Schizophrenia Research - Articles in Press

Psychopathology, social adjustment and personality correlates of schizotypy clusters in a large nonclinical sample - Corrected Proof

Neus Barrantes-Vidal, Kathryn E. Lewandowski, Thomas R. Kwapil — 2010-02-08

Abstract: Introduction: Correlational methods, unlike cluster analyses, cannot take into account the possibility that individuals score highly on more than one symptom dimension simultaneously. This may account for some of the inconsistency found in the literature of correlates of schizotypy dimensions. This study explored the clustering of positive and negative schizotypy dimensions in nonclinical subjects and whether schizotypy clusters have meaningful patterns of adjustment in terms of psychopathology, social functioning, and personality.Methods: Positive and negative schizotypy dimensional scores were derived from the Chapman Psychosis-Proneness Scales for 6137 college students and submitted to cluster analysis. Of these, 780 completed the NEO-PI-R and Social Adjustment Scale-self report version, and a further 430 were interviewed for schizophrenia-spectrum, mood, and substance use psychopathology.Results: Four clusters were obtained: low (nonschizotypic), high positive, high negative, and mixed (high positive and negative) schizotypy. The positive schizotypy cluster presented high rates of psychotic-like experiences, schizotypal and paranoid symptoms, had affective and substance abuse pathology, and was open to experience and extraverted. The negative schizotypy cluster had high rates of negative and schizoid symptoms, impaired social adjustment, high conscientiousness and low agreeableness. The mixed cluster was the most deviant on almost all aspects.Conclusions: Our cluster solution is consistent with the limited cluster analytic studies reported in schizotypy and schizophrenia, indicating that meaningful profiles of schizotypy features can be detected in nonclinical populations. The clusters identified displayed a distinct and meaningful pattern of correlates in different domains, thus providing construct validity to the schizotypy types defined.

Grey matter changes associated with host genetic variation and exposure to Herpes Simplex Virus 1 (HSV1) in first episode schizophrenia - Corrected Proof

2010-02-08

Abstract: Background: We previously reported reduced prefrontal cortex (PFC) grey matter volume among first episode, antipsychotic-naïve schizophrenia subjects (SZ) exposed to HSV1 but not among healthy subjects (HS) (Prasad et al., 2007). Independently, rs1051788, an exonic polymorphism of the MHC Class I polypeptide-related sequence B (MICB) gene was associated with HSV1 seropositivity, as well as SZ risk. In this study, we examined whether PFC grey matter changes associated with HSV1 exposure varied against the background of MICB genotypes.Methods: We examined Caucasian individuals from the sample we studied in our previous report (Prasad et al., 2007) (SZ, n=21 and HS, n=19). Whole brain voxelwise analysis of structural MRI scans was conducted using Statistical Parametric Mapping, ver 5 (SPM5). The impact of rs1051788 variation and HSV1 seropositivity on grey matter volumes was examined using regression models on the combined sample of cases and controls, and then within each diagnostic group.Results: In the combined sample of cases and controls, we observed the main effects of HSV1 seropositivity and genotypes, and a significant joint effect of HSV1 seropositivity and genotype mainly in the PFC. The joint effect was more prominent among cases than among controls.Discussion: Our observations suggest that rs1051788 and HSV1 seropositivity are associated individually and jointly with reduced PFC grey matter volume. The patterns of these associations differ by diagnostic status, and these factors explain only a “small” portion of the variance in the grey matter volume reductions.

Processing of facial configuration in individuals at ultra-high risk for schizophrenia - Corrected Proof

2010-02-05

Abstract: Background: Discrepancies in the ability to recognize faces constitute an important aspect of the impaired social cognitive abilities of patients with schizophrenia. Previous studies have suggested that specific problems with the processing of facial configuration affect the face-recognition deficit in patients with schizophrenia. However, little is known about whether these deficits in face recognition are present before the onset of schizophrenia.Method: This study compared performances on a face processing task among three groups: individuals at ultra-high risk for schizophrenia (n=20), patients with schizophrenia (n=18), and normal controls (n=20) using a face-discrimination task involving pairs of photographs depicting upright and inverted images with changing features and configurations. Chair stimuli were used as the control task.Results: The individuals at ultra-high risk for schizophrenia performed more poorly than did normal controls with regard to the processing of facial configuration but not the facial feature and did not differ significantly from the patients with schizophrenia with regard to the processing of facial configuration and upright facial features.Conclusion: This study suggests that a specific dysfunction in the processing of facial configuration, which has an impact on face recognition, might be present before and deteriorate in patients with schizophrenia. Deficits in face recognition among individuals at risk for psychosis might contribute significantly to the social dysfunction associated with schizophrenia.

Quality assessment and comparison of evidence for electroconvulsive therapy and repetitive transcranial magnetic stimulation for schizophrenia: A systematic meta-review - Corrected Proof

S.L. Matheson, M.J. Green, C. Loo, V.J. Carr — 2010-02-01

Abstract: Background: Randomized studies directly comparing the effects of electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) for depression generally favour ECT. ECT and rTMS have also been investigated for chronic symptoms of schizophrenia although there are no direct comparisons available.Aims: We sought to determine the relative benefits and adverse outcomes of ECT and rTMS by comparing effect sizes reported in systematic reviews and to quality assess this evidence using GRADE and QUOROM guidelines.Method: Included are systematic reviews with meta-analysis published since 2000, reporting results for people with a diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder or first episode schizophrenia. Medline, Embase, CINAHL, Current Contents, PsycINFO and the Cochrane library were searched and hand searching was conducted. Data extraction and quality assessment were completed by two independent reviewers.Results: Fifty-three of 58 reviews were excluded as they did not meet inclusion criteria. The remaining five have a low probability of reporting bias and show that high quality evidence suggests a short-term, medium to large treatment effect of rTMS for auditory hallucinations (d=0.88) but not other symptoms, for people treated with concurrent antipsychotics. For ECT, high quality evidence suggests a short-term small, significant effect for improvement in global symptoms, for people with or without concurrent antipsychotics (RR=0.76). There is no evidence for longer-term therapeutic or adverse effects of either treatment.Conclusions: It is worthwhile considering rTMS in cases where auditory hallucinations have not responded to antipsychotic medications and ECT where overall symptoms have not responded to antipsychotic medications.

Prenatal tobacco exposure in first-episode psychosis - Corrected Proof

2010-01-29

Recent research findings leave no reasonable doubt that prenatal tobacco exposure (PTE) impairs fetal brain development (). Smoking also impairs placental functioning and leads to fetal undernourishment and a dose-dependent restriction in growth (). Maternal smoking also results in fetal glucocorticoid over-activity and elevated stress hormones in newborns (). Finally, maternal smoking compromises fetal immune-system development and results in long-term suppression of the immune response (). The negative consequences of PTE for health, cognition and behavior during childhood and beyond are well documented (). Recent findings suggest that PTE may also increase the risk for psychosis (). Despite strong evidence for the neuroteratogenic effects of nicotine, few studies have assessed the risks associated with PTE in psychiatric patients.

Has an important test been overlooked? Closure flexibility in schizophrenia - Corrected Proof

Pamela D. Butler, Isaac Schechter, Nadine Revheim, Gail Silipo, Daniel C. Javitt — 2010-01-28

Abstract: Deficits in visual processing are now recognized as a core feature of schizophrenia. In the 1940s, Louis Thurstone developed a series of tests designed to evaluate specific aspects of visual perceptual processing including the Closure Flexibility Test (CFT), which was designed to measure “the ability to hold a configuration in mind despite distraction.” The present study evaluated patients' performance on this task and its relationship to other tests of neuropsychological function, particularly to a measure of sustained visual attention. Thirty-nine patients with schizophrenia or schizoaffective disorder and 40 controls participated. The CFT was administered both in its original form (10min) and also in a briefer form (3min) in which only a portion of stimuli were given. Patients showed highly significant large effect-size deficits on both the original (d=1.6) and brief (d=1.2) CFT. Between-group deficits in performance survived co-variation for IQ. In addition, the CFT score was significantly related to performance on the MATRICS measure of attention/vigilance, the Continuous Performance Test—Identical Pairs version (CPT-IP). This correlation remained significant even after controlling for non-specific intercorrelations among neurocognitive measures. Results confirm the severity of early visual processing deficits in schizophrenia. In addition, the CFT is a brief, easy to administer alphabet-independent, paper-and-pencil test with established psychometric properties that may be useful as an index of the sustained visual attention construct in schizophrenia.

