Neurocognition and NMDAR co-agonists pathways in individuals with treatment resistant first-episode psychosis: a 3-year follow-up longitudinal study.

This study aims to determine whether 1) individuals with treatment-resistant schizophrenia display early cognitive impairment compared to treatment-responders and healthy controls and 2) N-methyl-D-aspartate-receptor hypofunction is an underlying mechanism of cognitive deficits in treatment-resistance. In this case‒control 3-year-follow-up longitudinal study, n = 697 patients with first-episode psychosis, aged 18 to 35, were screened for Treatment Response and Resistance in Psychosis criteria through an algorithm that assigns patients to responder, limited-response or treatment-resistant category (respectively resistant to 0, 1 or 2 antipsychotics). Assessments at baseline: MATRICS Consensus Cognitive Battery; N-methyl-D-aspartate-receptor co-agonists biomarkers in brain by MRS (prefrontal glutamate levels) and plasma (D-serine and glutamate pathways key markers). Patients were compared to age- and sex-matched healthy controls (n = 114). Results: patient mean age 23, 27% female. Treatment-resistant (n = 51) showed lower scores than responders (n = 183) in processing speed, attention/vigilance, working memory, verbal learning and visual learning. Limited responders (n = 59) displayed an intermediary phenotype. Treatment-resistant and limited responders were merged in one group for the subsequent D-serine and glutamate pathway analyses. This group showed D-serine pathway dysregulation, with lower levels of the enzymes serine racemase and serine-hydroxymethyltransferase 1, and higher levels of the glutamate-cysteine transporter 3 than in responders. Better cognition was associated with higher D-serine and lower glutamate-cysteine transporter 3 levels only in responders; this association was disrupted in the treatment resistant group. Treatment resistant patients and limited responders displayed early cognitive and persistent functioning impairment. The dysregulation of NMDAR co-agonist pathways provides underlying molecular mechanisms for cognitive deficits in treatment-resistant first-episode psychosis. If replicated, our findings would open ways to mechanistic biomarkers guiding response-based patient stratification and targeting cognitive improvement in clinical trials.

Characterization of early psychosis patients carrying a genetic vulnerability to redox dysregulation: a computational analysis of mechanism-based gene expression profile in fibroblasts.

In view of its heterogeneity, schizophrenia needs new diagnostic tools based on mechanistic biomarkers that would allow early detection. Complex interaction between genetic and environmental risk factors may lead to NMDAR hypofunction, inflammation and redox dysregulation, all converging on oxidative stress. Using computational analysis, the expression of 76 genes linked to these systems, known to be abnormally regulated in schizophrenia, was studied in skin-fibroblasts from early psychosis patients and age-matched controls (N = 30), under additional pro-oxidant challenge to mimic environmental stress. To evaluate the contribution of a genetic risk related to redox dysregulation, we investigated the GAG trinucleotide polymorphism in the key glutathione (GSH) synthesizing enzyme, glutamate-cysteine-ligase-catalytic-subunit (gclc) gene, known to be associated with the disease. Patients and controls showed different gene expression profiles that were modulated by GAG-gclc genotypes in combination with oxidative challenge. In GAG-gclc low-risk genotype patients, a global gene expression dysregulation was observed, especially in the antioxidant system, potentially induced by other risks. Both controls and patients with GAG-gclc high-risk genotype (gclcGAG-HR) showed similar gene expression profiles. However, under oxidative challenge, a boosting of other antioxidant defense, including the master regulator Nrf2 and TRX systems was observed only in gclcGAG-HR controls, suggesting a protective compensation against the genetic GSH dysregulation. Moreover, RAGE (redox/inflammation interaction) and AGMAT (arginine pathway) were increased in the gclcGAG-HR patients, suggesting some additional risk factors interacting with this genotype. Finally, the use of a machine-learning approach allowed discriminating patients and controls with an accuracy up to 100%, paving the way towards early detection of schizophrenia.

Identification of four novel loci associated with psychotropic drug-induced weight gain in a Swiss psychiatric longitudinal study: A GWAS analysis.

