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International audience; Caffeine is the most consumed psychoactive substance worldwide. Previous studies suggested higher caffeine consumption in subjects with schizophrenia spectrum disorders (SSD) as well as associations with symptoms, medication and medication side-effects. In a large and well-characterized sample of SSD subjects we explored the association between caffeine consumption and clinical (psychosis related, severity, general health) as well as pharmacological (antipsychotic treatment, sedation potential) variables. Eight hundred four subjects with data on their caffeine (coffee and tea) consumption successively recruited were included in this study. After controlling for potential confounders (demographic variables, smoking) only the negative dimension of psychosis was associated with the amount of caffeine ingested. Less severe negative symptoms were associated with higher caffeine consumption. The effect size of this association was small (partial correlation coefficient = −0.12) but significant.

Catatonia has been defined by ICD-11 as a nosologically unspecific syndrome. Previous neuropsychiatric conceptions of catatonia such as Wernicke-Kleist-Leonhard's (WKL) one, have isolated chronic catatonic entities, such as progressive periodic catatonia (PPC) and chronic system catatonias (CSC). This study aimed at comparing the clinical and neuropsychological features of PPC, CSC and non-catatonic patients, all diagnosed with a schizophrenia spectrum disorder (SSD). The clinical and cognitive measures were compared among 53 SSD patients, first by separating catatonic (C-SSD, n = 27) and non-catatonic patients (NC-SSD, n = 26), and second, by separating PPC (n = 20), CSC (n = 6) and NC-SSD patients. Bayes factors were used to compare the model with 1 or 2 catatonic groups. We found that PPC had a more frequent schizo-affective presentation, higher levels of depression and less positive psychotic symptoms than both CSC and NC-SSD. CSC patients had an earlier illness onset, a poorer cognitive functioning, and higher antipsychotics doses than both PPC and NC-SSD. Most differences between C- and NC-SSD were accounted by characteristics of either PPC or CSC. The model with 2 catatonic groups clearly outperformed that with 1 catatonic group. Our results point to a substantial clinical heterogeneity of 'catatonia' within the SSD population and suggest that distinguishing (at least) 2 chronic catatonic phenotypes (PPC and CSC) may represent a relevant step to apprehend this heterogeneity. It is also a more parsimonious attempt than considering the around 32.000 distinct catatonic presentations resulting from the combinations of 3 out of 15 polythetic criteria for ICD-11 catatonia.

Background Tobacco use is common in subjects with schizophrenia (SZ) and has sometimes been associated with better functioning in short-term studies. Only few studies embrace an extensive examination of tobacco influence on clinical, cognitive and therapeutic characteristics in stabilized SZ outpatients. The objective of the present study was to assess the association between cognitive performances and smoking status in SZ subjects. Methods In total, 1233 SZ participants (73.9% men, mean age 31.5) were included and tested with a comprehensive battery. Tobacco status was self-declared (never-, ex-, or current smokers). Multivariable analyses including principal component analyses (PCA) were used. Results In total, 53.7% were smokers with 33.7% of them nicotine-dependent. Multiple factor analysis revealed that current tobacco smoking was associated with impaired general intellectual ability and abstract reasoning (aOR 0.60, 95% IC 0.41–0.88, p = 0.01) and with a lifetime alcohol use disorder (p = 0.026) and a lifetime cannabis use disorder (p < 0.001). Ex- and never-smokers differed for age, mean outcome, cannabis history and medication [ex-smokers being older (p = 0.047), likely to have higher income (p = 0.026), a lifetime cannabis use disorder (p < 0.001) and higher CPZeq doses (p = 0.005)]. Premorbid IQ in the three groups significantly differed with, from higher to lower: ex-smokers, never-smoker, current smokers (all p < 0.001). Conclusions This study is the largest to date providing strong evidence that chronic smoking is associated with cognitive impairment in SZ, arguing against the self-medication hypothesis as a contributor to the high prevalence of smoking in SZ. Ex-smokers may also represent a specific subgroup. Longitudinal studies are warranted to determine the developmental impact of tobacco on neurocognition.

