The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe.

BACKGROUND: We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe. METHODS: We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use. RESULTS: The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53). CONCLUSIONS: The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Multimorbidity and the Etiology of Schizophrenia.

PURPOSE OF REVIEW: A global study of multimorbidity in schizophrenia, especially of the association with physical conditions, might offer much needed etiological insights. RECENT FINDINGS: Our review suggests that life-style factors and medication related to schizophrenia are only part of the explanation of the increase in risk for cardiovascular, metabolic, pulmonary disorders, and some cancers. Positive associations with autoimmune disorders (with the exception of rheumatoid arthritis) and epilepsy are promising avenues of research but to date have not been fully exploited. The same holds for the negative comorbidity seen for rheumatoid arthritis and some cancers (e.g., prostate). As a whole, our review suggests that most of the explored conditions have a different prevalence in schizophrenia than in the general population. Several hypotheses emerged from this review such as the role of immune and genetic factors, of sex hormones, and of more general variability factors.

Tobacco use in first-episode psychosis, a multinational EU-GEI study.

BACKGROUND: Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis. METHODS: The sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use. RESULTS: After controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1-3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2-2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (ß = -2.3; p ⩽ 0.001; 95% CI [-3.7 to -0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0-1.8]); however, these results were no longer significant after controlling for cannabis use. CONCLUSIONS: Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.

The impact of parent history of severe mental illness on schizophrenia outcomes: results from the real-world FACE-SZ cohort.

Parent history of severe mental illness (PHSMI) may have long-term consequences in adult offspring due to genetic and early environmental factors in preliminary studies. To compare the outcomes associated in subjects with PHSMI to those in patients without PHSMI. The participants with schizophrenia and schizoaffective disorders were recruited in the ongoing FACE-SZ cohort at a national level (10 expert centers) and evaluated with a 1-day-long standardized battery of clinician-rated scales and patient-reported outcomes. PHSMI was defined as history of schizophrenia or bipolar disorders in at least one parent and was included as explanatory variable in multivariate models. Of the 724 included patients, 78 (10.7%) subjects were classified in the PHSMI group. In multivariate analyses, PHSMI patients had a better insight into schizophrenia and the need for treatment and reported more often childhood trauma history compared to patients without PHSMI. More specifically, those with paternal history of SMI reported more severe outcomes (increased childhood physical and emotional abuses, comorbid major depression and psychiatric hospitalizations). PHSMI is associated with increased risk of childhood trauma, major depressive disorder and psychiatric hospitalization and better insight in individuals with schizophrenia. Specific public health prevention programs for parents with SMI should be developed to help protect children from pejorative psychiatric outcomes. PHSMI may also explain in part the association between better insight and increased depression in schizophrenia.

Schizotypal dimensions are associated with current but not former tobacco consumption.

OBJECTIVES: We aimed to study the relationship between tobacco smoking and attenuated psychosis measures taking into account several aspects of tobacco consumption that to date have not been explored and that could help understand this association, such as age of onset, the influence of former consumption and the duration of abstinence. METHODS: We investigated, in a sample of 580 students, the relationship between schizotypy (using the schizotypal personality questionnaire-brief in a Likert format) and smoking status, nicotine dependence (measured with the Fagerström test for nicotine dependence), age of onset of smoking and in former smokers, duration of smoking abstinence. RESULTS: 35.2% of the students were current smokers and 13.4% were former smokers. We found that current but not former smokers had higher scores of schizotypy (total, positive and disorganized) than non-smokers. We found no association between schizotypy scores and nicotine dependence or earlier age of onset of smoking. The duration of smoking abstinence, in former smokers, was inversely correlated to the score of positive and total schizotypy. CONCLUSIONS: Our results suggest that tobacco has a reversible effect on schizotypy, but more studies with a different design (controlled, longitudinal) and a more thorough exploration of potential confounders (e.g. cannabis) are needed before a firm conclusion can be reached.

[Accelerated telomere erosion in schizophrenia: A literature review]. / Érosion prématurée des télomères et schizophrénies : synthèse et hypothèses.