Severe injuries in adolescence predict psychosis: A nested case control study of the Northern Finland 1966 Birth Cohort - Corrected Proof

Suvi Luoma, Helinä Hakko, Mauri Marttunen, Anja Taanila, Sari Lindeman — 2010-01-25

Abstract: Adolescents who later develop schizophrenia are likely to have problems with motor coordination and many adolescents with schizophrenia have self-injurious behaviour before treatment of first psychosis but association between injuries in adolescence and onset of psychotic disorder is unknown. The aim of this study was to describe what type of injuries psychotic individuals had during adolescence and in which age these injuries occurred. The study population consists of 155 members of the Northern Finland 1966 Birth Cohort with diagnosis of schizophrenia spectrum disease and 620 matched controls. All injuries which had occurred before onset of psychosis were extracted from Finnish Hospital Discharge Register. Individuals with psychotic disorder were more likely to have a history of severe injury. During the age 12–19, 11% of psychotic subjects and 5.3% of healthy controls had an injury (z=2.38; P=0.017) and the most common type of injury was fractures. Our findings suggest that severe injury in adolescence may be a predictor of psychosis.

Reduced white matter integrity as a neural correlate of social cognition deficits in schizophrenia - Corrected Proof

2010-01-25

Abstract: Background: The pathology of schizophrenia is thought to involve multiple gray and white matter regions. A number of studies have revealed impaired social cognition in schizophrenia. Some evidence suggests an association of this social cognition deficit with gray matter reductions in ‘social brain’ areas. However, no study has yet revealed the association between social cognition abilities and white matter abnormalities in schizophrenia patients.Methods: Twenty-six schizophrenia patients and 27 healthy controls underwent the Perception of Affect Task (PAT), which consisted of four subtasks measuring different aspects of emotion attribution. Voxelwise group comparison of white matter fractional anisotropy (FA) was performed using tract-based spatial statistics (TBSS). The relation between impaired social cognition ability and FA reduction was examined in patients for each subtask, using simple regression analysis within brain areas that showed a significant FA reduction in patients compared with controls. The same correlational analysis was also performed for healthy controls in the whole brain.Results: Schizophrenia patients showed reduced emotion attribution ability compared with controls in all four subtasks. The facial emotion perception subtask showed a significant correlation with FA reductions in the left occipital white matter region and left posterior callosal region. The correlational analyses in healthy controls revealed no significant correlation of FA with any of the PAT subtasks.Conclusions: Our voxelwise correlational analysis of white matter provided a potential neural basis for the social cognition impairments in schizophrenia, in support of the disconnection hypothesis.

Antipsychotic drug use is correlated with CRP40/mortalin mRNA expression in the dorsolateral prefrontal cortex of human postmortem brain specimens - Corrected Proof

2010-01-25

Abstract: Heat shock proteins act as intracellular chaperones by assisting with proper protein folding in response to various cellular stresses. In doing so, these proteins protect the cell from unwanted protein aggregation, which in turn, plays an important role in the pathogenesis of numerous disorders. Previous reports from our laboratory have described a 40kDa catecholamine regulated heat shock-like protein (CRP40), an alternate gene product of the 70kDa mitochondrial heat shock protein, mortalin. CRP40 shares an intimate association with dopaminergic activity, specifically as it pertains to dopamine dysregulation in schizophrenia. This study investigates human CRP40/mortalin mRNA expression within dorsolateral prefrontal cortex postmortem specimens from normal control, schizophrenic and bipolar patients obtained from the Stanley Medical Research Institute. Real-time polymerase chain reaction was carried out for all patient samples (n=105; n=35 per group) in a blinded manner. No significant alterations in CRP40/mortalin mRNA expression levels were observed between control, bipolar and schizophrenic patients. However, multiple regression demonstrated a distinct positive correlation between CRP40/mortalin mRNA expression and lifetime use of antipsychotic drugs within the schizophrenic patient profile, after controlling for important confounding factors. Thus, the data suggest that human CRP40/mortalin is modulated by dopaminergic activity and may act to protect neurons from excess catecholamine activity in regions of the brain associated with psychosis.

Subcortical alignment precision in patients with schizophrenia - Corrected Proof

2010-01-25

Abstract: Previous work has demonstrated less accurate alignment of cortical structures for patients with schizophrenia than for matched control subjects when using affine registration techniques. Such a mismatch presents a potential confound for functional neuroimaging studies conducting between-group comparisons. Critically, the same issues may be present for subcortical structures. However, to date no study has explicitly investigated alignment precision for major subcortical structures in patients with schizophrenia. Thus, to address this question we used methods previously validated for assessment of cortical alignment precision to examine alignment precision of subcortical structures. In contrasts to our results with cortex, we found that major subcortical structures (i.e. amygdala, caudate, hippocampus, pallidum, putamen and thalamus) showed similar alignment precision for schizophrenia (N=48) and control subjects (N=45) regardless of the template used (other individuals with schizophrenia or healthy controls). Taken together, the present results show that, unlike cortex, alignment for six major subcortical structures is not compromised in patients with schizophrenia and as such is unlikely to confound between-group functional neuroimaging investigations.

Decreased BDNF in patients with antipsychotic naïve first episode schizophrenia - Corrected Proof

2010-01-22

Abstract: Objective: Brain-derived neurotrophic factor (BDNF) is a key factor known to mediate neuronal proliferation, differentiation, survival and response to stress. Decreases in BDNF levels have been reported in schizophrenia, but studies in treatment naïve patients are few. Herein we report on serum BDNF levels in a series of patients with first-episode treatment naïve psychoses in comparison to age matched healthy controls.Method: Fasting serum BDNF levels were measured in 41 patients with treatment naive first episode psychosis (24 with schizophrenia, schizoaffective disorder or schizophreniform disorder, and 17 with non-schizophrenia psychotic disorders) and 41 age-matched healthy controls.Results: A three group analyses of covariance (ANCOVA) showed a diagnosis effect (p=.038) in which patients with schizophrenia had lesser serum BDNF levels than patient with non-schizophrenia psychosis, who in turn had lesser BDNF levels than matched healthy controls. Planned two-group ANCOVAs suggested that patients with schizophrenia had lower serum BDNF level than matched controls (p=.016), whereas patients with non-schizophrenia psychosis did not differ from controls. There were no age effects on BDNF, but there was a trend (p=.08) for a gender by group interaction with greater reductions in female patients with schizophrenia. The BDNF levels did not correlate with magnitude of smoking, body mass index, severity of positive and negative symptoms or overall functioning.Conclusions: Serum BDNF may be reduced at the onset of psychosis but its role in the pathogenesis of schizophrenia remains unclear. Elucidating the role of BDNF in schizophrenia and related psychotic disorders may provide an important therapeutic target. Further studies are also needed to examine if patients with schizophrenia have more pronounced reductions in BDNF than those with affective psychosis.

Schizophrenia patients with polydipsia and water intoxication are characterized by greater severity of psychotic illness and a more frequent history of alcohol abuse - Corrected Proof

2010-01-22

Abstract: Polydipsia and water intoxication (PWI) are relatively frequent among schizophrenic subjects, particularly in institutional settings and may lead to severe complications. However, little is known on their association with other characteristics of psychosis. Hence, we took advantage of a cohort of 114 subjects extensively assessed on natural history and clinical variables to examine the correlates of PWI in chronic schizophrenia.We randomly sampled DSM-IV schizophrenic subjects from: i) a lower functioning subgroup, i.e., long-term psychiatric wards or highly structured group housing facilities; and ii) a higher functioning subgroup, i.e., patients living in the community without supervision. Subjects were assessed from multiple sources for lifetime severity of positive, disorganisation, negative and depressive symptoms, premorbid adjustment, age of onset, level of functioning, comorbid diagnoses of substance abuse and lifetime history of PWI.Twelve subjects (10.5%) met our PWI criteria. We observed more severe psychotic symptoms, earlier onset, poorer current adjustment and more frequent prior alcohol use disorder in PWI subjects. When restricting comparisons to patients living in institutional setting, differences on clinical and natural history variables vanished but the association between PWI and prior alcohol abuse persisted (72.7% in PWI vs. 21.4% in non-PWI subjects, p<0.01). Onset of alcohol abuse predated the onset of PWI by a mean of 12.8years.PWI schizophrenic subjects are characterized by a non-specific greater severity on a broad array of clinical and natural history variables and by a specific association with prior alcohol abuse. Thus, our data suggest that a greater severity of illness and a prior history of alcohol use disorders interact in increasing the risk of developing PWI in chronic schizophrenic patients.