Resume L’existence d’un lien entre urbanicite et trouble psychotique est une donnee maintenant clairement etablie avec l’existence d’une relation dose–effet : plus le taux d’urbanicite est eleve, plus le risque de psychose est important. Pour expliquer cette association, plusieurs hypotheses ont ete proposees. La plupart des etudes ont evalue le role de facteurs psycho-sociaux comme le niveau socio-economique, le surpeuplement des logements, les inegalites sociales, le capital social pour expliquer ce lien. L’ensemble de ces facteurs ont pour denominateur commun une exposition repetee au stress, responsable d’une neuro-toxicite susceptible de faire le lit des decompensations psychotiques. Plus recemment, des etudes suggerent un role de la pollution de l’air. L’exposition aux polluants atmospheriques augmente la neuro-inflammation, le stress oxydatif, l’activation de la microglie, causant des dommages cerebraux et favorisant secondairement le developpement des troubles psychotiques. Ces facteurs restent pour l’heure insuffisamment explores et necessitent des investigations plus poussees, ce d’autant que contrairement a beaucoup d’autres facteurs etiologiques (environnementaux ou genetiques), les stress psycho-sociaux et la pollution atmospherique presentent l’avantage d’etre accessibles a des interventions et des mesures de prevention susceptibles de reduire l’incidence de la maladie.

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.

Particulate matter with a diameter of less than 10 µm (PM 10 ) or less than 2.5 µm (PM 2.5 ) are major air pollutants poorly studies regarding psychiatric disorders. We aimed to explore the association between PM 10 and PM 2.5 air pollution peaks and the daily number of emergency visits for psychotic and mood disorders. Clinical data were collected from the Emergency department of the Centre Hospitalo-Universitaire Henri-Mondor (Créteil, France) from 2008 to 2018. Air pollution data were collected from public databases. Pollution peaks periods were defined as days for which the daily mean level of PM was above nationally predefined warning thresholds (20 µg/m 3 for PM 2.5 , and 50 µg/m 3 for PM 10 ), and the 6 following days. Multivariable analyses compared the number of daily visits for psychotic and mood disorders according to pollution peak period. After adjustment on meteorological variables, the daily number of emergency visits for psychotic disorders was significantly higher during with PM 2.5 and PM 10 air pollution peaks periods; while the number of visits for unipolar depressive disorders was higher only during PM 10 peaks periods (β=0.059, p-value=0.034). There was no significant differences concerning bipolar disorders. Differences in the effects of PM air pollution on psychotic and mood disorders should be analyzed in further studies.

Particulate matters with a diameter of less than 10 µm (PM

Background There is growing concern about measuring patient experience with mental health care. There are currently numerous patient-reported experience measures (PREMs) available for mental health care, but there is little guidance for selecting the most suitable instruments. The objective of this systematic review was to provide an overview of the psychometric properties and the content of available PREMs. Methods A comprehensive review following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines was conducted using the MEDLINE database with no date restrictions. The content of PREMs was analyzed using an inductive qualitative approach, and the methodological quality was assessed according to Pesudovs quality criteria. Results A total of 86 articles examining 75 PREMs and totaling 1932 items were included. Only four PREMs used statistical methods from item response theory (IRT). The 1932 items covered seven key mental health care domains: interpersonal relationships (22.6%), followed by respect and dignity (19.3%), access and care coordination (14.9%), drug therapy (14.1%), information (9.6%), psychological care (6.8%) and care environment (6.1%). Additionally, a few items focused on patient satisfaction (6.7%) rather than patient experience. No instrument covered the latent trait continuum of patient experience, as defined by the inductive qualitative approach, and the psychometric properties of the instruments were heterogeneous. Conclusion This work is a critical step in the creation of an item library to measure mental health care patient-reported experience that will be used in France to develop, validate, and standardize item banks and computerized adaptive testing (CAT) based on IRT. It will also provide internationally replicable measures that will allow direct comparisons of mental health care systems. Trial registration NCT02491866.

BackgroundThe determinants of quality of life (QoL) in schizophrenia are largely debated, mainly due to methodological discrepancies and divergence about the concepts concerned. As most studies have investigated bi- or tri-variate models, a multivariate model accounting for simultaneous potential mediations is necessary to have a comprehensive view of the determinants of QOL. We sought to estimate the associations between cognitive reserve, cognition, functioning, insight, depression, schizophrenic symptoms, and QoL in schizophrenia and their potential mediation relationships.MethodsWe used structural equation modeling with mediation analyses to test a model based on existing literature in a sample of 776 patients with schizophrenia from the FondaMental Foundation FACE-SZ cohort.ResultsOur model showed a good fit to the data. We found better functioning to be positively associated with a better QoL, whereas better cognition, better insight, higher levels of depression, and schizophrenic symptoms were associated with a lower QoL in our sample. Cognitive reserve is not directly linked to QoL, but indirectly in a negative manner via cognition. We confirm the negative relationship between cognition and subjective QoL which was previously evidenced by other studies; moreover, this relationship seems to be robust as it survived in our multivariate model. It was not explained by insight as some suggested, thus the mechanism at stake remains to be explained.ConclusionThe pathways to subjective QoL in schizophrenia are complex and the determinants largely influence each other. Longitudinal studies are warranted to confirm these cross-sectional findings.

