Schizophrenia Research

Editorial Board

2012-05-01

Meeting report: The Schizophrenia International Research Society (SIRS) South America Conference (August 5–7, 2011)

2012-03-29

Abstract: On August 5–7, 2011, São Paulo was home to the first regional meeting of the Schizophrenia International Research Society (SIRS). Over 400 people from many countries attended the activities and contributed with around 200 submissions for oral and poster presentations. This article summarizes the data presented during the meeting, with an emphasis on the plenary talks and sessions for short oral presentations. For information on the poster presentations, readers are referred to the special issue of Revista de Psiquiatria Clínica (Brazil) dedicated to the conference (available at: http://www.hcnet.usp.br/ipq/revista/vol38/s1/).

Genetic and functional analysis of the gene encoding neurogranin in schizophrenia

2012-02-06

Abstract: Objectives: Schizophrenia is a highly heritable disorder, but many aspects of its etiology and pathophysiology remain poorly understood. Recently, a SNP rs12807809 located upstream of the neurogranin (NRGN) gene achieved genome-wide significance in this disorder.Methods: In order to find the causal variants of NRGN gene in schizophrenia, we searched for genetic variants in the promoter region and all the exons (including both UTR ends and rs12807809) using direct sequencing in a sample of patients with schizophrenia (n=346) and non-psychotic controls (n=345), both being Han Chinese from Taiwan, and conducted an association and functional study.Results: We identified 7 common polymorphisms in the NRGN gene. SNP and haplotype-based analyses displayed no associations with schizophrenia. Additionally, we identified 5 rare variants in 6 out of 346 patients, including 3 rare variants located at the promoter region (g.-620A>G, g.-578C>G, and g.-344G>A) and 2 rare variants located at 5′ UTR (c.-74C>G, and c.-41G>A). No rare variants were found in the control subjects. The results of the reporter gene assay demonstrated that the regulatory activity of construct containing g.-620G, g.-578G, g.-344A, c.-74G, and c.-41A was significantly lower as compared to the wild type construct (P<0.01 for g.-578G; P<0.001 for the other constructs). In silico analysis also demonstrated their influences on the regulatory function of NRGN gene.Conclusions: Our study lends support to the hypothesis of multiple rare mutations in schizophrenia, and provides genetic clues that indicate the involvement of NRGN in this disorder.

Genetic and functional analyses of the gene encoding synaptophysin in schizophrenia

2012-02-20

Abstract: Objectives: Synaptophysin (SYP) has been shown to be critical for regulating neurotransmitter release and synaptic plasticity, a process thought to be disrupted in schizophrenia. In addition, abnormal SYP expression in different brain regions has been linked to this disorder in postmortem brain studies. We investigated the involvement of the SYP gene in the susceptibility to schizophrenia.Methods: We searched for genetic variants in the promoter region, all exons, and both UTR ends of the SYP gene using direct sequencing in a sample of patients with schizophrenia (n=586) and non-psychotic controls (n=576), both being Han Chinese from Taiwan, and conducted an association and functional study.Results: We identified 2 common SNPs (c.*4+271A>G and c.*4+565T>C) in the SYP gene. SNP and haplotype-based analyses displayed no associations with schizophrenia. In addition, we identified 6 rare variants in 7 out of 586 patients, including 1 variant (g.-511T>C) located at the promoter region, 1 synonymous (A104A) and 2 missense variants (G293A and A324T) located at the exonic regions, and 2 variants (c.*31G>A and c.*1001G>T) located at the 3′UTR. No rare variants were found in the control subjects. The results of the reporter gene assay demonstrated the influence of g.-511T>C and c.*1001G>T on the regulatory function of the SYP gene, while that the influence of c.*31G>A may be tolerated. In silico analysis demonstrated the functional relevance of other rare variants.Conclusion: Our study lends support to the hypothesis of multiple rare mutations in schizophrenia, and provides genetic clues that indicate the involvement of SYP in this disorder.

Cortical gyrification in velo-cardio-facial (22q11.2 deletion) syndrome: A longitudinal study

2012-02-24

Abstract: Introduction: Velo-cardio-facial syndrome (VCFS) has been identified as an important risk factor for psychoses, with up to 32% of individuals with VCFS developing a psychotic illness. Individuals with VCFS thus form a unique group to identify and explore early symptoms and biological correlates of psychosis. In this study, we examined if cortical gyrification pattern, i.e. gyrification index (GI) can be a potential neurobiological marker for psychosis.Method: GIs of 91 individuals with VCFS were compared with 29 siblings and 54 controls. Further, 58 participants with VCFS, 21 siblings and 18 normal controls were followed up after 3years and longitudinal changes in GI were compared. Additionally, we also correlated longitudinal changes in GI in individuals with VCFS with prodromal symptoms of psychosis on the Scale of Prodromal Symptoms (SOPS).Result: Individuals with VCFS had significantly lower GIs as compared to their siblings and normal controls. Longitudinal examination of GI did not reveal any significant group–time interactions between the three groups. Further, longitudinal change in GI scores in the VCFS group was negatively correlated with positive prodromal symptoms, with the left occipital region reaching statistical significance.Conclusion: The study confirms previous reports that individuals with VCFS have reduced cortical folding as compared to normal controls. However over a period of three years, there is no difference in the rate of change of GI among both individuals with VCFS and normal controls. Finally, our results suggest that neuroanatomical alterations in areas underlying visual processing may be an early marker for psychosis.

Association between schizophrenia and genetic variation in DCC: A case–control study

Alanna Grant, Ferid Fathalli, Guy Rouleau, Ridha Joober, Cecilia Flores — 2012-03-14

Abstract: Schizophrenia is a highly heritable neurodevelopmental disorder associated with alterations in synaptic connectivity. Deleted in colorectal cancer (DCC), a receptor for the guidance cue netrin-1, plays a pivotal role in organizing neuronal circuitry by guiding growing axons and dendrites to their correct targets and by influencing synaptic connectivity. Results from experiments we previously conducted in dcc-heterozygous mice show that DCC plays a critical role in the developmental organization of the mesocorticolimbic dopamine (DA) circuitry. Furthermore we have shown that reduced expression of DCC during development and/or throughout life confers resilience to the development of schizophrenia-like DA and behavioural abnormalities. Importantly, this “protective” phenotype only emerges after puberty. Here we assess whether DCC may contribute to the risk of schizophrenia. We examined single nucleotide polymorphisms (SNPs) located in the DCC gene for association with schizophrenia using a case–control sample consisting of 556 unrelated schizophrenic patients and 208 healthy controls. We found one SNP, rs2270954, to be nominally associated with schizophrenia; patients were less likely to be heterozygous at this locus and more likely to be homozygous for the minor allele (χ2=9.84, df=2, nominal p=0.0071). Intriguingly, this SNP is located within the 3′ untranslated region, an area known to contain a number of regulatory sequences that determine the stability and translation efficacy of mRNA. These results, together with our previous findings from studies in rodents, point at DCC as a promising novel candidate gene that may contribute to the genetic basis behind individual differences in susceptibility to schizophrenia.

Behavioral effects of non-viral mediated RNA interference of synapsin II in the medial prefrontal cortex of the rat

2012-02-20

Abstract: Synapsin II is a synaptic vesicle-associated phosphoprotein that has been implicated in the pathophysiology of schizophrenia. Researchers have demonstrated reductions in synapsin II mRNA and protein in post-mortem prefrontal cortex and hippocampus samples from patients with schizophrenia. Synapsin II protein expression has been shown to be regulated by dopamine D1 and D2 receptor activation. Furthermore, behavioral testing of the synapsin II knockout mouse has revealed a schizophrenic-like behavioral phenotype in this mutant strain, suggesting a relationship between dysregulated and/or reduced synapsin II and schizophrenia. However, it remains unknown the specific regions of the brain of which perturbations in synapsin II play a role in the pathophysiology of this disease. The aim of this project was to evaluate animals with a selective knock-down of synapsin II in the medial prefrontal cortex through the use of siRNA technology. Two weeks after continuous infusion of synapsin II siRNAs, animals were examined for the presence of a schizophrenic-like behavioral phenotype. Our results reveal that rats with selective reductions in medial prefrontal cortical synapsin II demonstrate deficits in sensorimotor gating (prepulse inhibition), hyperlocomotion, and reduced social behavior. These results implicate a role for decreased medial prefrontal cortical synapsin II levels in the pathophysiology of schizophrenia and the mechanisms of aberrant prefrontal cortical circuitry, and suggest that increasing synapsin II levels in the medial prefrontal cortex may potentially serve as a novel therapeutic target for this devastating disorder.