Schizophrenia is associated with a weighted average of 14.5 years of potential life lost according to a recent meta-analysis. This is partly explained by high rates of suicide and a high prevalence of non-psychiatric comorbidity (cardiovascular diseases, diabetes, cancers…). However, all these causes could not fully explain the loss of life expectancy in people suffering from schizophrenia. Life expectancy has been strongly correlated with telomere length (TL). Telomeres are noncoding structures consisting of DNA TTAGGG tandem repeats and associated proteins located at the end of the chromosomes. Their role is to help preserve genome stability by protecting chromosomal ends from the loss of genetic material. The progressive loss of telomeric material during cell divisions has led researchers to consider telomeres as molecular clocks that measure the number of divisions left until cellular death. The fact that both shorter telomeres and schizophrenia have been associated with a decrease in life expectancy has fueled the interest in the study of TL in schizophrenia. In this article, after a detailed review of the literature on the relationships between telomere length and schizophrenia, we discuss the different pathophysiological mechanisms which might explain this association. Based on this analysis, in the last part of the article we discuss potential research, therapeutic and prevention prospects. To date, the majority of the studies and meta-analyses found a decrease in TL in subjects with schizophrenia compared to control subjects. Conversely, all the studies exploring the TL in subjects suffering from first episode psychosis (FEP) have shown no significant difference from TL in control subjects. This suggests that excessive shortening of telomeres occurs during the course of the disease, thus it seems more probable that schizophrenia (or processes associated with it) affects TL rather than telomere erosion being a cause of the disorder. Several pathophysiological, non-mutually exclusive mechanisms have been proposed to explain the observed data. A first hypothesis to explain the acceleration of the physiological process of telomere erosion in schizophrenia is the activation of inflammation processes and oxidative stress as a consequence of schizophrenia per se. However, it seems more probable that reduced TL may be a result of cumulative exposure to chronic stress related to schizophrenia. Indeed, in healthy individuals a growing body of evidence has linked chronic stress to accelerated shortening of TL. This might explain why telomere erosion is too small to be detected in FEP patients who are younger and have a shorter duration of illness than subjects with schizophrenia. Based on these both explanations, telomere alterations may be considered as a biomarker of illness progression and might be useful for illness staging. Identifying processes associated with TL reduction might improve our understanding of the increased mortality and morbidity in schizophrenia, improve reliability of diagnosis, and hopefully suggest means for prevention and/or treatment. Treatments that prevent exposure and/or vulnerability to stressful life events that ameliorate schizophrenia may also prevent or decelerate telomere erosion. In this perspective, engaging subjects suffering from schizophrenia in a healthy diet and regular activity could be both promising strategies to protect telomere maintenance and improve health span at old age. In addition, the inflammatory process and oxidative stress involved in the physiopathology in at least a subgroup of subjects with schizophrenia could also be responsible for telomere erosion. Thus, an efficient anti-inflammatory therapeutic approach that targets these specific pathways could be of interest in this subgroup to limit telomere erosion. Mindfulness-based stress reduction (MBSR) therapies have been shown to reduce telomere erosion by increasing telomerase activity, although these psychological therapies should be used carefully in psychosis. Finally, advancing our understanding of the relationship between stress, inflammation and TL is of great interest for psychiatric research and for understanding stress effects in this population.

[Social defeat and schizophrenia: Hypotheses, arguments, mechanisms]. / Défaite sociale et schizophrénie : hypothèses, arguments, mécanismes.

There is growing evidence for a main role of environment in the occurrence of mental disorders such as a psychosocial risk factor, for example, childhood trauma, discrimination linked to minority status, or migrant status. One hypothesis is that social adversity factors influence the risk of schizophrenia through a common pathway: social defeat which could be defined as the impotence of a subject in the face of a situation of social adversity, with a consequential experience of devaluation on the social scale. This review proposes to explain the animal model of social defeat which provides an overview of the neurobiological consequences of chronic stress. Then, we expose this topic in humans, the assessment methods, and its psychopathological field. Finally, we expose epidemiologic and neurobiological evidences, in particular the dopaminergic sensitization process, which provide evidence of a significant role of social defeat in schizophrenia risk due to exposure to psychosocial factors. This etiopathogenic hypothesis has several issues. First, a common pathway to several environmental risk factors could allow an ethiopathogenic model more parcimonious for schizophrenia. It could also allow the assessment and prevention of adversity factors involved in social defeat so as to finally improve the outcome of subjects who have an individual risk for schizophrenia.