OBJECTIVE Several studies have shown that psychiatric disorders can be associated with venous thromboembolism (VTE) risk, that is, pulmonary embolism (PE) and/or deep vein thrombosis (DVT). In this study, we provide a systematic review and meta-analyses of the studies addressing this issue. METHODS All studies addressing the risk of VTE phenomena (whole VTE, PE, DVT, fatal VTE) in individuals with psychotic, mood, and anxiety disorders published between 1998 and 2019 were reviewed and included in the meta-analyses. Main characteristics of the studies and data concerning VTE risk were extracted. The methodological qualities of the studies were also analyzed. A random-effects meta-analysis model was used. A meta-analysis was conducted separately for each disorder, as well as separately for unadjusted and adjusted studies. Meta-analyses were repeated considering only good-quality studies. Heterogeneity was assessed. RESULTS Sixteen studies were reviewed and 15 included in the meta-analyses. Psychotic and bipolar disorders were significantly associated with VTE risk (VTE, DVT, PE, and fatal VTE for psychotic disorder: odds ratios [ORs] between 1.29 and 2.20; VTE, DVT, and PE for bipolar disorder: ORs between 1.22 and 2.14). Depression and anxiety disorders were associated with VTE risk only in adjusted analyses (DVT and PE for depression: ORs = 1.29; VTE and PE for anxiety disorders: ORs between 1.14 and 1.49). CONCLUSIONS The risk of VTE among individuals with psychiatric disorders may be explained by hypercoagulability and stasis, with both being related to, and independent of, treatment adverse effects. VTE risk should be taken into consideration in the treatment for people with psychiatric disorders.

Numerous factors are known to influence quality of life of adults with schizophrenia. However, little is known regarding the potential predictors of quality of life in the increasing population of older adults with schizophrenia. The main objective of the present study was to propose a comprehensive model of quality of life in this specific population. Data were derived from the Cohort of individuals with Schizophrenia Aged 55 years or more (CSA) study, a large (N = 353) multicenter sample of older adults with schizophrenia or schizoaffective disorder recruited from French community mental-health teams. We used structural equation modeling to simultaneously examine the effects of six broad groups of clinical factors previously identified as potential predictors of quality of life in this population, including (1) severity of general psychopathology, (2) severity of depression, (3) severity of cognitive impairment, (4) psychotropic medications, (5) general medical conditions and (6) sociodemographic characteristics. General psychopathology symptoms, and in particular negative and depressive symptoms, cognitive impairment, reduced overall functioning and low education were significantly and independently associated with diminished quality of life (all p

Eighty years ago, schizophrenia was the first indication for electroconulsive therapy (ECT), and likewise ECT was one of the first treatments used for schizophrenia. This paper presents the history of ECT in the treatment of schizophrenia and its evolution, from it’s discovery in the 20th century, which is an example of empiricism with a sequence of “shock” therapies. Following this discovery, the use ECT in schizophrenia has been in expansion during several decades, in a context of lack of efficacy of the treatment in schizophrenia. Then, after World War II and the derivative use of ECT in Germany, the use of ECT has decline during several decades. However, in the last decades, the use of ECT in schizophrenia has reemerged. Indeed, among patients in schizophrenia, rates of resistance to treatment have always been and still are high. In 2017, the concept of “ultra-treatment resistant schizophrenia” was defined when clozapine was tried and failed; and ECT, that had been long since abandoned in the treatment of schizophrenia until recent renewed interest, has emerged especially concerning the add-on of ECT to clozapine. However, ECT remains highly stigmatized and underutilized. This article looks at the history of the practice of ECT in schizophrenia with a historical and clinical approach and makes connections between the history of the treatment and its influence on its current recommendation and practice.

High rates of non-right-handedness (NRH) including mixed-handedness have been reported in neurodevelopmental disorders. In schizophrenia (SZ), atypical handedness has been inconsistently related to impaired features. We aimed to determine whether SZ subjects with NRH and mixed-handedness had poorer clinical and cognitive outcomes compared to their counterparts.667 participants were tested with a battery of neuropsychological tests, and assessed for laterality using the Edinburg Handedness Inventory. Clinical symptomatology was assessed. Learning disorders and obstetrical complications were recorded. Biological parameters were explored.The prevalence of NRH and mixed-handedness was high (respectively, 42.4% and 34.1%). In the multivariable analyses, NRH was associated with cannabis use disorder (Non-right and mixed-handedness are very high in patients with SZ, possibly reflecting a neurodevelopmental origin. NRH is associated with learning disorders and cannabis use. Mixed-handedness is associated with positive symptoms, current depressive disorder, cannabis use and less akathisia. However, this study did not confirm greater cognitive impairment in these patients.

