Publications by authors named "Pierre-Michel Llorca"

210 Publications

Controversies Surrounding the Use of Long-Acting Injectable Antipsychotic Medications for the Treatment of Patients with Schizophrenia.

CNS Drugs 2021 Oct 11. Epub 2021 Oct 11.

Fondation FondaMental, Créteil, France.

Schizophrenia is a serious mental illness that requires continuous and effective long-term management to reduce symptoms, improve quality of life, and prevent relapse. Oral antipsychotic medications have proven efficacy for many patients taking these medications; however, a considerable number of patients continue to experience ongoing symptoms and relapse, often due to lack of adherence. The advent of long-acting injectable (LAI) formulations of antipsychotic medications provided an opportunity to improve treatment adherence and overall patient outcomes. Despite data to support LAI efficacy, safety, and improved adherence over oral formulations, there are several misconceptions about and barriers to LAI implementation within a standard of care for patients with schizophrenia. Areas of resistance around LAIs include (1) doubts regarding their benefits outside of improved adherence, (2) questions regarding their prescribing to a broader population of patients with schizophrenia, (3) when to initiate LAIs, (4) concerns regarding the safety of LAIs in comparison with oral medication, and (5) the most effective ways to educate healthcare providers, patients, and caretakers to enable appropriate LAI consideration and acceptance. Here, we discuss these key controversies associated with LAIs and provide supportive evidence to facilitate LAI use in a manner that is constructive to the clinician-patient relationship and successful treatment.
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http://dx.doi.org/10.1007/s40263-021-00861-6DOI Listing
October 2021

Controversies Surrounding the Use of Long-Acting Injectable Antipsychotic Medications for the Treatment of Patients with Schizophrenia.

CNS Drugs 2021 Oct 11. Epub 2021 Oct 11.

Fondation FondaMental, Créteil, France.

Schizophrenia is a serious mental illness that requires continuous and effective long-term management to reduce symptoms, improve quality of life, and prevent relapse. Oral antipsychotic medications have proven efficacy for many patients taking these medications; however, a considerable number of patients continue to experience ongoing symptoms and relapse, often due to lack of adherence. The advent of long-acting injectable (LAI) formulations of antipsychotic medications provided an opportunity to improve treatment adherence and overall patient outcomes. Despite data to support LAI efficacy, safety, and improved adherence over oral formulations, there are several misconceptions about and barriers to LAI implementation within a standard of care for patients with schizophrenia. Areas of resistance around LAIs include (1) doubts regarding their benefits outside of improved adherence, (2) questions regarding their prescribing to a broader population of patients with schizophrenia, (3) when to initiate LAIs, (4) concerns regarding the safety of LAIs in comparison with oral medication, and (5) the most effective ways to educate healthcare providers, patients, and caretakers to enable appropriate LAI consideration and acceptance. Here, we discuss these key controversies associated with LAIs and provide supportive evidence to facilitate LAI use in a manner that is constructive to the clinician-patient relationship and successful treatment.
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http://dx.doi.org/10.1007/s40263-021-00861-6DOI Listing
October 2021

Stigmatization toward People with Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder: A Scoping Review.

Nutrients 2021 Aug 18;13(8). Epub 2021 Aug 18.

Centre Troubles des Conduites Alimentaires (TCA), Service de Nutrition Clinique, Unité de Nutrition Humaine, CHU Gabriel Montpied, CRNH, Université Clermont Auvergne, 63003 Clermont-Ferrand, France.

Research about stigmatization in eating disorders (EDs) has highlighted stereotypes, prejudices, and discrimination against people with EDs, as well as their harmful effects on them, including self-stigma and a difficult recovery process. Whereas a recent review focused on the consequences of ED stigma, our work aimed to provide a broader synthesis of ED stigma, including its consequences, but also its content and distribution. More precisely, we focused on three EDs-namely, anorexia nervosa, bulimia nervosa, and binge eating disorder. Based on a systematic search of four major databases in psychology, the present scoping review includes 46 studies published between 2004 and 2021. We did not conduct any quality assessment of the studies included, because our aim was to provide a wide-ranging overview of these topics instead of an appraisal of evidence answering a precise research question. The review confirmed the existence of a common ED stigma: all individuals affected by EDs reviewed here were perceived as responsible for their situation, and elicited negative emotions and social distance. However, our review also depicted a specific stigma content associated with each ED. In addition, the demographic characteristics of the stigmatizing individuals had a notable influence on the extent of ED stigma: men, young adults, and low-income individuals appeared to be the most stigmatizing toward individuals with EDs. It is important to note that ED stigma had a negative effect on individuals' eating disorders, psychological wellbeing, and treatment-seeking behavior. There is an urgent need for further research on the adverse effects of ED stigma and its prevention.
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http://dx.doi.org/10.3390/nu13082834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400545PMC
August 2021

Mortality among inpatients with bipolar disorders and COVID-19: a propensity score matching analysis in a national French cohort study.

Psychol Med 2021 Aug 24:1-10. Epub 2021 Aug 24.

CEReSS-Health Service Research and Quality of Life Center, Aix-Marseille University, 27 Boulevard Jean Moulin, Marseille13005, France.

Background: It remains unknown whether coronavirus disease 2019 (COVID-19) patients with bipolar disorders (BDs) are at an increased risk of mortality. We aimed to establish whether health outcomes and care differed between patients infected with COVID-19 with BD and patients without a diagnosis of severe mental illness.

Methods: We conducted a population-based cohort study of all patients with identified COVID-19 and respiratory symptoms who were hospitalized in France between February and June 2020. The outcomes were in-hospital mortality and intensive care unit (ICU) admission. We used propensity score matching to control for confounding factors.

