Schizophrenia Research RSS feed: Articles in Press. As official journal of the Schizophrenia International Research Society (SIRS) Schizophrenia Research is THE journal of choice for international researchers and clinicians to share their work with the global schizophrenia research community. More than 6000 institutes have online or print (or both) access to this journal - the largest specialist journal in the field, with the largest readership! Schizophrenia Research's time to first decision is as fast as 6 weeks and its publishing speed is as fast as 4 weeks until online publication (corrected proof/Article in Press) after acceptance and 14 weeks from acceptance until publication in a printed issue. The journal publishes novel papers that really contribute to understanding the biology and treatment of schizophrenic disorders; Schizophrenia Research brings together biological, clinical and psychological research in order to stimulate the synthesis of findings from all disciplines involved in improving patient outcomes in schizophrenia. http://www.schres-journal.com//inpress?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. Schizophrenia Research0920-99642010-09-03 © 2010 Published by Elsevier Inc. healthpermissions@elsevier.comhttp://www.schres-journal.com/article/PIIS0920996410014520/abstract?rss=yesAbstract: The Graduated Recovery Intervention Program (GRIP) is a new individual cognitive–behavioral therapy program designed to facilitate functional recovery in people who have experienced an initial episode of psychosis. The purposes of this study were to evaluate the feasibility and tolerability of the GRIP intervention, and to compare the effectiveness of GRIP versus treatment as usual (TAU) for improving specific clinical and psychosocial outcomes. Forty-six individuals with first episode psychosis were randomized to GRIP+TAU or TAU alone. Primary outcomes focused on social and role functioning, and quality of life. Secondary outcomes included psychotic symptoms, depression, substance use, social support, attitudes toward medications, well-being, and hospitalizations. The results indicate that GRIP was well-tolerated, as evidenced by good attendance and low drop-out rates, and well-received (based on positive feedback from participants). Although the majority of mixed model analyses were not statistically significant, examination of within-group changes and effect sizes suggests an advantage for GRIP over TAU in improving functional outcomes. These advantages and the fact that the GRIP intervention demonstrated feasibility and tolerability suggest that this intervention is worthy of further investigation.A pilot investigation of the Graduated Recovery Intervention Program (GRIP) for first episode psychosis - Corrected ProofDavid L. Penn, Sarah R. Uzenoff, Diana Perkins, Kim T. Mueser, Robert Hamer, Evan Waldheter, Sylvia Saade, Liz Cook10.1016/j.schres.2010.08.006Schizophrenia Research (2010)2010-09-03Schizophrenia Research2010-09-03http://www.schres-journal.com/article/PIIS0920996410014568/abstract?rss=yesWith interest we read the report of a psychosis incidence study in the Dutch town of Utrecht (). The authors hypothesized that previous reports of an increased incidence of schizophrenia among Moroccan–Dutch people in the Netherlands were due to cross-cultural bias. They examined first-onset cases using a “culturally sensitive” version of the Comprehensive Assessment of Symptoms and History (CASH; ) and arrived at the conclusion that the first-contact incidence of schizophrenia among the Moroccan–Dutch was no longer significantly increased when this culturally sensitive instrument was applied. The purpose of this letter is to examine whether the authors have made a strong case.Incidence of schizophrenia among Moroccan immigrants to the Netherlands - Corrected ProofJ.P. Selten, W. Laan, N.D. Veen, J.D. Blom, W. Veling, H.W. Hoek10.1016/j.schres.2010.08.010Schizophrenia Research (2010)2010-09-03Schizophrenia Research2010-09-03LETTER TO THE EDITORhttp://www.schres-journal.com/article/PIIS0920996410014556/abstract?rss=yesAbstract: Patients with schizophrenia make decisions on the basis of less evidence when required to collect information to make an inference, a behavior often called jumping to conclusions. The underlying basis for this behavior remains controversial. We examined the cognitive processes underpinning this finding by testing subjects on the beads task, which has been used previously to elicit jumping to conclusions behavior, and a stochastic sequence learning task, with a similar decision theoretic structure. During the sequence learning task, subjects had to learn a sequence of button presses, while receiving a noisy feedback on their choices. We fit a Bayesian decision making model to the sequence task and compared model parameters to the choice behavior in the beads task in both patients and healthy subjects. We found that patients did show a jumping to conclusions style; and those who picked early in the beads task tended to learn less from positive feedback in the sequence task. This favours the likelihood of patients selecting early because they have a low threshold for making decisions, and that they make choices on the basis of relatively little evidence.Probabilistic learning and inference in schizophrenia - Corrected ProofBruno B. Averbeck, Simon Evans, Viraj Chouhan, Eleanor Bristow, Sukhwinder S. Shergill10.1016/j.schres.2010.08.009Schizophrenia Research (2010)2010-09-01Schizophrenia Research2010-09-01http://www.schres-journal.com/article/PIIS092099641001460X/abstract?rss=yesAbstract: Background: In a previous study, we found a reduced amplitude modulation of the visual P3 component of the event-related potential (ERP) in schizophrenic patients compared with healthy controls during inhibition in the Attention Network Test (ANT). The objective of the present study was to replicate this finding and to explore whether this cortical processing deficit is specific to schizophrenia.Methods: Sixteen schizophrenic patients, sixteen depressive patients, and sixteen healthy controls matched for age, sex, and education were included. Participants were tested with the ANT, a test of selective attention that provides behavioral estimates for alerting, orienting, and inhibition. 32-Channel electroencephalogram was recorded and visual P3 amplitudes were topographically analyzed and compared between groups.Results: There were no significant behavioral between-group differences in terms of mean reaction time, accuracy, and ANT effects alerting, orienting, and inhibition. Absolute visual P3 amplitude was not reduced in schizophrenia or depression. P3 amplitude modulation was defined as P3 amplitude at Pz as a function of ANT flanker conditions. We found a parietal P3 amplitude modulation deficit in schizophrenic patients (−.015) that was absent in both healthy controls (−.705; p = .002) and depressive patients (−1.022; p = .001).Conclusion: The results provide evidence that a deficit of visual P3 amplitude modulation distinguishes schizophrenia from healthy and disease controls and provides greater discriminative power than absolute visual P3 amplitude.Evidence of specificity of a visual P3 amplitude modulation deficit in schizophrenia - Corrected ProofAndres H. Neuhaus, Niklas R. Trempler, Eric Hahn, Alexander Luborzewski, Christine Karl, Constanze Hahn, Carolin Opgen-Rhein, Carsten Urbanek, Rainer Schaub, Michael Dettling10.1016/j.schres.2010.08.014Schizophrenia Research (2010)2010-09-01Schizophrenia Research2010-09-01http://www.schres-journal.com/article/PIIS0920996410014659/abstract?rss=yesAbstract: Objective: To investigate factors associated with homicide after discharge from hospital in patients with schizophrenia and other psychoses.Design: All homicides committed by patients with psychosis within 6months of hospital discharge were identified in Sweden from 1988–2001 and compared with patients with psychoses discharged over the same time period who did not subsequently commit any violent offences. Medical records were then collected, and data extracted using a validated protocol. Interrater reliability tests were performed on a subsample, and variables with poor reliability excluded from subsequent analyses.Results: We identified 47 cases who committed a homicide within 6months of discharge, and 105 controls who did not commit any violent offence after discharge. On univariate analyses, clinical factors on admission associated with homicide included evidence of poor self-care, substance misuse, and being previously hospitalized for a violent episode. Inpatient characteristics included having a severe mental illness for one year prior to admission. After-care factors associated with homicide were evidence of medication non-compliance and substance misuse. The predictive validity of combining two or three of these factors was not high. Depression appeared to be inversely associated with homicide, and there was no relationship with the presence of delusions or hallucinations.Conclusions: There are a number of potentially treatable factors that are associated with homicide in schizophrenia and other psychoses. Associations with substance misuse and treatment compliance could be the focus of therapeutic interventions if validated in other samples. However, their clinical utility in violence risk assessment remains uncertain.Homicide in discharged patients with schizophrenia and other psychoses: A national case-control study - Corrected ProofSeena Fazel, Petra Buxrud, Vladislav Ruchkin, Martin Grann10.1016/j.schres.2010.08.019Schizophrenia Research (2010)2010-09-01Schizophrenia Research2010-09-01http://www.schres-journal.com/article/PIIS0920996410012624/abstract?rss=yesWeight gain and metabolic complications associated with antipsychotics are areas of great concern among clinicians and researchers. In addition to medical consequences of obesity, weight gain may be related to changes in brain morphology. Evidence in the general population suggests a relationship between obesity and brain differences, including structure and/or volume, inverse correlations between body mass index (BMI) with brain volume, increased atrophy and hyperintensities (). Increasing BMI may be associated with functional consequences including cognitive performance (), cognitive decline () and dementias (). Cognitive and neurophysiological abnormalities associated with functional deficits are well-documented characteristics of serious mental illness. Differences between brain volumes in schizophrenia and the general population have been documented, such as lower brain and mean cerebral volume and increased ventricular volumes (). Changes have been reported throughout the course of illness in schizophrenia, and may also occur with antipsychotic treatment (). Therefore, the potential association of obesity with brain changes may be of additional