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Schizophrenia is associated with early neurodevelopmental disorders, including most frequently learning disorders (LD), among them dyslexia and dyspraxia. Despite the demonstrated links between schizophrenia and LD, specific clinical patterns of the schizophrenia with a history of LD subgroup remain unknown. The aim of the present study was to investigate cognitive impairment, symptoms and functional outcome associated with a history of LD in a large cross-sectional, multicentric, sample of schizophrenia subjects. 492 community-dwelling subjects with schizophrenia (75.6% male, mean age 30.8 years) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. The 51 (10.4%) subjects identified with a history of LD had significantly impaired general cognitive ability (Wechsler Adult Intelligence Scale Full Scale Total IQ: Cohen's d = 0.50, p = 0.001), processing speed (d = 0.19), verbal comprehension (d = 0.29), working memory (d = 0.31), cognitive inhibition and flexibility (d = 0.26), central executive functioning (d = 0.26), phonemic verbal fluency (d = 0.22) and premorbid intellectual ability (d = 0.48), as well as with a worse functional outcome (Global Assessment of Functioning, d = 0.21), independently of age, sex, education level, symptoms, treatments, and addiction comorbidities. These results indicate that a history of LD is associated with later cognitive impairment and functional outcome in schizophrenia. This suggests that history of LD is a relevant clinical marker to discriminate subgroups of patients with schizophrenia with different profiles in a precision psychiatry framework. [ABSTRACT FROM AUTHOR]

Background: The Community Assessment of Psychic Experiences (CAPE) is a 42-item self-report questionnaire that has been developed and validated to measure the dimensions of psychosis in the general population. The CAPE has a three-factor structure with dimensions of positive, negative and depression. Assessing the cross-national equivalence of a questionnaire is an essential prerequisite before pooling data from different countries. In this study, our aim was to investigate the measurement invariance of the CAPE across different countries. Methods: Data were drawn from the European Union Gene-Environment Interaction (EU-GEI) study. Participants (incident cases of psychotic disorder, controls and siblings of cases) were recruited in Brazil, France, Italy, the Netherlands, Spain and UK. To analyse the measurement invariance across these samples, we tested configural invariance (i.e. identical structures of the factors), metric invariance (i.e. equivalence of the factor loadings) and scalar invariance (i.e. equivalence of the thresholds) of the three CAPE dimensions using multigroup categorical confirmatory factor analysis methods. Results: The configural invariance model fits well, providing evidence for identical factorial structure across countries. In comparison with the configural model invariance, the fit indices were very similar in the metric and scalar invariance models, indicating that factor loadings and thresholds did not differ across the six countries. Conclusion: We found that, across six countries, the CAPE showed equivalent factorial structure, factor loadings and thresholds. Thus, differences observed in scores between individuals from different countries should be considered as reflecting different levels of psychosis. [ABSTRACT FROM AUTHOR]

Purpose: We sought to determine whether significant variation in the incidence of clinically relevant psychoses existed at an ecological level in an urban French setting, and to examine possible factors associated with this variation. We aimed to advance the literature by testing this hypothesis in a novel population setting and by comparing a variety of spatial models.Methods: We sought to identify all first episode cases of non-affective and affective psychotic disorders presenting in a defined urban catchment area over a 4 years period, over more than half a million person-years at-risk. Because data from geographic close neighbourhoods usually show spatial autocorrelation, we used for our analyses Bayesian modelling. We included small area neighbourhood measures of deprivation, migrants' density and social fragmentation as putative explanatory variables in the models.Results: Incidence of broad psychotic disorders shows spatial patterning with the best fit for models that included both strong autocorrelation between neighbouring areas and weak autocorrelation between areas further apart. Affective psychotic disorders showed similar spatial patterning and were associated with the proportion of migrants/foreigners in the area (inverse correlation). In contrast, non-affective psychoses did not show spatial patterning.Conclusions: At ecological level, the variation in the number of cases and the factors that influence this variation are different for non-affective and affective psychotic disorders. Important differences in results-compared with previous studies in different settings-point to the importance of the context and the necessity of further studies to understand these differences. [ABSTRACT FROM AUTHOR]