Cannabis use and anticipatory pleasure as reported by subjects with early psychosis and community controls

Clifford M. Cassidy, Martin Lepage, Philippe-Olivier Harvey, Ashok Malla — 2012-03-21

Abstract: Background: There is evidence of decreased pleasure and deficits in the anticipation of reward in both psychotic illness and drug addiction. Individuals with low anticipatory pleasure may preferentially engage in behaviours associated with immediate reward such as cannabis use.Method: Ninety-one psychosis patients and 91 controls without history of psychosis were administered the Temporal Experience of Pleasure Scale (TEPS), a self report which measures anticipatory and consummatory pleasure. Cannabis use diagnosis was assessed using the Structured Clinical Interview for DSM IV (SCID). Subjects reported the frequency of cannabis consumption and time since last use.Results: Patients did not show a significant deficit in anticipatory or consummatory pleasure compared to controls; however, patients with an active cannabis-use disorder tended to have lower consummatory pleasure than controls with active cannabis disorder (p<.05). Patients who continued to use cannabis during treatment of their first episode of psychosis reported significantly lower anticipatory pleasure compared to those who had a lifetime cannabis diagnosis but were able to maintain abstinence (F(1,60)=5.6, p=.021). Frequency of cannabis use was negatively correlated to anticipatory and consummatory pleasure (Pearson R=−.46, −.48 respectively) in 37 patients currently using cannabis but not in 46 cannabis-using controls (partial R=−.04, −.07 respectively).Conclusion: Anticipatory pleasure may not be decreased in early psychosis patients. Lower hedonic response may be associated with persistent, heavy cannabis use in patients in the early phase of psychotic disorders.

Early cannabis use and Schizotypal Personality Disorder Symptoms from adolescence to middle adulthood

2012-02-10

Abstract: Background: While increasing evidence suggests that cannabis use may play a role in the development of schizophrenia in some young people, less is known about the strength and specificity of its relationship to latent schizophrenia liability, i.e., schizotypal personality disorder traits.Aims: Determine the predictive value of cannabis use during childhood and early adolescence on schizotypal personality disorder (SPD) symptoms projecting into adulthood, using a community-based longitudinal cohort from upstate New York.Method: Prospective data from 804 participants was used to determine associations between early cannabis use and later schizotypal symptoms, accounting for important potential confounds (e.g., adolescent schizotypal symptoms).Results: Cannabis use with onset prior to age 14 strongly predicted SPD symptoms in adulthood, independent of early adolescent SPD symptoms, major depression, anxiety disorder, other drug use, and cigarette use. There was no interaction effect of early cannabis use and early adolescent SPD symptoms on SPD symptoms into adulthood.Conclusions: Our data provide further support for a strong association of early cannabis use with the development of symptoms characteristic of schizophrenia spectrum disorders. As with studies in schizophrenia, early SPD symptoms could not fully explain the association of early cannabis use with later schizotypal symptoms. The mechanisms that underlie the association of cannabis use and schizotypal symptoms in a developmental context deserve further exploration.

Effect of cannabis use on the course of schizophrenia in male patients: A prospective cohort study

2012-02-10

Abstract: Background: Findings on the impact of cannabis use on the course of schizophrenia are inconsistent and not conclusive.Aims: To study the effect of cannabis use on the course of schizophrenia taking into account the effects of the quantity of cannabis use and important confounders.Methods: Prospective cohort study with assessments of symptoms, confounders and hospitalizations at baseline, 6month and 12month follow up.Results: In a representative cohort of 145 male patients with schizophrenia, 68 (46.9%) used cannabis. Mean age at onset of schizophrenia in cannabis using patients was significantly lower than in non-cannabis using patients. No other cross-sectional demographic or clinical differences were observed between users and non-users. In a series of longitudinal analyses, cannabis use was not associated with differences in psychopathology, but relapse in terms of the number of hospitalizations was significantly higher in cannabis using patients compared to non-cannabis using patients.Conclusions: Patients with schizophrenia using cannabis are more frequently hospitalized than non-cannabis using patients but do not differ with respect to psychopathology. Possible explanations for these findings are discussed.

Decreased glutathione levels predict loss of brain volume in children and adolescents with first-episode psychosis in a two-year longitudinal study

2012-02-27

Abstract: Progressive loss of cortical gray matter (GM), as measured by magnetic resonance imaging, has been described early in the course of first-episode psychosis. This study aims to assess the relationship between oxidative balance and progression of cortical GM changes in a multicenter sample of first-episode early-onset psychosis (EOP) patients from baseline to two-year follow-up.A total of 48 patients (13 females, mean age 15.9±1.5years) and 56 age- and gender-matched healthy controls (19 females, 15.3±1.5years) were assessed. Magnetic resonance imaging (MRI) scans performed both at the time of the first psychotic episode and 2years later were used for volumetric measurements of left and right gray matter regions (frontal, parietal, and temporal lobes) and total sulcal cerebrospinal fluid (CSF). Total glutathione (GSH) blood levels were determined at baseline.In patients, after controlling for possible confounding variables, lower baseline GSH levels were significantly associated with greater volume decrease in left frontal (B=0.034, 95% confidence interval (CI): 0.011 to 0.056, r=0.620, p=0.006), parietal (B=0.039, 95% CI: 0.020 to 0.059, r=0.739, p=0.001), temporal (B=0.026, 95% CI: 0.016 to 0.036, r=0.779, p<0.001), and total (B=0.022, 95% CI: 0.014 to 0.031, r=0.803, p<0.001) gray matter, and with greater increase in total CSF (B=−0.560, 95% CI: −0.270 to −0.850, r=−0.722, p=0.001). Controls did not show significant associations between brain volume changes and GSH levels. GSH deficit during the first psychotic episode was related to greater loss of cortical GM two years later in patients with first-episode EOP, suggesting that oxidative damage may contribute to the progressive loss of cortical GM found in patients with first-episode psychosis.

Cognitive impairment is related to oxidative stress and chemokine levels in first psychotic episodes

2012-03-26

Abstract: Introduction: This study measures the levels of various markers of oxidative stress and inflammation in blood samples from first-episode psychosis (FEP) patients, and examines the association between these peripheral biomarkers and cognitive performance at 6months after treatment.Methods: Twenty-eight FEP patients and 28 healthy controls (matched by age, sex and educational level) had blood samples taken at admission for assessment of total antioxidant status, superoxide dismutase (SOD), total glutathione (GSH), catalase (CAT), glutathione peroxidase, lipid peroxidation, nitrites and the chemokine monocyte chemoattractant protein-1 (MCP-1). A battery of cognitive tests was also applied to the healthy controls and those FEP patients who were in remission at 6months after the acute episode.Results: FEP patients had significantly lower levels of total antioxidant status, catalase and glutathione peroxidase, compared with the healthy controls. Regression analyses found that MCP-1 levels were negatively associated with learning and memory (verbal and working), nitrite levels were negatively associated with executive function, and glutathione levels were positively associated with executive function.Conclusion: Our results suggest an association between certain peripheral markers of oxidative stress and inflammation and specific aspects of cognitive functioning in FEP patients. Further studies on the association between MCP-1 and cognition are warranted.

Is there a link between childhood trauma, cognition, and amygdala and hippocampus volume in first-episode psychosis?