The influence of psychosocial stressors on psychosis risk has usually been studied in isolation and after the onset of the disorder, potentially ignoring important confounding relationships or the fact that some stressors that may be the consequence of the disorder rather than preexisting. The study of subclinical psychosis could help to address some of these issues. In this study, we investigated whether there was (i) an association between dimensions of subclinical psychosis and several psychosocial stressors including: childhood trauma, self-reported discrimination experiences, low social capital, and stressful life experiences, and (ii) any evidence of environment-environment (ExE) interactions between these factors. Data were drawn from the EUGEI study, in which healthy controls (N = 1497) and siblings of subjects with a psychotic disorder (N = 265) were included in six countries. The association between psychosocial stressors and subclinical psychosis dimensions (positive, negative and depressive dimension as measured by the Community Assessment of Psychic Experiences (CAPE) scale) and possible ExE interactions were assessed using linear regression models. After adjusting for sex, age, ethnicity, country, and control/sibling status, childhood trauma (beta for positive dimension: 0.13, negative: 0.49, depressive: 0.26) and stressful life events (positive: 0.08, negative: 0.16, depressive: 0.17) were associated with the three dimensions. Lower social capital was associated with the negative and depression dimensions (negative: 0.26, depressive: 0.13), and self-reported discrimination experiences with the positive dimension (0.06). Our findings are in favor of independent, cumulative and non-specific influences of social adversities in subclinical psychosis in non-clinical populations, without arguments for E * E interactions. © The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The interest in social cognition in schizophrenia is justified by the relationship between deficits in these skills and negative functional outcomes. Although assessment batteries have already been described, there is no consensus about which measures are useful in predicting patient functioning or quality of life (QoL). We investigated a set of five measures of recognition of facial emotions, theory of mind (ToM), and empathy in a cohort of 143 patients with schizophrenia or schizoaffective disorder at inclusion and, amongst whom 79 were reassessed 1 year later. The distribution was satisfactory for the TREF (Facial Emotion Recognition Task), V-SIR (Versailles-Situational Intention Reading), and QCAE (Questionnaire of Cognitive and Affective Empathy). Internal consistency was satisfactory for the TREF, V-SIR, V-Comics (Versailles Intention Attribution Task), and QCAE. Sensitivity to change was acceptable for the TREF. The TREF and V-SIR showed a cross-sectional relationship with functioning beyond the clinical symptoms of schizophrenia but not beyond neurocognition. Moreover, the TREF and V-SIR at inclusion could not predict functioning one year later, whereas most neurocognitive and clinical dimensions at inclusion could. Finally, only affective QCAE showed a significant cross-sectional, but not longitudinal, association with QoL. In conclusion, the TREF had satisfactory psychometric properties and showed a cross-sectional, but not longitudinal, association with objective outcome measures, thus appearing to be reliable in clinical practice and research. The V-SIR also showed promising psychometric properties, despite a possible weakness to detect change. However, these measures should be interpreted within the context of the good predictive power of the neurocognitive and clinical status on the outcome.

The study of subclinical psychotic manifestations (quantitative schizotypy) represents clinical and public health issues. These manifestations are more common than schizophrenia or depression, but rarely identified while it impacts the quality of life. Screening schizotypy in the general population would make it possible to propose prevention strategies. The objectives of the present research is to better understand the determinants and mechanisms of schizotypy in order to identify population...