Patients suffering from mental disorders are at high risk of developing cardiovascular diseases, leading to a reduction in life expectancy. Genetic variants can display greater influence on cardiometabolic features in psychiatric cohorts compared to the general population. The difference is possibly due to an intricate interaction between the mental disorder or the medications used to treat it and metabolic regulations. Previous genome wide association studies (GWAS) on antipsychotic-induced weight gain included a low number of participants and/or were restricted to patients taking one specific antipsychotic. We conducted a GWAS of the evolution of body mass index (BMI) during early (i.e., ≤ 6) months of treatment with psychotropic medications inducing metabolic disturbances (i.e., antipsychotics, mood stabilizers and some antidepressants) in 1135 patients from the PsyMetab cohort. Six highly correlated BMI phenotypes (i.e., BMI change and BMI slope after distinct durations of psychotropic treatment) were considered in the analyses. Our results showed that four novel loci were associated with altered BMI upon treatment at genome-wide significance (p < 5 × 10-8): rs7736552 (near MAN2A1), rs11074029 (in SLCO3A1), rs117496040 (near DEFB1) and rs7647863 (in IQSEC1). Associations between the four loci and alternative BMI-change phenotypes showed consistent effects. Replication analyses in 1622 UK Biobank participants under psychotropic treatment showed a consistent association between rs7736552 and BMI slope (p = 0.017). These findings provide new insights into metabolic side effects induced by psychotropic drugs and underline the need for future studies to replicate these associations in larger cohorts.

Therapeutic Drug Monitoring of Olanzapine: Effects of Clinical Factors on Plasma Concentrations in Psychiatric Patients.

BACKGROUND: Therapeutic drug monitoring (TDM) is strongly recommended for olanzapine due to its high pharmacokinetic variability. This study aimed to investigate the impact of various clinical factors on olanzapine plasma concentrations in patients with psychiatric disorders. METHODS: The study used TDM data from the PsyMetab cohort, including 547 daily dose-normalized, steady-state, olanzapine plasma concentrations (C:D ratios) from 248 patients. Both intrinsic factors (eg, sex, age, body weight) and extrinsic factors (eg, smoking status, comedications, hospitalization) were examined. Univariate and multivariable, linear, mixed-effects models were employed, with a stepwise selection procedure based on Akaike information criterion to identify the relevant covariates. RESULTS: In the multivariable model (based on 440 observations with a complete data set), several significant findings emerged. Olanzapine C:D ratios were significantly lower in smokers (ß = -0.65, P < 0.001), valproate users (ß = -0.53, P = 0.002), and inpatients (ß = -0.20, P = 0.025). Furthermore, the C:D ratios decreased significantly as the time since the last dose increased (ß = -0.040, P < 0.001). The male sex had a significant main effect on olanzapine C:D ratios (ß = -2.80, P < 0.001), with significant interactions with age (ß = 0.025, P < 0.001) and body weight (ß = 0.017, P = 0.011). The selected covariates explained 30.3% of the variation in C:D ratios, with smoking status accounting for 7.7% and sex contributing 6.9%. The overall variation explained by both the fixed and random parts of the model was 67.4%. The model facilitated the prediction of olanzapine C:D ratios based on sex, age, and body weight. CONCLUSIONS: The clinical factors examined in this study, including sex, age, body weight, smoking status, and valproate comedication, remarkably influence olanzapine C:D ratios. Considering these factors, in addition to TDM and the clinical situation, could be important for dose adjustment.

French validation of the barriers to access to care evaluation (BACE-3) scale.

BACKGROUND: The aim of this study was to develop and evaluate a French version of the Barriers to Access to Care Evaluation (BACE-3) scale that is tailored to the socio-cultural and language setting of the study. METHODS: The translation of the BACE-3 into French and its validation were the two key components of this psychometric investigation. An online survey was created and circulated to French-speaking participants who volunteered to participate in the study. RESULTS: For all translated questions, the reliability analysis key results (Cronbach's alpha and McDonald's Omega) were both>0.95, which is an excellent reliability value. The BACE-3 items were shown to be positively related to one another, implying excellent validity. Results of exploratory and confirmatory factor analyses showed that all stigma-related items were loaded under the same factor. CONCLUSIONS: The BACE-3 has been validated in French, and its psychometric qualities have been thoroughly evaluated and found to be excellent.