concern in this population. To explore the potential association between obesity and brain weight, we analyzed autopsy reports of 60 young people with severe mental illness.The relationship of brain weight to body mass index (BMI) upon autopsy in young people with severe mental illness - Corrected ProofHeidi J. Wehring, Fang Liu, Robert P. McMahon, Elena A. Spieker, Kimberly R. Warren, Douglas L. Boggs, Raymond C. Love, Dwight Dickinson, Joo Cheol Shim, David Fowler, Deanna L. Kelly10.1016/j.schres.2010.04.009Schizophrenia Research (2010)2010-08-30Schizophrenia Research2010-08-30LETTER TO THE EDITORhttp://www.schres-journal.com/article/PIIS0920996410014507/abstract?rss=yesAbstract: Research investigating the relationships between executive functioning impairments and the positive, negative, and cognitive schizophrenia symptoms has produced inconsistent results. This inconsistency may be due to the tendency to view executive functioning as a unified process as opposed to multiple fractionated processes. A fractionated model of executive functioning has been supported in several studies of various populations, but few schizophrenia studies have used the factor analytic methods of these studies to empirically determine separate executive functioning components, causing conclusions regarding the relationships between these components and schizophrenia symptoms to be unreliable. The purposes of the present study were to (1) identify separate components of executive functioning by conducting a factor analysis of the performance of individuals with schizophrenia on the Delis Kaplan Executive Function System (D-KEFS) and (2) investigate the relationships between executive functioning components and the three schizophrenia symptom dimensions by correlating the derived factor scores with the scale scores of the Positive and Negative Symptom Scale (PANSS). An exploratory factor analysis revealed two separate components: inhibition/set shifting and mental flexibility. The results showed that the symptom dimensions were differentially related to impairments in executive functioning, with both negative and cognitive symptoms associated with the inhibition/set shifting component, cognitive symptoms alone associated with the mental flexibility component, and positive symptoms unrelated to either component.The relationships between schizophrenia symptom dimensions and executive functioning components - Corrected ProofLaura K. Clark, Debbie Warman, Paul H. Lysaker10.1016/j.schres.2010.08.004Schizophrenia Research (2010)2010-08-30Schizophrenia Research2010-08-30http://www.schres-journal.com/article/PIIS0920996410014441/abstract?rss=yesAbstract: Previous studies investigating feedback-driven reinforcement learning in patients with schizophrenia have provided mixed results. In this study, we explored the clinical predictors of reward and punishment learning using a probabilistic classification learning task. Patients with schizophrenia (n=40) performed similarly to healthy controls (n=30) on the classification learning task. However, more severe negative and general symptoms were associated with lower reward-learning performance, whereas poorer general psychosocial functioning was correlated with both lower reward- and punishment-learning performances. Multiple linear regression analyses indicated that general psychosocial functioning was the only significant predictor of reinforcement learning performance when education, antipsychotic dose, and positive, negative and general symptoms were included in the analysis. These results suggest a close relationship between reinforcement learning and general psychosocial functioning in schizophrenia.General functioning predicts reward and punishment learning in schizophrenia - Corrected ProofZsuzsanna Somlai, Ahmed A. Moustafa, Szabolcs Kéri, Catherine E. Myers, Mark A. Gluck10.1016/j.schres.2010.07.028Schizophrenia Research (2010)2010-08-27Schizophrenia Research2010-08-27http://www.schres-journal.com/article/PIIS0920996410014477/abstract?rss=yesOxidative stress has been previously suggested to be implicated in the pathophysiology of schizophrenia (for a review see ). Glutathione S-transferase mu 1 (GSTM1), a member of the cytosolic glutathione S-transferase superfamily, catalyzes the conjunction of reduced glutathione with electrophilic compounds including products of oxidative stress. A common copy number variation (CNV) has been identified in the GSTM1 gene, and the null genotype (zero copy) results in a lack of enzyme activity (). Importantly, recent studies have indicated that CNVs confer an increased susceptibility to schizophrenia (for a review see ). These findings suggest that it may be fruitful to examine the contribution of the GSTM1 CNV to vulnerability to schizophrenia. However, the results of earlier studies have been inconsistent (; ). To investigate discrepancy in these previous results, we conducted a case–control study and performed a meta-analysis.A case–control study and meta-analysis of association between a common copy number variation of the glutathione S-transferase mu 1 (GSTM1) gene and schizophrenia - Corrected ProofYuichiro Watanabe, Ayako Nunokawa, Naoshi Kaneko, Toshiyuki Someya10.1016/j.schres.2010.08.001Schizophrenia Research (2010)2010-08-27Schizophrenia Research2010-08-27LETTER TO THE EDITORhttp://www.schres-journal.com/article/PIIS0920996410014490/abstract?rss=yesAbstract: Several studies in schizophrenia found a positive association between cognitive performance and work status, and it has been reported that good cognitive performance at the outset does predict the success of vocational interventions. However little has been done to investigate whether vocational interventions itself benefit cognitive performance. To test this hypothesis we performed a randomized, placebo-controlled trial to investigate in remitted schizophrenic patients the effect of a 6-months vocational rehabilitation program on cognitive performance. We recruited 112 remitted and clinically stable schizophrenic patients who aimed to enter a vocational rehabilitation program. From these, 57 immediately entered a 6-months vocational rehabilitation program, whereas the remaining 55 were allocated to a waiting-list; the latter formed our control group, which received during the 6months out-clinic follow-up treatment. Before and after the 6-months period we assessed changes in cognitive performance through a neuropsychological test battery, as well as changes in the psychopathological status and in quality of life. We found that vocational rehabilitation significantly improved patients' performance in cognitive measures that assess executive functions (concept formation, shifting ability, flexibility, inhibitory control, and judgment and critics abilities). Moreover, after 6months the vocational group improved significantly in the negative symptoms and in quality of life, as compared to controls. Together with results from the literature, our findings reinforce the notion that the inclusion of vocational interventions may enhance the effectiveness of therapeutic strategies for schizophrenia patients.Vocational rehabilitation improves cognition and negative symptoms in schizophrenia - Corrected ProofDanielle Soares Bio, Wagner Farid Gattaz10.1016/j.schres.2010.08.003Schizophrenia Research (2010)2010-08-27Schizophrenia Research2010-08-27http://www.schres-journal.com/article/PIIS0920996410014350/abstract?rss=yesI read, with great interest, the study by published in Schizophrenia Research. In their longitudinal meta-analysis, found that, over time, people with schizophrenia have progressively more ventricular enlargement than is found in normal controls due to aging. The authors argue that their finding supports three models. One model is that progressive ventricular enlargement in people with schizophrenia starts very early in life. A second model is that before the prodromal stage of the first schizophrenic episode, there are no differences in ventricle size, and progressive ventricular enlargement begins during the prodromal stage. A third model is that there are no differences in ventricle size until the beginning of the first schizophrenic episode, and progressive ventricular enlargement begins then. The authors also discuss studies by , explaining that those authors conducted meta-analyses of patients in their first episode of schizophrenia, and found that, compared to normal controls, the ventricles of these patients were enlarged. Kempton et al. then posit that the studies by Vita et al. and Steen et al. suggest that their third model is incorrect.Critique of Kempton et al. - Corrected ProofScott Kaplan10.1016/j.schres.2010.06.023Schizophrenia Research (2010)2010-08-23Schizophrenia Research2010-08-23LETTER TO THE EDITORShttp://www.schres-journal.com/article/PIIS0920996410014416/abstract?rss=yesAbstract: Introduction: The current criteria for detecting a Clinical High-Risk (CHR) state for psychosis do not address cognitive impairment. A first step for identifying cognitive markers of psychosis risk would be to determine which aspects of neurocognitive performance are related with more severe psychotic-like symptoms. This study assessed cognitive impairment associated with prodromal symptoms in adolescents receiving public psychiatric treatment.Methods: 189 adolescents were recruited from consecutive new patients aged 15–18 attending mainly outpatient adolescent psychiatric units in Helsinki. They had been screened for prodromal symptoms using the Prodromal Questionnaire, and all screen-positives as well as a random sample of screen-negatives were interviewed using the Structured Interview for Prodromal Symptoms (SIPS) and underwent testing using a large, standardized neurocognitive test battery. The sample included 62 adolescents who met the CHR criteria (CHR) and 112 who did not (non-CHR). A healthy control sample (n=72) was also included to provide age- and gender-matched norms.Results: The CHR group performed worse on visuospatial tasks than the non-CHR group. Among CHR adolescents, negative symptoms were associated with slower processing speed and poorer performance on verbal tasks. Among non-CHR adolescents, positive symptoms were associated with poorer performance on visuospatial tasks, and negative symptoms with poorer performance on verbal tasks.Conclusion: Clinical high-risk status is associated with impaired visuospatial task performance. However, both positive, psychotic-like symptoms and negative symptoms are associated with lower levels of neurocognitive functioning among adolescents in psychiatric treatment regardless of whether CHR criteria are met. Thus, even mild positive and negative symptoms may have clinical relevance in adolescents in psychiatric care. Adolescents with both psychotic-like symptoms and neurocognitive deficits constitute a group requiring special attention.The