Results: In total, 50 407 patients were included, of whom 480 were patients with BD. Patients with BD were 2 years older, more frequently women and had more comorbidities than controls without a diagnosis of severe mental illness. Patients with BD had an increased in-hospital mortality rate (26.6% v. 21.9%; p = 0.034) and similar ICU admission rate (27.9% v. 28.4%, p = 0.799), as confirmed by propensity analysis [odds ratio, 95% confidence interval (OR, 95% CI) for mortality: 1.30 (1.16-1.45), p < 0.0001]. Significant interactions between BD and age and between BD and social deprivation were found, highlighting that the most important inequalities in mortality were observed in the youngest [OR, 95% CI 2.28 (1.18-4.41), p = 0.0015] and most deprived patients with BD [OR, 95% CI 1.60 (1.33-1.92), p < 0.001].

Conclusions: COVID-19 patients with BD were at an increased risk of mortality, which was exacerbated in the youngest and most deprived patients with BD. Patients with BD should thus be targeted as a high-risk population for severe forms of COVID-19, requiring enhanced preventive and disease management strategies.
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http://dx.doi.org/10.1017/S0033291721003676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438351PMC
August 2021

The relationship of symptom dimensions with premorbid adjustment and cognitive characteristics at first episode psychosis: Findings from the EU-GEI study.

Schizophr Res 2021 10 14;236:69-79. Epub 2021 Aug 14.

Department of Psychiatry, Early Psychosis Section, Amsterdam UMC, University of Amsterdam, Meibergdreef 5, 1105 AZ Amsterdam, the Netherlands; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.

Premorbid functioning and cognitive measures may reflect gradients of developmental impairment across diagnostic categories in psychosis. In this study, we sought to examine the associations of current cognition and premorbid adjustment with symptom dimensions in a large first episode psychosis (FEP) sample. We used data from the international EU-GEI study. Bifactor modelling of the Operational Criteria in Studies of Psychotic Illness (OPCRIT) ratings provided general and specific symptom dimension scores. Premorbid Adjustment Scale estimated premorbid social (PSF) and academic adjustment (PAF), and WAIS-brief version measured IQ. A MANCOVA model examined the relationship between symptom dimensions and PSF, PAF, and IQ, having age, sex, country, self-ascribed ethnicity and frequency of cannabis use as confounders. In 785 patients, better PSF was associated with fewer negative (B = -0.12, 95% C.I. -0.18, -0.06, p < 0.001) and depressive (B = -0.09, 95% C.I. -0.15, -0.03, p = 0.032), and more manic (B = 0.07, 95% C.I. 0.01, 0.14, p = 0.023) symptoms. Patients with a lower IQ presented with slightly more negative and positive, and fewer manic, symptoms. Secondary analysis on IQ subdomains revealed associations between better perceptual reasoning and fewer negative (B = -0.09, 95% C.I. -0.17, -0.01, p = 0.023) and more manic (B = 0.10, 95% C.I. 0.02, 0.18, p = 0.014) symptoms. Fewer positive symptoms were associated with better processing speed (B = -0.12, 95% C.I. -0.02, -0.004, p = 0.003) and working memory (B = -0.10, 95% C.I. -0.18, -0.01, p = 0.024). These findings suggest that the negative and manic symptom dimensions may serve as clinical proxies of different neurodevelopmental predisposition in psychosis.
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http://dx.doi.org/10.1016/j.schres.2021.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473991PMC
October 2021

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.

Transl Psychiatry 2021 08 10;11(1):423. Epub 2021 Aug 10.

Department of Psychiatry, Early Psychosis Section, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03-0.33) and positive (B = 0.19; 95%CI 0.03-0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11-0.52) and in controls (B = 0.26; 95%CI 0.06-0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.
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http://dx.doi.org/10.1038/s41398-021-01526-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355107PMC
August 2021

Handedness in bipolar disorders is associated with specific neurodevelopmental features: results of the BD-FACE cohort.

Eur Arch Psychiatry Clin Neurosci 2021 Aug 10. Epub 2021 Aug 10.

Fondation Fondamental, Créteil, France.

Objectives: High rates of non-right-handedness (NRH) and mixed-handedness exist in neurodevelopmental disorders. Dysfunctional neurodevelopmental pathways may be implicated in the underlying pathophysiology of bipolar disorders (BD), at least in some subgroups. Yet little is known about correlates of NRH and mixed-handedness in BD. The objectives of this national study are to determine (i) the prevalence of NRH and mixed-handedness in a well-stabilized sample of BD individuals; (ii) if NRH/mixed-handedness in BD is associated with a different clinical, biological and neurocognitive profile.

Methods: We included 2174 stabilized individuals. Participants were tested with a comprehensive battery of neuropsychological tests. Handedness was assessed using a single oral question. Learning and/or language disorders and obstetrical complications were recorded using childhood records. Common environmental, clinical and biological parameters were assessed.

Results: The prevalence of NRH and mixed-handedness were, respectively, 11.6 and 2.4%. Learning/language disorders were found in 9.7% out of the total sample and were associated with atypical handedness (only dyslexia for mixed-handedness (p < 0.01), and dyslexia and dysphasia for NRH (p = 0.01 and p = 0.04, respectively). In multivariate analyses, NRH was associated with a younger age of BD onset (aOR 0.98 (95% CI 0.96-0.99) and lifetime substance use disorder (aOR 1.40 (95% CI 1.03-1.82) but not with any of the cognitive subtasks. Mixed-handedness was associated in univariate analyses with lifetime substance use disorder, lifetime cannabis use disorder (all p < 0.01) and less mood stabilizer prescription (p = 0.028). No association was found between NRH or mixed-handedness and the following parameters: trauma history, obstetrical complications, prior psychotic symptoms, bipolar subtype, attention deficit/hyperactivity disorder, peripheral inflammation or body mass index.

Conclusions: Handedness may be associated with specific features in BD, possibly reflecting a specific subgroup with a neurodevelopmental load.
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http://dx.doi.org/10.1007/s00406-021-01314-3DOI Listing
August 2021

Dosing antipsychotics in special populations of patients with schizophrenia: severe psychotic agitation, first psychotic episode and elderly patients.