Memory profiles in schizophrenia: Categorization validity and stability - Corrected Proof

Morris D. Bell, Jason K. Johannesen, Tamasine C. Greig, Bruce E. Wexler — 2010-01-20

Abstract: Background: Memory profiles corresponding to nearly normal (NN), Subcortical impairment (Sub) and Cortical impairment (Cort) have been identified in schizophrenia by several investigators using cluster analytic techniques. Specific aims of the current study were to (1) perform a K means cluster analysis using Hopkins Verbal Learning Test-R scores (2) create classification rules based upon cluster distributions and expected memory profiles and to determine their concordance with cluster analysis; (3) explore differences among classified groups on demographic, neurocognitive and social cognitive domains; and (4) determine the stability of the classifications 12months later.Methods: Clinical and neuropsychological assessments were obtained at intake and 12months from 151 outpatients with schizophrenia or schizoaffective disorder from an urban community mental health center.Results: Clusters corresponded to those of the three expected subgroups. Using simple decision rules, rationally-derived groups were created and had 90% classification agreement with cluster groups. Groups did not differ on illness characteristics. Groups differed significantly in neurocognitive and social cognitive domains with NN>Cort and NN>Sub in all domains except visual/motor speed. Sub>Cort in verbal working memory. NN>Cort in social cognition. Rationally derived groupings showed fair stability at 12month follow-up with 65% classification agreement. Specificity was good for NN (82.4%).Discussion: Results support validity of memory profiles and offer some support for their stability at 12months. The simple rules for classification can be used by other investigators for neuroimaging and other studies. Findings support the hypothesis that verbal memory may be an important source of heterogeneity in schizophrenia.

Challenging the assumption that improvement in functional outcomes is delayed relative to improvement in symptoms in the treatment of schizophrenia - Corrected Proof

2010-01-18

Abstract: Objectives: Functional improvement is generally thought to be distal to improvement in psychiatric symptoms in patients with schizophrenia. In this study, we assessed the effects of early response/non-response to an atypical antipsychotic across multiple outcome measures.Methods: This was a randomized, double-blind, flexible-dose, 12-week study that enrolled chronically-ill patients (n=628) diagnosed with schizophrenia or schizoaffective disorder who were experiencing acute symptom exacerbation. Patients were initially assigned to risperidone drug therapy (2–6mg/day), and their response status at 2weeks was determined. Early responders (ERs) continued with risperidone therapy, whereas early non-responders (ENRs) were randomized (1:1) in a double-blind manner to either continue on risperidone or switch to another atypical antipsychotic for 10 additional weeks of therapy. Subsequent treatment outcomes were measured by the Quality of Life Scale (QLS), Schizophrenia Objective Functioning Instrument (SOFI), and Subjective Well-being under Neuroleptics (SWN-K) scale.Results: Compared to ENRs, ERs to risperidone showed significantly more improvement from baseline to endpoint on the QLS total score and all 4 categories (p<.01), the SOFI overall global score and all 4 domains (p<.001), and the SWN-K total score and all 5 subscales (p<.05). Among ERs, the majority of improvement had already been attained by Week 2. There was concordance among clinician- and patient-rated scales across outcomes.Conclusion: Improvement across multiple outcome dimensions was not delayed relative to improvement in psychiatric symptoms. Rather, patients who showed an early response to antipsychotic treatment as defined by improvement in psychiatric symptoms also showed early and consistent improvement in functioning, quality of life, and subjective well-being.

Diagnostic classification of schizophrenia by neural network analysis of blood-based gene expression signatures - Corrected Proof

2010-01-18

Abstract: Gene expression profiling with microarray technology suggests that peripheral blood cells might be a surrogate for postmortem brain tissue in studies of schizophrenia. The development of an accessible peripheral biomarker would substantially help in the diagnosis of this disease. We used a bioinformatics approach to examine whether the gene expression signature in whole blood contains enough information to make a specific diagnosis of schizophrenia. Unpaired t-tests of gene expression datasets from 52 antipsychotics-free schizophrenia patients and 49 normal controls identified 792 differentially expressed probes. Functional profiling with DAVID revealed that eleven of these genes were previously reported to be associated with schizophrenia, and 73 of them were expressed in the brain tissue. We analyzed the datasets with one of the supervised classifiers, artificial neural networks (ANNs). The samples were subdivided into training and testing sets. Quality filtering and stepwise forward selection identified 14 probes as predictors of the diagnosis. ANNs were then trained with the selected probes as the input and the training set for known diagnosis as the output. The constructed model achieved 91.2% diagnostic accuracy in the training set and 87.9% accuracy in the hold-out testing set. On the other hand, hierarchical clustering, a standard but unsupervised classifier, failed to separate patients and controls. These results suggest analysis of a blood-based gene expression signature with the supervised classifier, ANNs, might be a diagnostic tool for schizophrenia.

A reappraisal of the association between Dysbindin (DTNBP1) and schizophrenia in a large combined case–control and family-based sample of German ancestry - Corrected Proof

2010-01-18

Abstract: Background: Dysbindin (DTNBP1) is a widely studied candidate gene for schizophrenia (SCZ); however, inconsistent results across studies triggered skepticism towards the validity of the findings. In this HapMap-based study, we reappraised the association between Dysbindin and SCZ in a large sample of German ethnicity.Method: Six hundred thirty-four cases with DSM-IV SCZ, 776 controls, and 180 parent–offspring trios were genotyped for 38 Dysbindin SNPs. We also studied two phenotypically-defined subsamples: 147 patients with a positive family history of SCZ (FH-SCZ+) and SCZ patients characterized for cognitive performance with Trail-Making Tests A and B (TMT-A: n=219; TMT-B: n=247). Given previous evidence of gene–gene interactions in SCZ involving the COMT gene, we also assessed epistatic interactions between Dysbindin markers and 14 SNPs in COMT.Results: No association was detected between Dysbindin markers and SCZ, or in the FH-SCZ+ subgroup. Only one marker (rs1047631, previously reported to be part of a risk haplotype), showed a nominally significant association with performance on TMT-A and TMT-B; these findings did not remain significant after correction for multiple comparisons. Similarly, no pair-wise epistatic interactions between Dysbindin and COMT markers remained significant after correction for 504 pair-wise comparisons.Conclusions: Our results, based on one of the largest samples of European Caucasians and using narrowly-defined criteria for SCZ, do not support the etiological involvement of Dysbindin markers in SCZ. Larger samples may be needed in order to unravel Dysbindin's possible role in the genetic basis of proposed intermediate phenotypes of SCZ or to detect epistatic interactions.