[Psychiatry: what's new in 2023]. / Psychiatrie : ce qui a changé en 2023.

Resistance to treatment in psychiatry can arise from a variety of causes, and here we look at two strategies that can improve this problem. First, we discuss the role of patients' relatives; in addition to family therapy interventions, setting up groups of relatives makes it possible to increase their skills in helping their sick relative and to help each other in this process. And finally, we look at the option of interventional psychiatry. These methods, which have been greatly enriched in recent years, are now available in the interventional psychiatry unit recently opened in the new Cery psychiatric hospital in Lausanne.

La résistance au traitement en psychiatrie peut découler de multiples causes ; deux stratégies pouvant améliorer ce problème sont abordées dans cet article. En premier lieu, le rôle des proches des patients ; au-delà d'interventions de thérapie de famille, la mise en place de groupes de proches permet d'augmenter leurs compétences à aider leur proche malade et de s'entraider dans cette démarche. Et enfin, l'option que peuvent constituer les approches de psychiatrie interventionnelle. Ces méthodes se sont grandement enrichies au cours des dernières années et sont maintenant accessibles dans l'Unité de psychiatrie interventionnelle récemment ouverte dans le nouvel hôpital psychiatrique de Cery, récemment inauguré à Lausanne.

The co-occurrence of manic and depressive dimensions in early psychosis: a latent transition analysis.

BACKGROUND: Frequently associated with early psychosis, depressive and manic dimensions may play an important role in its course and outcome. While manic and depressive symptoms can alternate and co-occur, most of the studies in early intervention investigated these symptoms independently. The aim of this study was therefore to explore the co-occurrence of manic and depressive dimensions, their evolution and impact on outcomes. METHODS: We prospectively studied first-episode psychosis patients (N = 313) within an early intervention program over 3 years. Based on latent transition analysis, we identified sub-groups of patients with different mood profiles considering both manic and depressive dimensions, and studied their outcomes. RESULTS: Our results revealed six different mood profiles at program entry and after 1.5 years follow-up (absence of mood disturbance, co-occurrence, mild depressive, severe depressive, manic and hypomanic), and four after 3 years (absence of mood disturbance, co-occurrence, mild depressive and hypomanic). Patients with absence of mood disturbance at discharge had better outcomes. All patients with co-occurring symptoms at program entry remained symptomatic at discharge. Patients with mild depressive symptoms were less likely to return to premorbid functional level at discharge than the other subgroups. Patients displaying a depressive component had poorer quality of physical and psychological health at discharge. CONCLUSIONS: Our results confirm the major role played by mood dimensions in early psychosis, and show that profiles with co-occurring manic and depressive dimensions are at risk of poorer outcome. An accurate assessment and treatment of these dimensions in people with early psychosis is crucial.

Evolution of impulsivity levels in relation to early cannabis use in violent patients in the early phase of psychosis.

BACKGROUND: Prevention of violent behaviors (VB) in the early phase of psychosis (EPP) is a real challenge. Impulsivity was shown to be strongly related to VB, and different evolutions of impulsivity were noticed along treatments. One possible variable involved in the relationship between VB and the evolution of impulsivity is cannabis use (CU). The high prevalence of CU in EPP and its relationship with VB led us to investigate: 1/the impact of CU and 2/the impact of early CU on the evolution of impulsivity levels during a 3-year program, in violent and non-violent EPP patients. METHODS: 178 non-violent and 62 violent patients (VPs) were followed-up over a 3 year period. Age of onset of CU was assessed at program entry and impulsivity was assessed seven times during the program. The evolution of impulsivity level during the program, as a function of the violent and non-violent groups of patients and CU precocity were analyzed with linear mixed-effects models. RESULTS: Over the treatment period, impulsivity level did not evolve as a function of the interaction between group and CU (coef. = 0.02, p = 0.425). However, when including precocity of CU, impulsivity was shown to increase significantly only in VPs who start consuming before 15 years of age (coef. = 0.06, p = 0.008). CONCLUSION: The precocity of CU in VPs seems to be a key variable of the negative evolution of impulsivity during follow-up and should be closely monitored in EPP patients entering care since they have a higher risk of showing VB.

