Using functional magnetic resonance imaging, it has been found that the large-scale resting-state functional connectivity (rsFC) in schizophrenia — measured as the temporal correlations of the blood-oxygen-level-dependent (BOLD) signal — exhibit altered network topology, with lower small-world index. The origin of these rsFC alterations and link with the underlying structural connectivity remain unclear. In this work, we used a computational model of spontaneous large-scale brain activity to explore the role of the structural connectivity in the large-scale dynamics of the brain in health and schizophrenia. The structural connectomes from 15 adolescent patients with early-onset schizophrenia and 15 age- and gender-matched controls were built from diffusion tensor imaging data to detect the white matter tracts between 90 brain areas. Brain areas, simulated using a reduced dynamic mean-field model, receive excitatory input from other areas in proportion to the number of fibre tracts between them. The simulated mean field activity was transformed into BOLD signal, and the properties of the simulated functional networks were analyzed. Our results suggest that the functional alterations observed in schizophrenia are not directly linked to alterations in the structural topology. Instead, subtly randomized and less small-world functional networks appear when the brain operates with lower global coupling, which shifts the dynamics from the optimal healthy regime

Structural connectivity in schizophrenia and its impact on the dynamics of spontaneous functional networks

Energy Technology Data Exchange (ETDEWEB)

Cabral, Joana [Theoretical and Computational Neuroscience Group, Center of Brain and Cognition, Universitat Pompeu Fabra, Barcelona 08018 (Spain); Department of Psychiatry, University of Oxford, Oxford OX3 7JX (United Kingdom); Fernandes, Henrique M.; Van Hartevelt, Tim J.; Kringelbach, Morten L. [Department of Psychiatry, University of Oxford, Oxford OX3 7JX (United Kingdom); Center of Functionally Integrative Neuroscience (CFIN), Aarhus University, Aarhus (Denmark); James, Anthony C. [Department of Psychiatry, University of Oxford, Oxford OX3 7JX (United Kingdom); Highfield Unit, Warneford Hospital, Oxford OX3 7JX (United Kingdom); Deco, Gustavo [Theoretical and Computational Neuroscience Group, Center of Brain and Cognition, Universitat Pompeu Fabra, Barcelona 08018 (Spain); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010 (Spain)

2013-12-15

The neuropathology of schizophrenia remains unclear. Some insight has come from modern neuroimaging techniques, which offer an unparalleled opportunity to explore in vivo the structure and function of the brain. Using functional magnetic resonance imaging, it has been found that the large-scale resting-state functional connectivity (rsFC) in schizophrenia — measured as the temporal correlations of the blood-oxygen-level-dependent (BOLD) signal — exhibit altered network topology, with lower small-world index. The origin of these rsFC alterations and link with the underlying structural connectivity remain unclear. In this work, we used a computational model of spontaneous large-scale brain activity to explore the role of the structural connectivity in the large-scale dynamics of the brain in health and schizophrenia. The structural connectomes from 15 adolescent patients with early-onset schizophrenia and 15 age- and gender-matched controls were built from diffusion tensor imaging data to detect the white matter tracts between 90 brain areas. Brain areas, simulated using a reduced dynamic mean-field model, receive excitatory input from other areas in proportion to the number of fibre tracts between them. The simulated mean field activity was transformed into BOLD signal, and the properties of the simulated functional networks were analyzed. Our results suggest that the functional alterations observed in schizophrenia are not directly linked to alterations in the structural topology. Instead, subtly randomized and less small-world functional networks appear when the brain operates with lower global coupling, which shifts the dynamics from the optimal healthy regime.

Early and late onset depression in young and middle aged adults : Differential symptomatology, characteristics and risk factors?

NARCIS (Netherlands)

Korten, Nicole C. M.; Comijs, Hannie C.; Lamers, Femke; Penninx, Brenda W. J. H.