relationship between psychotic-like symptoms and neurocognitive performance in a general adolescent psychiatric sample - Corrected ProofMaija Lindgren, Marko Manninen, Taina Laajasalo, Ulla Mustonen, Hely Kalska, Jaana Suvisaari, Kari Moilanen, Tyrone D. Cannon, Matti Huttunen, Sebastian Therman10.1016/j.schres.2010.07.025Schizophrenia Research (2010)2010-08-23Schizophrenia Research2010-08-23http://www.schres-journal.com/article/PIIS0920996410014428/abstract?rss=yesAbstract: As an extension of the early intervention in psychosis paradigm, different focused treatments are now offered to individuals at ultra high risk of psychosis (UHR) to prevent transition to schizophrenia, however the effectiveness of these treatments is unclear. A systematic literature search in PubMed/Medline and PsycINFO was performed to derive information on randomized control trials (RCTs) in UHR samples. Seven reports were identified detailing results from five independent RCT studies. Two studies used antipsychotic drugs (one in combination with cognitive behavior therapy); one study employed cognitive therapy; one study used a two-year program of intensive community care with family psychoeducation; one study assessed the effectiveness of 3-months omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) supplementation. Intensive community care and the Omega-3 PUFAs supplementation were effective in reducing the transition to psychosis at 12months. Overall, rates of transition to psychosis at 1year were 11% for focused treatment groups (n=180) and 31.6% for control UHR groups (n=157). Receiving any of the focused treatment was associated with a lower risk of developing psychosis if compared with no treatment or treatment as usual (Relative Risk=0.36; 95%CI: 0.22–0.59). The available evidence at 2/3years follow-up indicates that the effects of focused treatments are not stable after intervention cessation and when treatment is delivered over a restricted time (e.g. 6months or less), it may achieve only a delay in psychosis onset. Due to the heterogeneity in the interventions considered, the current results do not allow recommendation for any specific treatment.Randomized-controlled trials in people at ultra high risk of psychosis: A review of treatment effectiveness - Corrected ProofAntonio Preti, Matteo Cella10.1016/j.schres.2010.07.026Schizophrenia Research (2010)2010-08-23Schizophrenia Research2010-08-23REVIEWhttp://www.schres-journal.com/article/PIIS0920996410014465/abstract?rss=yesPeople with severe mental illness have nearly twice the normal risk of dying from cardiovascular disease (CVD) (). Metabolic syndrome (MetS) is a risk predictor for diabetes and cardiovascular disease, which is highly prevalent in people with schizophrenia ().A head-to-head comparison of sertindole and risperidone on metabolic parameters - Corrected ProofMarc De Hert, Aurélia Mittoux, Yuan He, Joseph Peuskens10.1016/j.schres.2010.07.030Schizophrenia Research (2010)2010-08-23Schizophrenia Research2010-08-23LETTER TO THE EDITORhttp://www.schres-journal.com/article/PIIS0920996410014489/abstract?rss=yesAbstract: Although dyskinesias may be one of the first behavioral indicators of progressive striatal dysfunction, a mechanism critically implicated in the pathogenesis of psychotic disorders, little is known about the association between striatal structures and abnormal movements in high-risk populations. Thirty participants with a prodromal syndrome were rated for dyskinetic movements and underwent structural magnetic resonance imaging (MRI). Volumes of striatal brain structures were delineated. Elevated hyperkinetic movements were found to be associated with smaller putamen and results were replicated in the antipsychotic naïve portion of the sample. Participants who converted over a 2-year follow-up period showed significantly smaller striatal volumes and a trend towards elevated dyskinetic movements, relative to those who did not convert. Movement abnormalities may reflect a striatal pathology that is present before formal psychosis onset, and potentially reflective of a heightened vulnerability for conversion.Striatal volumes and dyskinetic movements in youth at high-risk for psychosis - Corrected ProofVijay A. Mittal, Melita Daley, Marisa F. Shiode, Carrie E. Bearden, Joseph O'Neill, Tyrone D. Cannon10.1016/j.schres.2010.08.002Schizophrenia Research (2010)2010-08-23Schizophrenia Research2010-08-23http://www.schres-journal.com/article/PIIS0920996410014325/abstract?rss=yesIn individuals with fragile X syndrome (FXS), there is a silencing of the fragile X mental retardation (FMR1) gene, usually due to an expansion of a CGG repeat in the 5′ untranslated region (). The subsequent loss of the FMR1 gene product, fragile X mental retardation protein (FMRP), an RNA-binding protein that travels between the nucleus and cytoplasm, results in disruption of post-transcriptional regulation of many target RNAs (), leading ultimately to multiple pathologies associated with FXS.Fragile X mental retardation protein levels are decreased in major psychiatric disorders - Corrected ProofS. Hossein Fatemi, Rachel E. Kneeland, Stephanie B. Liesch, Timothy D. Folsom10.1016/j.schres.2010.07.017Schizophrenia Research (2010)2010-08-20Schizophrenia Research2010-08-20LETTER TO THE EDITORShttp://www.schres-journal.com/article/PIIS0920996410014192/abstract?rss=yesAbstract: Abnormalities in the frontal lobe are considered to be central to the pathology of schizophrenia. Neuroimaging studies indeed report abnormal function of the frontal lobe in schizophrenia patients. However, the nature of these functional abnormalities is unclear, in particular whether they are affected by medication. We therefore investigated whether frontal functioning is already abnormal in first-episode medication-naive schizophrenia, and if so, if this dysfunction is related to symptomatology. Thirty medication-naive male patients with first-episode schizophrenia and 36 matched healthy controls performed a modified working memory task while fMRI data were acquired. During the task, subjects were presented with novel task (NT) and practiced task (PT) memory sets. Compared to controls, patients showed reduced performance during NT and PT. However, both groups performed better during PT, indicating that practice improved performance. Importantly, practice reduced brain activation in both patients and controls, but this effect of practice was significantly smaller in patients compared to controls, specifically in the left dorsolateral prefrontal cortex (DLPFC; p=0.01). The reduced effect of practice on brain activation was related to the severity of negative symptoms and disorganization. These results suggest that DLPFC function is deficient in the early phases of schizophrenia and cannot be attributed to the use of antipsychotics.Left dorsolateral prefrontal cortex dysfunction in medication-naive schizophrenia - Corrected ProofNicoletta M.J. van Veelen, Matthijs Vink, Nick F. Ramsey, René S. Kahn10.1016/j.schres.2010.07.004Schizophrenia Research (2010)2010-08-19Schizophrenia Research2010-08-19http://www.schres-journal.com/article/PIIS0920996410014362/abstract?rss=yesAbstract: A salience network, comprising bilateral insula and anterior cingulate cortex (ACC), is thought to play a role in recruiting relevant brain regions for the processing of sensory information. Here, we present a functional network connectivity (FNC) analysis of spatial networks identified during somatosensation, performed to test the hypothesis that salience network connectivity is disturbed during information processing in schizophrenia. 19 medicated individuals with schizophrenia and 19 matched healthy controls participated in a functional magnetic resonance imaging study. 100Hz vibrotactile stimuli were presented to the right index fingertip while whole-head blood oxygenation level-dependent contrast gradient-echo echo-planar images were acquired. Six spatial components of interest were identified using group independent component analysis: (1) bilateral insula, superior temporal and precentral gyrus (INS); (2) dorsal ACC; (3) left dorsolateral frontal and parietal cortex (left central executive network (LCEN)); (4) right dorsolateral frontal and parietal cortex (RCEN); (5) ventromedial frontal cortex (FDMN); and (6) precuneus, posterior cingulate and angular gyrus (PDMN). Maximal-lagged correlation was examined between all pairwise combinations of components. Significantly reduced FNC was observed in schizophrenia compared to controls between: INS and ACC; INS and FDMN; and LCEN and PDMN. There was no evidence of increased FNC in schizophrenia. Reduced salience network connectivity during information processing in schizophrenia suggests disturbance to the system which effects changes between contextually-relevant functional brain states. This aberrance may provide a mechanistic explanation of several clinical features of the disorder.Aberrant salience network (bilateral insula and anterior cingulate cortex) connectivity during information processing in schizophrenia - Corrected ProofThomas P. White, Verghese Joseph, Susan T. Francis, Peter F. Liddle10.1016/j.schres.2010.07.020Schizophrenia Research (2010)2010-08-19Schizophrenia Research2010-08-19http://www.schres-journal.com/article/PIIS0920996410014404/abstract?rss=yesDuration of untreated psychosis (DUP) has been measured in many studies and a considerable variation was found in mean, median and range (). A positive relation between non-native background and DUP is suggested, but not consistently found (). Since half of Amsterdam's 743,000 inhabitants have a non-Dutch ethnic background (), we investigated whether differences in DUP existed in Amsterdam between ethnic groups.Duration of untreated psychosis and ethnicity - Corrected ProofBouke Sterk, Eline M. Slief, Matthijs Blankers, Don H. Linszen, Lieuwe de Haan10.1016/j.schres.2010.07.024Schizophrenia Research (2010)2010-08-19Schizophrenia Research2010-08-19LETTER TO THE EDITORhttp://www.schres-journal.com/article/PIIS0920996410014453/abstract?rss=yesAbstract: Do physiological changes occur shortly prior to psychotic relapse in schizophrenia outpatients? We addressed this question in a group of schizophrenia outpatients by measuring changes in symptoms and changes in activation of the sympathetic nervous system, as indexed by changes in skin conductance level (SCL), on a biweekly basis for between one and two years. All six outpatients exhibited heightened SCL within two weeks prior to relapse or exacerbation, compared to SCL proceeding continued remission. These results shed light on the psychotic relapse process and are consistent with neural diathesis-stress models of schizophrenia.Psychophysiological prodromal signs of schizophrenic relapse: A pilot study - Corrected ProofMichael E. Dawson, Anne M. Schell, Anthony Rissling, Joseph Ventura, Kenneth L. Subotnik, Keith