2012-02-21

Abstract: Patients with psychosis have higher rates of childhood trauma, which is also associated with adverse effects on cognitive functions such as attention, concentration and mental speed, language, and verbal intelligence. Although the pathophysiological substrate for this association remains unclear, these cognitive deficits may represent the functional correlate of changes observed in relation to trauma exposure in structures such as the amygdala and the hippocampus. Interestingly, these structures are often reported as altered in psychosis. This study investigated the association between childhood trauma, cognitive function and amygdala and hippocampus volume, in first-episode psychosis. We investigated 83 patients with first-episode psychosis and 63 healthy controls. All participants underwent an MRI scan acquired with a GE Sigma 1.5-T system, and a standardized neuropsychological assessment of general cognition, memory, processing speed, executive function, visuo-spatial abilities, verbal intelligence, and language. In a subsample of the patients (N=45) information on childhood trauma was collected with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q). We found that amygdala, but not hippocampus, volume was significantly smaller (p=0.001) in patients compared to healthy controls. There was a trend level interaction for hippocampus volume between group and sex (p=0.056). A history of childhood trauma was associated with both worse cognitive performance and smaller amygdala volume. This smaller amygdala appeared to mediate the relationship between childhood trauma and performance on executive function, language and verbal intelligence in patients with psychosis. This points to a complex relationship between childhood trauma exposure, cognitive function and amygdala volume in first-episode psychosis.

Diffusion tensor imaging tractography of the fornix and belief confidence in first-episode psychosis

2012-03-15

Abstract: Previous studies have demonstrated that patients with psychosis are more confident in beliefs and judgments compared to healthy participants and psychiatric controls with major depression. A recent study conducted by our research group has provided evidence for hippocampal pathology in association with overconfidence in a first-episode psychosis sample. The fornix is the primary efferent neural pathway of the hippocampus and may also play a role in self-certainty pathophysiology. The current investigation applied diffusion tensor imaging tractography to a first-episode psychosis sample to explore whether integrity of the fornix is associated with self-certainty. High resolution structural magnetic resonance and diffusion tensor images were obtained in 44 people with a first-episode psychosis. Diffusion tensor imaging tractography was used to estimate fractional anisotrophy (FA), a measure of white matter integrity, in the fornix. Confidence in beliefs and judgments was measured with the self-certainty subscale of the Beck Cognitive Insight Scale (BCIS). The analysis showed that self-certainty significantly correlated to FA values in the right fornix but was nonsignificant for the left fornix. The findings indicate anatomical dysconnectivity of the right fornix in correlation with BCIS-rated self-certainty in our first-episode psychosis sample. When considered with our previously published self-certainty—hippocampus result in a first-episode psychosis sample, overlapping with that of this study, the results indicate a concurrence of volumetric reductions in hippocampus and fornix pathology in correlation with self-certainty.

MTR abnormalities in subjects at ultra-high risk for schizophrenia and first-episode schizophrenic patients compared to healthy controls

2012-02-29

Abstract: Background: Neuroimaging studies have suggested gray (GM) and white matter (WM) abnormalities in early stages of schizophrenia. We aimed at evaluating subtle parenchymal alterations in individuals at ultra-high risk (UHR) for transition into psychosis and first-episode schizophrenic (FES) patients by measuring the magnetization transfer ratio (MTR).Methods and materialIn a cross-sectional study magnetization transfer images and high-resolution volumetric T1-weighted images were acquired in 70 age- and gender-matched subjects (25 UHR subjects, 16 FES patients and 29 controls) in a 1.5Tesla scanner. Following normalization of MTR-maps the intensity histograms were analyzed by performing a Kruskal–Wallis-test.Results: Gray matter MTR decreases were depicted in UHR subjects solely, involving the cingulate gyrus and precentral cortex. WM MTR alterations were more pronounced in FES than in UHR patients and exclusively affected the frontal lobe bilaterally. In addition, UHR subjects showed bilateral MTR decreases at the stria terminalis though statistically significant only on the left side (p=0.018.)Conclusion: Our results indicate GM affection earlier on during disease progression as well as cumulative WM affection within frontal lobes during transition from UHR to FES. MTR reductions at the stria terminalis of UHR patients points to the involvement of the extended amygdala in the prodromal disease stage.

Language processing abnormalities in adolescents with psychotic-like experiences: An event related potential study

2012-02-14

Abstract: Language impairments are a well established finding in patients with schizophrenia and in individuals at-risk for psychosis. A growing body of research has revealed shared risk factors between individuals with psychotic-like experiences (PLEs) from the general population and patients with schizophrenia. In particular, adolescents with PLEs have been shown to be at an increased risk for later psychosis. However, to date there has been little information published on electrophysiological correlates of language comprehension in this at-risk group. A 64 channel EEG recorded electrical activity while 37 (16 At-Risk; 21 Controls) participants completed the British Picture Vocabulary Scale (BPVS-II) receptive vocabulary task. The P300 component was examined as a function of language comprehension. The at-risk group were impaired behaviourally on receptive language and were characterised by a reduction in P300 amplitude relative to the control group. The results of this study reveal electrophysiological evidence for receptive language deficits in adolescents with PLEs, suggesting that the earliest neurobiological changes underlying psychosis may be apparent in the adolescent period.

Electroconvulsive therapy improves antipsychotic and somnographic responses in adolescents with first-episode psychosis — A case–control study

2012-02-20

Abstract: Objective: Previous studies have demonstrated the effectiveness of electroconvulsive therapy (ECT) in pharmacotherapy-resistant neuropsychiatric conditions. This study aimed to evaluate the efficacy and safety of ECT in adolescents with first-episode psychosis.Method: This case–control study was conducted in inpatients aged 13–20years with first-episode psychosis. Every three similar age and same gender patients consecutively recruited were randomly allocated to control and ECT group at a ratio of 1:2, while they had antipsychotic treatment. ECT treatment was performed for 3 sessions per week with a maximum of 14 sessions. The endpoint was discharge from hospital. Clinical outcomes were measured using hospital stay days, the Positive and Negative Syndrome Scale (PANSS) and response rate. Polysomnography (PSG) was conducted at baseline and at week 2. Safety and tolerability were also evaluated.Results: Between March 2004 and November 2009, 112 eligible patients were allocated to control (n=38) and ECT (n=74) group. Additional ECT treatment significantly reduced hospital stay compared to controls (23.2±8.2days versus 27.3±9.3days, mean±SD, P=0.018). Survival analysis revealed that the ECT-treated group had a significantly higher cumulative response rate than controls (74.3% versus 50%, relative risk (RR)=1.961, P=0.001). Additional ECT also produced significantly greater improvement in sleep efficiency, rapid eye movement (REM) latency and density than control condition. The PSG improvement significantly correlated with reduction in scores on overall PANSS, positive symptoms, and general psychopathology. No patients discontinued ECT treatment regimen during hospital stay. The incidence of most adverse events was not different in the two groups, but ECT-treated group had more complaints of transient headache and dizziness than controls.Conclusions: ECT is an effective and safe intervention used in adolescents with first-episode psychosis. Its antipsychotic effects are associated with improved PSG variables. ECT can be considered as an early psychosis intervention.

Is deterioration of IQ a feature of first episode psychosis and how can we measure it?

2012-02-20

Abstract: Estimates of pre-morbid IQ are widely used to measure the trajectory of cognitive function and decline in people with schizophrenia. This study examined the usefulness of two indices of decline to identify cognitive subtypes in first episode psychosis, and to determine the specificity of non-IQ neuropsychological impairments in this population. Neuropsychological data were collected from 118 first episode psychosis patients and compared to 118 epidemiologically matched controls. The National Adult Reading Test (NART) and the Information subtest of the WAIS-III were compared as indicators of crystallised intelligence or ‘pre-morbid IQ’. Measurement of NART minus current full scale IQ (FSIQ) (where 10 points discrepancy is the decline criterion) did not reveal a large group of individuals with ‘deteriorating’ IQ patterns. Using the Information subtest and the same decline criteria, a ‘deteriorating’ patient group emerged (36%) but was matched by a larger ‘deteriorating’ control group (45%). The ‘deteriorating’ patient group performed at a low IQ level for tasks that loaded highly on performance ability but a relatively high level for tasks measuring verbal skills. Verbal memory discriminated patients from controls better than IQ. Compared to controls, patients showed large selective impairments of verbal episodic memory (effect size, d=1.4) These data suggest that in first episode populations, caution should be exercised in inferring deterioration of IQ from discrepancies between reading-based and other IQ tests. Rather, sub-groups of patients and controls do show greater verbal aptitude in comparison to performance skills. Memory is generally impaired in first episode patients regardless of IQ.