Subunit and whole molecule specificity of the anti-bovine casein immune response in recent onset psychosis and schizophrenia - Corrected Proof

2010-01-14

Abstract: Previous studies show increased antibody levels to bovine casein in some individuals with schizophrenia. The immunogenicity of specific domains of bovine casein varies among people with milk sensitivities and thus could vary among different neuropsychiatric disorders. Using ELISAs and immunoblotting, we characterized IgG class antibody specificity to whole bovine casein and to the αs, β, and κ subunits in individuals with recent onset psychosis (n=95), long-term schizophrenia (n=103), and non-psychiatric controls (n=65). In both patient groups, we found elevated IgG to casein proteins, particularly to whole casein and the αs subunit (p≤0.0001). Odds ratios of casein seroprevalence for recent onset psychosis (age-, gender-, race-, smoking-adjusted) were significant for whole casein (8.13, p≤0.0001), and the αs (7.89, p≤0.0001), β (5.23, p≤0.001) and κ (5.70, p≤0.0001) subunits. Odds ratios for long-term schizophrenia were significant for whole casein (7.85, p≤0.0001), and the αs (4.78, p≤0.003) and κ (4.92, p≤0.004) subunits. Within the recent onset group, odds ratios were particularly significant for a subgroup of people with psychotic disorders that included major depressive disorders (8.22–16.48, p≤0.0001). In a different recent onset subgroup (schizophrenia-spectrum disorders), PANSS scores for negative symptoms were correlated with casein antibody levels for the αs and κ subunits (p≤0.001–0.01). Immunoblotting patterns also exhibited group specificity, with κ predominant in recent onset and αs in schizophrenia (Fisher's Exact Test, p≤0.001). The elevated IgG and unique patterns of antibody specificity to bovine casein among diagnostic groups provide a rationale for clinical trials to evaluate efficacies of dietary modifications in individuals with neuropsychiatric diseases.

Cognitive differences between men and women: A comparison of patients with schizophrenia and healthy volunteers - Corrected Proof

Julia Longenecker, Dwight Dickinson, Daniel R. Weinberger, Brita Elvevåg — 2010-01-13

Gender modulates cognition with women displaying advantages in verbal memory and processing speed and men in visuospatial tasks (). Patients with schizophrenia have shown similar patterns (). However, these clinical findings have been based on small samples (n<100) and select tests. Therefore, we examined gender differences in cognitive performance in (i) a large sample of patients and controls; and (ii) using a comprehensive test battery — from the “NIMH Sibling Study” ().

Higher cortisol levels are associated with smaller left hippocampal volume in first-episode psychosis - Corrected Proof

2010-01-13

Abstract: This study investigated the relationship between cortisol secretion and hippocampal volume in first-episode psychosis and healthy controls. Hippocampal volume was measured by magnetic resonance imaging (MRI) in 24 first-episode psychosis patients and in 18 healthy controls, together with diurnal cortisol levels. Twelve patients received a second MRI scan at 3-month follow-up. Diurnal cortisol levels were inversely correlated with left hippocampal volume in patients, both at baseline and at follow-up, while no correlation was found in controls. Our findings suggest that smaller hippocampal volume in first-episode psychosis can partly be explained by stress-related processes in the brain, as measured by cortisol hyper-secretion.

DSM-IV catatonia signs and criteria in first-episode, drug-naive, psychotic patients: Psychometric validity and response to antipsychotic medication - Corrected Proof

Victor Peralta, Maria S. Campos, Elena Garcia de Jalon, Manuel J. Cuesta — 2010-01-13

Abstract: Objective: To examine the prevalence, psychometric validity and response to antipsychotic drugs of DSM-IV catatonia signs and criteria in patients with a first-episode psychotic disorder.Methods: Two-hundred antipsychotic-naive patients with a DSM-IV nonaffective psychosis were assessed for catatonia signs and criteria using the Modified Rogers Scale, and the psychometric validity of the 12 DSM-IV catatonia signs and diagnostic criteria was examined. Treatment response of catatonia was assessed in 173 patients who completed one-month trial with haloperidol (n=23), risperidone (n=93) or olanzapine (n=57).Results: Sixty-two patients (31%) endorsed at least one catatonia sign and 24 (12%) met DSM-IV criteria for catatonia. DSM-IV catatonia signs showed an excellent convergent validity (r>0.8) with other rating scales, and DSM-IV criteria showed moderate to fair concordance with other criteria (κ from 0.57 to 0.77). The total number of signs reflected catatonia severity and demonstrated excellent diagnostic performance against alternative diagnostic criteria. The presence of at least any three signs accurately identified patients with catatonia. Three catatonia domains were identified (hyperkinesia, volitional and hypokinesia), which showed a different association pattern with external variables. Overall, catatonia ratings were particularly related to both dyskinesia and disorganization symptoms and lacked diagnostic specificity for schizophrenia. Patients with catatonia responded well to antipsychotic medication irrespective of the type of antipsychotic drug used, although treatment response was dependent upon the remission of psychotic symptoms.Conclusions: These results may inform the DSM-V development on diagnosis and classification of catatonia, and indicate that catatonia signs and syndromes are highly responsive to antipsychotic drugs.

Criminal behavior among persons with schizophrenia in rural China - Corrected Proof

2010-01-13

Abstract: Objective: This study is to explore the prevalence and risk factors for self-reported criminal behavior among persons with schizophrenia in rural China.Methods: We used data from a 14-year prospective follow-up study (1994–2008) of criminal behavior among a cohort (N=510) of persons with schizophrenia in Xinjin County, China.Results: The rate of criminal behavior was 10.0% among persons with schizophrenia in a rural community during the follow-up period. Bivariate analyses showed that the risk of criminal behavior was significantly associated with being male, unmarried, previous violent behavior, homelessness, no family caregivers, and high scores on measures of total symptoms of illness. In multivariate logistic regression analyses being male and previous violent behavior were identified as independent predictors of increased criminal behavior in persons with schizophrenia in the follow-up period.Conclusions: Criminal behavior is a common phenomenon among patients with schizophrenia in rural China. The findings of the risk factors for criminal behavior should be considered in planning mental health interventions for high-risk patients and their families.

Pro-apoptotic Par-4 and dopamine D2 receptor in temporal cortex in schizophrenia, bipolar disorder and major depression - Corrected Proof

2010-01-13

Abstract: Although the etiology of schizophrenia remains unknown, diverse neuropathological evidence suggests a disorder of synaptic connectivity. Apoptosis is a form of cell death that helps determine synaptic circuitry during neurodevelopment and altered regulation of apoptosis has been implicated in schizophrenia. Prostate apoptosis response-4 (Par-4) is an upstream regulator of apoptosis preferentially localized to synapses. Brain Par-4 levels are upregulated in response to pro-apoptotic stimuli in rodent models and in patients with classic neurodegenerative diseases. Recently, Par-4 was also found to form a complex with the dopamine D2 receptor (D2DR) in competition with the calcium-binding protein calmodulin, implicating Par-4 as an important regulatory component in normal dopamine signaling. Interestingly, mutant mice with disrupted Par-4/D2DR interaction demonstrated depressive-like behaviors, suggesting a potential role for Par-4 in both depression and schizophrenia. In this study, Par-4, D2DR and calmodulin protein levels were measured using semiquantitative Western blotting in postmortem temporal cortex in subjects with schizophrenia, major depression and bipolar disorder. Compared to normal controls, mean Par-4 levels appeared slightly lower in schizophrenia and bipolar disorder. However, in major depression, Par-4 was decreased by 67% compared to normal controls. No differences were found between any groups for calmodulin or for the D2DR 48kDa band. The D2DR 98kDa band was lower by 50% in the schizophrenia compared to control groups. Changes in the Par-4/D2DR signaling pathway represent a novel mechanism that may link apoptotic and dopamine signaling pathways in major depression and schizophrenia.

Theory of Mind in first-episode schizophrenia patients: Correlations with cognition and personality traits - Corrected Proof

2010-01-11

Abstract: Introduction: There is substantial evidence for Theory of Mind (ToM) deficits in patients with schizophrenia. Many psychotic symptoms may best be understood in light of an impaired capacity to infer one's own and other persons' mental states and to relate those to executing behavior. The aim of our study was to investigate ToM abilities in first-episode schizophrenia patients and to analyze them in relation to neuropsychological and psychopathological functioning.Materials and methods: A modified Moving Shapes paradigm was used to assess ToM abilities in 23 first-episode patients with schizophrenia and 23 matched healthy controls. Participants had to describe animated triangles which moved (1) randomly, (2) goal-directed, or (3) in complex, socially interactive ways (ToM video sequences). Neuropsychological functioning, psychopathology, autistic and alexithymic features as well as empathetic abilities were correlated with ToM performance.Results: Compared to healthy controls, first-episode schizophrenia patients gave more incorrect descriptions and used less ToM-related vocabulary when responding to socially complex ToM video sequences. No group differences were revealed for videos with random movements. ToM abilities correlated significantly with positive symptoms, reasoning, verbal memory performance and verbal IQ, but not with empathetic abilities or autistic and alexithymic features. When controlling for reasoning, verbal memory performance and verbal IQ, the correctness of video descriptions was still significantly worse in schizophrenia patients.Discussion: The results of our study in first-episode schizophrenia patients underline recent findings on ToM deficits in the early course of schizophrenia. Only a moderate influence of neurocognitive deficits on ToM performance was observed. Impairment in ToM abilities seems to be predominantly independent of clinical state, alexithymia and empathy.

