Immuno-metabolic profile of patients with psychotic disorders and metabolic syndrome. Results from the FACE-SZ cohort

Background: Metabolic syndrome (MetS) is a highly prevalent and harmful medical disorder often comorbid with psychosis where it can contribute to cardiovascular complications. As immune dysfunction is a key shared component of both MetS and schizophrenia (SZ), this study investigated the relationship between immune alterations and MetS in patients with SZ, whilst controlling the impact of confounding clinical characteristics including psychiatric symptoms and comorbidities, history of childhood maltreatment and psychotropic treatments. Method: A total of 310 patients meeting DSM-IV criteria for SZ or schizoaffective disorders (SZA), with or without MetS, were systematically assessed and included in the FondaMental Advanced Centers of Expertise for Schizophrenia (FACE-SZ) cohort. Detailed clinical characteristics of patients, including psychotic symptomatology, psychiatric comorbidities and history of childhood maltreatment were recorded and the serum levels of 18 cytokines were measured. A penalized regression method was performed to analyze associations between inflammation and MetS, whilst controlling for confounding factors. Results: Of the total sample, 25% of patients had MetS. Eight cytokines were above the lower limit of detection (LLOD) in more than 90% of the samples and retained in downstream analysis. Using a conservative Variable Inclusion Probability (VIP) of 75%, we found that elevated levels of interleukin (IL)-6, IL-7, IL-12/23 p40 and IL-16 and lower levels of tumor necrosis factor (TNF)-α were associated with MetS. As for clinical variables, age, sex, body mass index (BMI), diagnosis of SZ (not SZA), age at the first episode of psychosis (FEP), alcohol abuse, current tobacco smoking, and treatment with antidepressants and anxiolytics were all associated with MetS. Conclusion: We have identified five cytokines associated with MetS in SZ suggesting that patients with psychotic disorders and MetS are characterized by a specific “immuno-metabolic” profile. This may help to design tailored treatments for this subgroup of patients with both psychotic disorders and MetS, taking one more step towards precision medicine in psychiatry. © 2022 The AuthorsImmuno-Génétique, Inflammation, retro-Virus, Environnement : de l'étiopathogénie des troubles psychotiques aux modèles animauxRéseau d'Innovation sur les Voies de Signalisation en Sciences de la Vi

Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

Influence of Venus and Mars in the cognitive sky of schizophrenia. Results from the first-step national FACE-SZ cohort

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Cigarette smoking and schizophrenia: a specific clinical and therapeutic profile? Results from the FACE-Schizophrenia cohort

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A multi-dimensional approach to the relationship between insight and aggressiveness in schizophrenia: Findings from the FACE-SZ cohort

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A multi-dimensional approach to the relationship between insight and aggressiveness in schizophrenia: Findings from the FACE-SZ cohort

International audienceBackground: Aggressiveness is a stigma frequently associated with schizophrenia. The role of insight as a risk factor of aggressiveness remains contradictory; mainly because single measures of these states mask their complexity and heterogeneity.Methods: This study was conducted on 666 patients aged 15 and above with a DSM-IV-TR diagnosis of schizophrenia spectrum disorder, drawn from the French national network of schizophrenia expert center database. Collected data comprised socio-demographics and standardized psychiatric assessments. Aggressiveness was evaluated using the Buss-Perry Aggression Questionnaire and insight using the Scale to assess Unawareness of Mental Disorder (SUMD) and Birchwood Insight Scale (BIS).Results: Hostility was the aggressiveness dimension the most strongly associated with SUMD insight dimensions. Patients aware of their illness were nearly twice as likely to show hostility than those seriously unaware (OR = 1.95, 95% CI.: 1.08-3.5), but not when further adjusting for depression. Similarly, those aware of the consequences of their illness and of their symptoms were more hostile. Patients moderately aware of illness consequences had a higher risk of both anger and physical aggressiveness than those unaware (OR = 2.63, 95% CI.: 1.42-4.86, OR = 2.47, 95% CI.: 1.33-4.60, respectively), even when adjusting for depression for anger.Conclusion: Our study confirms that a multi-dimensional approach to insight and aggressiveness is essential to understand the types of links between these clinical states. Insight may trigger the expression of an underlying hostile tendency, maybe via depression and self-stigmatisation. This should be taken into account in therapeutic approaches to improve insight

Risk factors for increased duration of untreated psychosis. Results from the FACE-SZ dataset

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Predictors of rapid high weight gain in schizophrenia: Longitudinal analysis of the French FACE-SZ cohort

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Centres Experts Schizophrénie, un outil pour le soin et la recherche : retour sur 10 ans d’expérience

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Relationship between childhood trauma and level of insight in schizophrenia: A path-analysis in the national FACE-SZ dataset

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