Cognitive changes following antidepressant or antipsychotic treatment in adolescents at clinical risk for psychosis

2012-02-29

Abstract: Background: Improving neurocognitive abilities is a treatment priority in schizophrenia, however, pharmacological efforts to enhance deficits after illness onset have resulted in quite modest results that are of questionable clinical meaningfulness. Individuals at clinical risk for psychosis demonstrate neurocognitive impairments intermediate to the level of deficits observed in schizophrenia and normative performance, suggesting that a similar magnitude of improvement might result in more clinically meaningful change. In this study, we examined neurocognitive changes after six months of treatment in adolescents with clinical signs of risk for psychosis.Methods: Adolescents who were referred to the Recognition and Prevention program, which is focused on treatment and research for individuals at a clinical high risk for psychosis, were followed in a naturalistic treatment design. At study entry and approximately six months after starting treatment, we examined neuropsychological functioning and clinical symptoms for patients who remained off medications (OFF; N=27), started selective serotonin reuptake inhibitor antidepressant medication (AD; N=15), or started a second-generation antipsychotic medication (AP; N=11) within three months of study entry. We also included a locally recruited healthy comparison group (HC; N=17).Results: The clinical groups were not significantly different on baseline demographic, neurocognitive, or clinical symptom measures. Linear mixed models were used to examine cognitive changes, with time between assessments, depressive symptom severity, and attenuated positive symptom severity as random effects. Group by time effects were observed in sustained attention and verbal learning, with the AD group showing a more favorable response than the AP group. The AD group's improvements were not significantly different from the HC or OFF group.Conclusion: Early intervention for those at clinical high risk for psychosis may result in neurocognitive improvements. These improvements were observed for those prescribed antidepressant, but not antipsychotic medications even though the groups did not differ in clinical symptom severity or treatment response.

Longitudinal changes in semantic categorization performance after symptomatic remission from first-episode psychosis: A 3-year follow-up study

2012-03-27

Abstract: Semantic categorization abnormalities have been observed in schizophrenia, but studies have rarely focused on the longitudinal trajectory. In this study, we consider semantic performance and the relationship with symptomatic changes during recovery from a first-episode of schizophrenia over a period of 3years. Thirty-seven first-episode patients with schizophrenia were compared to thirty-seven matched controls in a categorization task. Patients were assessed at first episode, after clinical stabilization, and annually for the subsequent 3years. In the task, participants indicated whether a word belonged to a given category. Each category contained words of varying degrees of semantic relatedness: typical, atypical, borderline, related-but-outside, and unrelated. Reaction times and proportion of ‘yes’ responses were analyzed. At first assessment, semantic categorization abnormalities were observed in first-episode patients. Patients assigned more semantically-dissimilar words to the categories than controls. As patients stabilized from acute states, their semantic categorization performance improved and then remained stable throughout the entire follow up period of 3years. Interestingly, semantic performance deficits, particularly a diminished typicality effect, correlated with negative symptoms in the initial episode, but not at stabilization when symptoms subsided. No significant associations between positive and negative symptoms, or pre-defined categorization measures were identified. The data demonstrated semantic memory abnormalities in first-episode schizophrenia. However, an improvement of semantic categorization performance was observed in stabilized schizophrenia patients. Overall, the data are suggestive of a state effect in semantic abnormalities rather than a trait effect. The correlation between degree of impairment and symptoms may explain previous inconsistent findings.

Localized gray matter volume reductions in the pars triangularis of the inferior frontal gyrus in individuals at clinical high-risk for psychosis and first episode for schizophrenia

2012-03-19

Abstract: Recent studies have suggested an important role for Broca's region and its right hemisphere counterpart in the pathophysiology of schizophrenia, owing to its roles in language and interpersonal information processing. Broca's region consists of the pars opercularis (PO) and the pars triangularis (PT). Neuroimaging studies have suggested that they have differential functional roles in healthy individuals and contribute differentially to the pathogenesis of schizophrenic symptoms. However, volume changes in these regions in subjects with ultra-high risk for psychosis (UHR) or first-episode schizophrenia (FES) have not been clarified. In the present 3Tesla magnetic resonance imaging study, we separately measured the gray matter volumes of the PO and PT using a reliable manual-tracing volumetry in 80 participants (20 with UHR, 20 with FES, and 40 matched controls). The controls constituted two groups: the first group was matched for age, sex, parental socioeconomic background, and intelligence quotient to UHR (n=20); the second was matched for those to FES (n=20). Compared with matched controls, the volume of the bilateral PT, but not that of the PO, was significantly reduced in the subjects with UHR and FES. The reduced right PT volume, which showed the largest effect size among regions-of-interest in the both UHR and FES groups, correlated with the severity of the positive symptoms also in the both groups. These results suggest that localized gray matter volume reductions of the bilateral PT represent a vulnerability to schizophrenia in contrast to the PO volume, which was previously found to be reduced in patients with chronic schizophrenia. The right PT might preferentially contribute to the pathogenesis of psychotic symptoms.

Self-determination and first-episode psychosis: Associations with symptomatology, social and vocational functioning, and quality of life

Nicholas J.K. Breitborde, Petra Kleinlein, Vinod H. Srihari — 2012-03-26

Abstract: Self-determination theory (SDT) postulates that satisfaction of three basic psychological needs (i.e., autonomy, competence, and well-being) promotes motivation, well-being, and growth across domains of functioning. Thus, per SDT, we examined satisfaction of basic psychological needs among individuals with first-episode psychosis. First, we quantified the level of need satisfaction among a sample of individuals with first-episode psychosis and compared their level of need satisfaction to that of individuals without psychosis. Second, we examined the association between need satisfaction and several domains of well-being among individuals with first-episode psychosis (i.e., symptomatology, social/vocational functioning, and quality of life). Our results indicated that individuals with first-episode psychosis experience less satisfaction of basic psychological needs as compared to their same-aged counterparts. There was a modest association between need satisfaction and well-being among individuals with first-episode, with the need of relatedness being the need most frequently associated with indices of well-being. Although modest in scope, the results of the current study raise the possibility that further investigation of SDT among individuals with first-episode psychosis may reveal important strategies through which early intervention services can better promote well-being and recovery.

Impact of the CATIE trial on antipsychotic prescribing patterns at a state psychiatric facility

Angela M. Koranek, Tawny L. Smith, Lisa M. Mican, Karen L. Rascati — 2012-02-27

Abstract: Introduction: Results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) indicate that, with the exception of olanzapine, no substantial overall differences were identified between second generation antipsychotics (SGAs) and the first generation antipsychotic (FGA) perphenazine.Methods: This study evaluated the effect of CATIE on antipsychotic prescribing. A retrospective review of 1807 adults with schizophrenia was conducted and relative quarterly percentages of FGA versus SGA prescriptions were calculated.Results: Time series analysis did not identify significant differences in rates of FGA prescriptions.Conclusions: Critiques of the methods used in CATIE may have mitigated its potential impact on antipsychotic prescribing despite cost-effectiveness of perphenazine treatment.