International audience; Introduction: Deficits in theory of mind (ToM) can vary depending on the predominant schizophrenia symptoms, and though most neurocognitive functions are involved in ToM, all may not be associated with the same symptoms. With consideration to the relationships between symptoms, neurocognition and ToM, the aim of the present study is to identify the neurocognitive functions influencing ToM capacities according to symptomatic profile. Methods: The study is based on a sample of 124 adults with schizophrenia from a French national cohort. Patients were divided into two groups according to their scores on the five Wallwork factors of the Positive and Negative Syndrome Scale using hierarchical clustering before carrying out multivariable analyses. Results: The “disorganised group” (n = 89) showed high scores on the disorganised factor, and had a ToM associated with reasoning, visual recognition and speed of processing. The “positive group” (n = 35) showed high scores on the positive and depressive factors, and had a ToM associated with working memory. Conclusions: These results suggest that neurocognitive predictors of ToM in schizophrenia are different according to the predominant clinical dimension, thus refining our knowledge of the relationship between symptoms, neurocognition and ToM, and acknowledging their status as important predictors of patients’ functional status. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients was, respectively, 20% and 7.7% and was defined using multivariable analysis elevated by high levels of interleukin (IL)-12/IL-23p40, IL-17A, IL-10, and beta 2 microglobulin (B2M) and IL-12/IL-23p40, IL-17A, IL-6, IL-10, IFNγ, and B2M, respectively. These observations suggest that resistance and ultra resistance to CLZ treatment are underpinned by pro-inflammatory molecules mainly belonging to the T helper 17 pathway, a finding making sense given the interplay between inflammation and antipsychotic treatment responses. If confirmed, our findings may allow us to consider IL-23/IL-17 pathway as a therapeutic target for patients with resistance to antipsychotics.

International audience; 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.

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.

International audience; Both shorter telomeres and schizophrenia have been associated with a decrease in life expectancy. Furthermore, several studies found a shorter telomere length (TL) in schizophrenia. Understanding whether or not telomere shortening is directly related to pathophysiology of schizophrenia or is a consequence of a cumulative exposure to chronic stress is of major importance. Comparing the TL of subjects at the very beginning of the disease (FEP) and control subjects could help to decide between these two hypotheses. The aim of the present study was to compare TL between FEP subjects (N=91) and controls (N=137). After accounting for multiple potential confounders, no significant association was observed between FEP and TL. Our result is consistent with the hypothesis that psycho-social stress / adversities and stressful situations in people with schizophrenia affect TL rather than that telomere erosion contributes to the development of this disorder.

International audience; A new etiological model is proposed for schizophrenia that combines variability-enhancing nonspecific factors acting during development with more specific risk factors. This model is better suited than the current etiological models of schizophrenia, based on the risk factors paradigm, for predicting and/or explaining several important findings about schizophrenia: high co-morbidity rates, low specificity of many risk factors, and persistence in the population of the associated genetic polymorphisms. Compared with similar models, e.g., de-canalization, common psychopathology factor, sexual-selection, or differential sensitivity to the environment, this proposal is more general and integrative. Recently developed research methods have proven the existence of genetic and environmental factors that enhance developmental variability. Applying such methods to newly collected or already available data can allow for testing the hypotheses upon which this model is built. If validated, this model may change the understanding of the etiology of schizophrenia, the research models, and preventionbrk paradigms.

AimsThe COVID-19 pandemic and associated lockdown may have psychiatric consequences and increase the number of psychiatric emergency consultations. This study aimed to compare the number and characteristics of emergency psychiatric consultations during the four first weeks of the lockdown in three psychiatric emergency services from Paris and its suburbs, and to compare them to the same period in 2019.MethodsThree psychiatric centers in Paris and its suburbs took part in the study. We compared the number of total psychiatric emergency consultations during the 4 first weeks of the lockdown in France to the corresponding 4 weeks in 2019. We also compared the number of consultations during these 4-week time periods in 2020 and 2019 across different diagnostic categories.ResultsIn the 4 first weeks of the lockdown in France, 553 emergency psychiatry consultations were carried out, compared to 1224 consultations during the corresponding period of 2019, representing a 54.8 % decrease. This decrease was evident across all psychiatric disorders, including anxiety (number of consultations in 2020 representing 36.1 % of 2019), mood (41.1 %), and psychotic disorders (57.3 %). The number of suicide attempts also decreased (number of suicide attempts in 2020 representing 42.6 % of 2019). In comparison to 2019, the proportion of total consultations for anxiety disorders also decreased (16.6 % vs. 20.8 %), whilst the proportion of total consultations increased for psychotic disorders (31.1 % vs. 24.1 %).ConclusionsThe total number of psychiatric emergency consultations during lockdown dramatically decreased. The psychological consequences of lockdown may be delayed, indicating that psychiatric services should be prepared for a secondary increase in emergency presentations.