Background: The aim of our study is to provide data on the incidence of psychotic disorders in France and compare the incidence rates in populations with different levels of urbanization. Methods: We prospectively included the incident cases of psychotic disorders from two catchment areas with contrasted levels of urbanization. In the more rural area, we also calculated incidence rates in three different groups of population defined by the size of towns in which they live (small, medium and large towns). Results: The annual incidence of psychosis was greater in the urban area (36.02/100000 person-year at risk) than in the rural area (17.2/100000 person-year at risk). Non-affective psychoses were the majority of cases and their incidence was greater in males and younger subjects. The affective psychoses were slightly more frequent in women and showed less variation with age. In the rural centre, greater levels of urbanicity were associated with an increase in the incidence of all psychoses (affective and non-affective). Conclusions: Our study confirms previous observations of increased incidence rates for non-affective psychoses in the more urbanized areas and suggests that a similar pattern might be present for affective psychoses. [ABSTRACT FROM AUTHOR]

Objective: To explore the sociodemographic characteristics that might explain the increased incidence of psychosis among immigrants and their descendants in France. Methods: Data were collected for all subjects with first contact for psychosis aged between 18 and 64 years, in two catchment areas in the Paris region. Incidence rates (IR) and incidence rate ratios (IRR) were adjusted for gender and age. Results: During 805,396 persons‐year at risk, we identified 321 cases of first‐episode psychosis, of which 129 were immigrants and 78 descendants of immigrants. We found that the geographic origin was associated with the risk of psychosis although generation has little impact. Sub‐Saharan African immigrants and their descendants showed the highest risk (IRR = 3.1 and IRR = 2.9, respectively). We observed that living in deprived areas increased the incidence of psychosis (IRR = 1.3, 95CI%: 1.0–1.6), particularly among immigrants (IRR = 1.6; 95% CI: 1.1–2.5). Finally, our study showed that subjects having unstable housing (a proxy for "hard to count population") could inflate the incidence rates among immigrants. Conclusion: The current study shows that the increased risk of psychosis in groups with an immigration background in France is associated with their origin and highlights the importance of socioeconomic factors in modulating this risk. The aim of the present study is to explore the characteristics that might explain this increase: geographic origin, generation (immigrants or their descendants), social environment, and living conditions. We observed that living in deprived areas increased the incidence of psychosis, particularly among immigrants. Geographic origin was associated with the risk of psychosis although generation has little impact and Sub‐Saharan African immigrants and their descendants showed the highest risk. [ABSTRACT FROM AUTHOR]