Treatment response trajectories and antipsychotic medications: Examination of up to 18months of treatment in the CATIE chronic schizophrenia trial

2012-02-10

Abstract: Background: Trajectory studies highlight heterogeneity in treatment response, although they are yet to systematically differentiate between antipsychotic medications.Aims: To compare treatment response trajectories across antipsychotic medication groups.Method: Data were analyzed from Phase 1 of CATIE, an 18-month double-blind randomized controlled trial of chronic schizophrenia. Change on recurrent Positive and Negative Syndrome Scale (PANSS) administrations for 1124 patients was used to index treatment response trajectories up to 18months. Trajectory groups were identified with mixed-mode latent class regression modeling. Groups were derived for all participants, and separately for completers, dropouts, and each antipsychotic medication (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone) and then characterized.Results: Trajectory analysis of the entire sample identified that 18.9% of participants belonged to a group of responders. This figure increased to 31.5% for completers, and fell to 14.5% for dropouts. Olanzapine treated patients were significantly more likely than other treatment groups to belong to the trajectory of responders (n=69, 32.55%; Chi=20.13, df=2, p<.01). Separate trajectory analyses of each medication group showed that all medication groups showed two trajectories except olanzapine that had three trajectories and the only trajectory that attained a 20% PANSS reduction by endpoint.Conclusions: Trajectories of treatment response differ between antipsychotic medications and demonstrate substantial heterogeneity in chronic schizophrenia.

Negative symptoms have greater impact on functioning than positive symptoms in schizophrenia: Analysis of CATIE data

2012-02-10

Abstract: Increased attention has been given to treatment of negative symptoms and its potential impact on functional outcomes, however previous inferences have been confounded by the fact that measures of functional outcomes often use items similar to those of negative symptoms. We attempted to discern the relative effects of negative symptoms on functioning, as compared to other symptoms, using data from the National Institute of Mental Health CATIE trial of chronic schizophrenia (n=1447) by examining correlations of Positive and Negative Syndrome Scale factors, Calgary Depression Rating Scale and select items from Heinrich's and Lehman's Quality of Life Scales measuring aspects of functioning that did not overlap with negative symptoms. Baseline functioning and change in functioning were more strongly related to PANSS negative factor than any of the other symptoms — though the amount of variance explained by symptom changes in general was small. The data suggests that improvement in negative symptoms may have a distinctive and independent effect on functional outcome relative to other symptoms. This should be further tested in studies where negative symptoms improve without concomitant improvement of other symptoms.

Medical and developmental risk factors of catatonia in children and adolescents: A prospective case–control study

2012-03-09

Abstract: Context: Rare diseases have been associated with more and more genetic and non genetic causes and risk factors. But this has not been systematically assessed in catatonia, one of the psychiatric syndromes, that is most frequently associated with medical condition.Objective: We sought to assess the medical and developmental risk factors of catatonia in children and adolescents.Methods: From 1993 to 2009, 58 youths aged 10 to 18years were prospectively admitted for catatonia and were followed up after discharge. A multidisciplinary approach assessed patients' medical condition and developmental history. A causality assessment scored medical risk (maximum score=10; κ=0.91). We compared the prevalence of catatonia in these patients to that of 80 inpatients with bipolar I disorder admitted from 1993 to 2003 who were also followed up.Results: We found that 13 (22.4%) patients had medical conditions and 18 (31%) had a history of developmental disorder in the catatonia group, whereas 1 (1.3%) and 17 (22.6%) patients had the same conditions in the bipolar group (p<0.001; p=0.17, respectively). Medical conditions associated with catatonia included auto-immune encephalitis (systemic lupus erythematosus [N=3] and anti-NMDA-receptor encephalitis [N=1]), seizures (N=1), ciclosporin encephalitis (N=1), post hypoglycaemic coma encephalitis (N=1), and genetic or metabolic conditions (chorea [N=2], 5HT cerebrospinal fluid deficit [N=1], storage disease [N=1], fatal familial insomnia [FFI; N=1], and PRODH mutations [N=1]). Six patients responded to a specific treatment approach related to their medical condition (e.g., plasma exchange in the case of auto-immune encephalitis).Conclusion: Catatonia in children and adolescents is associated with a high prevalence of medical conditions. This needs to be acknowledged as it may greatly delay the treatment of catatonia and the diagnosis of medically related catatonia. Tragically, this may deny patients treatment opportunities.

Low maternal retinol as a risk factor for schizophrenia in adult offspring

2012-03-01

Abstract: Background: Prenatal micronutrient deficiency has been linked to later development of schizophrenia among offspring; however, no study has specifically investigated the association between vitamin A and this disorder. Vitamin A is an essential nutrient which is required by the early embryo and fetus for gene expression and regulation, cell differentiation, proliferation and migration. Previous work suggests that vitamin A deficiency in the second trimester may be particularly relevant to the etiopathogenesis of neurobehavioral phenotypes some of which are observed in schizophrenia.Methods: We examined whether low maternal vitamin A levels in the second trimester are associated with the risk of schizophrenia and other schizophrenia spectrum disorders (SSD) in the Prenatal Determinants of Schizophrenia study; third trimester vitamin A levels were also examined in relation to SSD. The cases were derived from a population-based birth cohort; all cohort members belonged to a prepaid health plan. Archived maternal serum samples were assayed for vitamin A in cases (N=55) and up to 2 controls per case (N=106) matched on length of membership in the health plan, date of birth (±28days), sex, and gestational timing and availability of archived maternal sera.Results: For the second trimester, low maternal vitamin A, defined as values in the lowest tertile of the distribution among controls, was associated with a greater than threefold increased risk of SSD, adjusting for maternal education and age (OR=3.04, 95% CI=1.06, 8.79, p=.039). No association between third trimester maternal vitamin A and SSD was observed.Conclusions: Although further investigations are warranted, this is the first birth cohort study to our knowledge to report an association between low maternal vitamin A levels and SSD among offspring.

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

2012-03-02

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

Structural correlates of auditory hallucinations in schizophrenia: A meta-analysis

Lena Palaniyappan, Vijender Balain, Joaquim Radua, Peter F. Liddle — 2012-02-20

Abstract: Background: Despite being one of the most common symptoms of schizophrenia, determining the neural correlates of auditory hallucinations still remains elusive with various studies providing inconsistent results.Methods: We conducted a voxel-based meta-analysis of studies investigating the structural correlates of auditory hallucinations in schizophrenia.Results: 7 datasets including 350 patients were identified. There was a significant negative correlation between the severity of hallucinations and gray matter volume in the left insula and right superior temporal gyrus.Conclusion: With its key role in stimulus evaluation and optimizing prediction (proximal salience), the insula is likely to be a cardinal region along with superior temporal gyrus in the mechanism of auditory hallucinations in schizophrenia.

The effect of rTMS on auditory hallucinations: Clues from an EEG-rTMS study

2012-01-30

Abstract: Objective: Repetitive transcranial magnetic stimulation (rTMS) to the temporoparietal region has been proposed as a therapeutic option for auditory verbal hallucinations (AVH). However, most large randomized controlled trials failed to demonstrate a superior effect of rTMS treatment as compared to sham. Previous studies applied daily rTMS sessions for one or more weeks to summate its effects. However, the effect of a single rTMS treatment on AVH-severity has never been studied, making it unclear if there is an initial effect that could be increased by repeated treatment.Methods: In three separate sessions, twenty-four patients with a psychotic disorder received 1-Hz rTMS to the left temporoparietal cortex, its right-sided homologue or a centro-occipital control site. Severity of AVH was assessed before and after each rTMS session and resting-state EEGs were recorded to investigate the neuronal effects of rTMS.Results: Stimulation of the temporoparietal cortices was not more effective in reducing AVH-severity than control-site stimulation. In addition, EEG-related power and connectivity measures were not affected differently across stimulation sites and changes in neuronal activity did not correlate with changes in AVH-severity.Conclusions: These results may suggest a placebo effect of a single session of 1-Hz rTMS treatment on AVH-severity.