Background: Early onset depression (EOD) and late onset depression (LOD) may be different phenomena. In this study, differences between EOD and LOD in symptomatology, psychiatric characteristics and psychosocial/somatic factors were examined. Methods: Baseline data were from 1104 participants with a

The Role of Inflammation in Schizophrenia

Directory of Open Access Journals (Sweden)

Norbert eMüller

2015-10-01

Full Text Available AbstractHigh levels of pro-inflammatory substances such as cytokines have been described in the blood and cerebrospinal fluid of schizophrenia patients. Animal models of schizophrenia show that under certain conditions an immune disturbance during early life, such as an infection-triggered immune activation, might trigger lifelong increased immune reactivity. A large epidemiological study clearly demonstrated that severe infections and autoimmune disorders are risk factors for schizophrenia. Genetic studies have shown a strong signal for schizophrenia on chromosome 6p22.1, in a region related to the human leucocyte antigen (HLA system and other immune functions. Another line of evidence demonstrates that chronic (disstress is associated with immune activation. The vulnerability-stress-inflammation model of schizophrenia includes the contribution of stress on the basis of increased genetic vulnerability for the pathogenesis

Extent of Spine Deformity Predicts Lung Growth and Function in Rabbit Model of Early Onset Scoliosis.

Directory of Open Access Journals (Sweden)

J Casey Olson

Full Text Available Early onset deformity of the spine and chest wall (initiated <8 years of age is associated with increased morbidity at adulthood relative to adolescent onset deformity of comparable severity. Presumably, inhibition of thoracic growth during late stage alveolarization leads to an irreversible loss of pulmonary growth and thoracic function; however the natural history of this disease from onset to adulthood has not been well characterized. In this study we establish a rabbit model of early onset scoliosis to establish the extent that thoracic deformity affects structural and functional respiratory development. Using a surgical right unilateral rib-tethering procedure, rib fusion with early onset scoliosis was induced in 10 young New Zealand white rabbits (3 weeks old. Progression of spine deformity, functional residual capacity, total lung capacity, and lung mass was tracked through longitudinal breath-hold computed tomography imaging up to skeletal maturity (28 weeks old. Additionally at maturity forced vital capacity and regional specific volume were calculated as functional measurements and histo-morphometry performed with the radial alveolar count as a measure of acinar complexity. Data from tethered rib rabbits were compared to age matched healthy control rabbits (N = 8. Results show unilateral rib-tethering created a progressive spinal deformity ranging from 30° to 120° curvature, the severity of which was strongly associated with pulmonary growth and functional outcomes. At maturity rabbits with deformity greater than the median (55° had decreased body weight (89%, right (59% and left (86% lung mass, right (74% and left (69% radial alveolar count, right lung volume at total lung capacity (60%, and forced vital capacity (75%. Early treatment of spinal deformity in children may prevent pulmonary complications in adulthood and these results provide a basis for the prediction of pulmonary development from thoracic structure. This model may

Socio-demographic and clinical correlates of lifetime suicide attempts and their impact on quality of life in Chinese schizophrenia patients.

Science.gov (United States)

Xiang, Yu-Tao; Weng, Yong-Zhen; Leung, Chi-Ming; Tang, Wai-Kwong; Ungvari, Gabor Sandor

2008-05-01

This study determines the socio-demographic and clinical correlates of suicide attempts in Chinese schizophrenia outpatients and their impact on patients' quality of life (QOL). Two hundred and fifty-five clinically stable schizophrenia outpatients were randomly selected in Hong Kong (HK) and their counterparts matched according to sex, age, age at onset and length of illness were recruited in Beijing (BJ). All subjects at both sites were interviewed by the same investigator using standardized assessment instruments. Basic socio-demographic and clinical data and history of suicide attempts were collected. The lifetime prevalence of suicide attempts was 26.7% in the whole sample and 20% and 33.6% in the HK and BJ samples, respectively. Patients with a history of suicide attempts were less likely to receive depot antipsychotic (AP) medication, more likely to receive clozapine, benzodiazepines (BZD) and higher doses of APs; were younger at onset, had more hospitalizations; had more severe positive, depressive, anxiety and extrapyramidal (EPS) symptoms; were poorer QOL in the physical, psychological, social and environmental domains; and were more likely to be BJ residents. In multiple logistic regression analysis, early age at onset, poor physical QOL, use of clozapine and BZDs, and study site (HK vs BJ) were significant contributors to lifetime suicide attempts. Significant difference was found between matched samples in HK and BJ with respect to suicide attempts. HK is a cosmopolitan city with a Western social structure and mental health system, whereas in BJ more traditional Chinese cultural values predominate, with a mental health policy radically different from that of HK. These differences suggest that socio-cultural factors play a significant role in determining suicide attempts in schizophrenia.