Expert Opin Pharmacother 2021 Aug 17:1-13. Epub 2021 Aug 17.

Department of Psychiatry, University Hospital, Clermont Ferrand, France.

Antipsychotic (AP) dosing is well established in nonelderly patients with acute exacerbations of schizophrenia, but not in special populations.This review describes the AP dosing procedures that have been used in clinical studies for acute psychotic agitation, a first episode of psychosis (FEP), and elderly patients. AP dosing data was extracted from the databases of drug regulatory authorities, and from clinical studies available in the medical literature. In acute psychotic agitation, intramuscular and oral APs are frequently prescribed in higher doses than those that saturate D2 receptors. Supersaturating doses of APs should be avoided due to an increased risk of adverse effects. In FEP, many studies showed efficacy of low doses of APs. Studies with risperidone and haloperidol suggested a dose reduction of approximately one third. Titration with a lower starting dose is recommended in elderly patients, due to possible decreases in pharmacokinetic clearance, and due to the risk of concomitant diseases and drug interactions. Exposure to some APs has been associated with QTc prolongation and arrhythmias, and a small but significant increase in the risk of stroke and mortality with APs has been seen, particularly in older people with dementia-related psychosis.
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http://dx.doi.org/10.1080/14656566.2021.1958781DOI Listing
August 2021

Association Between Mental Health Disorders and Mortality Among Patients With COVID-19 in 7 Countries: A Systematic Review and Meta-analysis.

JAMA Psychiatry 2021 Jul 27. Epub 2021 Jul 27.

Aix-Marseille University, CEReSS-Health Service Research and Quality of Life Center, Marseille, France.

Importance: Heterogeneous evidence exists for the association between COVID-19 and the clinical outcomes of patients with mental health disorders. It remains unknown whether patients with COVID-19 and mental health disorders are at increased risk of mortality and should thus be targeted as a high-risk population for severe forms of COVID-19.

Objective: To determine whether patients with mental health disorders were at increased risk of COVID-19 mortality compared with patients without mental health disorders.

Data Sources: For this systematic review and meta-analysis, MEDLINE, Web of Science, and Google Scholar were searched from inception to February 12, 2021. Bibliographies were also searched, and the corresponding authors were directly contacted. The search paradigm was based on the following combination: (mental, major[MeSH terms]) AND (COVID-19 mortality[MeSH terms]). To ensure exhaustivity, the term mental was replaced by psychiatric, schizophrenia, psychotic, bipolar disorder, mood disorders, major depressive disorder, anxiety disorder, personality disorder, eating disorder, alcohol abuse, alcohol misuse, substance abuse, and substance misuse.

Study Selection: Eligible studies were population-based cohort studies of all patients with identified COVID-19 exploring the association between mental health disorders and mortality.

Data Extraction And Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used for abstracting data and assessing data quality and validity. This systematic review is registered with PROSPERO.

Main Outcomes And Measures: Pooled crude and adjusted odds ratios (ORs) for the association of mental health disorders with mortality were calculated using a 3-level random-effects (study/country) approach with a hierarchical structure to assess effect size dependency.

Results: In total, 16 population-based cohort studies (data from medico-administrative health or electronic/medical records databases) across 7 countries (1 from Denmark, 2 from France, 1 from Israel, 3 from South Korea, 1 from Spain, 1 from the UK, and 7 from the US) and 19 086 patients with mental health disorders were included. The studies covered December 2019 to July 2020, were of good quality, and no publication bias was identified. COVID-19 mortality was associated with an increased risk among patients with mental health disorders compared with patients without mental health disorders according to both pooled crude OR (1.75 [95% CI, 1.40-2.20]; P < .05) and adjusted OR (1.38 [95% CI, 1.15-1.65]; P < .05). The patients with severe mental health disorders had the highest ORs for risk of mortality (crude OR: 2.26 [95% CI, 1.18-4.31]; adjusted OR: 1.67 [95% CI, 1.02-2.73]).

Conclusions And Relevance: In this systematic review and meta-analysis of 16 observational studies in 7 countries, mental health disorders were associated with increased COVID-19-related mortality. Thus, patients with mental health disorders should have been targeted as a high-risk population for severe forms of COVID-19, requiring enhanced preventive and disease management strategies. Future studies should more accurately evaluate the risk for patients with each mental health disorder. However, the highest risk seemed to be found in studies including individuals with schizophrenia and/or bipolar disorders.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.2274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317055PMC
July 2021

Childhood maltreatment and metabolic syndrome in bipolar disorders: In search of moderators.

Psychoneuroendocrinology 2021 Sep 15;131:105327. Epub 2021 Jun 15.

Fondation FondaMental, Créteil, France; Assistance Publique des Hôpitaux de Paris (AP-HP) Paris. Nord, GHU Saint-Louis - Lariboisière - Fernand Widal, DMU Neurosciences, Département de Psychiatrie et de Médecine Addictologique, INSERM UMRS 1144, Université de Paris, Paris, France.

As compared to the general population, adult individuals with bipolar disorders (BD) have higher mortality rates due to cardiovascular diseases and higher prevalence of Metabolic Syndrome (MetS). Recent evidence suggests that childhood maltreatment may contribute to the cardiovascular burden in individuals with BD. However, studies are scarce, with limited sample sizes and inconsistent results. We explored the associations between a self-reported history of childhood maltreatment and MetS (and its subcomponents) in a large sample of 2390 individuals with BD. Childhood maltreatment was assessed using the Childhood Trauma Questionnaire and MetS was defined according to the revised criteria of the ATEP III. We suggested associations between childhood maltreatment and the presence of MetS in men and in younger individuals. The association between childhood maltreatment and the presence of MetS in the early onset subgroup was not significant after adjustment for site of recruitment and level of education. Hence, some links between childhood maltreatment and MetS might exist only in specific subgroups of individuals with BD, but confirmation is required in independent and large samples, while taking into account potential confounders. This would help defining how psychosocial interventions that target childhood maltreatment and its consequences may be beneficial for physical health.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105327DOI Listing
September 2021

Comparison of three scales (BIS, SUMD and BCIS) for measuring insight dimensions and their evolution after one-year of follow-up: Findings from the FACE-SZ Cohort.