Caught in vicious circles: a perspective on dynamic feed-forward loops driving oxidative stress in schizophrenia.

A growing body of evidence has emerged demonstrating a pathological link between oxidative stress and schizophrenia. This evidence identifies oxidative stress as a convergence point or "central hub" for schizophrenia genetic and environmental risk factors. Here we review the existing experimental and translational research pinpointing the complex dynamics of oxidative stress mechanisms and their modulation in relation to schizophrenia pathophysiology. We focus on evidence supporting the crucial role of either redox dysregulation, N-methyl-D-aspartate receptor hypofunction, neuroinflammation or mitochondria bioenergetics dysfunction, initiating "vicious circles" centered on oxidative stress during neurodevelopment. These processes would amplify one another in positive feed-forward loops, leading to persistent impairments of the maturation and function of local parvalbumin-GABAergic neurons microcircuits and myelinated fibers of long-range macrocircuitry. This is at the basis of neural circuit synchronization impairments and cognitive, emotional, social and sensory deficits characteristic of schizophrenia. Potential therapeutic approaches that aim at breaking these different vicious circles represent promising strategies for timely and safe interventions. In order to improve early detection and increase the signal-to-noise ratio for adjunctive trials of antioxidant, anti-inflammatory and NMDAR modulator drugs, a reverse translation of validated circuitry approach is needed. The above presented processes allow to identify mechanism based biomarkers guiding stratification of homogenous patients groups and target engagement required for successful clinical trials, paving the way towards precision medicine in psychiatry.

Mitochondrial, exosomal miR137-COX6A2 and gamma synchrony as biomarkers of parvalbumin interneurons, psychopathology, and neurocognition in schizophrenia.

Early detection and intervention in schizophrenia requires mechanism-based biomarkers that capture neural circuitry dysfunction, allowing better patient stratification, monitoring of disease progression and treatment. In prefrontal cortex and blood of redox dysregulated mice (Gclm-KO ± GBR), oxidative stress induces miR-137 upregulation, leading to decreased COX6A2 and mitophagy markers (NIX, Fundc1, and LC3B) and to accumulation of damaged mitochondria, further exacerbating oxidative stress and parvalbumin interneurons (PVI) impairment. MitoQ, a mitochondria-targeted antioxidant, rescued all these processes. Translating to early psychosis patients (EPP), blood exosomal miR-137 increases and COX6A2 decreases, combined with mitophagy markers alterations, suggest that observations made centrally and peripherally in animal model were reflected in patients' blood. Higher exosomal miR-137 and lower COX6A2 levels were associated with a reduction of ASSR gamma oscillations in EEG. As ASSR requires proper PVI-related networks, alterations in miR-137/COX6A2 plasma exosome levels may represent a proxy marker of PVI cortical microcircuit impairment. EPP can be stratified in two subgroups: (a) a patients' group with mitochondrial dysfunction "Psy-D", having high miR-137 and low COX6A2 levels in exosomes, and (b) a "Psy-ND" subgroup with no/low mitochondrial impairment, including patients having miR-137 and COX6A2 levels in the range of controls. Psy-D patients exhibited more impaired ASSR responses in association with worse psychopathological status, neurocognitive performance, and global and social functioning, suggesting that impairment of PVI mitochondria leads to more severe disease profiles. This stratification would allow, with high selectivity and specificity, the selection of patients for treatments targeting brain mitochondria dysregulation and capture the clinical and functional efficacy of future clinical trials.

Gene set enrichment analysis of pathophysiological pathways highlights oxidative stress in psychosis.