We aimed to examine the association between religious beliefs and observance and the prevalence of psychiatric disorders, psychotic symptoms and history of suicide attempts in the French general population. The cross-sectional survey interviewed 38,694 subjects between 1999 and 2003, using the MINI. Current religious beliefs and observance were identified by means of two questions: "are you a believer?" and "are you religiously observant?". We studied the association between religiosity and psychiatric outcomes using a multivariable logistic regression model adjusted for sociodemographic characteristics, including migrant status. Religious beliefs were positively associated with psychotic symptoms and disorders [OR = 1.37, 95% CI (1.30-1.45) and OR = 1.38, 95% CI (1.20-1.58)], unipolar depressive disorder [OR = 1.15, 95% CI (1.06-1.23)] and generalized anxiety disorder [OR = 1.13, 95% CI (1.06-1.21)], but negatively associated with bipolar disorder [OR = 0.83, 95% CI (0.69-0.98)], alcohol use disorders [OR = 0.69, 95% CI (0.62-0.77)], substance use disorders [OR = 0.60, 95% CI (0.52-0.69)] and suicide attempts [OR = 0.90, 95% CI (0.82-0.99)]. Religious observance was positively associated with psychotic symptoms and disorders [OR = 1.38, 95% CI (1.20-1.58) and OR = 1.25, 95% CI (1.07-1.45)], but negatively associated with social anxiety disorder [OR = 0.87, 95% CI (0.76-0.99)], alcohol use disorders [OR = 0.60, 95% CI (0.51-0.70)], substance use disorders [OR = 0.48, 95% CI (0.38-0.60)] and suicide attempts [OR = 0.80, 95% CI (0.70-0.90)]. Among believers, religious observance was not associated with psychotic outcomes. Religiosity appears to be a complex and bidirectional determinant of psychiatric symptoms and disorders. In this respect, religiosity should be more thoroughly assessed in epidemiological psychiatric studies, as well as in clinical practice., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Objective: To compare the clinical symptomatology in patients with Early-Onset Schizophrenia (EOS, N = 176), especially the subgroup Very Early Onset Schizophrenia (VEOS) and Adult Onset Schizophrenia (AOS, N = 551)., Method: In a large French multicentric sample, 727 stable schizophrenia patients, classified by age at onset of the disorder, were assessed using standardized and extensive clinical and neuropsychological batteries: AOS with onset ≥ 18 years and EOS with onset < 18 years (including 22 VEOS < 13 years)., Results: The importance of better diagnosing EOS group, and in particularly VEOS, appeared in a longer DUP Duration of Untreated Psychosis (respectively, 2.6 years ± 4.1 and 8.1 years ± 5.7 vs. 1.0 years ± 2.5), more severe symptomatology (PANSS Positive And Negative Syndrome Scale scores), and lower educational level than the AOS group. In addition, the VEOS subgroup had a more frequent childhood history of learning disabilities and lower prevalence of right-handedness quotient than the AOS., Conclusion: The study demonstrates the existence of an increased gradient of clinical severity from AOS to VEOS. In order to improve the prognosis of the early forms of schizophrenia and to reduce the DUP, clinicians need to pay attention to the prodromal manifestations of the disease., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Objectives: The aim of this study is to design a questionnaire, the Versailles Metacognitive Strategies Evaluation Questionnaire, for assessing the use of metacognitive and help-seeking strategies in three key-domains of impaired daily functioning in schizophrenia. To evaluate its psychometric properties (internal consistency, factor structure, convergent and divergent validity, and stability)., Design: Development of a questionnaire and psychometric validation procedure in patients with schizophrenia compared with healthy controls. Stability over one year was assessed in the patient group., Setting: Schizophrenia Centers of Expertise (French FondaMental Network)., Subjects: A total of 141 patients with schizophrenia, among whom 77 participated in the second evaluation; 97 healthy subjects., Main Measures: The Versailles Metacognitive Strategies Evaluation Questionnaire, Positive and Negative Symptoms Scale, Personal and Social Performance Scale, Evaluation of Cognitive Processes involved in Disability in Schizophrenia Scale, Schizophrenia Quality of Life Questionnaire, and Stages of Recovery Instrument., Results: From the 36-items version, stepwise exploratory factor analysis (oblimin) produced a 25-items scale which had a 3-factors structure (hygiene concern, social relationships, and hygiene help-seeking). Cronbach's were respectively equal to 0.91, 0.82, and 0.78. One-year stability was good (intra-class correlation coefficient = 0.7). The three factors showed good convergent validity with measures of quality of life (rho = 0.34, P  ⩽ 0.001). The first two factors correlated with recovery ( N  = 34, rho = 0.53, P  ⩽ 0.001). On the contrary, the factors exhibited divergent validity, with no significant correlation, with symptoms and cognitive and psychosocial functioning ( P  > 0.05). Factor structure in healthy controls did not match with that of patients, all items but one were found significantly different among groups., Conclusion: The Versailles Metacognitive Strategies Evaluation Questionnaire provides a simple and valid means to assess metacognitive strategies in individuals with schizophrenia.

Current medical research has focused on diseases and their associated risk factors. As such, these factors are assumed to have a deleterious effect. An alternative hypothesis is that some of these risk factors would also increase the chance for an opposite, positive outcome. To test this hypothesis, we considered exceptional social achievement and schizophrenia as opposite outcomes. Sixty years ago, researchers in France collected data on socio-demographic factors associated with exceptional social achievement. As the number of female subjects in the original database was very limited, we restricted our analyses to men. We tested the odds of achieving prominence in the presence of factors known to be associated with an increased risk of schizophrenia, namely migration, urbanicity, seasonality of birth, birth order, and paternal age. Three of the five factors tested significantly increased the odds for exceptional social achievement (urban birth, being the first-born and father's age over 35). Our findings suggest that some of the factors that are currently considered as risk factors for schizophrenia could diversifying factors. Widening the focus of research to include all potential effects of factors associated with disease could have important consequences on our understanding of causal mechanisms and for designing public health interventions.