Converging models of schizophrenia - Network alterations of prefrontal cortex underlying cognitive impairments

Science.gov (United States)

Sakurai, Takeshi; Gamo, Nao J; Hikida, Takatoshi; Kim, Sun-Hong; Murai, Toshiya; Tomoda, Toshifumi; Sawa, Akira

2015-01-01

The prefrontal cortex (PFC) and its connections with other brain areas are crucial for cognitive function. Cognitive impairments are one of the core symptoms associated with schizophrenia, and manifest even before the onset of the disorder. Altered neural networks involving PFC contribute to cognitive impairments in schizophrenia. Both genetic and environmental risk factors affect the development of the local circuitry within PFC as well as development of broader brain networks, and make the system vulnerable to further insults during adolescence, leading to the onset of the disorder in young adulthood. Since spared cognitive functions correlate with functional outcome and prognosis, a better understanding of the mechanisms underlying cognitive impairments will have important implications for novel therapeutics for schizophrenia focusing on cognitive functions. Multidisciplinary approaches, from basic neuroscience to clinical studies, are required to link molecules, circuitry, networks, and behavioral phenotypes. Close interactions among such fields by sharing a common language on connectomes, behavioral readouts, and other concepts are crucial for this goal. PMID:26408506

Impulsivity in abstinent early- and late-onset alcoholics : differences in self-report measures and a discounting task

NARCIS (Netherlands)

Dom, G.; D'Haene, P.; Hulstijn, W.; Sabbe, B.G.C.

2006-01-01

Aims: To test the hypothesis that early-onset alcoholics (EOAs) can be differentiated from late-onset alcoholics (LOAs) by more severe substance-related problems and higher levels of impulsivity and aggression. Design and measurements: A cross-sectional patient survey with a community comparison

Risk factors for suicide in schizophrenia: systematic review and clinical recommendations.

Science.gov (United States)

Popovic, D; Benabarre, A; Crespo, J M; Goikolea, J M; González-Pinto, A; Gutiérrez-Rojas, L; Montes, J M; Vieta, E

2014-12-01

To identify risk factors associated with suicide of patients with schizophrenia and provide clinical recommendations, which integrate research findings into a consensus based on clinical experience and evidence. A task force formed of experts and clinicians iteratively developed consensus through serial revisions using the Delphi method. Initial survey items were based on systematic literature review published up to June 2013. Various risk factors were reported to be implicated in suicide in schizophrenia. Our findings indicate that suicide risk in schizophrenia is mainly related to affective symptoms, history of a suicide attempt and number of psychiatric admissions. Other risk factors identified are given by younger age, closeness to illness onset, older age at illness onset, male sex, substance abuse and period during or following psychiatric discharge. Integrating the evidence and the experience of the task force members, a consensus was reached on 14 clinical recommendations. Identification of risk factors for suicide in individuals diagnosed with schizophrenia is imperative to improve clinical management and develop strategies to reduce the incidence of suicide in this population. This study provides the critical overview of available data and clinical recommendations on recognition and management of the above-mentioned risk factors. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Breastfeeding and risk of schizophrenia in the Copenhagen Perinatal Cohort

DEFF Research Database (Denmark)

Sørensen, Holger Jelling; Mortensen, Erik Lykke; Reinisch, J M

2005-01-01

OBJECTIVE: The aim was to study whether early weaning from breastfeeding may be associated with increased risk of schizophrenia. METHOD: The current sample comprises 6841 individuals from the Copenhagen Perinatal Cohort of whom 1671 (24%) had been breastfed for 2 weeks or less (early weaning...... odds ratio 1.73 with 95% CI: 1.13-2.67). CONCLUSION: No or breastfeeding was associated with elevated risk of schizophrenia. The hypothesis of some protective effect of breastfeeding against the risk of later schizophrenia is supported by our data....

[Pathological hobbies and interests in schizophrenia].