Polygenic risk prediction remains an important aim of genetic association studies. Currently, the predictive power of schizophrenia polygenic risk scores (PRSs) is not large enough to allow highly accurate discrimination between cases and controls and thus is not adequate for clinical integration. Since PRSs are rarely used to reveal biological functions or to validate candidate pathways, to fill this gap, we investigated whether their predictive ability could be improved by building genome-wide (GW-PRSs) and pathway-specific PRSs, using distance- or expression quantitative trait loci (eQTLs)- based mapping between genetic variants and genes. We focused on five pathways (glutamate, oxidative stress, GABA/interneurons, neuroimmune/neuroinflammation and myelin) which belong to a critical hub of schizophrenia pathophysiology, centred on redox dysregulation/oxidative stress. Analyses were first performed in the Lausanne Treatment and Early Intervention in Psychosis Program (TIPP) study (n = 340, cases/controls: 208/132), a sample of first-episode of psychosis patients and matched controls, and then validated in an independent study, the epidemiological and longitudinal intervention program of First-Episode Psychosis in Cantabria (PAFIP) (n = 352, 224/128). Our results highlighted two main findings. First, GW-PRSs for schizophrenia were significantly associated with early psychosis status. Second, oxidative stress was the only significantly associated pathway that showed an enrichment in both the TIPP (p = 0.03) and PAFIP samples (p = 0.002), and exclusively when gene-variant linking was done using eQTLs. The results suggest that the predictive accuracy of polygenic risk scores could be improved with the inclusion of information from functional annotations, and through a focus on specific pathways, emphasizing the need to build and study functionally informed risk scores.

Risk and protective factors for recovery at 3-year follow-up after first-episode psychosis onset: a multivariate outcome approach.

PURPOSE: Recovery in people with first-episode psychosis (FEP) remains a major issue. When risk factors are studied in relation to the disorder, potential protective factors should also be considered since they can modulate this relationship. This study is aimed at exploring which premorbid and baseline characteristics are associated with a good and poor global recovery in patients with FEP at 3-year follow-up. METHODS: We categorized patients' outcome by using a Latent Class Analysis (LCA) considering a multimodal set of symptomatic and functional outcomes. A Mixed effects Models Repeated Measures analysis of variance (MMRM) was used to highlight group differences over time on symptomatic and functional outcomes assessed during the 3-year follow-up. RESULTS: A total of 325 patients with FEP aged between 18 and 35 years were included. Two groups were identified. A total of 187 patients (57.5%) did not achieve recovery, and 138 patients (42.5%) achieved recovery. Recovered patients had generally a better premorbid and baseline profile in comparison with non-recovered patients (as among which shorter duration of untreated psychosis (DUP), higher degree of insight, better functional level and lower illness severity at baseline). The trajectories for the psychopathological and functional outcomes over 36 months differed between the non-recovered and the recovered group of patients. CONCLUSIONS: Our results pointed to some variables associated with recovery, acting as potential protective factors. These should be considered for early intervention programs to promote psychological resilience specifically in those with a worse prognosis in order to mitigate the effects of the variables that make them more vulnerable to poorer outcome.

[Diagnostic of a first psychotic episode : role of the general practitioner]. / Diagnostic d'un premier épisode psychotique : le rôle clé du médecin généraliste.

As psychoses can have a long-term impact, they need to be diagnosed as quickly as possible in order to provide appropriate care and avoid the onset of comorbid complications. As general practitioners are often the first to be approached, it is important that they think about this diagnosis in young patients, even if the manifestations are often atypical or if patients are reluctant to talk about it. Specialized programs have sprung up all over the world, staffed by mobile teams and professionals specialized in this type of treatment, with far superior results at a lower overall cost than the usual treatments. In the absence of a clear national policy in this area, Switzerland remains poorly equipped, although successful programs do exist in some regions.

Les psychoses pouvant avoir un impact à long terme, les diagnostiquer aussi rapidement que possible permet d'offrir des soins adaptés aux patients et d'éviter la survenue de complications comorbides. Les médecins généralistes étant souvent sollicités en premier, il est important qu'ils pensent à ce diagnostic chez des patients jeunes, même si les manifestations sont souvent atypiques ou les patients réticents à en parler. Des programmes spécialisés se sont développés dans le monde entier, dotés d'équipes mobiles et de professionnels spécialisés dans ce type de traitements, avec des résultats nettement supérieurs à un coût global moindre que ceux habituels. En l'absence d'une politique nationale claire à cet égard, la Suisse reste mal dotée dans ce domaine bien que des programmes performants existent dans quelques régions.