Genetic analysis of glutamate cysteine ligase modifier (GCLM) gene and schizophrenia in Han Chinese - Corrected Proof

2010-01-11

Recently, the glutamate cysteine ligase modifier (GCLM) subunit, which is a key enzyme in one of the GSH metabolic pathways, was reported by and to be significantly associated with schizophrenia in a European population. However, subsequent studies failed to replicate this finding in a Japanese population (). To further investigate the role of the GCLM locus in schizophrenia susceptibility, we studied three SNPs and haplotypes in the region of GCLM using Han Chinese case–control samples.

Social functioning in urban, predominantly African American, socially disadvantaged patients with first-episode nonaffective psychosis - Corrected Proof

Sandra M. Goulding, Lauren Franz, Erin Bergner, Michael T. Compton — 2010-01-11

Abstract: Background: Social functioning impairments develop and accumulate even prior to initial treatment-seeking for first-episode psychosis. This study, the first to examine social functioning in low-income, urban, predominantly African American first-episode patients: (1) assesses the internal consistency of Social Functioning Scale (SFS) subscales in this relatively unique sample; (2) identifies demographic and clinical variables that may be predictive of poor social functioning in this particular population; and (3) assesses changes in SFS scores in a subsample re-assessed six months after initial hospitalization.Methods: 109 participants (age, 23.1±4.7years; 76.1% male; 89.9% African American) hospitalized for a first episode of nonaffective psychosis in an urban, public-sector setting were administered the SFS along with other clinical research instruments. 34 (31.2%) returned for a follow-up clinical research assessment six months after baseline assessment. Associations between the variables of interest were analyzed utilizing independent samples Student's t-tests and Pearson correlations.Results: Associations were observed between social functioning domains and negative symptoms (r=−.21–−.32, p<.05), depressive symptoms (r=−.20–−.23, p<.05), and general psychopathology symptoms (r=−.23–−.24, p<.05). No significant differences were found in SFS subscale scores between baseline and six-month follow-up.Conclusions: Deficits in social functioning are meaningfully related to several domains of symptoms, and such deficits may be relatively stable in the early course of psychotic disorders. Such findings may inform development of psychosocial interventions targeting social functioning in first-episode patients.

The investigator and the IRB: A survey of depression and schizophrenia researchers - Corrected Proof

Bernard A. Fischer, Praveen George — 2010-01-11

Abstract: Despite the integral part Institutional Review Boards (IRBs) play in U.S. research, research on IRBs is lacking. This is especially true in the area of mental health investigator–IRB interactions. It was hypothesized that schizophrenia researchers would have a different experience with IRBs as compared to depression researchers. This would include longer turn-around time and fewer protocols approved on first submission. It was also thought that schizophrenia researchers would be more hesitant to submit ethically complex protocols for IRB review. 396 NIH-funded schizophrenia and depression investigators were invited to participate in a survey study on IRBs. 108 usable responses were returned, 45 of which were from schizophrenia researchers.Schizophrenia researchers were significantly less likely to submit ethically complex protocols for IRB review than depression researchers even when controlling for academic rank, years of research experience, type of research done, and the need to submit to multiple IRBs. However, there was no significant difference between researcher groups in IRB review turn-around time or initial approval rates. As a group, respondents found IRB submission paperwork burdensome but necessary and were almost evenly split as to whether IRB comments were helpful (54.8%) or not (45.2%). Time to initial review was 3weeks or longer for most respondents. 94.4% agreed IRBs should enforce subject privacy and 68.2% agreed they should monitor conflict of interest, but only 37.% agreed IRBs should review study design. Conclusions are that 1. the population studied may have profound impacts on the type of protocols submitted to IRBs even within the field of mental health, 2. IRBs may not draw as large a distinction between depression and schizophrenia protocols as researchers believe, and 3. facilitating IRB review by eliminating evaluation of design may be possible if the protocol has already been vetted by a credible funding agency (such as the U.S. National Institutes of Health).

The synthetic cannabinoid Spice as a trigger for an acute exacerbation of cannabis induced recurrent psychotic episodes - Corrected Proof

2010-01-08

It is established that cannabis consumption cannot only trigger transient psychotic episodes but also predisposes for the development of lasting paranoid schizophrenia in a dose dependent manner (). Patients with a positive family history are at a higher risk for such drug induced schizophrenic disorders (). Cross-reactions between different drugs to trigger recurrence of schizophrenic episodes are rare (). We present the case of a 25year old man who had a history of cannabis induced recurrent psychotic episodes and an acute reactivation of symptoms after abuse of the synthetic cannabinoid “Spice”.

Cognitive remediation therapy in schizophrenia: Cost-effectiveness analysis - Corrected Proof

2010-01-07

Abstract: Purpose: There is a lack of evidence on the cost-effectiveness of cognitive remediation therapy (CRT).Methods: Randomised controlled trial comparing usual care plus CRT with usual care alone. Participants had a diagnosis of schizophrenia and cognitive and social functioning difficulties. Health/social care and societal costs were estimated at 14weeks (time 2) and 40weeks (time 3) after randomisation. The outcome, proportion of participants improving their working memory since baseline, was combined with costs to explore cost-effectiveness.Results: 85 participants were recruited. There were no differences in total health/social care or societal costs between the two groups at either time 2 or time 3. An additional 21% of participants in the CRT group improved their working memory at both follow-ups. When placing these cost and outcomes in hypothetical scenarios concerning how much policy-makers would pay for another 1% of participants improving their working memory, there was more than an 80% chance that CRT would be cost-effective compared to usual care; at time 3, the likelihood of cost-effectiveness peaked at 30% even for investments up to £5000.Conclusions: CRT can improve memory among people with schizophrenia and cognitive deficits at no additional cost. Although cost-effective in the short term, CRT may have limited potential to save costs in the medium term because it could increase take up of services. This could confer important longer term benefits for the patient group examined here, in terms of improved social functioning and less reliance on services. This can only be ascertained through longer follow-up.

Do atypical antipsychotic drugs reduce the risk of ischemic heart disease and mortality? Possible role of 5-HT2A receptor blockade - Corrected Proof

Hilario Blasco-Fontecilla, Enrique Baca-Garcia, Jose de Leon — 2010-01-07

Abstract: A recent Finnish study reported that long-term cumulative exposure to any antipsychotic treatment was related to lower mortality than was no drug exposure. We hypothesize that the antipsychotic 5-HT2A receptor blockade might protect from ischemic heart disease and buffer the deleterious metabolic effects of antipsychotics. The 5-HT2A receptor may be involved in vascular smooth muscle contraction, coronary artery spasms, platelet aggregation and thrombus formation. 5-HT2A receptor blockade might protect from ischemic heart disease by decreasing platelet aggregation and myocardium hypertrophy. Long-term follow-up studies are needed to clearly establish the long-term contribution of the various antipsychotic drugs to ischemic heart disease, and to explore our hypothesis that 5-HT2A receptor blockade may be protective for cardiovascular disease.

Attenuated positive symptoms of psychosis in adolescents with chromosome 22q11.2 deletion syndrome - Corrected Proof

Joel Stoddard, Tara Niendam, Robert Hendren, Cameron Carter, Tony J. Simon — 2010-01-07

Abstract: Thirty percent of individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) develop a psychotic disorder, particularly schizophrenia. We assessed attenuated positive, negative and disorganized symptoms of psychosis and clinical-high-risk syndromes in 20 adolescents with 22q11.2DS (median age 15.1years) using the Structured Interview for Prodromal Symptoms (SIPS). Two participants met criteria for the Attenuated Positive Symptom Syndrome, while nine participants (45%) experienced positive symptoms rated in the “moderate” to “severe and psychotic” range on the SIPS. Almost all presented with moderate to severe symptoms in the negative, disorganized, and general symptom domains.