Psychiatry Res 2021 09 20;303:114044. Epub 2021 Jun 20.

Service Universitaire de Psychiatrie Adulte, Hôpital la Colombière, CHU Montpellier, Montpellier, France; Univ Paul Valéry Montpellier 3, Univ. Montpellier, EPSYLON EA, Montpellier, France.

The aim of our study was to compare the performance of three different instruments measuring clinical and cognitive dimensions of insight. Data on 182 outpatients with schizophrenia and one-year follow-up assessments was drawn from the FACE-SZ cohort. Awareness of clinical state (« clinical insight ») was measured using both a clinician-rated measure (the Scale to assess Unawareness of Mental Disorder (SUMD)), and a self-report measure (the Birchwood Insight Scale (BIS). Cognitive insight was measured using a self-report measure (the Beck Cognitive Insight Scale (BCIS)). For each scale, change in insight was examined at the follow-up. Correlations between SUMD and BIS subscales measuring same dimensions were significant. BIS-BCIS correlations were weak for all combinations except between BIS illness dimension and BCIS composite score. At the follow-up, BIS and SUMD awareness of treatment need improved whereas illness and symptom awareness increased only on the SUMD. Conversely, cognitive insight composite scores decreased. Despite relatively good overall agreement between the two clinical insight instruments, considerable variability for similar insight dimensions measured by different instruments was found. Agreement between cognitive and clinical insight is moderate. Our study strengthens the argument that insight is harder to operationalize than other symptoms and may explain why it is so seldom explicitly targeted in schizophrenia treatment.
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http://dx.doi.org/10.1016/j.psychres.2021.114044DOI Listing
September 2021

Patients' adherence to smartphone apps in the management of bipolar disorder: a systematic review.

Int J Bipolar Disord 2021 Jun 3;9(1):19. Epub 2021 Jun 3.

Department of Psychiatry, CHU Clermont-Ferrand, University of Clermont Auvergne, CNRS, Clermont Auvergne INP, Institut Pascal, Clermont-Ferrand, France.

Background: Despite an increasing number of available mental health apps in the bipolar disorder field, these tools remain scarcely implemented in everyday practice and are quickly discontinued by patients after downloading. The aim of this study is to explore adherence characteristics of bipolar disorder patients to dedicated smartphone interventions in research studies.

Methods: A systematic review following PRISMA guidelines was conducted. Three databases (EMBASE, PsychInfo and MEDLINE) were searched using the following keywords: "bipolar disorder" or "mood disorder" or "bipolar" combined with "digital" or "mobile" or "phone" or "smartphone" or "mHealth" or "ehealth" or "mobile health" or "app" or "mobile-health".

Results: Thirteen articles remained in the review after exclusion criteria were applied. Of the 118 eligible studies, 39 did not provide adherence characteristics. Among the selected papers, study length, sample size and definition of measures of adherence were strongly heterogeneous. Activity rates ranged from 58 to 91.6%.

Conclusion: The adherence of bipolar patients to apps is understudied. Standardised measures of adherence should be defined and systematically evaluated in future studies dedicated to these tools.
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http://dx.doi.org/10.1186/s40345-021-00224-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175501PMC
June 2021

The Independent Effects of Psychosocial Stressors on Subclinical Psychosis: Findings From the Multinational EU-GEI Study.

Schizophr Bull 2021 Oct;47(6):1674-1684

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.

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 (β 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.
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http://dx.doi.org/10.1093/schbul/sbab060DOI Listing
October 2021

End of life breast cancer care in women with severe mental illnesses.

Sci Rep 2021 05 13;11(1):10167. Epub 2021 May 13.

Faculté de Médecine - Secteur Timone, EA 3279: CEReSS -Centre d'Etude et de Recherche sur les Services de Santé et la Qualité de vie, Aix-Marseille Univ., 27 Boulevard Jean Moulin, 13005, Marseille, France.

Little is known on the end-of-life (EOL) care of terminal breast cancer in women with severe psychiatric disorder (SPD). The objective was to determine if women with SPD and terminal breast cancer received the same palliative and high-intensity care during their end-of-life than women without SPD. Study design, setting, participants. This population-based cohort study included all women aged 15 and older who died from breast cancer in hospitals in France (2014-2018). Key measurements/outcomes. Indicators of palliative care and high-intensity EOL care. Multivariable models were performed, adjusted for age at death, year of death, social deprivation, duration between cancer diagnosis and death, metastases, comorbidity, smoking addiction and hospital category. The analysis included 1742 women with SPD (287 with bipolar disorder, 1075 with major depression and 380 with schizophrenia) and 36,870 women without SPD. In multivariate analyses, women with SPD had more palliative care (adjusted odd ratio aOR 1.320, 95%CI [1.153-1.511], p < 0.001), longer palliative care follow-up before death (adjusted beta = 1.456, 95%CI (1.357-1.555), p < 0.001), less chemotherapy, surgery, imaging/endoscopy, and admission in emergency department and intensive care unit. Among women with SPD, women with bipolar disorders and schizophrenia died 5 years younger than those with recurrent major depression. The survival time was also shortened in women with schizophrenia. Despite more palliative care and less high-intensity care in women with SPD, our findings also suggest the existence of health disparities in women with bipolar disorders and schizophrenia compared to women with recurrent major depression and without SPD. Targeted interventions may be needed for women with bipolar disorders and schizophrenia to prevent these health disparities.
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http://dx.doi.org/10.1038/s41598-021-89726-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119688PMC
May 2021

Duration of Untreated Psychosis in First-Episode Psychosis is not Associated With Common Genetic Variants for Major Psychiatric Conditions: Results From the Multi-Center EU-GEI Study.