H. Nuechterlein10.1016/j.schres.2010.07.029Schizophrenia Research (2010)2010-08-19Schizophrenia Research2010-08-19http://www.schres-journal.com/article/PIIS0920996410014283/abstract?rss=yesThe onset of a psychotic illness in late adolescence or early adulthood can heighten the challenges associated with redefining familial roles and navigating peer group relationships during this pivotal developmental phase (). Research has demonstrated the significance of peers to young adults (), yet the social networks of individuals recently diagnosed with schizophrenia tend to be smaller and comprised of higher proportions of family members than non-patients (). These social network differences highlight the potential importance of the family environment as part of the context within which individuals with schizophrenia manage their illness. Evidence from research using vulnerability-stress models suggests that the adverse effects of environmental stressors, such as stressful life events, are modulated by the social-environmental context of the affected individual (). The present study examined the relationship between schizophrenia patients’ perceptions of their family environment and perceptions of their ability to cope with stressful life events during the first year of their illness.Relationships between perceptions of the family environment and of negative life events in recent-onset schizophrenia patients - Corrected ProofDenise Gretchen-Doorly, Nicole R. Detore, Joseph Ventura, Gerhard Hellemann, Kenneth L. Subotnik, Keith H. Nuechterlein10.1016/j.schres.2010.07.013Schizophrenia Research (2010)2010-08-18Schizophrenia Research2010-08-18LETTER TO THE EDITORShttp://www.schres-journal.com/article/PIIS0920996410014386/abstract?rss=yesAbstract: Primary polydipsia, defined as excessive fluid intake not explained by medical causes, has been reported to occur in over 20% of chronically ill psychiatric inpatients and is especially common in schizophrenic populations. We tested the hypothesis that in an animal model of schizophrenia-like symptoms (subchronic injections of MK-801, 0.5mg/kg twice daily for 7days) an increase in the acquisition of schedule-induced polydipsia (SIP) will occur. Young adult, male rats acquired SIP when food-restricted and placed on a non-contingent fixed-time 1-min food schedule. In comparison with saline-treated control animals, subchronic MK-801 treatment significantly increased SIP. These findings suggest an animal model of polydipsia associated with schizophrenia in humans.Increased schedule-induced polydipsia in the rat following subchronic treatment with MK-801 - Corrected ProofEmily R. Hawken, Nicholas J. Delva, James N. Reynolds, Richard J. Beninger10.1016/j.schres.2010.07.022Schizophrenia Research (2010)2010-08-18Schizophrenia Research2010-08-18http://www.schres-journal.com/article/PIIS0920996410014209/abstract?rss=yesAbstract: Background: There is an increased interest in early intervention strategies for severe mental disorders with hopes of mitigating the emergence and impact of the illness. Individuals at clinical high-risk (CHR) for schizophrenia have been primarily identified by the presence of attenuated positive symptoms. Although bipolar disorder and schizophrenia may have overlapping etiologies, few studies have investigated the potential prodrome in bipolar disorder. We sought to determine if there is a prodrome to bipolar disorder and if clinical or neurocognitive measures could distinguish between the bipolar and schizophrenia prodromes.Methods: We examined subjects who were initially identified as CHR for schizophrenia during the prodromal phase of the illness and followed them prospectively. Unexpectedly, eight subjects developed bipolar disorder. Baseline data from subjects who eventually developed bipolar disorder (pre-BP; N=8), schizophrenia or a psychotic disorder (pre-SZ; N=24) and a non-converter comparison group (NCC; N=115) were compared.Results: The pre-BP and pre-SZ groups did not differ on attenuated positive symptom severity, global measures of functioning or on the global neurocognitive score. Compared to NCC individuals, both pre-BP and pre-SZ patients reported more severe attenuated positive symptoms and were more likely to be on antipsychotic medication at baseline. The pre-SZ group had a significantly lower current IQ and was significantly more impaired than the NCC group on the overall neurocognitive score.Conclusions: This study provides preliminary support for a bipolar prodrome, which may be indistinguishable from the schizophrenia prodrome based on clinical and neurocognitive measures currently used in high-risk schizophrenia programs.Comparing clinical and neurocognitive features of the schizophrenia prodrome to the bipolar prodrome - Corrected ProofDoreen M. Olvet, Walter H. Stearns, Danielle McLaughlin, Andrea M. Auther, Christoph U. Correll, Barbara A. Cornblatt10.1016/j.schres.2010.07.005Schizophrenia Research (2010)2010-08-17Schizophrenia Research2010-08-17http://www.schres-journal.com/article/PIIS0920996410014398/abstract?rss=yesAbstract: Studies suggest that the affective response is impaired in both schizophrenia and adolescent offspring of schizophrenia patients. Adolescent offspring of patients are developmentally vulnerable to impairments in several domains, including affective responding, yet the bases of these impairments and their relation to neuronal responses within the limbic system are poorly understood. The amygdala is the central region devoted to the processing of emotional valence and its sub-nuclei including the baso-lateral and centro-medial are organized in a relative hierarchy of affective processing. Outputs from the centro-medial nucleus converge on regions involved in the autonomous regulation of behavior, and outputs from the baso-lateral nucleus modulate the response of reward processing regions. Here using fMRI we assessed the intra-amygdala response to positive, negative, and neutral valenced faces in a group of controls (with no family history of psychosis) and offspring of schizophrenia parents (n=44 subjects in total). Subjects performed an affective continuous performance task during which they continually appraised whether the affect signaled by a face on a given trial was the same or different from the previous trial (regardless of facial identity). Relative to controls, offspring showed reduced activity in the left centro-medial nucleus to positively (but not negatively or neutral) valenced faces. These results were independent of behavioral/cognitive performance (equal across groups) suggesting that an impaired affective substrate in the intra-amygdala response may lie at the core of deficits of social behavior that have been documented in this population.Reduced intra-amygdala activity to positively valenced faces in adolescent schizophrenia offspring - Corrected ProofTracy Barbour, Eric Murphy, Patrick Pruitt, Simon B. Eickhoff, Matcheri S. Keshavan, Usha Rajan, Caroline Zajac-Benitez, Vaibhav A. Diwadkar10.1016/j.schres.2010.07.023Schizophrenia Research (2010)2010-08-17Schizophrenia Research2010-08-17http://www.schres-journal.com/article/PIIS0920996410014374/abstract?rss=yesAbstract: It has been suggested that the study of the stigma of mental illness should include more behavioral measures and further investigation of the possible importance of implicit evaluations in predicting responses to those with such illness. In the current paper, we report a study testing the relationship of implicit and explicit evaluations to physical proximity and cortisol levels in anticipation of meeting someone with schizophrenia. The results showed that both explicit evaluations and cortisol levels independently predicted physical proximity. Implicit evaluations were not related to either physical proximity or cortisol levels. The findings suggest that there are aspects of emotional response to those with mental illness that are not reflected in explicit measures of evaluation and that these, as well as explicit responses, can contribute to the prediction of behavior.Physical proximity in anticipation of meeting someone with schizophrenia: The role of explicit evaluations, implicit evaluations and cortisol levels - Corrected ProofRoss M.G. Norman, Bertram Gawronski, Elizabeth Hampson, Richard M. Sorrentino, Andrew Szeto, Yang Ye10.1016/j.schres.2010.07.021Schizophrenia Research (2010)2010-08-16Schizophrenia Research2010-08-16http://www.schres-journal.com/article/PIIS0920996410014246/abstract?rss=yesCentral pontine myelinolysis (CPM) is a demyelinating condition of the central pons that was first detected at necropsy of patients with alcoholism and malnutrition (). A possible mechanism includes hyperosmotically induced demyelination resulting from rapid changes in the intracellular/extracellular water pools, which leads to relative glial dehydration, myelin degradation, and/or oligodendroglial apoptosis (). CPM most often occurs during rapid rebalancing of electrolyte parameters in hyponatremic patients (). The nutritional status of the patient plays a major role, with poor nutrition impairing the mechanisms that protect against cell shrinkage and membrane damage ().Central pontine demyelinolysis following water intoxication in schizophrenia - Corrected ProofMichitaka Funayama, Tetsuya Hisamatsu, Akihiro Koreki10.1016/j.schres.2010.07.009Schizophrenia Research (2010)2010-08-13Schizophrenia Research2010-08-13LETTER TO THE EDITORhttp://www.schres-journal.com/article/PIIS0920996410013721/abstract?rss=yesAbstract: Background:: Regional prefrontal cortex gray matter reductions have been identified in schizophrenia, likely reflecting a combination of genetic vulnerability and disease effects. Few morphometric studies to date have examined regional prefrontal abnormalities in non-psychotic biological relatives who have not passed through the age range of peak risk for onset of psychosis. We conducted a region-of-interest morphometric study of prefrontal subregions in adolescent and young adult relatives of schizophrenia patients.Methods:: Twenty-seven familial high-risk (FHR) first-degree relatives of schizophrenia patients and forty-eight control subjects without a family history of psychosis (ages 13–28) underwent high-resolution magnetic resonance imaging at 1.5Tesla. The prefrontal cortex was parcellated into polar, dorsolateral, ventrolateral, ventromedial and orbital subregions. The Chapman scales measured subpsychotic symptoms. General linear models examined associations of prefrontal subregion volumes with familial risk and subpsychotic symptoms.Results:: FHR subjects had significantly reduced bilateral ventromedial prefrontal and frontal pole gray matter volumes compared with controls. Ventromedial volume was significantly negatively correlated with magical ideation and anhedonia scores in FHR subjects.Conclusions:: Selective, regional