White matter abnormalities in first-episode schizophrenia: A combined structural MRI and DTI study - Corrected Proof

2010-01-07

Abstract: This study examined white matter volume change and integrity jointly in patients with first-episode schizophrenia using an empirically derived region of interest approach and novel Diffusion Tensor Imaging (DTI) geometric indices. Structural images from 103 individuals comprising of 39 patients with first-episode schizophrenia and 64 healthy controls were examined for regions of white matter volume change using voxel-based morphometry (VBM). These regions were then further interrogated for group differences employing geometric indices in addition to fractional anisotropy (FA).VBM analyses revealed that patients with first-episode schizophrenia had lower white matter volume in the right temporal–occipital region (p<0.005) corresponding to the inferior longitudinal fasciculus. Further analyses of diffusion anisotropy in the right temporal–occipital region revealed lower planar anisotropy, and higher linear anisotropy (p=0.012) in patients. FA in the implicated region was also found to be correlated with severity of delusions (r=0.47, p=0.004).We confirmed previous findings of lower white matter volume in the region of inferior longitudinal fasciculus. The presence of changes in geometric diffusion indices in the implicated white matter region suggested that pathophysiological processes which underlie cerebral white matter volume reduction may not be reflected by changes in FA. Further research is needed to better understand the nature of these white matter changes and its progression in schizophrenia over time.

Reasons for smoking among individuals with schizophrenia - Corrected Proof

2010-01-06

As compared to smokers in the general population, smokers with schizophrenia have increased smoking rates (), increased nicotine dependence (), and reduced success in smoking cessation (). While states that studying motives for smoking are important because smoking patterns are heterogeneous, studies examining motives to smoke in schizophrenia have been limited by the assessment measures with poor psychometric properties. The primary objective of this study was to examine differences between motives to smoke among smokers with and without schizophrenia as measured by the WISDM-68 scale ().

Avoidant personality disorder symptoms in first-degree relatives of schizophrenia patients predict performance on neurocognitive measures: The UCLA family study - Corrected Proof

2010-01-06

Abstract: Whether avoidant personality disorder symptoms are related to neurocognitive impairments that aggregate in relatives of schizophrenics is unknown. We report the relationship between avoidant personality disorder symptoms and neurocognitive performance in the first-degree relatives of probands with schizophrenia.367 first-degree relatives of probands with schizophrenia and 245 relatives of community controls were interviewed for the presence of avoidant personality symptoms and symptoms of paranoid and schizotypal personality disorders and administered neurocognitive measures. Relationships between neurocognitive measures and avoidant symptoms were analyzed using linear mixed models.Avoidant dimensional scores predicted performance on the span of apprehension (SPAN), 3–7 Continuous Performance Test (3–7 CPT), and Trail Making Test (TMT-B) in schizophrenia relatives. These relationships remained significant on the SPAN even after adjustment for paranoid or schizotypal dimensional scores and on the TMT-B after adjustment for paranoid dimensional scores. Moreover, in a second set of analyses comparing schizophrenia relatives to controls there were significant or trending differences in the degree of the relationship between avoidant symptoms and each of these neurocognitive measures even after adjustments for paranoid and schizotypal dimensional scores. The substantial correlation between avoidant and schizotypal symptoms suggests that these personality disorders are not independent.Avoidant and in some cases schizotypal dimensional scores are significant predictors of variability in these neurocognitive measures. In all analyses, higher levels of avoidant symptoms were associated with worse performance on the neurocognitive measures in relatives of schizophrenia probands. These results support the hypothesis that avoidant personality disorder may be a schizophrenia spectrum phenotype.

The interaction of working memory and emotion in persons clinically at risk for psychosis: An fMRI pilot study - Corrected Proof

2010-01-06

Abstract: Subtle emotional and cognitive dysfunctions may already be apparent in individuals at risk for psychosis. However, there is a paucity of research on the neural correlates of the interaction of both domains. It remains unclear whether those correlates are already dysfunctional before a transition to psychosis.We used functional magnetic resonance imaging to examine the interaction of working memory and emotion in 12 persons clinically at high risk for psychosis (CHR) and 12 healthy subjects individually matched for age, gender and parental education. Participants performed an n-back task while negative or neutral emotion was induced by olfactory stimulation.Although healthy and psychosis-prone subjects did not differ in their working memory performance or the evaluation of the induced emotion, decreased activations were found in CHR subjects in the superior parietal lobe and the precuneus during working memory and in the insula during emotion induction. Looking at the interaction, CHR subjects, showed decreased activation in the right superior temporal gyrus, which correlated negatively with psychopathological scores. Decreased activation was also found in the thalamus. However, an increase of activation emerged in several cerebellar regions.Dysfunctions in areas associated with controlling whether incoming information is linked to emotional content and in the integration of multimodal information might lead to compensatory activations of cerebellar regions known to be involved in olfactory and working memory processes. Our study underlines that cerebral dysfunctions related to cognitive and emotional processes, as well as their interaction, can emerge in persons with CHR, even in absence of behavioral differences.

A follow-up MRI study of the superior temporal subregions in schizotypal disorder and first-episode schizophrenia - Corrected Proof

2010-01-05

Abstract: While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the superior temporal gyrus (STG) during the early phases of schizophrenia, it remains unknown whether patients with schizotypal features exhibit similar STG changes. In this study, longitudinal MRI data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The volumes of the STG and its subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT), rostral STG, and caudal STG] were measured on baseline and follow-up (mean: 2.7years) scans and were compared across groups. At the baseline, both the schizophrenia and schizotypal patients had smaller left PT and left caudal STG than the controls. In a longitudinal comparison, the schizophrenia patients showed significant gray matter reduction of the STG over time (left: −2.8%/year; right: −1.5%/year) compared with the schizotypal patients (left: −0.6%/year; right: −0.3%/year) and controls (left: 0.0%/year; right: −0.1%/year) without a prominent effect of subregion or type of antipsychotic (typical/atypical). In the schizophrenia patients, greater annual volume reductions of the left PP and right PT were correlated with less improvement of positive psychotic symptoms. A higher cumulative dose of antipsychotics during follow-up in schizophrenia was significantly correlated with less severe gray matter reductions in the left PT and bilateral caudal STG. Our findings suggest that the left posterior STG subregions are commonly reduced in diseases of the schizophrenia spectrum; whereas, schizophrenia patients exhibit further progressive STG changes associated with overt psychosis in the early years of the illness.

Emotional experience predicts social adjustment independent of neurocognition and social cognition in schizophrenia - Corrected Proof

Ivy F. Tso, Tyler B. Grove, Stephan F. Taylor — 2010-01-05

Abstract: Background: Emotional abnormalities are prominent features of schizophrenia. While the capacity for emotions is essential to social adaptation, little is known about the role of emotional experience in the social dysfunction observed in schizophrenia.Objective: This study examined the contribution of emotional experience, neurocognition, and social cognition to functional outcome in schizophrenia.Method: Self-reported emotional experience (anhedonia, affect intensity, and emotion frequency) was assessed in 33 stable schizophrenic/schizoaffective patients and 33 healthy controls. Symptoms, neurocognition, social cognition, and functional outcome were also assessed.Results: Patients and controls exhibited good internal reliability on all self-report scales, except for negative affect intensity. Patients reported equally intense but less frequent positive emotions, more intense and frequent negative emotions, and more anhedonia. Results of hierarchical regression analyses showed that emotional experience accounted for significant amounts of variance of social adjustment independent of neurocognition and social cognition.Conclusion: These data show that emotional experience can be reliably assessed and is an important determinant of functional outcome in schizophrenia.