Schizotypal Personality Questionnaire-Brief: Effect of invalid responding on factor structure analysis and scores of schizotypy.

OBJECTIVES: We assessed the effect of invalid responding on factor structure and on scores of schizotypy through the factor analysis of the Schizotypal Personality Questionnaire-Brief (SPQ-B) in a sample of 580 Romanian students using 3 validity items and 5 social desirability items. METHODS: We examined the factor structure of the SPQ-B, we compared the mean SPQ-B scores between reliable and unreliable responders and between high vs. low social desirability responders, and we re-run the factor analysis restricting the sample to the reliable or low social desirability responders. RESULTS: Factor analysis resulted in a 3-factor solution: Cognitive-perceptual, Interpersonal and Disorganized dimensions. Unreliable responders had lower scores of positive, negative and total schizotypy. Subjects with high social desirability scores had lower scores of disorganized schizotypy. Factor analyses in the samples of "good" responders showed minor differences in reliable responders, whereas, after taking into account the effect of social desirability, 2 items correctly loaded on expected dimensions. CONCLUSIONS: Random responding and social desirability could influence scores of schizotypy and factor structure. Simple methods could be used to identify invalid responses. The effect of social desirability could be linked to the phrasing of items.

[Schizotypal Personality Questionnaire-Brief - Likert format: Factor structure analysis in general population in France]. / Analyse de la structure factorielle de la version brève du questionnaire de personnalité schizotypique (SPQ-B) ­ format Likert ­ en population générale en France.

INTRODUCTION: The main objective of the study was to explore the factorial structure of the French version of the Schizotypal Personality Questionnaire-Brief (SPQ-B) in a Likert format, in a representative sample of the general population. In addition, differences in the dimensional scores of schizotypy according to gender and age were analyzed. As the study in the general population of schizotypal traits and its determinants has been recently proposed as a way toward the understanding of aetiology and pathophysiology of schizophrenia, consistent self-report tools are crucial to measure psychometric schizotypy. A shorter version of the widely used Schizotypal Personality Questionnaire (SPQ-Brief) has been extensively investigated in different countries, particularly in samples of students or clinical adolescents, and more recently, a few studies used a Likert-type scale format which allows partial endorsement of items and reduces the risk of defensive answers. METHOD: A sample of 233 subjects representative of the adult population from an urban area near Paris (Créteil) was recruited using the "itinerary method". They completed the French version of the SPQ-B with a 5-point Likert-type response format (1=completely disagree; 5=completely agree). We examined the dimensional structure of the French version of the SPQ-B with a Principal Components Analysis (PCA) followed by a promax rotation. Factor selection was based on Eigenvalues over 1.0 (Kaiser's criterion), Cattell's Scree-plot test, and interpretability of the factors. Items with loadings greater than 0.4 were retained for each dimension. The internal consistency estimate of the dimensions was calculated with Cronbach's α. In order to study the influence of age and gender, we carried out a simple linear regression with the subscales as dependent variables. RESULTS: Our sample was composed of 131 women (mean age=52.5±18.2 years) and 102 men (mean age=53±18.1 years). SPQ-B Likert total scores ranged from 22 to 84 points (mean=43.6±13). Factor analysis resulted in a 3-factor solution that explained 47.7% of the variance. Factor 1 (disorganized; 10 items) included items related to "odd behavior", "odd speech", as well as "social anxiety", one item of "constricted affect" and one item of "ideas of reference". Factor 2 (interpersonal; 7 items) included items related to "no close friends", "constricted affect", and three of the items of "suspiciousness". Factor 3 (cognitive-perceptual; 5 items) included items related to "ideas of reference", "magical thinking", "unusual perceptual experiences" and one item of "suspiciousness". Coefficient α for the three subscales and total scale were respectively 0.81, 0.81, 0.77 and 0.88. We found no differences in total schizotypy and the three dimensions scores according to age and sex. CONCLUSION: Factor analysis of the French version of the SPQ-B in a Likert format confirmed the three-factor structure of schizotypy. We found a pure cognitive perceptual dimension including the most representative positive features. As expected, "Suspiciousness" subscale is included in both positive and negative dimensions, but mainly in the negative dimension. Surprisingly, "social anxiety" subscale is included in the disorganized dimension in our analysis. The SPQ-B in a Likert format demonstrated good internal reliability for both total and subscales scores. Unlike previous published results, we did not find any influence of age or gender on schizotypal dimensions.

