15 research outputs found
RÎle central de l'insomnie dans la dépression caractérisée : lien avec les polymorphismes de GSK3B et le métabolisme glucido-lipidique
Introduction : lâinsomnie dans lâĂ©pisode dĂ©pressif caractĂ©risĂ© (EDC) est un symptĂŽme central prĂ©sent chez 80 Ă 90% des patients. Il existe une association entre EDC et une Ă©lĂ©vation de la morbi-mortalitĂ© cardiovasculaire. Lâinsomnie en population gĂ©nĂ©rale semble, elle aussi, liĂ©e Ă cette surmortalitĂ©. GlycogĂšne Synthase Kinase-3 Beta (GSK3B) est un enzyme cellulaire ubiquitaire qui a Ă©tĂ© dĂ©couvert pour son effet sur le mĂ©tabolisme glucidique. De plus, il a Ă©tĂ© montrĂ© sur divers modĂšles cellulaires et animaux quâil interagissait avec les protĂ©ines de lâhorloge biologique influençant ainsi les rythmes circadiens et par consĂ©quent le sommeil. GSK3B Ă©tant une protĂ©ine candidate dans les troubles de lâhumeur nous avons Ă©tudiĂ© lâassociation entre 5 polymorphismes nuclĂ©otidiques simples (SNP) de cette protĂ©ine, lâinsomnie et les facteurs de risque cardio-vasculaires durant lâEDC. MĂ©thodes : ce travail est basĂ© sur les donnĂ©es issues de la cohorte METADAP. Il sâagit dâune cohorte prospective de 624 patients en EDC dans le cadre dâun trouble dĂ©pressif caractĂ©risĂ© suivis sur 6 mois et Ă©valuĂ©s Ă 4 temps (M0, M1, M3, M6). Ces 4 temps ont permis la constitution dâune sĂ©roplasmathĂšque dont sont extraits nos 5 SNPs de GSK3B. Les patients avaient Ă©galement Ă©tĂ© Ă©valuĂ©s pour le syndrome mĂ©tabolique (objectif principal de lâĂ©tude METADAP). LâĂ©valuation clinique a permis dâextraire les donnĂ©es dâinsomnie Ă partir de lâĂ©chelle de dĂ©pression de Hamilton (HDRS). A partir de ces donnĂ©es, 2 marqueurs cliniques ont Ă©tĂ© confrontĂ©s Ă nos variables gĂ©nĂ©tiques et mĂ©taboliques : lâinsomnie totale et lâinsomnie sĂ©vĂšre. Ce travail a recherchĂ© des associations statistiques entre SNPs de GSK3B, insomnie et mĂ©tabolisme glucido-lipidique des patients. Puis, nous avons recherchĂ© un lien entre insomnie et mĂ©tabolisme glucido-lipidique Ă chacun des temps de lâĂ©tude. RĂ©sultats : 1) Nous avons retrouvĂ© une association entre le polymorphisme rs334558 (SNP du promoteur) et une plus grande frĂ©quence dâinsomnie sĂ©vĂšre pour les porteurs de lâallĂšle mineur (C+). 2) Il existe une amĂ©lioration de lâinsomnie significativement plus Ă©levĂ©e Ă M6 chez les patients porteurs de lâallĂšle mineur du polymorphisme rs334558. 3) LâĂ©tude de lâassociation des SNPs de GSK3B avec le mĂ©tabolisme glucido-lipidique nâa pas Ă©tĂ© concluante. 4) Nous retrouvons une association entre insomnie sĂ©vĂšre et triglycĂ©ridĂ©mie Ă jeun spĂ©cifiquement chez les femmes. 5) Nous retrouvons une association entre insomnie sĂ©vĂšre et syndrome mĂ©tabolique spĂ©cifiquement chez les femmes. Conclusion : Nos travaux ont permis de mieux caractĂ©riser les liens entre SNPs de GSK3B, insomnie et mĂ©tabolisme glucido-lipidique. En partant de dĂ©couvertes biologiques sur la protĂ©ine GSK3B, nous avons mis en Ă©vidence et dĂ©fini un marqueur clinique simple, lâinsomnie sĂ©vĂšre, qui pourrait rendre compte de risques cardiovasculaires particuliĂšrement importants chez les femmes en EDC. Ce marqueur est Ă©galement associĂ© Ă un polymorphisme gĂ©nĂ©tique particulier de GSK3B (rs334558) du fait quâil est situĂ© en rĂ©gion promotrice du gĂšne et pourrait avoir un effet sur la transcription de la protĂ©ine. Lâinsomnie sĂ©vĂšre pourrait servir de marqueur endophĂ©notypique dâintĂ©rĂȘt dans lâEDC. Lâanalyse de donnĂ©es de mĂ©tabolomique et de biologie cellulaire Ă disposition au sein de notre Ă©quipe pourrait permettre de rĂ©pliquer nos rĂ©sultats et dâaller plus loin dans les explications mĂ©canistiques de ces observations.No abstrac