Niacin subsensitivity is associated with functional impairment in schizophrenia

Erik Messamore — 2012-03-26

Abstract: Objective: Sensitivity to the skin flush effect of niacin is reduced in a portion of patients with schizophrenia. Though this peripheral physiological abnormality has been widely replicated, its relevance to neuropsychiatric manifestations of the illness has been unclear. The goal of this study was to determine if the niacin response abnormality in schizophrenia is associated with functional impairment.Methods: Following psychiatric assessment, a Global Assessment of Functioning (GAF) score was assigned to each of 40 volunteers with schizophrenia. For each subject, the blood flow responses to several concentrations of topical methylnicotinate were recorded. Blood flow was measured objectively, using laser Doppler flowmetry. From the dose–response data, EC50 values were derived. GAF scores were assigned without knowledge of the participants' niacin response data.Results: There was a significant negative correlation between GAF scores and EC50 values for methylnicotinate (Pearson r=−0.42; p=0.007).Conclusions: Reduced niacin sensitivity is associated with greater functional impairment among patients with schizophrenia. These findings raise the possibility that a subset of schizophrenia patients possesses a biochemical abnormality that reduces niacin sensitivity in the skin and contributes to functional impairment from the disease.

Self-esteem as a mediator of the relationship between role functioning and symptoms for individuals with severe mental illness: A prospective analysis of Modified Labeling theory

Lisa Davis, Seth Kurzban, John Brekke — 2012-02-29

Abstract: Background: Despite a growing body of evidence supporting the efficacy of psychosocial rehabilitation for individuals with severe mental illness (SMI), a large proportion of these individuals remain unable to maintain basic social roles such as employee, parent, or spouse. This study investigated whether changes in role functioning over time impact symptom severity indirectly through the mechanism of changes in self-esteem as posited by Modified Labeling theory.Methods: The study sample was composed of 148 individuals diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, and major depression with psychotic features who elected to participate in community-based psychosocial rehabilitation services. Measures of role functioning, self-esteem, and psychiatric symptoms were gathered at baseline and six months through a combination of structured clinical interviews and self-report surveys.Results: SEM results at baseline provided support for a model in which self-esteem fully mediated the relationship between role functioning and psychiatric symptoms. The final model explained 20% of the variance in psychiatric symptoms. Analyses at six months post-baseline (time 2) indicate that changes in self-esteem fully mediated the relationship between changes in role functioning and changes in psychiatric symptoms. The final change model explained 23% of the variance in changes in psychiatric symptoms.Conclusion: Results provide empirical support for the principles underlying Modified Labeling theory. Implications include the need for interventions that focus on social participation as a means of improving self-esteem, thereby decreasing symptom exacerbation and future relapse for people with SMI.

Predictors of the accuracy of self assessment of everyday functioning in people with schizophrenia

2012-03-05

Abstract: Despite multiple lines of evidence suggesting that people with schizophrenia have substantial problems in self-reporting everyday functioning and cognitive performance, self-report methods are still widely used to assess functioning. This study attempted to identify predictors of accuracy in self report, both in terms of accurate self-assessment and over-estimation of current functioning. As part of the larger Validating Assessments of Everyday Real-World Outcomes (VALERO) study, 195 patients with schizophrenia were asked to self report their everyday functioning with the Specific Levels of Functioning (SLOF) scale, which includes subscales assessing social functioning, everyday activities, and vocational functioning. They were also assessed with measures of neuropsychological (NP) performance and functional capacity (FC), and were assessed for psychiatric symptomatology. In addition, a friend, relative or clinician informant was interviewed with the SLOF, and an interviewer with access to all information provided by the patient and informant (exclusive of performance-based data) generated “best estimate” ratings of actual, everyday functioning. Patients significantly (p<.001) overestimated their vocational functioning and everyday activities compared to the interviewer judgments. Lower levels of NP and FC performance and everyday functioning on the part of patients were consistently associated with overestimation of their functioning. Patient self-reports were not correlated with any performance-based measures, while interviewer judgments were significantly correlated with patients' performance on NP and FC measures (p<.005). In regression analyses, adjusting for interviewer ratings of functioning, several predictors of the discrepancy between self and interviewer judgments emerged. Higher levels of depressive symptoms were associated with less overestimation in self-reports (p<.001). Delusions, suspiciousness, grandiosity and poor rapport were all significantly (p<.001) associated with over-estimation of functioning compared to interviewer judgments. Poorer NP and FC performance were also associated with over-estimation of everyday functioning, but these results were not statistically significant in multivariate regression models. Consistent with previous studies in schizophrenia, other neuropsychiatric conditions and non-clinical populations, higher levels of depression were associated with increased accuracy in self-assessment. Similarly, lower scores on performance-based measures and judgments of everyday functioning also predicted over-estimation of functioning. Thus, we identified bi-directional predictors of mis-estimation of everyday functioning, even when poor baseline scores were considered. These data suggest that it may be possible to screen patients for their ability to self-report their functioning, but that performance-based measures of functioning provide a less biased assessment.

Self-reported empathy deficits are uniquely associated with poor functioning in schizophrenia

2012-02-10

Abstract: Background: Social cognitive deficits have been proposed to be among the causes of poor functional outcome in schizophrenia. Empathy, or sharing and understanding the unique emotions and experiences of other people, is one of the key elements of social cognition, and prior studies suggest that empathic processes are impaired in schizophrenia. The current study examined whether impairments in self-reported empathy were associated with poor functioning, above and beyond the influences of neurocognitive deficits and psychopathology.Methods: Individuals with schizophrenia (n=46) and healthy controls (n=37) completed the Interpersonal Reactivity Index (IRI), a measure of emotional and cognitive empathy. Participants also completed a neuropsychological test battery, clinical ratings of psychopathology, and functional outcome measures assessing both functional capacity and community functioning. After testing for between-group differences, we assessed the relationships between self-reported empathy and the measures of functioning, neurocognition, and psychopathology. Regression analyses examined whether empathic variables predicted functional outcomes.Results: Individuals with schizophrenia reported lower IRI scores for perspective-taking and empathic concern, and higher IRI scores for personal distress than controls. Among individuals with schizophrenia, lower perspective-taking, greater disorganized symptoms, and deficits in working memory and episodic memory were correlated with poorer functional capacity and community functioning. Lower scores for perspective-taking explained significant incremental variance in both functional capacity (ΔR2=.09, p<.05) and community functioning (ΔR2=.152, p<.01) after accounting for relevant neurocognitive and psychopathological variables.Conclusions: Impaired perspective-taking, a component of cognitive empathy, is associated with poor functioning even after taking into account the influences of neurocognitive deficits and psychopathology. These findings support further efforts to clarify the underlying causes of empathic disturbances and suggest that treatments for these disturbances may help functional recovery in schizophrenia.

A meta-analysis of emotion perception and functional outcomes in schizophrenia

Farzin Irani, Sarah Seligman, Vidyulata Kamath, Christian Kohler, Ruben C. Gur — 2012-02-17

Abstract: Introduction: Emotion perception (EP) is impaired in schizophrenia, is stable across clinical state, resistant to antipsychotic treatment and linked to symptom severity. Given its pervasive nature, there is a need to quantitatively examine whether this dysfunction impacts functional outcomes. We used a meta-analytic strategy to combine results from several studies and examine synthesized effect sizes.Methods: A Meta-analysis of Observational Studies in Epidemiology standard was used to extract data following a PubMed and PsychInfo search. Studies reporting correlations between measures of EP and functional outcomes in schizophrenia spectrum disorders were selected. The impact of potential methodological (task type), demographic (sex, age, race, education, marital status) and clinical (age of onset, duration of illness, setting, symptoms, anti-psychotic medication) moderators on effect sizes were examined.Results: Twenty-five studies met inclusion criteria and included 1306 patients who were 37years old, with 12years of education, 64% male and 63% Caucasian. There was a significant relationship between EP and functional outcomes in individuals with schizophrenia or schizoaffective disorder, with effect sizes in the medium range. Medium to large range positive correlations were observed between emotion identification and functional outcome domains involving social problem solving, social skills and community functioning. Significant moderators included task type (emotion identification tasks), sex (% male in sample), race (% Caucasian in sample) and clinical symptoms (negative and positive).Conclusions: Emotion identification deficits are associated with functional impairments in schizophrenia and moderated by sex, race and symptoms. This has implications for treatment efforts to improve outcomes.