Common variant at 16p11.2 conferring risk of psychosis.

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).

Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis.

OBJECTIVE: To perform a meta-analysis on studies reporting prevalence of Toxoplasma gondii (T. gondii) infection in any psychiatric disorder compared with healthy controls. Our secondary objective was to analyze factors possibly moderating heterogeneity. METHOD: A systematic search was performed to identify studies into T. gondii infection for all major psychiatric disorders versus healthy controls. Methodological quality, publication bias, and possible moderators were assessed. RESULTS: A total of 2866 citations were retrieved and 50 studies finally included. Significant odds ratios (ORs) with IgG antibodies were found in schizophrenia (OR 1.81, P < 0.00001), bipolar disorder (OR 1.52, P = 0.02), obsessive-compulsive disorder (OR 3.4, P < 0.001), and addiction (OR 1.91, P < 0.00001), but not for major depression (OR 1.21, P = 0.28). Exploration of the association between T. gondii and schizophrenia yielded a significant effect of seropositivity before onset and serointensity, but not IgM antibodies or gender. The amplitude of the OR was influenced by region and general seroprevalence. Moderators together accounted for 56% of the observed variance in study effects. After controlling for publication bias, the adjusted OR (1.43) in schizophrenia remained significant. CONCLUSION: These findings suggest that T. gondii infection is associated with several psychiatric disorders and that in schizophrenia reactivation of latent T. gondii infection may occur.

Schizophrenia and other psychotic disorders in Caribbean-born migrants and their descendants in England: systematic review and meta-analysis of incidence rates, 1950-2013.

PURPOSE: Increased risk of schizophrenia and other psychotic disorders among black Caribbean migrants and their descendants have been described since the 1960s. It remains unclear whether this risk varies over time, between rural and urban areas, or according to methodological artefact. METHODS: We conducted a systematic review of the incidence of adult-onset psychotic disorders in black Caribbean groups relative to the baseline population in England, published 1950-2013. Subject to sufficient data (N ≥ 5) we used random effects meta-analyses to estimate pooled incidence rates (IR) and rate ratios (IRR) of seven psychotic disorder outcomes, and meta-regression to inspect whether any variation was attributable to study-level methodological features, including case ascertainment, denominator reliability, choice of baseline population and study quality. RESULTS: Eighteen studies met inclusion for review. Sixteen demonstrated statistically significant elevated incidence rates in the black Caribbean group, present across all major psychotic disorders, including schizophrenia and bipolar disorder. Methodological quality increased over time (p = 0.01), but was not associated with estimated IR or IRR. For schizophrenia (N = 11 studies) the pooled IRR in the black Caribbean group was 4.7 (95 % CI 3.9-5.7) relative to the baseline; no evidence of publication bias was observed. We found weak evidence to suggest schizophrenia IRRs were smaller from studies in more urban settings (odds ratio 0.98; 95 % CI 0.96-1.00; p = 0.06). CONCLUSIONS: Higher incidence rates of psychotic disorders have been present for more than 60 years amongst black Caribbean ethnic groups in England, despite improved study methodologies over time. Aetiological explanations appear to more parsimoniously account for this excess than methodological biases.