Schizophr Bull 2021 Oct;47(6):1653-1662

Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy.

Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0-38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8-30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.
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http://dx.doi.org/10.1093/schbul/sbab055DOI Listing
October 2021

Relationship between childhood physical abuse and clinical severity of treatment-resistant depression in a geriatric population.

PLoS One 2021 20;16(4):e0250148. Epub 2021 Apr 20.

Fondation FondaMental, Creteil, France.

Introduction: We assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample.

Methods: Patients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres.

Results: Our sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0-60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0-27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0-30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β = 0.274; p = 0.07) and QIDS-SR (β = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β = 0.304; p = 0.03) and QIDS-SR (β = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly's Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect.

Conclusion: To our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250148PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057608PMC
October 2021

The course of bipolar disorder as a function of the presence and sequence of onset of comorbid alcohol use disorders in outpatients attending the Fondamental Advanced Centres of Expertise.

J Affect Disord 2021 05 19;287:196-203. Epub 2021 Mar 19.

Fondation Fondamental, Créteil, France; Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France; PSNREC, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.

Objectives: The comorbidity of alcohol use disorder (AUD) and bipolar disorder (BD) has been repeatedly associated with poorer clinical outcomes than BD without AUD. We aimed to extend these findings by focusing on the characteristics associated with the sequence of onset of BD and AUD.

Methods: 3,027 outpatients from the Fondamental Advanced Centres of Expertise were ascertained for BD-1, BD-2 and AUD diagnoses, including their respective ages at onset (AAOs, N =2,804). We selected the variables associated with both the presence and sequence of onset of comorbid AUD using bivariate analyses corrected for multiple testing to enter a binary regression model with the sequence of onset of BD and AUD as the dependent variable (AUD first - which also included 88 same-year onsets, vs. BD first).

Results: BD patients with comorbid AUD showed more severe clinical profile than those without. Compared to BD-AUD (N =269), AUD-BD (N =276) was independently associated with a higher AAO of BD (OR =1.1, p <0.001), increased prevalence of comorbid cannabis use disorder (OR =2.8, p <0.001) a higher number of (hypo)manic/mixed BD episodes per year of bipolar illness (OR =3, p <0.01).

Limitations: The transversal design prevents from drawing causal conclusions.

Conclusion: Increased severity of BD with AUD compared to BD alone did not differ according to the sequence of onset. A few differences, though, could be used to better monitor the trajectory of patients showing either one of these disorders.
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http://dx.doi.org/10.1016/j.jad.2021.03.041DOI Listing
May 2021

[Mortality in schizophrenia: Towards a new health scandal? COVID-19 and schizophrenia].

Ann Med Psychol (Paris) 2021 Apr 17;179(4):353-362. Epub 2021 Feb 17.

FondaMental Academic Centers of Expertise for Schizophrenia, Créteil, France.

Patients with schizophrenia represent a vulnerable population who have been understudied in COVID-19 research. We aimed to establish whether health outcomes and care differed between patients with schizophrenia and patients without a diagnosis of severe mental illness. We conducted a population-based cohort study of all patients with identified COVID-19 and respiratory symptoms who were hospitalized in France between February and June 2020. Cases were patients who had a diagnosis of schizophrenia. Controls were patients who did not have a diagnosis of severe mental illness. The outcomes were in-hospital mortality and intensive care unit (ICU) admission. A total of 50,750 patients were included, of whom 823 were schizophrenia patients (1.6%). The schizophrenia patients had an increased in-hospital mortality (25.6% vs. 21.7%; adjusted odds ratio (aOR) 1.30 [95% CI 1.08-1.56], p = 0.0093) and a decreased ICU admission rate (23.7% vs. 28.4%; aOR 0.75 [95% CI 0.62-0.91], p = 0.0062) compared to controls. Significant interactions between schizophrenia and age for mortality and ICU admission were observed (p = 0.0006 and p < 0.0001). Schizophrenia patients between 65 and 80 years had a significantly higher risk of death than controls of the same age (+7.89%). schizophrenia patients younger than 55 years had more ICU admissions (+13.93%) and schizophrenia patients between 65 and 80 years and older than 80 years had less ICU admissions than controls of the same age (-15.44% and -5.93%, respectively). Our findings report the existence of disparities in health and health care between schizophrenia patients and patients without a diagnosis of severe mental illness. These disparities differed according to the age and clinical profile of schizophrenia patients, suggesting the importance of personalized COVID-19 clinical management and health care strategies before, during and after hospitalization for reducing health disparities in this vulnerable population.
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http://dx.doi.org/10.1016/j.amp.2021.02.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969983PMC
April 2021

Perceived major experiences of discrimination, ethnic group, and risk of psychosis in a six-country case-control study.

Psychol Med 2021 Mar 2:1-9. Epub 2021 Mar 2.

Department of Psychiatry, University of Cambridge, CambridgeCB2 0SZ, UK.

Background: Perceived discrimination is associated with worse mental health. Few studies have assessed whether perceived discrimination (i) is associated with the risk of psychotic disorders and (ii) contributes to an increased risk among minority ethnic groups relative to the ethnic majority.

Methods: We used data from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions Work Package 2, a population-based case-control study of incident psychotic disorders in 17 catchment sites across six countries. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between perceived discrimination and psychosis using mixed-effects logistic regression models. We used stratified and mediation analyses to explore differences for minority ethnic groups.