[Psychiatry: what's new in 2022]. / Psychiatrie : ce qui a changé en 2022.

The period of study and/or vocational training coincides with the phase of life where a large proportion of psychiatric disorders emerge. It is therefore common to be asked by a young person in training to make adjustments to his or her training for psychological reasons. Some disorders that were thought to occur in childhood also exist in adults: this is the case of attention deficit disorder with or without hyperactivity, which must be detected and treated appropriately. The tools available for the treatment of psychiatric disorders are not limited to medication and the usefulness of psychotherapy or physical approaches, for example, is well known. We are less aware of the beneficial effects of exposure to nature and green spaces, which are however solidly supported by scientific studies - and which we should not underestimate.

La période des études et/ou de la formation professionnelle est une phase de vie au cours de laquelle émergent une grande partie des troubles psychiques. Il n'est donc pas rare d'être sollicité par un jeune en formation au sujet d'un aménagement de la formation pour des raisons psychiques. Certains des troubles qu'on pensait survenir dans l'enfance existent aussi chez l'adulte. C'est le cas du trouble de déficit de l'attention avec ou sans hyperactivité. Les outils à disposition pour le traitement des troubles psychiques ne se restreignent pas aux médicaments : on connaît l'utilité des psychothérapies ou des approches corporelles par exemple. On connaît moins les effets bénéfiques de l'exposition à la nature et aux espaces verts, qui sont pourtant solidement étayés par des études scientifiques et que l'on aurait tort de sous-estimer.

Topology predicts long-term functional outcome in early psychosis.

Early intervention in psychosis is crucial to improving patient response to treatment and the functional deficits that critically affect their long-term quality of life. Stratification tools are needed to personalize functional deficit prevention strategies at an early stage. In the present study, we applied topological tools to analyze symptoms of early psychosis patients, and detected a clear stratification of the cohort into three groups. One of the groups had a significantly better psychosocial outcome than the others after a 3-year clinical follow-up. This group was characterized by a metabolic profile indicative of an activated antioxidant response, while that of the groups with poorer outcome was indicative of oxidative stress. We replicated in a second cohort the finding that the three distinct clinical profiles at baseline were associated with distinct outcomes at follow-up, thus validating the predictive value of this new stratification. This approach could assist in personalizing treatment strategies.

Prevalence and risk factors of self-reported psychotic experiences among high school and college students: A systematic review, meta-analysis, and meta-regression.

BACKGROUND: Adolescents are at high risk of incident psychopathology. Fleeting psychotic experiences (PEs) that emerge in young people in response to stress may be warning signs that are missed by research that fails to study stressed populations, such as late high school and college/university students. Our aim in this systematic review was to conduct a meta-analysis that estimates prevalence rates of PEs in students, and to assess whether these rates differ by gender, age, culture, and COVID-19 exposure. METHOD: We searched nine electronic databases, from their inception until January 31, 2022 for relevant studies. We pooled the estimates using the DerSimonian-Laird technique and random-effects meta-analysis. Our main outcome was the prevalence of self-reported PEs in high school and college/university students. We subsequently analyzed our data by age, gender, population, country, culture, evaluation tool, and COVID-19 exposure. RESULTS: Out of 486 studies retrieved, a total of 59 independent studies met inclusion criteria reporting 210' 024 students from 21 different countries. Nearly one in four students (23.31%; 95% CI 18.41%-29.05%), reported having experienced PEs (heterogeneity [Q = 22,698.23 (62), p = 0.001] τ2  = 1.4418 [1.0415-2.1391], τ = 1.2007 [1.0205-1.4626], I2  = 99.7%, H = 19.13 [18.59-19.69]). The 95% prediction intervals were 04.01%-68.85%. Subgroup analyses showed that the pooled prevalence differed significantly by population, culture, and COVID-19 exposure. CONCLUSION: This meta-analysis revealed high prevalence rates of self-reported PEs among teen and young adult students, which may have significance for mental health screening in school settings. An important realization is that PEs may have very different mental health meaning in different cultures.