Long-term neurocognitive effects of antipsychotics in schizophrenia: a network meta-analysis.

PURPOSE: Most schizophrenic patients have mild to moderate cognitive impairment in the early stages of schizophrenia. The aim was to compare the long-term effects of various antipsychotic drugs on overall cognition and on specific cognitive domains in patients with schizophrenia or related disorders. METHODS: We searched MEDLINE and EMBASE for randomized controlled trials in which oral formulations of second-generation antipsychotic drugs were compared head-to-head or against placebo or against haloperidol. Trials had to be of at least 6 months duration to be included. We used a network meta-analysis to combine direct and indirect comparisons of the cognitive effects between antipsychotics. RESULTS: Nine studies were eligible. The median trial duration was 52 weeks. Quetiapine, olanzapine and risperidone had better effects on global cognitive score than amisulpride (p < 0.05) and haloperidol (p < 0.05). When memory tasks were considered, ziprasidone had better effect than amisulpride (0.28 [0.02-0.54]) and haloperidol (0.32 [0.09-0.55]). Quetiapine was better than other drugs (p < 0.001) on attention and processing speed tasks, followed by ziprasidone (p < 0.05) and olanzapine (p < 0.05). The effects of quetiapine, risperidone and olanzapine were better than those of amisulpride (p < 0.05) on executive functions. CONCLUSIONS: Our results suggest differences between antipsychotics in their effect on the overall cognitive score in schizophrenia. Quetiapine and olanzapine had the most positive effects, followed by risperidone, ziprasidone, amisulpride and haloperidol in that order. Significant differences were also observed according to specific cognitive tasks.

Universal prevention of schizophrenia and surrogate endpoints at population level.

Despite significant progresses in our knowledge of the risk factors for schizophrenia, we still are several steps short of implementing effective prevention strategies. Universal prevention strategies have several theoretical advantages but their implementation has been limited to date by their costs and lack of methods to assess their efficiency. To overcome this limitation, we suggest, based on research from therapeutic trials at individual level, the use of surrogate endpoints (SEs) at population level. We further suggest that subclinical measures of psychosis at population level are good SEs candidates for assessing universal measures for schizophrenia prevention.

Predictive value of magnetic resonance imaging diffusion parameters using artificial intelligence in low-and intermediate-risk prostate cancer patients treated with stereotactic ablative radiotherapy: A pilot study.

INTRODUCTION: To investigate the predictive value of the pre-treatment diffusion parameters of diffusion-weighted magnetic resonance imaging (DW-MRI) using artificial intelligence (AI) for prostate-specific antigen (PSA) response in patients with low- and intermediate-risk prostate cancer (PCa) treated with stereotactic ablative radiotherapy (SABR). METHODS: Retrospective evaluation was performed for 30 patients using pre-treatment multi-parametric MR image datasets between 2017 and 2021. MR-based mean- and minimum apparent diffusion coefficients (ADCmean, ADCmin) were calculated for the intraprostatic dominant lesion. Therapeutic response was assessed using PSA levels. Predictive performance was assessed by the receiver operating characteristic (ROC) analysis. Statistics performed with a significance level of p ≤ 0.05. RESULTS: No biochemical relapse was detected after a median follow-up of twenty-three months (range: 3-50), with a median PSA of 0.01 ng/ml (range: 0.006-2.8) at the last examination. Significant differences were observed between the pre-treatment ADCmean, ADCmin parameters, and the group averages of patients with low and high 1-year-PSA measurements (p < 0.0001, p < 0.0001). In prediction, the random forest (RF) model outperformed the decision tree (DT) and support vector machine (SVM) models by yielding area under the curves (AUC), with 0.722, 0.685, and 0.5, respectively. CONCLUSION: Our findings suggest that pre-treatment MR diffusion data may predict therapeutic response using the novel approach of machine learning in PCa patients treated with SABR. IMPLICATIONS FOR PRACTICE: Clinicians shall measure and implement the evaluation of the suggested parameters (ADCmin, ADCmean) to provide the most accurate therapy for the patient.