Antibodies to measles in individuals with recent onset psychosis - Corrected Proof

2010-01-05

Abstract: Background: Measles virus is a highly prevalent neurotropic virus capable of causing persistent infections within the central nervous system.Methods: We measured IgG class antibodies to measles in 820 individuals including 138 with recent onset psychosis, 378 with persistent schizophrenia, and 304 non-psychiatric controls.Levels of antibodies among the groups were compared by bivariate and by multivariate analyses and correlated with clinical and demographic variables.Results: The level of measles antibodies in individuals with a recent onset of psychosis was greater than the level of antibodies in individuals with persistent schizophrenia or individuals without a history of a psychiatric disorder (p<.00001). The level of measles antibodies in the individuals with persistent schizophrenia was greater than the level of measles antibodies in the controls (p<.001). Recent onset of psychosis was associated with having elevated levels of measles antibodies, defined as the 90th percentile of the levels of the controls, with an odds ratio of 8.0 (95% CI 4.6, 14.0); persistent schizophrenia was associated with having this level with an odds ratio of 2.3 (95% CI 1.4, 3.7). Within the psychiatric groups, measles antibody levels were associated with age, race, and current treatment with the antipsychotic medication, olanzapine.Conclusions: The reasons for elevated levels of measles antibodies in the psychiatric groups are not known with certainty and should be studied in prospective investigations.

Smoking initiation and schizophrenia: A replication study in a Chinese Han population - Corrected Proof

2009-12-18

Abstract: Schizophrenia is associated with a greater probability of ever smoking daily and with higher rates of initiation of daily smoking after age 20 in Caucasian populations. The aims of the current study were to replicate that schizophrenia is associated with smoking and higher risk of initiating daily smoking before schizophrenia starts among a large sample of male Chinese patients. A survival analysis of onset age for daily smoking compared 776 DSM-IV male inpatients with schizophrenia to 560 male controls. The results showed that the cumulative hazard curves for age of smoking initiation in schizophrenia and controls were significantly different (p<0.001), even after controlling for education (p<0.001). After excluding the patients who started smoking within 5years before schizophrenia started, the cumulative hazard curve for schizophrenia was significantly different from ever-smoked controls (p<0.001), even after adjusting for education (p<0.001). These findings suggest that schizophrenic patients have a higher risk of starting daily smoking suggesting that vulnerability to schizophrenia may be associated with a higher risk of becoming a daily smoker.

Neural correlates of reward processing in schizophrenia — Relationship to apathy and depression - Corrected Proof

2009-12-14

Abstract: The present study employs a new framework to categorise the heterogeneous findings on the relationship between impaired reward processing and negative and affective symptoms of schizophrenia. Based on previous behavioural and neuroimaging studies we postulate that “wanting” (i.e. anticipation) of a reward is specifically related to apathy, whereas “liking” (i.e. hedonic impact) is related to anhedonia and depression — symptoms commonly observed in schizophrenia. Fifteen patients with schizophrenia or schizoaffective disorder treated with atypical antipsychotic drugs and fifteen healthy controls performed a probabilistic monetary incentive delay task while undergoing functional magnetic resonance imaging. At the group level we found no significant differences between patients and controls in neural activation during anticipation or receipt of a reward. However, in patients with schizophrenia specific relationships between ventral–striatal activation and symptoms were observed. Ventral–striatal activation during reward anticipation was negatively correlated with apathy, while activation during receipt of reward was negatively correlated with severity of depressive symptoms. These results suggest that the link between negative symptoms and reward anticipation might specifically relate to apathy, i.e. a lack of motivation and drive. Impaired hedonic reward processing might contribute to the development of depressive symptoms in patients with schizophrenia, but it is not directly associated with self-rated anhedonia. These results indicate the necessity of more specifically differentiating negative and affective symptoms in schizophrenia in order to understand the role of the reward system in their pathogenesis.

Developmental instability in social anhedonia: An examination of minor physical anomalies and clinical characteristics - Corrected Proof

Jack J. Blanchard, Minu Aghevli, Amy Wilson, Marsha Sargeant — 2009-11-30

Abstract: Developmental instability (DI) refers to the inability of the developing brain to buffer the effects of genetic and environmental insults. This concept has been invoked to better understand how fetal brain development goes awry in schizophrenia and related spectrum disorders. This study examined one marker of DI, minor physical anomalies (MPAs), and its association with a putative indicator of schizotypy, the trait of social anhedonia. MPAs and clinical symptoms were assessed within a community sample of psychometrically identified individuals high in social anhedonia and a matched group of healthy controls. Results indicated that, compared to the controls, MPAs were elevated in the social anhedonia group. Additionally, within the social anhedonia group, MPAs were significantly correlated with clinical ratings of schizoid personality disorder characteristics and also showed strong associations with schizotypal personality disorder ratings. These findings indicate a relationship between developmental anomalies and negative schizotypy and suggest that, when combined with psychometrically identified risk, the presence of MPAs may further elevate the probability of clinical manifestations of schizophrenia-spectrum characteristics.

Deficit schizophrenia does not co-aggregate with high nailfold plexus visibility - Corrected Proof

2009-11-30

Deficit status and high levels of nailfold plexus visibility (NPV) are two traits used to designate putative subtypes of schizophrenia. Both traits are described as occurring in a substantial minority of patients with schizophrenia, and as identifying more familial cases characterized by an excess of negative symptoms and poor prognosis (). Given the similarities in these descriptions, we speculated that assessments for deficit schizophrenia (DS) and high NPV might be different measures of the same underlying construct. In keeping with this hypothesis, we found that scales of negative symptoms including only the items consistent with DS did a better job of distinguishing high NPV from low NPV schizophrenia subjects than did standard negative symptoms scales ().

Superior size–weight illusion performance in patients with schizophrenia: Evidence for deficits in forward models - Corrected Proof

2009-11-20

Abstract: When non-psychiatric individuals compare the weights of two similar objects of identical mass, but of different sizes, the smaller object is often perceived as substantially heavier. This size–weight illusion (SWI) is thought to be generated by a violation of the common expectation that the large object will be heavier, possibly via a mismatch between an efference copy of the movement and the actual sensory feedback received. As previous research suggests that patients with schizophrenia have deficits in forward model/efference copy mechanisms, we hypothesized that schizophrenic patients would show a reduced SWI. The current study compared the strength of the SWI in schizophrenic patients to matched non-psychiatric participants; weight discrimination for same-sized objects was also assessed. We found a reduced SWI for schizophrenic patients, which resulted in better (more veridical) weight discrimination performance on illusion trials compared to non-psychiatric individuals. This difference in the strength of the SWI persisted when groups were matched for weight discrimination performance. The current findings are consistent with a dysfunctional forward model mechanism in this population. Future studies to elucidate the locus of this impairment using variations on the current study are also proposed.

Age at onset in Canadian Schizophrenia patients: Admixture analysis - Corrected Proof

2009-11-18

Abstract: Despite considerable amount of data from several studies, none of the thresholds used to define age at onset (AAO) in schizophrenia have been validated. The aim of this study is to assess the presence of different homogenous subgroups in schizophrenics based on the age at onset. Admixture analysis was applied to identify model(s) of separate normal distributions of AAO characterized by different means, variances and population proportions. This helped us in identifying different subgroups in our sample of 440 schizophrenia patients.The model that best fits the observed AAO distribution was a mixture of two Gaussian distributions with an ideal cut-off point. The mean ages estimated in this model were 18.01years (SD=2.46) and 26.07years (SD=8.11). The cut-off point was 22years.These results suggest the existence of two homogeneous subgroups in schizophrenia patients. This may have important implications for searching schizophrenia susceptibility factors.

Anticipated, on-line and remembered positive experience in schizophrenia - Corrected Proof

2009-11-11

Abstract: Background: Three temporal stages in the evaluation of positive affect can be identified: anticipation, experience (hedonia) and memory. In schizophrenia, despite research indicating non-impaired hedonic capacities, little is known about anticipation and memory of positive affect. Moreover, the role of positive affect evaluations on motivation has rarely been studied in schizophrenia.Method: Seventy individuals with schizophrenia and 35 non-patient control participants completed an evocative emotional task consisting of pictures and sounds. Following each presentation, participants rated their hedonic experience. Ratings of pre-test anticipated and post-test remembered pleasures were also obtained. Finally, explicit motivation to repeat the task was assessed.Results: Compared to control participants, schizophrenia participants demonstrated similar levels of anticipation, hedonia and motivation, as well as significantly increased remembered pleasure. In schizophrenia, affective processes had lower correlations with motivation than in controls, and only remembered pleasure predicted motivation. Moreover, the predictive value of hedonia was significantly lower in schizophrenia.Conclusions: The affective and cognitive processes involved in the anticipation, experience and memory of positive affective events showed no deficit, and to the contrary, immediately remembered pleasure was higher in schizophrenia. However, important deficits resided in the inter-connectivity between affective evaluations and motivational processes. The major deficit in schizophrenia participants' reward system was not in hedonic experiences but in the translation of pleasurable experiences into motivational states.