Insomnia disorders are associated with increased cardiometabolic disturbances and death risks from cardiovascular diseases in psychiatric patients treated with weight-gain-inducing psychotropic drugs: results from a Swiss cohort.

STUDY OBJECTIVES: Insomnia disorders as well as cardiometabolic disorders are highly prevalent in the psychiatric population compared to the general population. We aimed to investigate their association and evolution over time in a Swiss psychiatric cohort. METHODS: Data for 2861 patients (8954 observations) were obtained from two prospective cohorts (PsyMetab and PsyClin) with metabolic parameters monitored routinely during psychotropic treatment. Insomnia disorders were based on the presence of ICD-10 "F51.0" diagnosis (non-organic insomnia), the prescription of sedatives before bedtime or the discharge letter. Metabolic syndrome was defined using the International Diabetes Federation definition, while the 10-year risk of cardiovascular event or death was assessed using the Framingham Risk Score and the Systematic Coronary Risk Estimation, respectively. RESULTS: Insomnia disorders were observed in 30% of the cohort, who were older, predominantly female, used more psychotropic drugs carrying risk of high weight gain (olanzapine, clozapine, valproate) and were more prone to suffer from schizoaffective or bipolar disorders. Multivariate analyses showed that patients with high body mass index (OR = 2.02, 95%CI [1.51-2.72] for each ten-kg/m2 increase), central obesity (OR = 2.20, [1.63-2.96]), hypertension (OR = 1.86, [1.23-2.81]), hyperglycemia (OR = 3.70, [2.16-6.33]), high density lipoprotein hypocholesterolemia in women (OR = 1.51, [1.17-1.95]), metabolic syndrome (OR = 1.84, [1.16-2.92]) and higher 10-year risk of death from cardiovascular diseases (OR = 1.34, [1.17-1.53]) were more likely to have insomnia disorders. Time and insomnia disorders were associated with a deterioration of cardiometabolic parameters. CONCLUSIONS: Insomnia disorders are significantly associated with metabolic worsening and risk of death from cardiovascular diseases in psychiatric patients.

[Psychiatry]. / Psychiatrie.

The media often discuss the impact of climate change on physical health, but much less its influence on mental health, although it appears that it is already present and will be major if nothing concrete is done to fight global warming. The role of patients is paramount in psychiatry, not only in defining individual treatment goals, but also as mental health professionals, in the role of Peer Practitioner in Mental Health, and in defining the care policies and therapeutic offer of our public psychiatric institutions. While many psychotropic drugs induce metabolic disorders and weight gain, it is possible to identify from the first month of treatment those at risk of such complications.

L'impact du changement climatique sur la santé physique est régulièrement discuté mais son influence sur la santé mentale l'est beaucoup moins, bien qu'il apparaisse qu'elle est déjà présente et qu'elle sera majeure si rien de concret n'est entrepris pour lutter contre le réchauffement de la planète. Le rôle des patients est primordial en psychiatrie, non seulement pour définir les objectifs de traitement individuel, mais également comme professionnel de la santé mentale, dans le rôle de pair praticien en santé mentale, et dans la définition des politiques de soins et de l'offre théra peutique de nos institutions de psychiatrie publique. Alors que plusieurs psychotropes induisent des troubles métaboliques et une prise de poids, il est possible d'identifier dès le premier mois de traitement les personnes à risque de telles complications.

Understanding urbanicity: how interdisciplinary methods help to unravel the effects of the city on mental health.

Twenty-first century urbanization poses increasing challenges for mental health. Epidemiological studies have shown that mental health problems often accumulate in urban areas, compared to rural areas, and suggested possible underlying causes associated with the social and physical urban environments. Emerging work indicates complex urban effects that depend on many individual and contextual factors at the neighbourhood and country level and novel experimental work is starting to dissect potential underlying mechanisms. This review summarizes findings from epidemiology and population-based studies, neuroscience, experimental and experience-based research and illustrates how a combined approach can move the field towards an increased understanding of the urbanicity-mental health nexus.

Correction: MMP9/RAGE pathway overactivation mediates redox dysregulation and neuroinflammation, leading to inhibitory/excitatory imbalance: a reverse translation study in schizophrenia patients.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.