The search for the genetic factors underlying complex neuropsychiatric disorders has proceeded apace in the past decade. Despite some advances in identifying genetic variants associated with psychiatric disorders, most variants have small individual contributions to risk. By contrast, disease risk increase appears to be less subtle for disease-predisposing environmental insults. In this study, we sought to identify associations between environmental pollution and risk of neuropsychiatric disorders. We present exploratory analyses of 2 independent, very large datasets: 151 million unique individuals, represented in a United States insurance claims dataset, and 1.4 million unique individuals documented in Danish national treatment registers. Environmental Protection Agency (EPA) county-level environmental quality indices (EQIs) in the US and individual-level exposure to air pollution in Denmark were used to assess the association between pollution exposure and the risk of neuropsychiatric disorders. These results show that air pollution is significantly associated with increased risk of psychiatric disorders. We hypothesize that pollutants affect the human brain via neuroinflammatory pathways that have also been shown to cause depression-like phenotypes in animal studies., Exploratory analyses of two independent datasets comprising 151 million Americans and 1.4 million Danes revealed that polluted air was associated with a significantly increased risk of psychiatric disorders, including bipolar disorder and schizophrenia.

Acyl coenzyme A binding protein (ACBP), also known as diazepam binding inhibitor (DBI) is a multifunctional protein with an intracellular action (as ACBP), as well as with an extracellular role (as DBI). The plasma levels of soluble ACBP/DBI are elevated in human obesity and reduced in anorexia nervosa. Accumulating evidence indicates that genetic or antibody-mediated neutralization of ACBP/DBI has anorexigenic effects, thus inhibiting food intake and inducing lipo-catabolic reactions in mice. A number of anorexiants have been withdrawn from clinical development because of their side effects including an increase in depression and suicide. For this reason, we investigated the psychiatric impact of ACBP/DBI in mouse models and patient cohorts. Intravenously (i.v.) injected ACBP/DBI protein conserved its orexigenic function when the protein was mutated to abolish acyl coenzyme A binding, but lost its appetite-stimulatory effect in mice bearing a mutation in the γ2 subunit of the γ-aminobutyric acid (GABA) A receptor (GABAAR). ACBP/DBI neutralization by intraperitoneal (i.p.) injection of a specific mAb blunted excessive food intake in starved and leptin-deficient mice, but not in ghrelin-treated animals. Neither i.v. nor i.p. injected anti-ACBP/DBI antibody affected the behavior of mice in the dark–light box and open-field test. In contrast, ACBP/DBI increased immobility in the forced swim test, while anti-ACBP/DBI antibody counteracted this sign of depression. In patients diagnosed with therapy-resistant bipolar disorder or schizophrenia, ACBP/DBI similarly correlated with body mass index (BMI), not with the psychiatric diagnosis. Patients with high levels of ACBP/DBI were at risk of dyslipidemia and this effect was independent from BMI, as indicated by multivariate analysis. In summary, it appears that ACBP/DBI neutralization has no negative impact on mood and that human depression is not associated with alterations in ACBP/DBI concentrations.

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.

Cet article aborde les déterminants des troubles psychotiques à travers l’étude des manifestations psychotiques « atténuées » (ou schizotypie quantitative) ; manifestations plus fréquentes que les troubles constitués (telle que la schizophrénie) mais rarement identifiés et pris en charge alors qu’ils impactent la qualité de vie. Si les déterminants individuels de ces troubles « atténués » sont plutôt bien connus, l’impact des déterminants contextuels (caractéristiques sociales, urbanistiques) des lieux de vie sur leur présence ou leur intensité n’a, par contre, pas encore été étudié. Les relations entre contexte de résidence et schizophrénie ont, en revanche, fait l’objet de recherches spécifiques. A partir de données recueillies auprès de 255 adultes résidant dans trois quartiers de la commune de Créteil, cette étude s’intéresse aux relations entre les représentations (dont l’étendue) du quartier de résidence, les caractéristiques (socio-démographiques et urbanistiques) du quartier et les scores de schizotypie. The study of subclinical psychotic manifestations (quantitative schizotypy) represents clinical and public health issues. These manifestations are more common than schizophrenia or depression, but rarely identified while it impacts the quality of life. Screening schizotypy in the general population would make it possible to propose prevention strategies. The objectives of the present research is to better understand the determinants and mechanisms of schizotypy in order to identify population at risk and hopefully be able to improve prevention and care. The hypothesis is that schizotypy is influenced both by individual and contextual characteristics (social, built). Based on data collected during a survey in the city of Créteil, the aims of this article were to explore the relationships between representations (including size), socioeconomic and urban planning characteristics of the neighborhood of residence and schizotypy scores. In addition, a methodological contribution of this article is to measure and characterize self-defined neighborhoods.