The psychiatric symptomatology of deficit schizophrenia: A meta-analysis - Corrected Proof

Alex S. Cohen, Laura A. Brown, Kyle S. Minor — 2009-11-04

Abstract: A relatively large literature has emerged supporting the notion that the deficit syndrome reflects a distinct illness within schizophrenia. One topic that has received limited attention is how deficit schizophrenia differs from nondeficit schizophrenia in terms of psychiatric symptomatology. The present study conducted a meta-analysis of 47 published studies to compare deficit and nondeficit patients in severity of positive, disorganization, negative, mood and total psychiatric symptoms. The patient groups did not differ in terms of positive or total psychiatric symptoms but deficit patients showed less severe mood symptoms and slightly more severe disorganization symptoms. Not surprisingly, deficit patients had much more severe negative symptoms. These results are discussed in terms of the construct validity of the deficit syndrome and the larger heterogeneity of schizophrenia. Additionally, diagnostic issues regarding the deficit syndrome are considered.

Executive function in schizophrenia: Influence of substance use disorder history - Corrected Proof

2009-10-26

Abstract: Cognitive function in schizophrenia has been associated with different sociodemographic and clinical variables. Substance use disorder (SUD) history has also been associated with cognition in schizophrenia; however, contradictory results have been found regarding its influence on cognitive function. Our aim was to study the relationship between executive function and a) age, b) duration of illness, c) number of psychotic episodes, d) positive symptoms, and e) negative symptoms, in a sample of schizophrenic patients, and secondly to study whether these relationships persisted after stratification of the sample according to the presence or absence of SUD history. A final sample of 203 schizophrenic patients were evaluated for psychotic symptoms using the PANSS, and assessed using a neuropsychological battery to calculate a composite executive function score. Linear regression analyses were performed, with this executive score as the dependent variable, and age, duration of illness, number of psychotic episodes, positive PANSS score and negative PANSS score as independent variables. For the total sample, the regression model showed three variables to be significant predictors of the executive score: age (p=0.004), number of episodes (p=0.027), and PANSS negative score (p=0.003). However, once the sample was stratified, the regression model showed age (p=0.011) and number of episodes (p=0.011) to be predictor variables for the executive score in the group of schizophrenic patients with SUD history, while age (p=0.028) and PANSS negative score (p=0.006) were predictors in the group of schizophrenic patients without such history. These findings highlight the importance of considering SUD history in studies of cognitive function in schizophrenia.

A comparison of insight into clinical symptoms versus insight into neuro-cognitive symptoms in schizophrenia - Corrected Proof

Alice Medalia, Julie Thysen — 2009-10-19

Abstract: Background: Schizophrenia is associated with neuropsychological deficits that have been linked to poor functional outcome. To address this problem, pharmacologic and behavioral treatments are being developed for cognitive impairments, but they will not be well utilized if people with schizophrenia do not perceive a need for treatment.Aims: This study compared whether people with schizophrenia have a similar degree of insight into neuro-cognitive symptoms as clinical symptoms, and whether neuro-cognitive and clinical symptoms are similarly related to degree of insight into these two aspects of the illness.Method: Seventy-one patients with schizophrenia were administered measures of clinical and neuro-cognitive status as well as clinician rated measures of insight into clinical and neuro-cognitive symptoms.Results: Patients had significantly less insight into their neuro-cognitive symptoms than their clinical symptoms. On average, patients had good insight into clinical symptoms and partial insight into neuro-cognitive symptoms. Neuropsychological variables were related to insight into clinical symptoms, but not insight into neuro-cognition. Clinical variables were not significantly related to either type of insight.Conclusions: Insight is not a unitary concept and the differences between awareness of neuro-cognition and awareness of clinical symptoms suggest that they have to be addressed separately in treatment. Specific education about cognitive symptoms may be necessary to improve awareness of this aspect of the schizophrenia.

A reliable digital photomicroscopic method of nailfold plexus visibility assessment in schizophrenia - Corrected Proof

Susan K. Miranowski, John P. Vuchetich — 2009-10-05

Abstract: High nailfold plexus visibility (NPV) is a trait identifying a putative endophenotype for schizophrenia. We describe a new method of NPV assessment using computer storage of digital photomicrographs. We performed a reliability study of this method using 40 subjects. The intraclass correlation between two blinded raters was 0.83. The kappa coefficient for a 3 level division of NPV was 0.72, while the kappa for reliability at the cutting score for designating high NPV was 0.94. This method provides immediate image quality feedback, ease of reliability assessment, the option of blinded ratings, and a method for continuous enhancement of rating consensus.

Family context and duration of untreated psychosis (DUP): Results from the Sao Paulo Study - Corrected Proof

2009-09-23

Abstract: Background: Duration of untreated psychosis (DUP) depends on several factors, including socio-demographic, socioeconomic, clinical and contextual circumstances, such as availability of mental health services. Living arrangements may also play a role, especially in low- and middle-income countries, where most people who develop psychosis live with their relatives.Methods: Population-based study of first-episode psychosis in São Paulo, Brazil. Participants were aged 18–64years, lived in a defined geographic area of the city and had a first contact in life with mental health services due to a psychotic episode. Duration of untreated psychosis was defined as the period between onset of first psychotic symptom and first contact with health service due to psychosis. The median DUP was used to classify participants into short and long DUP. Psychopathology, social adjustment and psychiatric diagnoses were made with standardized assessments. Type of service sought and living arrangements were examined.Results: Two hundred participants were included (52% women, 61% non-affective psychoses). The median DUP was 4.1weeks (inter-quartile range: 1.9–11.4), and was shorter for affective psychoses. Most participants had their first contact with psychiatric emergency services. Those who did not live with a relative (children older than 18years, parents, partner) were more likely to present long DUP (OR: 2.63; 95%CI: 0.98–7.04); p=0.05).Conclusion: The DUP in São Paulo was shorter than expected. Living arrangements may play an important role in shortening the DUP in urban centres of low- and middle income countries that have a network of mental health services.

Novel immune response to gluten in individuals with schizophrenia - Corrected Proof

2009-09-14

Abstract: A link between celiac disease and schizophrenia has been postulated for several years, based primarily on reports of elevated levels of antibody to gliadin in patients. We sought to examine the proposed connection between schizophrenia and celiac disease by characterizing the molecular specificity and mechanism of the anti-gliadin immune response in a subset of individuals with schizophrenia. Blood samples from individuals with schizophrenia and elevated anti-gliadin antibody titer were examined for celiac disease-associated biomarkers, including antibodies to transglutaminase 2 (TG2) enzyme and deamidated gliadin peptides, as well as the HLA-DQ2 and -DQ8 MHC genes. The anti-gliadin antibody response was further characterized through examination of reactivity towards chromatographically separated gluten proteins. Target proteins of interest were identified by peptide mass mapping. In contrast to celiac disease patients, an association between the anti-gliadin immune response and anti-TG2 antibody or HLA-DQ2 and -DQ8 markers was not found in individuals with schizophrenia. In addition, the majority of individuals with schizophrenia and anti-gliadin antibody did not exhibit antibody reactivity to deamidated gliadin peptides. Further characterization of the antibody specificity revealed preferential reactivity towards different gluten proteins in the schizophrenia and celiac disease groups. These findings indicate that the anti-gliadin immune response in schizophrenia has a different antigenic specificity from that in celiac disease and is independent of the action of transglutaminase enzyme and HLA-DQ2/DQ8. Meanwhile, the presence of elevated levels of antibodies to specific gluten proteins points to shared immunologic abnormalities in a subset of schizophrenia patients. Further characterization and understanding of the immune response to gluten in schizophrenia may provide novel insights into the etiopathogenesis of specific disease phenotypes.