prefrontal gray matter reductions may differentially mark genetic vulnerability and early symptom processes among non-psychotic young adults at familial risk for schizophrenia.Regional prefrontal cortex gray matter volumes in youth at familial risk for schizophrenia from the Harvard Adolescent High Risk Study - Corrected ProofIsabelle M. Rosso, Nikos Makris, Heidi W. Thermenos, Steven M. Hodge, Ariel Brown, David Kennedy, Verne S. Caviness, Stephen V. Faraone, Ming T. Tsuang, Larry J. Seidman10.1016/j.schres.2010.06.015Schizophrenia Research (2010)2010-08-12Schizophrenia Research2010-08-12http://www.schres-journal.com/article/PIIS0920996410013782/abstract?rss=yesAbstract: Background: Characterizing neuropsychological (NP) functioning of individuals at clinical high risk (CHR) for psychosis may be useful for prediction of psychosis and understanding functional outcome. The degree to which NP impairments are associated with general cognitive ability and/or later emergence of full psychosis in CHR samples requires study with well-matched controls.Methods: We assessed NP functioning across eight cognitive domains in a sample of 73 CHR youth, 13 of whom developed psychotic-level symptoms after baseline assessment, and 34 healthy comparison (HC) subjects. Groups were matched on age, sex, ethnicity, handedness, subject and parent grade attainment, and median family income, and were comparable on WRAT-3 Reading, an estimate of premorbid IQ. Profile analysis was used to examine group differences and the role of IQ in profile shape.Results: The CHR sample demonstrated a significant difference in overall magnitude of NP impairment but only a small and nearly significant difference in profile shape, primarily due to a large impairment in olfactory identification. Individuals who subsequently developed psychotic-level symptoms demonstrated large impairments in verbal IQ, verbal memory and olfactory identification comparable in magnitude to first episode samples.Conclusions: CHR status may be associated with moderate generalized cognitive impairments marked by some degree of selective impairment in olfaction and verbal memory. Impairments were greatest in those who later developed psychotic symptoms. Future study of olfaction in CHR samples may enhance early detection and specification of neurodevelopmental mechanisms of risk.Neuropsychological profiles in individuals at clinical high risk for psychosis: Relationship to psychosis and intelligence - Corrected ProofKristen A. Woodberry, Larry J. Seidman, Anthony J. Giuliano, Mary B. Verdi, William L. Cook, William R. McFarlane10.1016/j.schres.2010.06.021Schizophrenia Research (2010)2010-08-09Schizophrenia Research2010-08-09http://www.schres-journal.com/article/PIIS0920996410013794/abstract?rss=yesAbstract: Disturbance in the integration of visual information is one of the hallmarks of schizophrenia. In the spatial domain, visual integration is compromised, resulting in impaired perceptual grouping and contour integration. In the time domain, in contrast, visual integration is enhanced, as manifested by increased backward masking and lower ability of patients to detect successively presented visual stimuli as asynchronous. There is much evidence that integrative processes in the brain are supported by dynamic synchronization, or phase-locking, of neural firing. In particular, synchrony in the gamma band (>30Hz) has been related to local visual information binding whereas synchrony in lower frequencies has been linked to global-scale integration. We recorded EEG signals evoked by steady-state gamma-frequency (40Hz) photic stimulation in order to directly test the phase-locking of neural responses in schizophrenia. Compared with healthy control subjects, patients showed higher phase-locking of early evoked activity in the gamma band (36–44Hz) over the posterior cortex, but lower phase-locking in theta (4–8Hz), alpha (8–13Hz) and beta (13–24Hz) frequencies over the anterior cortex. Phase-locking of evoked responses separated schizophrenia and control subjects with accuracy of 86%. This result suggests that schizophrenia is associated with an enhanced early low-level integration in the visual cortex but a deficient high-level integration of visual information within the brain global workspace.Aberrant EEG responses to gamma-frequency visual stimulation in schizophrenia - Corrected ProofIgor Riečanský, Tomáš Kašpárek, Jitka Řehulová, Stanislav Katina, Radovan Přikryl10.1016/j.schres.2010.06.022Schizophrenia Research (2010)2010-08-09Schizophrenia Research2010-08-09http://www.schres-journal.com/article/PIIS0920996410014258/abstract?rss=yesAbstract: Objective: Olfactory identification deficits are found in a significant proportion of patients with schizophrenia spectrum psychotic disorders and appear to be predictive of incomplete remission of negative and cognitive symptoms. In the current study, we examined whether patients with first episode psychosis who have olfactory identification deficits (microsmic) have poorer functional outcome than those whose olfactory status is normal (normosmic).Method: Sixty-six (66) first episode psychosis patients (46 M and 20 F) were assessed with the University of Pennsylvania Smell Identification Test (UPSIT) at baseline. UPSIT scores served to classify patients into subgroups. The patients' psychiatrists completed the Social and Occupational Functioning Assessment Scale (SOFAS) and the Levels of Functioning Scale (LOFS) after at least 6months of treatment. The Premorbid Assessment Scale (PAS) was rated by a parent at baseline.Results: Thirty-eight percent (38%) of the sample was identified as ‘microsmic’. LOFS and SOFAS scores were significantly lower in the microsmic group than in the normosmic group. Symptoms were significantly worse in the microsmic group in comparison to the normosmic group. PAS scores did not differ between groups.Conclusions: First episode patients identified as microsmic at baseline assessment went on to demonstrate poorer functional outcome compared to normosmic patients despite no differences in premorbid adjustment. Olfactory identification deficits at first episode may provide a marker for poorer outcome. Testing olfaction is simple and inexpensive, and could provide clinically valuable information at first episode to identify those patients who might benefit from more intensive interventions promoting functional recovery.An investigation of a possible relationship between olfactory identification deficits at first episode and four-year outcomes in patients with psychosis - Corrected ProofKimberley P. Good, Philip Tibbo, Heather Milliken, David Whitehorn, Maria Alexiadis, Nancy Robertson, Lili C. Kopala10.1016/j.schres.2010.07.010Schizophrenia Research (2010)2010-08-09Schizophrenia Research2010-08-09http://www.schres-journal.com/article/PIIS092099641001426X/abstract?rss=yesAbstract: Methylenetetrahydrofolate reductase (MTHFR) is a critical molecule for single-carbon transfer reactions. Recent evidence suggests that polymorphisms of MTHFR are related to neural tube deficits and the pathogenesis of schizophrenia. While several studies have demonstrated associations between the gene encoding the MTHFR (MTHFR) polymorphisms and schizophrenia, these studies lack consistency. Therefore, we conducted a gene-wide association study (patients with schizophrenia=696, control subjects=747) and performed imputation analysis. Additionally, we performed meta-analysis on currently available data from 18 studies for two common functional polymorphisms (rs1801131 and rs1801133).There were no significant associations with schizophrenia in the single marker analysis for the seven tagging SNPs of MTHFR. In the haplotypic analysis, a nominally significant association was observed between the haplotypes, which included four SNPs (rs1801133, rs17421511, rs17037396, and rs9651118) and the schizophrenic patients. Additionally, the imputation analysis demonstrated there were several associated markers on the MTHFR chromosomal region. However, confirmatory analyses of three tagging SNPs (rs1801133, rs17037396, and rs9651118) and the top SNP (rs17421511) for the imputation results (patients with schizophrenia=797, control subjects=1025) failed to replicate the haplotypic analysis and the imputation results. These findings suggest that MTHFR polymorphisms are unlikely to be related to the development of schizophrenia in the Japanese population. However, since our meta-analysis results demonstrated strong support for association of rs1801133 with schizophrenia, further replication studies based on a gene-wide approach need to be considered.Gene-wide association study between the methylenetetrahydrofolate reductase gene (MTHFR) and schizophrenia in the Japanese population, with an updated meta-analysis on currently available data - Corrected ProofAkira Yoshimi, Branko Aleksic, Yukiko Kawamura, Nagahide Takahashi, Shinnosuke Yamada, Hinako Usui, Shinichi Saito, Yoshihito Ito, Nakao Iwata, Toshiya Inada, Yukihiro Noda, Kiyofumi Yamada, Norio Ozaki10.1016/j.schres.2010.07.011Schizophrenia Research (2010)2010-08-09Schizophrenia Research2010-08-09http://www.schres-journal.com/article/PIIS0920996410014271/abstract?rss=yesAbstract: Objective: The metabolic side effects of second-generation antipsychotics (SGA) are serious and have not been compared head to head in a meta-analysis. We conducted a meta-analysis of studies comparing the metabolic side effects of the following SGAs head-to-head: amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, zotepine.Method: We searched the register of the Cochrane schizophrenia group (last search May 2007), supplemented by MEDLINE and EMBASE (last search January 2009) for randomized, blinded studies comparing the above mentioned SGA in the treatment of schizophrenia or related disorders. At least three reviewers extracted the data independently. The primary outcome was weight change. We also assessed changes of cholesterol and glucose. The results were combined in a meta-analysis.Results: We included 48 studies with 105 relevant arms. Olanzapine produced more weight gain than all other second-generation antipsychotics except for clozapine where no difference was found. Clozapine produced more weight gain than risperidone, risperidone more than amisulpride, and sertindole more than risperidone. Olanzapine produced more cholesterol increase than aripiprazole, risperidone and ziprasidone. (No differences with amisulpride, clozapine and quetiapine were found). Quetiapine produced more cholesterol increase than risperidone and ziprasidone. Olanzapine produced more increase in glucose than amisulpride, aripiprazole, quetiapine, risperidone and ziprasidone; no difference was found with clozapine.Conclusions: Some SGAs lead to substantially more metabolic side effects than other SGAs. When choosing an SGA for an individual patient these side effects with their potential cause of secondary diseases must be weighed against efficacy and characteristics of the individual patient.Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: A systematic review and meta-analysis - Corrected ProofChristine Rummel-Kluge, Katja Komossa, Sandra Schwarz, Heike Hunger, Franziska Schmid, Claudia Asenjo Lobos, Werner Kissling, John M. Davis, Stefan Leucht10.1016/j.schres.2010.07.012Schizophrenia Research (2010)2010-08-09Schizophrenia Research2010-08-09http://www.schres-journal.com/article/PIIS0920996410014295/abstract?rss=yesAbstract: Background: Earlier studies of patients with schizophrenia have investigated suicide risk in relation to specific psychiatric symptoms, but it remains to be better understood how suicide risk relates to the diagnostic profile in these patients.Methods: We identified all patients with a first clinical ICD-diagnosis of schizophrenia, schizophreniform or schizoaffective disorder in Stockholm County between 1984 and 2000. Patients who died by suicide within five years from diagnosis were defined as cases (n=84) and were individually matched with a similar number of living controls from the same population. Sociodemographic and clinical variables were retrieved from hospital records through a blind process. DSM-IV lifetime diagnoses for cases and controls were derived using the OPCRIT algorithm.Results: A schizophrenia spectrum diagnosis (i.e. schizophrenia, schizophreniform or schizoaffective disorder) was assigned by OPCRIT to 50% of the suicide cases and 62% of the controls. Criteria for schizophrenia were met by 41% of the cases and 51% of the controls; for schizoaffective disorder by 8% of the cases and 10% of the controls; for other psychosis by 23% of the cases and 25% of the controls; and for mood disorder by 26% of the cases and 12% of the controls. Using the schizophrenia diagnosis as a reference, suicide risk was significantly higher in patients meeting criteria for a mood disorder diagnosis with an adjusted odds ratio of 3.3 (95% CI 1.2–9.0).Conclusion: In patients with a clinical schizophrenia spectrum diagnosis, a DSM-IV mood disorder diagnosis increases the suicide risk more than three-fold.Diagnostic profile and suicide risk in schizophrenia spectrum disorder - Corrected ProofJohan Reutfors, Shahram Bahmanyar, Erik G. Jönsson, Anders Ekbom, Peter Nordström, Lena Brandt, Urban Ösby10.1016/j.schres.2010.07.014Schizophrenia Research (2010)2010-08-09Schizophrenia Research2010-08-09http://www.schres-journal.com/article/PIIS0920996410014301/abstract?rss=yesThe second generation antipsychotic ziprasidone is well-tolerated and efficacious in the treatment of adults with schizophrenia () and bipolar disorder () and is available for intramuscular use in the management of acute agitation associated with schizophrenia (). However, accumulating evidence suggests that ziprasidone is associated with prolongation of the QT interval (). Nonetheless, there has been considerable debate surrounding the clinical significance of QTc prolongation induced by ziprasidone administration (). To this end, reports of cardiac adverse events which are clearly linked to ziprasidone remain scarce and are these reports are often complicated by the administration of multiple concomitant medications (). Herein, we report a case of bradycardia with third-degree atrioventricular block (complete heart block) and subsequent pulseless electrical activity following a single intramuscular dose of ziprasidone in an elderly patient.Third degree heart block following intramuscular ziprasidone - Corrected ProofRabindra Tambyraja, Jeffrey R. Strawn10.1016/j.schres.2010.07.015Schizophrenia Research (2010)2010-08-09Schizophrenia Research2010-08-09LETTER TO THE EDITORhttp://www.schres-journal.com/article/PIIS0920996410014349/abstract?rss=yesWe thank Scott Kaplan for his interest in our study () and his comments. There are two key questions to consider, 1) Is it valid to compare the effect sizes from a meta-analyses of first episode patients to a meta-analysis of chronic patients with schizophrenia? 2) If this is a valid comparison, would one expect to see a significant difference in the effect sizes if progressive changes exist?Response to letter by Scott Kaplan - Corrected ProofMatthew J. Kempton10.1016/j.schres.2010.07.019Schizophrenia Research (2010)2010-08-06Schizophrenia Research2010-08-06LETTER TO THE EDITORShttp://www.schres-journal.com/article/PIIS0920996410013630/abstract?rss=yesAbstract: Background: Neurocognitive impairments in executive and mnemonic domains are already evident in the pre-psychotic phases. The longitudinal dynamic course of the neurofunctional abnormalities underlying liability to psychosis and their relation to clinical outcomes is unknown.Methods: In this study we used functional magnetic resonance imaging (fMRI) in a cohort of subjects at ultra high clinical risk for psychosis (with an “At Risk Mental State”, ARMS) and in healthy controls. Images were acquired at baseline and again after one year on a 1.5 Tesla Signa, while patients were performing a visuospatial working memory task. Psychopathological assessment of the prodromal symptoms was conducted at the same time points by using the CAARMS and the PANSS instruments.Results: There were no significant differences between the ARMS and control groups with respect to age or IQ. Although both groups performed the PAL task with a high degree of accuracy, the ARMS showed an increased latency in answers during the most demanding level of the task. At baseline, such cognitive impairment was associated with reduced activation in the left precuneus, left superior parietal lobule, right middle temporal gyrus in the ARMS as compared to controls. In addition, the ARMS failed to activate parietal areas with increasing difficulty of the task. Between presentation and follow-up the overall clinical status of the ARMS sample improved, despite 2 out of the 15 subjects having developed a full-blown psychosis: the CAARMS (perceptual disorder and thought disorder subscales) and the PANNS general scores decreased, while the GAF score increased. Such clinical amelioration was associated with a longitudinal compensatory increase in occipitoparietal regions.Conclusions: The prodromal phase of psychosis is associated with functional alterations in parietal and temporal networks subserving visuospatial working memory which are more evident under high cognitive loads. The clinical improvement at one year is associated with a compensatory increase in occipitoparietal regions.Spatial working memory in individuals at high risk for psychosis: Longitudinal fMRI study - Corrected ProofP. Fusar-Poli, M.R. Broome, P. Matthiasson, J.B. Woolley, L.C. Johns, P. Tabraham, E. Bramon, L. Valmaggia, S.C. Williams, P. McGuire10.1016/j.schres.2010.06.008Schizophrenia Research (2010)2010-08-05Schizophrenia Research2010-08-05http://www.schres-journal.com/article/PIIS0920996410014234/abstract?rss=yesAbstract: Whilst visual backward masking deficits in schizophrenia have been reliably reported and may reveal magnocellular dysfunction, forward masking, which may rely more heavily on the parvocellular system, has been under investigated. In a group of 64 schizophrenia patients and 65 matched controls we undertook a visual masking paradigm containing both conditions, together with tests of ‘global motion’ and ‘global form’ perception, two ‘down-stream’ visual tasks reflecting later processing linked to magnocellular and parvocellular function respectively. In the patient group, a significant but small deficit on the masking task, equivalent across forward and backward conditions was seen. Correlations between the masking and motion/form tasks supported the predominant theoretical framework describing the neural processes involved in masking. Performance on the motion and form tasks was differentiated by a trend-level motion processing deficit but near-normal form processing. The results suggest an ‘early visual’ processing deficit in both magno- and parvocellular systems but one which is only transferred to ‘down-stream’ processing areas with predominantly magnocellular input.Backward and forward visual masking in schizophrenia and its relation to global motion and global form perception - Corrected ProofP.J. Brittain, S. Surguladze, A.M. McKendrick, D.H. ffytche10.1016/j.schres.2010.07.008Schizophrenia Research (2010)2010-08-05Schizophrenia Research2010-08-05http://www.schres-journal.com/article/PIIS0920996410014313/abstract?rss=yesA paucity of studies exists in evaluating long acting risperidone injectable (LAR) in treatment refractory patients. The objective of this pilot study (NCT00272597 http://www.clinicaltrials.gov) was to determine if LAR is effective and well tolerated in this patient group.Long-acting injectable risperidone in treatment refractory patients: A 14-week open-label pilot study - Corrected ProofRic M. Procyshyn, Alasdair M. Barr, Sean Flynn, Chris Schenk, Soma Ganesan, William G. Honer10.1016/j.schres.2010.07.016Schizophrenia Research (2010)2010-08-05Schizophrenia Research2010-08-05LETTER TO THE EDITORShttp://www.schres-journal.com/article/PIIS0920996410014222/abstract?rss=yesAbstract: Objectives: Although several structural MRI studies report significant thalamus volume reduction in patients with schizophrenia, many other studies do not. Therefore, the present meta-analyses aimed to clarify whether a reduction in thalamic volume characterizes patients diagnosed with schizophrenia by considering first-episode and chronic phases of the illness and right and left thalamus separately.Methods: Using Pubmed databases, we made a detailed literature search for structural MRI studies on patients with schizophrenia that reported physical volumetric measures of the right and left thalamus. Thirteen structural MRI studies were considered eligible for meta-analysis of the entire sample of patients and of the healthy control subjects. Individual meta-analyses were also performed on 6 studies of first-episode patients only and on 7 studies of chronic patients only. These were followed by additional meta-analyses to investigate the role of the factors “illness phase” and “side” on thalamic volume reduction.Results: Overall, the patient group showed a significant bilateral thalamus volume reduction compared to healthy control subjects. This was found in both first-episode and chronic patients. Furthermore, left thalamus was smaller than right in both patients and healthy control subjects.Conclusions: When only studies that used physical volumetric measures were considered, the present meta-analyses confirmed that thalamic volume reduction characterizes patients with schizophrenia, both at the first-episode and chronic phases of the illness.Updated meta-analyses reveal thalamus volume reduction in patients with first-episode and chronic schizophrenia - Corrected