Social cognition and quality of life in schizophrenia

Arija Maat, Anne-Kathrin Fett, Eske Derks, GROUP Investigators — 2012-03-09

Abstract: Schizophrenia is associated with poor quality of life (QOL). Whereas the effects of neurocognitive deficits and psychopathology on QOL of schizophrenia patients have recently been elucidated, little is known about social cognitive deficits in this regard. This study investigated the influence of social cognition on QOL in schizophrenia. A sample of 1032 patients, 1011 of their siblings, and 552 healthy controls was recruited from the Dutch Genetic Risk and Outcome in Psychosis (GROUP) study. Participants completed a battery of cognitive tests, including social cognitive tests on theory of mind and emotion perception. To assess QOL the World Health Organization QOL Assessment-BREF (WHOQOL-BREF) was used. Schizophrenia symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Social cognitive performance was significantly worse in patients compared to siblings and healthy controls. Patients had the poorest QOL, while QOL in healthy controls was better than in siblings. Theory of mind but not emotion perception or neurocognition was associated with QOL in patients, whereas neurocognition was the only significant predictor of QOL in siblings and healthy controls. There was a significant interaction between theory of mind and symptom severity with respect to QOL. Our study indicates that social cognition is associated with QOL in schizophrenia. Theory of mind rather than emotion perception is associated with QOL, and this association is moderated by schizophrenia symptoms. In particular, patients with relatively unimpaired theory of mind and more severe schizophrenia symptoms have poor QOL and could therefore benefit from therapeutic intervention.

Dissociation and social cognition in schizophrenia spectrum disorder

Selwyn B. Renard, Marieke Pijnenborg, Paul H. Lysaker — 2012-03-01

Abstract: While there is emerging evidence that dissociation is linked with trauma history and possibly symptoms in schizophrenia, it remains unclear whether dissociation represents a symptom dimensions in its own right in schizophrenia and as such is uniquely related to other features of illness. To explore this issue the current study sought to find out whether dissociation was uniquely related to an index of social cognition closely linked to social functioning, namely affect recognition. We hypothesized that dissociation would be linked with affect recognition because symptoms of dissociation may uniquely disrupt processes which are expected to be needed for correctly recognizing emotions. The sample contained 49 participants diagnosed with a schizophrenia spectrum disorder who were in a non-acute phase of disorder. Participants were concurrently administered the Bell–Lysaker Emotion Recognition Task, the Dissociative Experiences Scale, the Post Traumatic Stress Disorder Checklist and the Positive and Negative Symptoms Scale. Stepwise linear regression analyses were performed in which dissociative symptoms were forced to enter after the other symptoms in order to predict deficits in affect recognition. These analyses revealed that greater levels of dissociative symptoms predicted poorer recognition of negative emotions over and above that of positive, negative, cognitive and PTSD symptoms. Results are consistent with the possibility that dissociation represents a unique dimension o f psychopathology in schizophrenia which may be linked to function.

Theory of mind in patients with schizophrenia: Is mentalizing delayed?

2012-03-09

Abstract: Objective: Functional imaging studies have used numerous neurocognitive designs to investigate brain activation during theory of mind (ToM) tasks in patients with schizophrenia. The majority of studies asks participants to retrospectively attribute mental states to others. We used a novel animated task to investigate implicit mentalizing online. Because behavioral studies have revealed slower ToM performance reaction times in patients with schizophrenia, we hypothesized that time would influence functional MRI (fMRI) activation patterns also.Methods: We applied the “Moving Shapes” paradigm, which involves two interacting triangles, to a functional MRI block design and investigated the neural activation patterns of 15 patients with schizophrenia and 14 healthy controls. We additionally analyzed the first and second halves of each video separately to assess time-related differences.Results: Overall, patients with schizophrenia showed increased activation in the inferior and middle frontal gyri, the superior temporal gyrus, the precuneus and the cerebellum compared with controls during ToM versus non-ToM videos. Most importantly, patients with schizophrenia had predominantly increased activation in ToM-related brain areas during the second half of the ToM paradigm, whereas the activation in areas of the ToM-network in healthy controls occurred during the first half of the presentation.Conclusions: Our results confirm recent findings of significantly stronger neural activations that encompass the fronto-temporo-parietal cerebral areas in patients with schizophrenia compared with controls during ToM tasks. The observation of slower cognitive processing in patients with schizophrenia during mentalizing might explain some of the contradictory imaging findings in these patients and have implications for cognitive remediation.

Comparing three screening tools for drug-induced parkinsonism in patients with advanced schizophrenia: A pilot study

Pierre J. Blanchet, Louise Normandeau, Pierre H. Rompré — 2012-02-10

Abstract: Background: Drug-induced parkinsonism (DIP) is seen in one third of patients exposed to antipsychotic drugs and may lead to complications related to dysphagia and falls. Aside from skilled neurological examination, no tool has been validated to facilitate detection and follow-up.Objective: In this pilot study, three validated screening instruments were tested in an age-biased cohort of schizophrenia patients, including four items of the Liverpool University Neuroleptic Side-Effects Rating Scale (LUNSERS) and two brief questionnaires designed for community survey of parkinsonism.Method: Fifty-six subjects living with chronic schizophrenia between 50 and 75years of age underwent a motor evaluation along the original Unified Parkinson's Disease Rating Scale-section III and answered questions along the selected screening instruments, and results compared to those of 16 patients with Parkinson's disease (PD) and 15 neurologically unimpaired volunteers. Odds ratios, sensitivity, specificity, and their 95% confidence intervals, were calculated.Results: All three screening instruments correctly identified the PD state and distinguished PD from healthy participants. Eighteen (32%) schizophrenic patients displayed objective motor signs of parkinsonism. A single item of the LUNSERS (shakiness) significantly distinguished DIP from DIP-free patients, with a sensitivity of 61.1% and a specificity of 83.3%. The positive predictive value was 63.5% and the negative predictive value was 81.9%. The two other screening methods showed insufficient predictive value.Conclusion: Apart from a single query on shakiness, none of the tools examined were adequate to screen for DIP in patients treated for schizophrenia. A different instrument is necessary to monitor this important adverse effect in schizophrenia.

More than just tapping: Index finger-tapping measures procedural learning in schizophrenia

2012-02-20

Abstract: Background: Finger-tapping has been widely studied using behavioral and neuroimaging paradigms. Evidence supports the use of finger-tapping as an endophenotype in schizophrenia, but its relationship with motor procedural learning remains unexplored. To our knowledge, this study presents the first use of index finger-tapping to study procedural learning in individuals with schizophrenia or schizoaffective disorder (SCZ/SZA) as compared to healthy controls.Methods: A computerized index finger-tapping test was administered to 1169 SCZ/SZA patients (62% male, 88% right-handed), and 689 healthy controls (40% male, 93% right-handed). Number of taps per trial and learning slopes across trials for the dominant and non-dominant hands were examined for motor speed and procedural learning, respectively.Results: Both healthy controls and SCZ/SZA patients demonstrated procedural learning for their dominant hand but not for their non-dominant hand. In addition, patients showed a greater capacity for procedural learning even though they demonstrated more variability in procedural learning compared to healthy controls. Left-handers of both groups performed better than right-handers and had less variability in mean number of taps between non-dominant and dominant hands. Males also had less variability in mean tap count between dominant and non-dominant hands than females. As expected, patients had a lower mean number of taps than healthy controls, males outperformed females and dominant-hand trials had more mean taps than non-dominant hand trials in both groups.Conclusions: The index finger-tapping test can measure both motor speed and procedural learning, and motor procedural learning may be intact in SCZ/SZA patients.