Results: Reporting any perceived experience of major discrimination (e.g. unfair treatment by police, not getting hired) was higher in cases than controls (41.8% v. 34.2%). Pervasive experiences of discrimination (≥3 types) were also higher in cases than controls (11.3% v. 5.5%). In fully adjusted models, the odds of psychosis were 1.20 (95% CI 0.91-1.59) for any discrimination and 1.79 (95% CI 1.19-1.59) for pervasive discrimination compared with no discrimination. In stratified analyses, the magnitude of association for pervasive experiences of discrimination appeared stronger for minority ethnic groups (OR = 1.73, 95% CI 1.12-2.68) than the ethnic majority (OR = 1.42, 95% CI 0.65-3.10). In exploratory mediation analysis, pervasive discrimination minimally explained excess risk among minority ethnic groups (5.1%).

Conclusions: Pervasive experiences of discrimination are associated with slightly increased odds of psychotic disorders and may minimally help explain excess risk for minority ethnic groups.
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http://dx.doi.org/10.1017/S0033291721000453DOI Listing
March 2021

The Early Impact of the COVID-19 Lockdown on Stress and Addictive Behaviors in an Alcohol-Consuming Student Population in France.

Front Psychiatry 2021 9;12:628631. Epub 2021 Feb 9.

CHU Clermont-Ferrand, Pôle Psychiatrie B, Clermont-Ferrand, France.

This study evaluated factors linked with perceived stress related to the COVID-19 pandemic and lockdown and addictive behaviors prior to and during lockdown in a sample of students who indicated engaging in alcohol consumption behaviors before lockdown. Cross-sectional study. French students from four universities participated in this study, and 2,760 students reported alcohol use. During the first week of lockdown, students reported their perceived levels of stress regarding COVID-19. Substance use and addictive behaviors were reported before and during lockdown, and media exposure, demographical, living conditions, and environmental stressors were reported during lockdown. Women reported greater levels of stress (95% CI: 1.18 to 1.93, < 0.001). Highly-stressed students also report less social support (95% CI: -1.04 to -0.39, < 0.001) and were more likely to worry about the lockdown (95% CI: 0.27 to -0.65, < 0.001). Alcohol-related problemswere more prevalent among the most stressed students (95% CI: 0.02 to 0.09, = 0.004) as well as eating problems (95% CI: 0.04 to 0.36, = 0.016) and problematic internet use (95% CI, 0.06 to 0.14, < 0.001). Students reporting the highest levels of stress also indicated more compulsive eating during the previous seven days (95% CI, 0.21 to 1.19, = 0.005). The level of stress was strongly related to four categories of variables: (i) intrinsic characteristics, (ii) addictive behaviors before lockdown, (iii) lockdown-specific conditions, and (iv) addictive behaviors during the lockdown. Several variables linked to COVID-19 were not directly linked with perceived stress, while perceived stress was found to correlate with daily life organization-related uncertainty and anticipated consequences of lockdown. Importantly, social support seems to be a protective factor on high level of stress.
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http://dx.doi.org/10.3389/fpsyt.2021.628631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900161PMC
February 2021

Trajectories of medication adherence in patients with Bipolar Disorder along 2 years-follow-up.

J Affect Disord 2021 03 31;282:812-819. Epub 2020 Dec 31.

Pôle de Psychiatrie, Assistance Publique Hôpitaux de Marseille, Marseille, France; Fondation FondaMental, fondation de coopération scientifique, Créteil, France; INT-UMR7289, CNRS, Aix-Marseille Université, Marseille, France. Electronic address:

Background: Bipolar disorder (BD) is a chronic and severe mental illness. It requires a non-discontinued pharmacological treatment to prevent mood recurrences but nonadherence to medication is frequent. To this date, medication adherence in BD has been mostly evaluated in cross-sectional studies and often considered as a stable trait. We aimed to study medication adherence using a prospective person-oriented approach.

Methods: 1627 BD patients were followed on a 2 years period and assessed every 6 months. Medication adherence was evaluated at each visit with the Medication Adherence Rating Scale (MARS). A latent class mixed model (LCMM) was used to identify trajectory classes of adherence over time. Regression analyses and linear mixed model were used to search for predictors and covariables of the trajectories.

Results: Three distinct and robust trajectories of medication adherence have been identified: one that starts poorly and keeps deteriorating (4.8%), one that starts poorly but improves (9%) and one that starts well and keeps improving (86.2%). A good tolerance to psychotropic medications, low depressive symptoms, the absence of comorbid eating disorders and anticonvulsant medication were associated to a better prognosis of adherence. Along the follow-up, the lower were the depressive symptoms, the better was the medication adherence (p < .001) LIMITATIONS: The use of a single measure of medication adherence although it is a validated instrument and a possible positive selection bias that might limit the generalization of our findings.

Conclusions: This study demonstrates that medication adherence in BD patients is a heterogeneous and potentially variable phenomenon.
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http://dx.doi.org/10.1016/j.jad.2020.12.192DOI Listing
March 2021

Migration history and risk of psychosis: results from the multinational EU-GEI study.

Psychol Med 2021 Feb 10:1-13. Epub 2021 Feb 10.

Univ Paris Est Creteil (UPEC), AP-HP, Hôpitaux Universitaires « H. Mondor », DMU IMPACT, INSERM, IMRB, Fondation FondaMental, F-94010Creteil, France.

Background: Psychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration.

Methods: We used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case-control study. We defined a set of three indicators of social disadvantage for each phase: pre-migration, migration and post-migration. We examined whether social disadvantage in the pre- and post-migration phases, migration adversities, and mismatch between achievements and expectations differed between first-generation migrants with first-episode psychosis and healthy first-generation migrants, and tested whether this accounted for differences in odds of psychosis in multivariable logistic regression models.

Results: In total, 249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95% CI 1.06-2.44, p = 0.027) and post-migration social disadvantages (OR 1.89, 95% CI 1.02-3.51, p = 0.044), along with expectations/achievements mismatch (OR 1.14, 95% CI 1.03-1.26, p = 0.014) were all significantly associated with psychosis. Migration adversities (OR 1.18, 95% CI 0.672-2.06, p = 0.568) were not significantly related to the outcome. Finally, we found a dose-response effect between the number of adversities across all phases and odds of psychosis (⩾6: OR 14.09, 95% CI 2.06-96.47, p = 0.007).