ProofFulvia Adriano, Ilaria Spoletini, Carlo Caltagirone, Gianfranco Spalletta10.1016/j.schres.2010.07.007Schizophrenia Research (2010)2010-08-04Schizophrenia Research2010-08-04REVIEWhttp://www.schres-journal.com/article/PIIS0920996410014337/abstract?rss=yesAbstract: Introduction: Suicidal behaviour is prevalent in psychotic disorders. Insight has been found to be associated with increased risk for suicidal behaviour, but not consistently. A possible explanation for this is that insight has different consequences for patients depending on their beliefs about psychosis. The present study investigated whether a relationship between insight, negative beliefs about psychosis and suicidality was mediated by depressive symptoms, and if negative beliefs about psychosis moderated the relationship between insight and suicidality in patients with a first episode of psychosis (FEP).Method: One hundred ninety-four FEP-patients were assessed with a clinical interview for diagnosis, symptoms, functioning, substance use, suicidality, insight, and beliefs about psychosis.Results: Nearly 46% of the patients were currently suicidal. Depressive symptoms, having a schizophrenia spectrum disorder, insight, and beliefs about negative outcomes for psychosis were independently associated with current suicidality; contradicting a mediating effect of depressive symptoms. Negative beliefs about psychosis did not moderate the effect of insight on current suicidality.Conclusion: The results indicate that more depressive symptoms, higher insight, and negative beliefs about psychosis increase the risk for suicidality in FEP-patients. The findings imply that monitoring insight should be part of assessing the suicide risk in patients with FEP, and that treating depression and counteracting negative beliefs about psychosis may possibly reduce the risk for suicidality.Suicidality in first episode psychosis is associated with insight and negative beliefs about psychosis - Corrected ProofElizabeth A. Barrett, Kjetil Sundet, Ann Faerden, Ingrid Agartz, Unni Bratlien, Kristin Lie Romm, Erlend Mork, Jan Ivar Rossberg, Nils Eiel Steen, Ole A. Andreassen, Ingrid Melle10.1016/j.schres.2010.07.018Schizophrenia Research (2010)2010-08-04Schizophrenia Research2010-08-04http://www.schres-journal.com/article/PIIS0920996410013770/abstract?rss=yesDeficits in temporal judgment in schizophrenia have been observed in behavioral and electrophysiological studies for years. The functional neuroanatomy of temporal judgment in schizophrenia is, however, poorly understood. Recent neurophysiological research suggests that timing deficits in this population may not be widespread across all timing tasks, but specifically associated with high levels of difficulty. We evaluated differences between individuals with schizophrenia (N=16) and healthy subjects (N=18) during a temporal discrimination task at two levels of difficulty. Subjects were studied with functional magnetic resonance imaging (fMRI) at 3T while discriminating tone durations. Behaviorally, the schizophrenia group performed worse than the control group at both levels of difficulty. Similarly, group differences in patterns of brain activation were observed across both difficulty conditions. In the easy condition, individuals with schizophrenia showed less activation in the supplementary motor area and insula/opercula, regions known to be involved in temporal processing. These group differences increased in the difficult condition. In addition, the striatum was less active in individuals with schizophrenia in the difficult condition.Comparing the difficult to easy conditions revealed robust differences in the bilateral striatum and the insula/opercula, suggesting that the striatum plays a key role in temporal processing deficits in schizophrenia, especially under difficult conditions. These observations suggest that temporal judgment deficits reflect widespread neuroanatomical network involvement in schizophrenia, some of which are not directly related to task difficulty. These findings shed light on disparate findings in the timing literature regarding the role of task difficulty in temporal judgment deficits in schizophrenia.Temporal processing in schizophrenia: Effects of task-difficulty on behavioral discrimination and neuronal responses - Corrected ProofDeana B. Davalos, Donald C. Rojas, Jason R. Tregellas10.1016/j.schres.2010.06.020Schizophrenia Research (2010)2010-08-02Schizophrenia Research2010-08-02http://www.schres-journal.com/article/PIIS0920996410013812/abstract?rss=yesAbstract: MicroRNAs (miRNAs) are a large family of small non-coding RNAs which negatively control gene expression at both the mRNA and protein levels. The number of miRNAs identified is growing rapidly and approximately one-third is expressed in the brain where they have been shown to affect neuronal differentiation, synaptosomal complex localization and synapse plasticity, all functions thought to be disrupted in schizophrenia. Here we investigated the expression of 667 miRNAs (miRBase v.13) in the prefrontal cortex of individuals with schizophrenia (SZ, N=35) and bipolar disorder (BP, N=35) using a real-time PCR-based Taqman Low Density Array (TLDA). After extensive QC steps, 441 miRNAs were included in the final analyses. At a FDR of 10%, 22 miRNAs were identified as being differentially expressed between cases and controls, 7 dysregulated in SZ and 15 in BP. Using in silico target gene prediction programs, the 22miRNAs were found to target brain specific genes contained within networks overrepresented for neurodevelopment, behavior, and SZ and BP disease development.In an initial attempt to corroborate some of these predictions, we investigated the extent of correlation between the expressions of hsa-mir-34a, -132 and -212 and their predicted gene targets. mRNA expression of tyrosine hydroxylase (TH), phosphogluconate dehydrogenase (PGD) and metabotropic glutamate receptor 3 (GRM3) was measured in the SMRI sample. Hsa-miR-132 and -212 were negatively correlated with TH (p=0.0001 and 0.0017) and with PGD (p=0.0054 and 0.017, respectively).MicroRNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders - Corrected ProofAlbert H. Kim, Mark Reimers, Brion Maher, Vernell Williamson, Omari McMichael, Joseph L. McClay, Edwin J.C.G. van den Oord, Brien P. Riley, Kenneth S. Kendler, Vladimir I. Vladimirov10.1016/j.schres.2010.07.002Schizophrenia Research (2010)2010-08-02Schizophrenia Research2010-08-02http://www.schres-journal.com/article/PIIS0920996410014180/abstract?rss=yesAbstract: Background: Cannabis use may decrease age at onset in both schizophrenia and bipolar disorder, given the evidence for substantial phenotypic and genetic overlap between both disorders.Methods: 766 patients, aged 16 to 65years, were assessed with the Composite International Diagnostic Interview (CIDI) for substance abuse/use. 676 subjects were diagnosed with schizophrenia and 90 subjects with bipolar disorder. The influence of cannabis use on age at onset in both schizophrenia and bipolar disorder was examined using regression analysis.Results: Cannabis and other substance use was more frequent in patients with schizophrenia compared to the bipolar group. Both cannabis use and a schizophrenia diagnosis predicted earlier age at onset. There was a significant interaction between cannabis use and diagnosis, cannabis having a greater effect in bipolar patients. Age at onset in users of cannabis was comparable in both diagnostic groups whereas bipolar non-users were significantly older than schizophrenia non-users at onset.Conclusion: Cannabis use may decrease age at onset in both schizophrenia and bipolar patients and reduce the effect of diagnosis. This is consistent with the view that cannabis use may unmask a pre-existing genetic liability that is partly shared between patients with schizophrenia and bipolar disorder.Effects of cannabis use on age at onset in schizophrenia and bipolar disorder - Corrected ProofMarc De Hert, Martien Wampers, Tihana Jendricko, Tomislav Franic, Domagoj Vidovic, Nele De Vriendt, Kim Sweers, Joseph Peuskens, Ruud van Winkel10.1016/j.schres.2010.07.003Schizophrenia Research (2010)2010-08-02Schizophrenia Research2010-08-02http://www.schres-journal.com/article/PIIS0920996410014210/abstract?rss=yesAbstract: Background: There is mounting evidence for shared genetic liability to psychoses, particularly with respect to Schizophrenia (SZ) and Bipolar Disorder (BD), which may also involve aspects of cognitive dysfunction. Impaired sustained attention is considered a cardinal feature of psychoses but its association with genetic liability and disease expression in BD remains to be clarified.Methods: Visual sustained attention was assessed using the Degraded Symbol Continuous Performance Test (DS-CPT) in a sample of 397 individuals consisting of 50 remitted SZ patients, 119 of their first degree relatives, 47 euthymic BD patients, 88 of their first degree relatives and 93 healthy controls. Relatives with a personal history of schizophrenia or bipolar spectrum disorders were excluded. Performance on the DS-CPT was evaluated based on the response criterion (the amount of perceptual evidence required to designate a stimulus as a target) and sensitivity (a signal-detection theory measure of signal/noise discrimination).Results: We found no effect of genetic risk or diagnosis for either disorder on response criterion. In contrast, impaired sensitivity was seen in SZ patients and to a lesser degree in their relatives but not in BD patients and their relatives. These findings were not attributable to IQ, medication, age of onset or duration of illness.Conclusions: Our results argue for the specificity of visual sustained attention impairment in differentiating SZ from BD. They also suggest that compromised visual information processing is a significant contributor to these deficits in SZ.Deficits in visual sustained attention differentiate genetic liability and disease expression for Schizophrenia from Bipolar Disorder - Corrected ProofC.T.S. Kumar, T. Christodoulou, N.S. Vyas, M. Kyriakopoulos, R. Corrigall, A. Reichenberg, S. Frangou10.1016/j.schres.2010.07.006Schizophrenia Research (2010)2010-08-02Schizophrenia Research2010-08-02http://www.schres-journal.com/article/PIIS0920996410013769/abstract?rss=yesAbstract: Research suggests paranoia among persons with schizophrenia may be the result of a number of different psychological processes including deficits in theory of mind (ToM) and social anxiety. To test this hypothesis, this study sought to determine whether a group of highly paranoid persons with and without a ToM deficit could be detected and whether the group with paranoia and better ToM might have high levels of social anxiety. To explore this, a cluster analysis was performed on a group of 102 adults with schizophrenia spectrum disorders in a non-acute