Science.gov (United States)

Sergeev, I I; Malinochka, S A

2008-01-01

Pathological hobbies have been studied in 82 inpatients with schizophrenia, 48 men and 34 women, aged 18-65 years. Inclusion criteria of pathology were (1) overvalued character of a hobby, (2) insufficient criticism towards this hobby, (3) fringe, singularity interests and methods of their realization; (4) inconsistency between the hobby and previous life experience, (5) low efficiency, (6) strong linkage with other psychopathological presentations, (7) chronological coincidence between the onset of pathological hobbies and schizophrenia manifestation or exacerbation, (8) susceptibility to progressive dynamics, (9) distinct social-maladaptive influence. Regarding the content, pathological hobbies are presented by creative art, scientific work, collecting, gambling, sport and health activities, "spiritual" development. Three clinical variants - obsessive-compulsive, overvalued and paranoic can be singled out by clinical presentations. The overvalued variant appears to be more favorable due to the predominantly adaptive social influence and weak relation to the dynamics of schizophrenia. Other variants are less productive exerting mostly decompensation effect with less favorable dynamics.

Genetic Analysis of PARK2 and PINK1 Genes in Brazilian Patients with Early-Onset Parkinson's Disease

Directory of Open Access Journals (Sweden)

Karla Cristina Vasconcelos Moura

2013-01-01

Full Text Available Parkinson's disease is the second most frequent neurodegenerative disorder in the world, affecting 1-2% of individuals over the age of 65. The etiology of Parkinson's disease is complex, with the involvement of gene-environment interactions. Although it is considered a disease of late manifestation, early-onset forms of parkinsonism contribute to 5–10% of all cases. In the present study, we screened mutations in coding regions of PARK2 and PINK1 genes in 136 unrelated Brazilian patients with early-onset Parkinson's disease through automatic sequencing. We identified six missense variants in PARK2 gene: one known pathogenic mutation, two variants of uncertain role, and three nonpathogenic changes. No pathogenic mutation was identified in PINK1 gene, only benign polymorphisms. All putative pathogenic variants found in this study were in heterozygous state. Our data show that PARK2 point mutations are more common in Brazilian early-onset Parkinson's disease patients (2.9% than PINK1 missense variants (0%, corroborating other studies worldwide.

Second-generation long-acting injectable antipsychotics in schizophrenia: patient functioning and quality of life

Directory of Open Access Journals (Sweden)

Montemagni C

2016-04-01

Full Text Available Cristiana Montemagni,1,2 Tiziana Frieri,1,2 Paola Rocca1,2 1Department of Neuroscience, Unit of Psychiatry, University of Turin, 2Department of Mental Health, Azienda Sanitaria Locale (ASL Torino 1 (TO1, Azienda Ospedaliero-Universitaria (AOU Città della Salute e della Scienza di Torino, Turin, Italy Abstract: Long-acting injectable antipsychotics (LAIs were developed to make treatment easier, improve adherence, and/or signal the clinician when nonadherence occurs. Second-generation antipsychotic LAIs (SGA-LAIs combine the advantages of SGA with a long-acting formulation. The purpose of this review is to evaluate the available literature concerning the impact of SGA-LAIs on patient functioning and quality of life (QOL. Although several studies regarding schizophrenia patients’ functioning and QOL have been performed, the quantity of available data still varies greatly depending on the SGA-LAI under investigation. After reviewing the literature, it seems that SGA-LAIs are effective in ameliorating patient functioning and/or QOL of patients with schizophrenia, as compared with placebo. However, while methodological design controversy exists regarding the superiority of risperidone LAI versus oral antipsychotics, the significant amount of evidence in recently published research demonstrates the beneficial influence of risperidone LAI on patient functioning and QOL in stable patients and no benefit over oral treatment in unstable patients. However, the status of the research on SGA-LAIs is lacking in several aspects that may help physicians in choosing the correct drug therapy. Meaningful differences have been observed between SGA-LAIs in the onset of their clinical efficacy and in the relationships between symptoms and functioning scores. Moreover, head-to-head studies comparing the effects of SGA-LAIs on classical measures of psychopathology and functioning are available mainly on risperidone LAI, while those comparing olanzapine LAI with other