Self-reported suicidal ideation among individuals with first episode psychosis and healthy controls: Findings from the international multicentre EU-GEI study.

INTRODUCTION: Suicidal ideation is common among individuals with first episode psychosis (FEP), with prevalence estimates up to 56.5 %. Despite its high prevalence, relatively little is known about how sociodemographic, clinical and/or developmental characteristics contribute to the experience of suicidal ideation in individuals with FEP. METHODS: In this cross-sectional study (FEP n = 551 and controls n = 857), univariate logistic regression analyses were performed to study the associations of sociodemographic, clinical, and developmental factors with suicidal ideation in individuals with FEP as well as controls. Suicidal ideation was assessed using the Community Assessment of Psychic Experiences (CAPE). In addition, multivariate logistic regression analyses were conducted based on a stepwise approach. RESULTS: In FEP, only depressive symptoms remained significantly associated with suicidal ideation when all correlates were integrated into one model. In the multivariate model in controls, depressive symptoms, positive symptoms, and traumatic childhood experiences were significantly associated with suicidal ideation. CONCLUSIONS: This study showed that depressive symptoms are an important factor relating to suicidal ideation in individuals with FEP, over and above other clinical, sociodemographic, and developmental factors. This underscores the relevance of screening for suicidal ideation in individuals with FEP, and highlights the need for a better understanding of the diagnostic uncertainty and course of mood symptoms in early psychosis. LIMITATIONS: Cross-sectional study design, self-reported questionnaires.

Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis.

OBJECTIVE: An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta-analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view. METHOD: Individual patient and control data were obtained from original authors for 11 measures from four common neuropsychological tests: California or Rey Verbal Learning Task (VLT), Trail Making Test (TMT), Digit Span and/or Wisconsin Card Sorting Task. RESULTS: Impairments were found for all 11 test-measures in the bipolar group after controlling for age, IQ and gender (Ps ≤ 0.001, E.S. = 0.26-0.63). Residual mood symptoms confound this result but cannot account for the effect sizes found. Impairments also seem unrelated to drug treatment. Some test-measures were weakly correlated with illness severity measures suggesting that some impairments may track illness progression. CONCLUSION: This reanalysis supports VLT, Digit Span and TMT as robust measures of cognitive impairments in bipolar disorder patients. The heterogeneity of some test results explains previous differences in meta-analyses. Better controlling for confounds suggests deficits may be smaller than previously reported but should be tracked longitudinally across illness progression and treatment.

[Environmental risk factors for schizophrenia: a review]. / Les facteurs de risque environnementaux de la schizophrénie.

BACKGROUND: Evidence of variations in schizophrenia incidence rates has been found in genetically homogenous populations, depending on changes within time or space of certain environmental characteristics. The consideration of the impact of environmental risk factors in etiopathogenic studies has put the environment in the forefront of research regarding psychotic illnesses. Various environmental factors such as urbanicity, migration, cannabis, childhood traumas, infectious agents, obstetrical complications and psychosocial factors have been associated with the risk of developing schizophrenia. These risk factors can be biological, physical, psychological as well as social and may operate at different times in an individual's life (fetal period, childhood, adolescence and early adulthood). Whilst some of these factors act on an individual level, others act on a populational level, modulating the individual risk. These factors can have a direct action on the development of schizophrenia, or on the other hand act as markers for directly implicated factors that have not yet been identified. LITERATURE FINDINGS: This article summarizes the current knowledge on this subject. An extensive literature search was conducted via the search engine Pubmed. Eight risk factors were selected and developed in the following paper: urbanicity (or living in an urban area), cannabis, migration (and ethnic density), obstetrical complications, seasonality of birth, infectious agents (and inflammatory responses), socio-demographic factors and childhood traumas. For each of these factors, we provide information on the importance of the risk, the vulnerability period, hypotheses made on the possible mechanisms behind the factors and the level of proof the current research offers (good, medium, or insufficient) according to the amount, type, quality and concordance of the studies at hand. Some factors, such as cannabis, are "unique" in their influence on the development of schizophrenia since it labels only one risk factor. Others, such as obstetrical complications, are grouped (or "composed") in that they include various sub-factors that can influence the development of schizophrenia. DISCUSSION: The data reviewed clearly demonstrates that environmental factors have an influence on the risk of developing schizophrenia. For certain factors - cannabis, migration, urbanicity, obstetrical complications, seasonality - there is enough evidence to establish an association with the risk of schizophrenia. This association, however, remains weak (especially for seasonality). With the exception of cannabis, no direct link can yet be established. Concerning the three remaining factors - childhood traumas, infectious agents, socio-demographic factors - the available proof is insufficient. One main limitation concerning all environmental factors is the generalization of results due to the fact that the studies were conducted on geographically limited populations. The current state of knowledge does not allow us to determine the mechanisms by which these factors may act. CONCLUSION: Further research is needed to fill the gaps in our understanding of the subject. In response to this need, a collaborative European project (European Study of Gene-Environment Interactions [EU GEI]) was set-up. This study proposes the analysis of those environmental factors that influence the incidence of schizophrenia in various European countries, in both rural and urban settings, migrant and native populations, as well as their interaction with genetic factors.