Conclusions: The cumulative effect of social disadvantages before, during and after migration was associated with increased odds of psychosis in migrants, independently of ethnicity or length of stay in the country of arrival. Public health initiatives that address the social disadvantages that many migrants face during the whole migration process and post-migration psychological support may reduce the excess of psychosis in migrants.
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http://dx.doi.org/10.1017/S003329172000495XDOI Listing
February 2021

Patient and physician perspectives of a smartphone application for depression: a qualitative study.

BMC Psychiatry 2021 01 29;21(1):65. Epub 2021 Jan 29.

Department of Psychiatry, CHU Clermont-Ferrand, University of Clermont Auvergne, EA 7280, Clermont-Ferrand, France.

Background: Despite an increasing number of smartphone apps, such therapeutic tools have not yet consistently demonstrated their efficacy and many suffer from low retention rates. To ensure the development of efficient apps associated with high adherence, we aimed to identify, through a user-centred design approach, patient and physician expectations of a hypothetical app dedicated to depression.

Methods: We conducted semi-structured interviews with physicians (psychiatrists and general practitioners) and patients who had experienced a major depressive episode during the last 12 months using the focus group method. The interviews were audio recorded, transcribed and analysed using qualitative content analysis to define codes, categories and emergent themes.

Results: A total of 26 physicians and 24 patients were included in the study. The focus groups showed balanced sex and age distributions. Most participants owned a smartphone (83.3% of patients, 96.1% of physicians) and were app users (79.2% of patients and 96.1% of physicians). The qualitative content analysis revealed 3 main themes: content, operating characteristics and barriers to the use of the app. Expected content included the data collected by the app, aiming to provide information about the patient, data provided by the app, gathering psychoeducation elements, therapeutic tools and functionalities to help with the management of daily life and features expected for this tool. The "operating characteristics" theme gathered aims considered for the app, its potential target users, considered modalities of use and considerations around its accessibility and security of use. Finally, barriers to the use of the app included concerns about potential app users, its accessibility, safety, side-effects, utility and functioning. All themes and categories were the same for patients and physicians.

Conclusions: Physician and patient expectations of a hypothetical smartphone app dedicated to depression are high and confirmed the important role it could play in depression care. The key points expected by the users for such a tool are an easy and intuitive use and a personalised content. They are also waiting for an app that gives information about depression, offers a self-monitoring functionality and helps them in case of emergency.
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http://dx.doi.org/10.1186/s12888-021-03064-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847000PMC
January 2021

Patient and physician perspectives of a smartphone application for depression: a qualitative study.

BMC Psychiatry 2021 01 29;21(1):65. Epub 2021 Jan 29.

Department of Psychiatry, CHU Clermont-Ferrand, University of Clermont Auvergne, EA 7280, Clermont-Ferrand, France.

Background: Despite an increasing number of smartphone apps, such therapeutic tools have not yet consistently demonstrated their efficacy and many suffer from low retention rates. To ensure the development of efficient apps associated with high adherence, we aimed to identify, through a user-centred design approach, patient and physician expectations of a hypothetical app dedicated to depression.

Methods: We conducted semi-structured interviews with physicians (psychiatrists and general practitioners) and patients who had experienced a major depressive episode during the last 12 months using the focus group method. The interviews were audio recorded, transcribed and analysed using qualitative content analysis to define codes, categories and emergent themes.

Results: A total of 26 physicians and 24 patients were included in the study. The focus groups showed balanced sex and age distributions. Most participants owned a smartphone (83.3% of patients, 96.1% of physicians) and were app users (79.2% of patients and 96.1% of physicians). The qualitative content analysis revealed 3 main themes: content, operating characteristics and barriers to the use of the app. Expected content included the data collected by the app, aiming to provide information about the patient, data provided by the app, gathering psychoeducation elements, therapeutic tools and functionalities to help with the management of daily life and features expected for this tool. The "operating characteristics" theme gathered aims considered for the app, its potential target users, considered modalities of use and considerations around its accessibility and security of use. Finally, barriers to the use of the app included concerns about potential app users, its accessibility, safety, side-effects, utility and functioning. All themes and categories were the same for patients and physicians.

Conclusions: Physician and patient expectations of a hypothetical smartphone app dedicated to depression are high and confirmed the important role it could play in depression care. The key points expected by the users for such a tool are an easy and intuitive use and a personalised content. They are also waiting for an app that gives information about depression, offers a self-monitoring functionality and helps them in case of emergency.
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http://dx.doi.org/10.1186/s12888-021-03064-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847000PMC
January 2021

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings.

Mol Psychiatry 2021 Jan 7. Epub 2021 Jan 7.

Department of Psychiatry, Dokuz Eylül University, School of Medicine, Izmir, Turkey.

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.
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http://dx.doi.org/10.1038/s41380-020-00969-zDOI Listing
January 2021

Clinical research in psychopharmacology, the current situation and its perspectives. A conversation with Pierre-Michel Llorca.

Therapie 2021 Mar-Apr;76(2):67-70. Epub 2020 Dec 5.

Lyon Neuroscience Research Centre, INSERM, CNRS, Université Claude Bernard Lyon 1, 69675 Bron, France; CERMEP, Hospices Civils de Lyon, 69500 Bron, France; National Institute for Nuclear Science and Technology INSTN, CEA, 91400 Saclay, France. Electronic address:

For this issue, Luc Zimmer, professor of pharmacology and chair of the Neuropsychopharmacology Committee of the French Society of Pharmacology and Therapeutics (SFPT), talked with Michel Llorca, professor of psychiatry at the Université d'Auvergne and head of a department of psychiatry at the University Hospital of Clermond-Ferrand. They discuss together the positioning of psychiatry in the neurosciences and the need to build bridges with other medical disciplines. Through examples and professional experiences, they also talk about the difficulties of developing clinical biomarkers for psychiatry and ultimately for psychopharmacology. Finally, they discuss the current difficulties facing research of drugs for psychiatry, pointing out some success stories.
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http://dx.doi.org/10.1016/j.therap.2020.12.003DOI Listing
September 2021

Clinical characteristics of bipolar disorders with postpartum depressive onset.