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, To describe schizophrenia from childhood to adulthood is complex and patients with early‐onset schizophrenia (EOS) remain undiagnosed or misclassified, especially the subgroup with very early‐onset schizophrenia (VEOS). In patients with VEOS, the DUP which exceeds 8 years, almost eight times higher than in patients with AOS, objective the problem of early diagnosis and the need to develop diagnostic programs and management cares.

Points essentiels Les mesures d’isolement et de contention mecanique font desormais l’objet d’une loi, ainsi que de recentes publications d’autorites administratives, tels qu’un rapport du Controleur General des Lieux de Privation de Liberte ou des recommandations de l’HAS. Les episodes d’agitation psychomotrice et l’auto- ou l’hetero-agressivite des episodes maniaques ou psychotiques constituent les indications les plus frequentes de leur prescription. La prescription de ces mesures obeit a des modalites de prescription particulieres qui sont detaillees dans ce travail. Les mesures d’isolement et de contention mecanique, bien qu’ayant montre leur efficacite, representent un dernier recours therapeutique, compte tenu notamment des complications physiques et du retentissement psychique. Dans les episodes d’agitation psychomotrice justifiant ces prescriptions, une prise en charge medicamenteuse specifique sera associee a visee anxiolytique, dont nous rappellerons les principales recommandations de bonnes pratiques. Enfin, la prevention et la prise en charge des complications physiques liees aux mesures d’isolement et de contention mecanique doivent faire l’objet d’une surveillance attentive. Nous presentons ici des protocoles de prevention des complications liees a la constipation et a la maladie thromboemboliques veineuse.

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.

Importance: Psychotic disorders contribute significantly to the global disease burden, yet the latest international incidence study of psychotic disorders was conducted in the 1980s. Objectives: To estimate the incidence of psychotic disorders using comparable methods across 17 catchment areas in 6 countries and to examine the variance between catchment areas by putative environmental risk factors. Design, Setting, and Participants: An international multisite incidence study (the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions) was conducted from May 1, 2010, to April 1, 2015, among 2774 individuals from England (2 catchment areas), France (3 catchment areas), Italy (3 catchment areas), the Netherlands (2 catchment areas), Spain (6 catchment areas), and Brazil (1 catchment area) with a first episode of nonorganic psychotic disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes F20-F33) confirmed by the Operational Criteria Checklist. Denominator populations were estimated using official national statistics. Exposures: Age, sex, and racial/ethnic minority status were treated as a priori confounders. Latitude, population density, percentage unemployment, owner-occupied housing, and single-person households were treated as catchment area-level exposures. Main Outcomes and Measures: Incidence of nonorganic psychotic disorders (ICD-10 codes F20-F33), nonaffective psychoses (ICD-10 codes F20-F29), and affective psychoses (ICD-10 codes F30-F33) confirmed by the Operational Criteria Checklist. Results: A total of 2774 patients (1196 women and 1578 men; median age, 30.5 years [interquartile range, 23.0-41.0 years]) with incident cases of psychotic disorders were identified during 12.9 million person-years at risk (crude incidence, 21.4 per 100 000 person-years; 95% CI, 19.4-23.4 per 100 000 person-years). A total of 2183 patients (78.7%) had nonaffective psychotic disorders. After direct standardization for age, sex, and racial/ethnic minority status, an 8-fold variation was seen in the incidence of all psychotic disorders, from 6.0 (95% CI, 3.5-8.6) per 100 000 person-years in Santiago, Spain, to 46.1 (95% CI, 37.3-55.0) per 100 000 person-years in Paris, France. Rates were elevated in racial/ethnic minority groups (incidence rate ratio, 1.6; 95% CI, 1.5-1.7), were highest for men 18 to 24 years of age, and were lower in catchment areas with more owner-occupied homes (incidence rate ratio, 0.8; 95% CI, 0.7-0.8). Similar patterns were observed for nonaffective psychoses; a lower incidence of affective psychoses was associated with higher area-level unemployment (incidence rate ratio, 0.3; 95% CI, 0.2-0.5). Conclusions and Relevance: This study confirmed marked heterogeneity in risk for psychotic disorders by person and place, including higher rates in younger men, racial/ethnic minorities, and areas characterized by a lower percentage of owner-occupied houses., The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework Programme. The Brazilian study was funded by grant 2012/0417-0 from the São Paulo Research Foundation. Dr Kirkbride is funded by the Wellcome Trust and grant 101272/Z/13/Z from the Royal Society. Ms Jongsma and Dr Jones are funded by the National Institute of Health Research Collaboration of Leadership in Applied Health Research and Care East of England.