Water and metabolite transverse T2 relaxation time abnormalities in the white matter in schizophrenia

Fei Du, Alissa Cooper, Bruce M. Cohen, Perry F. Renshaw, Dost Öngür — 2012-02-22

Abstract: Multiple lines of evidence suggest that microstructural abnormalities in the white matter are important in the pathophysiology of schizophrenia. Diffusion MRI approaches which can provide evidence on tissue structure have been widely used to probe these abnormalities in vivo, but transverse relaxation times (T2) may provide additional insights since they are determined by molecule–microenvironment interactions not revealed by diffusion MRI. T2 of water – located both intra and extracellularly – and N-acetylaspartate (NAA — located intracellularly) reflect related but distinct processes due to their differential localization and interactions with other molecules. In this study, we collected water and NAA T2 data from 16 healthy subjects (HC), and 16 patients with schizophrenia (SZ) at 4T in a 9cm3 voxel in the right prefrontal white matter. The SZ group had longer water but shorter NAA T2 relaxation times when compared with the HC group. This pattern resulted in a statistically significant metabolite×group interaction (F(18,1):4.980, p=0.039). Prolongation of water T2 and shortening of NAA T2 is consistent with an impoverishment of white matter macromolecule structures (including myelin) and abnormal intra-axonal milieu and volume in SZ.

Searching for a consensus five-factor model of the Positive and Negative Syndrome Scale for schizophrenia

R.S. Wallwork, R. Fortgang, R. Hashimoto, D.R. Weinberger, D. Dickinson — 2012-02-23

Abstract: Although the developers of the Positive and Negative Syndrome Scale (PANSS) grouped items into three subscales, factor analyses indicate that a five-factor model better characterizes PANSS data. However, lack of consensus on which model to use limits the comparability of PANSS variables across studies. We counted “votes” from published factor analyses to derive consensus models. One of these combined superior fit in our Caucasian sample (n=458, CFI=.970), and in distinct Japanese sample (n=164, CFI=.964), relative to the original three-subscale model, with a sorting of items into factors that was highly consistent across the studies reviewed.

Reduced arterial compliance in patients with psychiatric diagnoses

2012-02-29

Abstract: Background: Peripheral arterial compliance is a measure of elasticity of the arteries that has been found to be a robust predictor of prevalent arteriosclerosis as well as incident stroke and myocardial infarction. Psychiatric diagnoses and second generation antipsychotics may contribute to cardiovascular risk and stroke, but effects on peripheral arterial compliance are unknown. This study compared peripheral arterial compliance in healthy male controls to male patients with psychiatric diagnoses who were treated with quetiapine or risperidone or off antipsychotics at time of testing.Methods: The groups consisted of 63 patients with mental illness taking quetiapine, risperidone, or no antipsychotics. There were 111 males in the control group. Mean thigh and calf arterial compliance among four groups were compared by ANCOVA, adjusting for body mass index and Framingham Risk Score. All patients were also compared to the control group. Compliance was measured with a computerized plethysmography device.Results: Patients (n=63) had significantly lower arterial compliance in both thigh and calf than the controls. Arterial compliance in the calf was significantly lower in the subgroups of quetiapine (n=16) and risperidone (n=19) treated, and in unmedicated (n=28) patients than in controls. In the thigh, patients taking either quetiapine or risperidone had significantly lower arterial compliance than controls. These subgroups did not differ from each other in arterial compliance.Conclusion: The presence of psychiatric diagnoses is associated with reduced arterial compliance. A large study may be required to measure any specific affects of antipsychotics such as quetiapine and risperidone on compliance compared to controls.

The Beck Cognitive Insight Scale: Psychometric properties in a Canadian community sample

Lisa Buchy, Mathieu B. Brodeur, Martin Lepage — 2012-03-26

The Beck Cognitive Insight Scale (BCIS) () was developed to evaluate how individuals with psychosis understand their own reasoning processes, beliefs and judgments. In the original BCIS study, established a two factor structure for the measure. The first factor was interpreted as an expression of one's willingness to acknowledge fallibility, corrigibility and recognition of dysfunctional reasoning, and was labelled Self-Reflectiveness. The second factor focused on one's overconfidence and was considered to represent Self-Certainty. The main clinical finding was that patients with psychosis could be reliably distinguished from psychiatric controls with major depression on the basis of their BCIS scores: those with psychosis endorsed relatively less Self-Reflectiveness and greater Self-Certainty. The authors concluded that the BCIS may be a sensitive measure of cognitive insight impairments in psychosis.

The association between childhood rickets and nonaffective psychosis: A Danish record-linkage study

2012-03-23

It has been proposed that low pre- and/or perinatal vitamin D status may increase the risk of later schizophrenia (). This hypothesis was originally based on various clues from schizophrenia epidemiology (e.g. excess of winter births, higher prevalence at higher latitudes, increased risk in dark skinned migrants). We have recently completed the first examination of the relationship between neonatal vitamin D status and risk of schizophrenia (). This study was based on a linkage between the Danish Psychiatric Central Register and a biobank of neonatal dried blood spots. We found that the risk of schizophrenia was significantly associated with neonatal 25 hydroxyvitamin D concentrations. As predicted, those with lower concentrations had an increased risk of schizophrenia. Unexpectedly, neonates with the highest levels also had an increased risk (i.e. the exposure–risk relationship was non-linear).

Corpus callosum volumes in recent-onset schizophrenia are correlated to positive symptom severity after 1year of follow-up

2012-03-16

Predicting the prognosis of schizophrenia is of critical importance but there are no valid biomarkers for such purpose. In case–control studies of schizophrenia using magnetic resonance imaging (MRI), the corpus callosum (CC) consistently displays alterations in morphology (), microstructural integrity () and functioning (). In a previous voxel-based morphometry (VBM) study comparing recent-onset psychosis (ROP) patients to healthy controls, we reported CC volume reductions in schizophrenia spectrum subjects (). Herein, we investigated correlations between baseline CC volumes and the clinical prognosis of patients in regard to their symptom severity after 1year.

Metacognitive functioning and social cognition as predictors of accuracy of self-appraisals of vocational function in schizophrenia

2012-03-23

It has been increasingly recognized that many with schizophrenia spectrum disorders experience impairments in social cognition, which involves processes such as appraising the affects and intentions of others (), discrete metacognitive processes, which include accurately appraising one's own behavior (), and more synthetic metacognitive activities such as those involved in self-reflectivity or constructing a complex representation of oneself (). While these deficits are of interest given their links with social and vocational functioning, it is unclear how they are related to one another ().

Pro12Ala polymorphism of the PPAR-γ2 gene, metabolic syndrome and response to metformin in clozapine-treated patients

Erika Fernández, Edgardo Carrizo, Lisette Connell, Trino Baptista — 2012-02-29

The peroxisome proliferator-activated receptor gamma (PPAR-γ, PPARG or glitazone receptor) encoded by the PPAR-γ gene is implicated in obesity, diabetes, atherosclerosis and cancer ().

A two-stage case–control association study between the tryptophan hydroxylase 2 (TPH2) gene and schizophrenia in a Japanese population

2012-02-20

Serotonin has been shown to be involved in neurobiological mechanisms underlying schizophrenia (). The gene encoding tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme in brain serotonin synthesis (), could serve as a candidate gene for schizophrenia. Previous studies have failed to provide evidence for an association between TPH2 and schizophrenia (). However, these studies were performed with relatively small sample sizes and a limited number of markers. A two-stage case–control association study in Japanese individuals was performed to assess whether TPH2 is implicated in schizophrenia vulnerability.

Abnormal anterior cingulate cortex activity predicts functional disability in schizophrenia

2012-03-14

The anterior cingulate cortex (ACC) may play a critical role in mediating cognitive deficits in schizophrenia (). The ACC plays a critical role in conflict monitoring (e.g. ) and functional neuroimaging studies have implicated abnormal ACC activation during selective attention tasks in schizophrenia () and, in particular, while patients monitor conflict (). The relationship between these brain imaging deficits and real-world functioning has not been investigated and may be useful in predicting long-term outcome.

An autism dimension for schizophrenia in the next diagnostic and statistical manual?

Andrea L. Pelletier, Vijay A. Mittal — 2012-02-20

As the Diagnostic and Statistical Manual for Mental Disorders revision (DSM-Five) task force for schizophrenia moves towards a dimensional approach for capturing symptoms, it is important to consider that the nature of these dimensions still remains a subject of debate. With this in mind, we would like to weigh support and limiting factors behind an autism dimension for schizophrenia.