3-year incidence and predictors of metabolic syndrome in schizophrenia in the national FACE-SZ cohort.

AIMS: Metabolic Syndrome (MetS) is a major health epidemic of Western countries and patients with schizophrenia is a particularly vulnerable population due to lifestyle, mental illness and treatment factors. However, we lack prospective data to guide prevention. The aim of our study is then to determine MetS incidence and predictors in schizophrenia. METHOD: Participants were recruited in 10 expert centers at a national level and followed-up for 3 years. MetS was defined according to the International Diabetes Federation criteria. Inverse probability weighting methods were used to correct for attrition bias. RESULTS: Among the 512 participants followed-up for 3 years, 77.9% had at least one metabolic disturbance. 27.5% were identified with MetS at baseline and excluded from the analyses. Among the rest of participants (N = 371, mean aged 31.2 (SD = 9.1) years, with mean illness duration of 10.0 (SD = 7.6) years and 273 (73.6%) men), MetS incidence was 20.8% at 3 years and raised to 23.6% in tobacco smokers, 29.4% in participants receiving antidepressant prescription at baseline and 42.0% for those with 2 disturbed metabolic disturbances at baseline. Our multivariate analyses confirmed tobacco smoking and antidepressant consumption as independent predictors of MetS onset (adjusted odds ratios (aOR) = 3.82 [1.27-11.45], p = 0.016, and aOR = 3.50 [1.26-9.70], p = 0.0158). Antidepressant prescription predicted more specifically increased lipid disturbances and paroxetine was associated with the highest risk of MetS onset. CONCLUSION: These results are an alarm call to prioritize MetS prevention and research in schizophrenia. We have listed interventions that should be actively promoted in clinical practice.

Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study.

AIMS: Gene x environment (G×E) interactions, i.e. genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression, have not been reliably established regarding aetiology of psychotic disorders. Moreover, recent studies have shown associations between the polygenic risk scores for schizophrenia (PRS-SZ) and some risk factors of psychotic disorders, challenging the traditional gene v. environment dichotomy. In the present article, we studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the PRS-SZ on subclinical psychosis in a population-based sample. METHODS: Data were drawn from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (n = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. Associations between the PRS-SZ and the psychosocial stressors were tested. For each dimension, the interactions between genes and environment were assessed using linear models and comparing explained variances of 'Genetic' models (solely fitted with PRS-SZ), 'Environmental' models (solely fitted with each environmental stressor), 'Independent' models (with PRS-SZ and each environmental factor), and 'Interaction' models (Independent models plus an interaction term between the PRS-SZ and each environmental factor). Likelihood ration tests (LRT) compared the fit of the different models. RESULTS: There were no genes-environment associations. PRS-SZ was associated with positive dimensions (ß = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension. CONCLUSIONS: This study in subjects without psychotic disorders suggests that (i) the aetiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, (ii) genetic and environmental factors have independent effects on the level of this positive dimension, (iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.