Objective:: This study aimed to evaluate the validity of the Evaluation of Cognitive Processes involved in Disability in Schizophrenia scale (ECPDS) to discriminate for cognitive impairment in schizophrenia., Design:: This multicentre cross-sectional study used a validation design with receiver operating characteristic (ROC) curve analysis., Settings:: The study was undertaken in a French network of seven outward referral centres., Subjects:: We recruited individuals with clinically stable schizophrenia diagnosed based on the Structured Clinical Interview for assessing Diagnostic and Statistical Manual of Mental Disorders (4th ed., rev.; DSM-IV-R) criteria., Main Measures:: The index test for cognitive impairment was ECPDS (independent variable), a 13-item scale completed by a relative of the participant. The reference standard was a standardized test battery that evaluated seven cognitive domains. Cognitive impairment was the dependent variable and was defined as an average z-score more than 1 SD below the normative mean in two or more cognitive domains., Results:: Overall, 97 patients were included (67 with schizophrenia, 28 with schizoaffective disorder, and 2 with schizophreniform disorder). The mean age was 30.2 (SD 7.7) years, and there were 75 men (77.3%). There were 59 (60.8%) patients with cognitive impairment on the neuropsychological battery, and the mean ECPDS score was 27.3 (SD 7.3). The ROC curve analysis showed that the optimal ECPDS cut-off was 29.5. The area under the curve was 0.77, with 76.3% specificity and 71.1% sensitivity to discriminate against cognitive impairment., Conclusion:: The ECPDS is a valid triage tool for detecting cognitive impairment in schizophrenia, before using an extensive neuropsychological battery, and holds promise for use in everyday clinical practice.

Objectives: Incidence-prevalence-mortality (IPM) models have been developped to estimate incidence or prevalence when one of these two measures is unavailable. We aimed to test the consistency of an IPM model of psychotic disorders on a recent incidence-prevalence couple dataset and to identify potential causes of inconsistency by applying the model to (a) the whole population, (b) female and male subgroups, (c) migrant subgroups, and (d) psychotic disorders with age at onset (AAO) between 18 and 24 (18-24 AAO)., Methods: We modelled prevalence (MP) using incidence data and the expected mortality and remission values. We then compared the MP to the observed prevalence (OP)., Results: In the whole population, the model significantly underestimated the prevalence (MP = 3.30, 95% CI [2.97, 3.66]; OP = 4.98, 95% CI [4.58, 5.41]). The results were similar for the two genders. In the migrants group, results were in the opposite direction, the model significantly overestimating the prevalence. Finally, in the 18-24 AAO subgroup, the model performed well, with OP and MP not significantly different., Conclusion: These results suggest that standard IPM models do not perform well for psychotic disorders and more complex models taking into account the heterogeneity of the sample (in terms of remission, mortality, population movements, etc.) need to be developed., (Copyright © 2018 John Wiley & Sons, Ltd.)

Background: Major depressive disorder (MDD) is underdiagnosed and undertreated in schizophrenia, and has been strongly associated with impaired quality of life.AimsTo determine the prevalence and associated factors of MDD and unremitted MDD in schizophrenia, to compare treated and non-treated MDD., Method: Participants were included in the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment. MDD was defined by a Calgary score ≥6. Non-remitted MDD was defined by current antidepressant treatment (unchanged for >8 weeks) and current Calgary score ≥6., Results: 613 patients were included and 175 (28.5%) were identified with current MDD. MDD has been significantly associated with respectively paranoid delusion (odds ratio 1.8; P = 0.01), avolition (odds ratio 1.8; P = 0.02), blunted affect (odds ratio 1.7; P = 0.04) and benzodiazepine consumption (odds ratio 1.8; P = 0.02). Antidepressants were associated with lower depressive symptoms score (5.4 v. 9.5; P < 0.0001); however, 44.1% of treated patients remained in non-remittance MDD. Nonremitters were found to have more paranoid delusion (odds ratio 2.3; P = 0.009) and more current alcohol misuse disorder (odds ratio 4.8; P = 0.04). No antidepressant class or specific antipsychotic were associated with higher or lower response to antidepressant treatment. MDD was associated with Metabolic syndrome (31.4 v. 20.2%; P = 0.006) but not with increased C-reactive protein., Conclusions: Antidepressant administration is associated with lower depressive symptom level in patients with schizophrenia and MDD. Paranoid delusions and alcohol misuse disorder should be specifically explored and treated in cases of non-remission under treatment. MetS may play a role in MDD onset and/or maintenance in patients with schizophrenia.Declaration of interestNone.