phase of illness on the basis of ratings of paranoid features using the Positive and Negative Syndrome Scale and levels of ToM deficit using a factor score which summarized four different ToM assessments. Four groups were produced: High Paranoia/Poor ToM (n=14); Low Paranoia/Good ToM (n=22); Low Paranoia/Low Middle ToM (n=29); and High Paranoia/High Middle ToM (n=23). Groups were then compared on self report of social anxiety. As predicted, the group with levels of high paranoid features and relatively better ToM performance had significantly higher levels of social anxiety than all other groups.Deficits in theory of mind and social anxiety as independent paths to paranoid features in schizophrenia - Corrected ProofPaul H. Lysaker, Giampaolo Salvatore, Megan L.A. Grant, Michele Procacci, Kyle L. Olesek, Kelly D. Buck, Giuseppe Nicolò, Giancarlo Dimaggio10.1016/j.schres.2010.06.019Schizophrenia Research (2010)2010-07-23Schizophrenia Research2010-07-23http://www.schres-journal.com/article/PIIS0920996410013733/abstract?rss=yesAbstract: Introduction: Odd speech is prevalent in individuals with schizotypy compared to controls and this odd speech is particularly pronounced under stress-induced conditions. Despite a number of research studies that have examined odd speech, the mechanisms underlying this phenomenon remain unclear. There is reason to suspect that the increase in odd speech observed in schizotypy may reflect atypical semantic activation patterns, defined in terms of increased activation of weakly associated words within the semantic network.Methods: In this study, we compared atypical semantic activation in individuals with a broad set of cognitive–perceptual, interpersonal and disorganization schizotypal traits (n=83) and controls (n=23). Odd speech was measured using a behavior-based analysis of natural speech procured from a laboratory speech-task involving separate experimentally manipulated stressful, pleasant, and neutral conditions.Results: The schizotypy and control groups did not differ in semantic activation, but atypical semantic activation was more pronounced in individuals with disorganization traits and attenuated in those with interpersonal traits. Interestingly, the relationship between semantic activation and odd speech was observed for the stressful, but not pleasant or neutral conditions in the schizotypy group.Conclusions: These findings suggest that individuals with schizotypy may be able to inhibit atypical associations in nonstressful situations. However, their ability to prevent atypical semantic activation from affecting speech may be disrupted under stress, thus resulting in more odd speech. This study also highlights the dramatic differences in semantic activation across the various manifestations of schizotypy.The relationship between atypical semantic activation and odd speech in schizotypy across emotionally evocative conditions - Corrected ProofKyle S. Minor, Alex S. Cohen, Christopher R. Weber, Laura A. Brown10.1016/j.schres.2010.06.016Schizophrenia Research (2010)2010-07-20Schizophrenia Research2010-07-20http://www.schres-journal.com/article/PIIS0920996410013745/abstract?rss=yesAbstract: We examined tobacco craving and dependence in current smokers (18–65years) with schizophrenia (N=100) and those without a psychiatric disorder (normal controls, N=100). During the 2–3h visit participants completed demographic and smoking-related questionnaires and provided a breath CO sample. The Tobacco Craving Questionnaire-Short Form (TCQ-SF) was administered. Immediately after smoking one cigarette, no difference in TCQ-SF total score was noted (46.7±19.5 schizophrenia, 42.8±18.2 controls, p=0.15); however, after 15min TCQ-SF total score was significantly higher in people with schizophrenia (50.0±19.6) than in controls (38.6±19.4) (p=0.0014). TCQ-SF factors of emotionality (p=0.0015), compulsivity (p=0.0003) and purposefulness (p=0.0174) were significantly greater in the schizophrenia group than the control group. FTND scores (5.5±2.0 vs 5.3±2.0, p=0.62) number of cigarettes smoked daily (17.9±11.6 vs. 17.0±7.9), expired breath CO (28.0±14.5ppm vs. 22.0±8.0ppm) and age at smoking initiation (16.2±5.4 vs. 15.6±5.5years, p=0.44) did not differ in the schizophrenia and control groups respectively. In conclusion, tobacco craving as measured by the TCQ-SF was significantly greater in people with schizophrenia than controls 15min post-smoking, despite similar scores in dependence and similar smoking histories and current smoking patterns.Tobacco craving in smokers with and without schizophrenia - Corrected ProofSuzanne Lo, Stephen J. Heishman, Heather Raley, Katherine Wright, Heidi J. Wehring, Eric T. Moolchan, Stephanie Feldman, Fang Liu, Robert P. McMahon, Charles M. Richardson, Deanna L. Kelly10.1016/j.schres.2010.06.017Schizophrenia Research (2010)2010-07-16Schizophrenia Research2010-07-16http://www.schres-journal.com/article/PIIS0920996410013678/abstract?rss=yesAbstract: Social anhedonia is an important feature of schizophrenia and it is a promising indicator of schizotypy. Although social anhedonia is defined as an affective construct (less pleasure derived from social encounters), little is known about the emotional responsivity and expressivity of individuals with high levels of social anhedonia. After screening a large sample of female undergraduate students (N=1 085), a cohort of psychometrically identified individuals with high levels of social anhedonia (n=34) and normally hedonic controls (n=45) participated in laboratory assessments involving trait affectivity, self-reported dispositional emotional expressiveness, and the expression and experience of emotion in response to neutral, non-affiliative (i.e., comedy) and affiliative film clips. Results revealed that individuals with high levels of social anhedonia are characterized by lower positive affect, both as a trait and in response to emotionally evocative stimuli, and are less facially expressive, both by their own self-report and in response to film clips. Attenuated positive affect was observed across film stimuli, indicating a general reduction in affective response rather than a specific decrease in responsivity for affiliative stimuli. Future work should continue to investigate whether there is a unique role for social stimuli in the emotional lives of individuals with high levels of social anhedonia or whether these individuals tend to experience anhedonia more broadly regardless of social context.Is social anhedonia related to emotional responsivity and expressivity? A laboratory study in women - Corrected ProofWinnie W. Leung, Shannon M. Couture, Jack J. Blanchard, Stephanie Lin, Katiah Llerena10.1016/j.schres.2010.06.012Schizophrenia Research (2010)2010-07-12Schizophrenia Research2010-07-12http://www.schres-journal.com/article/PIIS0920996410013599/abstract?rss=yesAbstract: Background: Schizophrenia is associated with deficits in the ability to discriminate auditory features such as pitch and duration that localize to primary cortical regions. Lesions of primary vs. secondary auditory cortex also produce differentiable effects on ability to localize and discriminate free-field sound, with primary cortical lesions affecting variability as well as accuracy of response. Variability of sound localization has not previously been studied in schizophrenia.Methods: The study compared performance between patients with schizophrenia (n=21) and healthy controls (n=20) on sound localization and spatial discrimination tasks using low frequency tones generated from seven speakers concavely arranged with 30° separation.Results: For the sound localization task, patients showed reduced accuracy (p=0.004) and greater overall response variability (p=0.032), particularly in the right hemifield. Performance was also impaired on the spatial discrimination task (p=0.018). On both tasks, poorer accuracy in the right hemifield was associated with greater cognitive symptom severity. Better accuracy in the left hemifield was associated with greater hallucination severity on the sound localization task (p=0.026), but no significant association was found for the spatial discrimination task.Conclusion: Patients show impairments in both sound localization and spatial discrimination of sounds presented free-field, with a pattern comparable to that of individuals with right superior temporal lobe lesions that include primary auditory cortex (Heschl's gyrus). Right primary auditory cortex dysfunction may protect against hallucinations by influencing laterality of functioning.Spatial localization deficits and auditory cortical dysfunction in schizophrenia - Corrected ProofMegan A. Perrin, Pamela D. Butler, Joanna DiCostanzo, Gina Forchelli, Gail Silipo, Daniel C. Javitt10.1016/j.schres.2010.06.004Schizophrenia Research (2010)2010-07-09Schizophrenia Research2010-07-09http://www.schres-journal.com/article/PIIS0920996410013605/abstract?rss=yesAbstract: Objective: To determine the prevalence rates of hepatitis C in patients with schizophrenia and schizoaffective disorder being treated with clozapine.Methods: Clozapine-treated outpatients and inpatients were recruited from the Centre for Addiction and Mental Health Schizophrenia Program in Toronto, Canada. All subjects had liver function tests, and positive HCV status was defined as a positive qualitative HCV RNA assay. Subjects completed a self-report questionnaire assessing HCV risk factors, past history of liver disease, previous diagnosis of human immunodeficiency virus (HIV), past hepatitis B virus (HBV) infection and current alcohol use.Results: 110 subjects participated in the study and the HCV prevalence rate (antibody and viremia-positive) was 2.7%, compared to a 0.8% prevalence rate in Canada. All study subjects had established housing, none reported a history of HIV, and only one patient had a history of HBV infection. A total of 9% drank two or more drinks on a typical day drinking and 7% endorsed having six or more drinks on one occasion at least monthly. Two of 3HCV-viremia positive subjects had HCV risk factors, specifically intravenous drug use and intranasal cocaine use. There was no difference between HCV infected and HCV negative subjects on liver function tests.Conclusions: Our study demonstrates elevated rates of HCV in clozapine-treated patients compared to the general population in Canada and are congruent with reports from United States centres. Our study highlights the importance of homelessness and patterns of high-risk behaviour when interpreting HCV prevalence rates in this sub-population of patients and should be explored in future studies.Determining rates of hepatitis C in a clozapine treated cohort - Corrected ProofSanjeev Sockalingam, Chekkera Shammi, Valerie Powell, Lucy Barker, Gary Remington10.1016/j.schres.2010.06.005Schizophrenia Research (2010)2010-07-07Schizophrenia Research2010-07-07