The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant inSNAP25,rs6039769, that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combinedin vitroandin vivoapproaches in humans to understand the functional impact of the at-risk allele. Thus, we showedin vitrothat thers6039769C allele was sufficient to increase theSNAP25transcription level. In a postmortem expression analysis of 33 individuals affected with schizophrenia and 30 unaffected control subjects, we showed that theSNAP25b/SNAP25aratio was increased in schizophrenic patients carrying thers6039769at-risk allele. Last, using genetics imaging in a cohort of 71 subjects, we showed that male risk carriers had an increased amygdala–ventromedial prefrontal cortex functional connectivity and a larger amygdala than non-risk carriers. The latter association has been replicated in an independent cohort of 121 independent subjects. Altogether, results from these multilevel functional studies are bringing strong evidence for the functional consequences of this allelic variation ofSNAP25on modulating the development and plasticity of the prefrontal–limbic network, which therefore may increase the vulnerability to both early-onset bipolar disorder and schizophrenia.SIGNIFICANCE STATEMENTFunctional characterization of disease-associated variants is a key challenge in understanding neuropsychiatric disorders and will open an avenue in the development of personalized treatments. Recent studies have accumulated evidence that the SNARE complex, and more specifically the SNAP25 protein, may be involved in psychiatric disorders. Here, our multilevel functional studies are bringing strong evidence for the functional consequences of an allelic variation ofSNAP25on modulating the development and plasticity of the prefrontal–limbic network. These results demonstrate a common genetically driven functional alteration of a synaptic mechanism both in schizophrenia and early-onset bipolar disorder and confirm the shared genetic vulnerability between these two disorders.

International audience

Background: Extrapyramidal side effects (EPS) have been identified as a complication of antipsychotic treatment. Previous meta-analyses have investigated EPS prevalence and risk factors in randomized clinical trials with highly selected patients, but studies in real-world schizophrenia are missing. Objective: To examine the prevalence and clinical correlates associated with EPS in a nonselected national multicenter sample of stabilized patients with schizophrenia. Methods: Between 2010 and 2016, patients suffering from schizophrenia (DSM-IV-TR criteria) were recruited through the FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) network and data were collected during a comprehensive 1-day-long standardized evaluation. The Simpson-Angus Scale and the Abnormal Involuntary Movement Scale were used to assess drug-induced parkinsonism (DIP) and tardive dyskinesia, respectively. Results: The overall prevalence of DIP and tardive dyskinesia was 13.2% and 8.3%, respectively, in this community-dwelling sample of 674 patients. DIP was associated with negative symptoms (Positive and Negative Syndrome Scale [PANSS] subscore) (adjusted odds ratio [aOR] = 1.102, P < .001), first-generation antipsychotic prescription (aOR = 2.038, P = .047), and anticholinergic drug administration (aOR = 2.103, P = .017) independently of sex, age, disorganization (PANSS disorganized factor), and antipsychotic polytherapy. Tardive dyskinesia was associated with PANSS disorganized factor (aOR = 1.103, P = .049) independently of sex, age, negative symptoms, excitation, first-generation antipsychotic prescription, and benzodiazepine and anticholinergic drug administration. Conclusions: Our results indicate the high prevalence of EPS in a nonselected community-dwelling clinically stable sample of outpatients with schizophrenia. In the monitoring of antipsychotic treatment, EPS should be systematically evaluated, especially when negative symptoms and disorganization or cognitive alteration are present. Monotherapy with a second-generation antipsychotic should be preferentially initiated for patients with these side effects.

International audience; Purpose of Review This review will aim to summarize the current body of epidemiological, clinical and therapeutic knowledge concerning specific co-occurrence of obsessive-compulsive symptoms (OCS) and schizophrenia spectrum disorder.Recent Findings Almost 30 % of the patients with schizophrenia display OCS, and three main contexts of emergence are identified: prodromal symptoms of schizophrenia, co-occurrence of OCS and schizophrenia, and antipsychotics-induced OCS. Recent clinical studies show that patients with SZ and OCS has more severe psychotic and depressive symptoms, higher suicidality and lower social functioning. A recent cognitive investigation found that OCS and delusions share specific metacognitive profiles, particularly through a heightened need to control thoughts. Finally, a recent cross-sectional study of clozapine-induced OCS found a dose-response relationship between clozapine and OCS.Summary: OCS appeared reliably as linked to poorer outcomes among patients with schizophrenia. However, the specific clinical value of OCS among other prodromal symptoms of schizophrenia remains unknown.