Objective: Individuals with psychotic symptoms may actually correspond to various subgroups, characterized by different patterns of psychotic symptoms as well as specific sociodemographic and clinical correlates. We aimed to identify groups of individuals from the general population with specific patterns of psychotic symptoms., Methods: In a 38,694-subject survey, a latent class analysis was performed to identify subgroups based on the distribution of seven psychotic symptoms taken from the Mini International Neuropsychiatric Interview. The different classes were subsequently compared according to sociodemographic and clinical correlates., Results: The best fit was obtained with a four-class solution, including the following: (1) a class with a low prevalence of all psychotic symptoms ('LOW', 85.9%); (2) a class with a high prevalence of all psychotic symptoms ('HAL + DEL', 1.7%); and classes with a high prevalence of (3) hallucinations ('HAL', 4.5%) or (4) delusions ('DEL', 7.9%). The HAL + DEL class displayed higher rates of history of trauma, social deprivation and migrant status, while the HAL and DEL classes displayed intermediate rates between HAL + DEL and LOW. HAL + DEL displayed the highest rates of psychotic and non-psychotic disorders and the use of mental health treatment, while HAL and DEL displayed intermediate rates of these disorders between HAL + DEL and LOW. In comparison to the HAL class, psychotic and substance use disorders were more frequent in the DEL class, while anxiety and mood disorders were less frequent., Conclusion: These findings support the hypothesis of a continuum model relating the level of psychotic symptoms to the level of global psychopathology.

In two recent papers, polymorphisms located in U2AF homology motif kinase 1 (UHMK1) gene have been associated to schizophrenia. This gene encodes the serine/threonine kinase, kinase interacting with Stathmin, and has been functionally related to RNA metabolism and neurite outgrowth. In this study, we explored the contribution of this gene in schizophrenia susceptibility, using a case-control association study, a mutation screening, a transcription level analysis, and by the investigation of the phosphorylation status of the splicing factor, SF1, in B-lymphoblastoid cell lines of patients and controls. No association was observed in our French cohort, and no amino acid substitution was predicted in the subsample studied for mutation screening. No difference was observed in expression level or in SF1 phosphorylation between patients and controls. Despite a slight difference persisting in the meta-analysis carried out using four European populations, these data suggest, altogether, that UHMK1 does not play a major role in susceptibility to schizophrenia.

Reelin is a glycoprotein involved in the migration and positioning of proliferating neurons and synaptic connectivity during neurodevelopment. It may also modulate neuronal plasticity throughout life. Therefore, the reelin gene is a candidate gene for schizophrenia. We examined the association of the CGG repeat polymorphism in the 5'-untranslated region of the reelin gene with schizophrenia in 266 unrelated French Caucasian patients, 156 of their parents, and 103 controls. We found no difference in the allele distribution between patients and controls although there was a significant higher prevalence of the genotype 8-8 in controls (CLUMP T3: chi(2) = 6.3, P = 0.035). There was no significant transmission disequilibrium in intrafamilial analysis. To refine our phenotypic characterization and in accordance with converging evidence suggesting that treatment resistance is associated with indices of abnormal neurodevelopment, we studied the association between reelin gene polymorphism and response to antipsychotics. Patients who responded to antipsychotics had a higher frequency of both the (CGG)(10) allele and (CGG)(10)-containing genotypes (P = 0.02; P = 0.006, respectively), with an odd ratio for genotypes of 4.2 (CI = [1.4;12.4]). Our results weakly support an association of reelin gene variants with schizophrenia as a whole, yet suggest that reelin could be associated with treatment-resistant schizophrenia., ((c) 2005 Wiley-Liss, Inc.)

Schizophrenic disorders are complex genetic disorders that may involve multiple genes of small effect. Apolipoprotein E (ApoE) gene variants are associated with alterations in brain function and an increased risk of Alzheimer's disease (AD). However, conflicting results have been reported in schizophrenia. We compared the ApoE genotypes of 114 French Caucasian schizophrenic patients and 91 normal controls. No differences in ApoE allele or genotype frequencies were observed between the two groups. However, we observed a possible association between male schizophrenic patients and the ApoE epsilon 2 epsilon 3 genotype. In addition, a meta-analysis of all published case-control studies on ApoE and schizophrenia did not support a major role for ApoE gene variants in schizophrenia as a whole. However, ApoE may be associated with particular forms of schizophrenia., (Copyright 2003 Wiley-Liss, Inc.)