Prog Neuropsychopharmacol Biol Psychiatry 2021 04 19;107:110225. Epub 2020 Dec 19.

AP-HP, Groupe Hospitalo-Universitaire AP-HP Nord, DMU ESPRIT, service de Psychiatrie et Addictologie, Hopital Louis Mourier, Colombes, Inserm U1266, Faculté de médecine, Université de Paris, France; Fondation Fondamental, Creteil 94000, France.

Background: Postpartum period is associated with an increased risk of bipolar disorder diagnosis and relapse, mainly major depressive episode. Onset during this period might be associated with specific characteristics.

Aim: To compare the socio-demographic and clinical characteristics of parous women presenting with bipolar disorder and an index depressive episode occurring during or outside the postpartum period.

Methods: Using the multicenter cohort FACE-BD (FondaMental Academic Centers of Expertise for Bipolar Disorders), we considered all women who started their BD with a major depressive episode and have at least one child. We compared two groups depending on the onset: in or outside the postpartum period.

Results: Among the 759 women who started BD with a major depressive episode, 93 (12.2%) had a postpartum onset, and 666 (87.8%) had not. Women who started BD in the postpartum period with a major depressive episode have a more stable family life, more children, an older age at onset, more Bipolar 2 disorder, less history of suicide attempts, less depressive episodes and more mood stabilizer treatments as compared to those who started with a major depressive episode outside the postpartum period. The multivariable logistic regression showed that women with an onset in the postpartum period had significantly more children, less lifetime depressive episodes and a lower rate of history of suicide attempts as compared to women with an onset outside the postpartum period.

Discussion: Our results suggest that women starting their BD with postpartum depression have a more favorable course of BD, especially less history of suicide attempt and less lifetime depressive episodes.
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http://dx.doi.org/10.1016/j.pnpbp.2020.110225DOI Listing
April 2021

Treatment-Resistant Depression in a Real-World Setting: First Interim Analysis of Characteristics, Healthcare Resource Use, and Utility Values of the FondaMental Cohort.

Brain Sci 2020 Dec 10;10(12). Epub 2020 Dec 10.

Janssen, 97132 Issy-Les-Moulineaux, France.

Background: Major depressive disorder (MDD) is among the most common psychiatric disorders. One-third of patients are usually unresponsive to several lines of treatment. This study aimed to describe the FondaMental French cohort of patients with treatment-resistant depression (TRD) and to estimate utility and healthcare resource use outcomes.

Methods: Patients with TRD were evaluated prospectively over four years (baseline, 6, 12, 18, 24, 36 and 48 months) in a real-world clinical setting. Interim analyses focused on the first two consecutive years. Four MDD-related states (major depressive episode (MDE), response, remission, recovery) were defined based on the MADRS (Montgomery-Åsberg depression rating scale) and other clinical events. Health status was assessed with the EuroQol 5 Dimensions 5 Level (EQ-5D-5L) questionnaire. Utility values were estimated as preference measures that the patients assigned to their overall health status.

Results: This study was based on 252 patients with TRD. The mean utility value by health state was 0.41, 0.63, 0.80, and 0.90, for MDE, response, remission, and recovery, respectively. At baseline, 59% of patients had an MADRS score of at least 28. Their baseline average utility value was lower compared to the other patients (0.43 versus 0.58, < 0.001). This significant difference persisted at the following visits. The rate of patients in MDEs having at least one hospitalisation for depression or other reasons than depression was generally higher than that in the other health states.

Conclusion: This study documented patterns in healthcare resource consumption, quality of life, and other characteristics in patients with TRD, both globally and by health state and depression severity.
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http://dx.doi.org/10.3390/brainsci10120962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764571PMC
December 2020

Comorbid Major Depressive Disorder in Schizophrenia: A Systematic Review and Meta-Analysis.

Schizophr Bull 2021 03;47(2):298-308

Hôpitaux Universitaires de Marseille, Department de Psychiatrie Universitaire, EA 3279: Aix-Marseille Université, CEReSS-Health Service Research and Quality of Life Center, Marseille, France.

Comorbid major depressive disorder (MDD) in schizophrenia (SZ; SZ-MDD) has been identified as a major prognostic factor. However, the prevalence and associated factors of SZ-MDD have never been explored in a meta-analysis. All studies assessing the prevalence of SZ-MDD in stabilized outpatients with a standardized scale or with structured interviews were included. The Medline, Web of Science, PsycINFO, and Google Scholar databases were searched. Using random effects models, we calculated the pooled estimate of the prevalence of SZ-MDD. We used meta-regression and subgroup analyses to evaluate the potential moderators of the prevalence estimates, and we used the leave-one-out method for sensitivity analyses. Of the 5633 potentially eligible studies identified, 18 studies (n = 6140 SZ stabilized outpatients) were retrieved in the systematic review and included in the meta-analysis. The pooled estimate of the prevalence of SZ-MDD was 32.6% (95% CI: 27.9-37.6); there was high heterogeneity (I2 = 92.6%), and Egger's test did not reveal publication bias (P = .122). The following factors were found to be sources of heterogeneity: publication in or after 2015, the inclusion of patients from larger studies, the assessment tools, the inclusion of patients with substance use disorder or somatic chronic diseases, age, education level, the lifetime number of hospitalizations, and antidepressant use. Two-thirds of the extracted variables could not be explored due to an insufficient amount of published data. The prevalence of MDD is high among SZ individuals. Healthcare providers and public health officials should have an increased awareness of the burden of SZ-MDD.
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http://dx.doi.org/10.1093/schbul/sbaa153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451068PMC
March 2021
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