RÎle central de l'insomnie dans la dépression caractérisée : lien avec les polymorphismes de GSK3B et le métabolisme glucido-lipidique
Introduction: Insomnia in the characterized depressive episode (CDE) is a central symptom present in 80 to 90% of patients. There is an association between CDE and an increase in cardiovascular morbidity and mortality. Insomnia in the general population also seems to be linked to this excess mortality. Glycogen Synthase Kinase-3 Beta (GSK3B) is a ubiquitous cellular enzyme that was discovered for its effect on carbohydrate metabolism. Furthermore, it has been shown in various cellular and animal models to interact with biological clock proteins, thus influencing circadian rhythms and consequently sleep. GSK3B being a candidate protein in mood disorders, we studied the association between 5 single nucleotide polymorphisms (SNPs) of this protein, insomnia and cardiovascular risk factors during CDE. Methods: This work is based on data from the METADAP cohort. This is a prospective cohort of 624 patients with CDE in the context of a characterized depressive disorder followed up for 6 months and evaluated at 4 time points (M0, M1, M3, M6). These 4 times allowed the constitution of a serum library from which our 5 GSK3B SNPs were extracted. Patients were also evaluated for metabolic syndrome (main objective of the METADAP study). The clinical evaluation allowed the extraction of insomnia data from the Hamilton Depression Rating Scale (HDRS). From these data, 2 clinical markers were compared with our genetic and metabolic variables: total insomnia and severe insomnia. This work looked for statistical associations between GSK3B SNPs, insomnia and patients' carbohydrate-lipid metabolism. Then, we looked for an association between insomnia and glucido-lipid metabolism at each time point of the study. Results: 1) We found an association between the rs334558 polymorphism (promoter SNP) and a higher frequency of severe insomnia for carriers of the minor allele (C+). 2) There is a significantly higher improvement of insomnia at M6 in patients carrying the minor allele of the rs334558 polymorphism. 3) The study of the association of GSK3B SNPs with carbohydrate-lipid metabolism was inconclusive. 4) We found an association between severe insomnia and fasting triglyceridemia specifically in women. 5) We found an association between severe insomnia and metabolic syndrome specifically in women. Conclusion: Our work has allowed us to better characterize the links between GSK3B SNPs, insomnia and glucido-lipid metabolism. Based on biological findings on GSK3B protein, we have identified and defined a simple clinical marker, severe insomnia, which may account for particularly high cardiovascular risks in women with CDE. This marker is also associated with a particular genetic polymorphism of GSK3B (rs334558) because it is located in the promoter region of the gene and could have an effect on protein transcription. Severe insomnia could serve as an endophenotypic marker of interest in CDE. The analysis of metabolomics and cell biology data available within our team could allow us to replicate our results and to go further in the mechanistic explanations of these observations.Introduction : lâinsomnie dans lâĂ©pisode dĂ©pressif caractĂ©risĂ© (EDC) est un symptĂŽme central prĂ©sent chez 80 Ă 90% des patients. Il existe une association entre EDC et une Ă©lĂ©vation de la morbi-mortalitĂ© cardiovasculaire. Lâinsomnie en population gĂ©nĂ©rale semble, elle aussi, liĂ©e Ă cette surmortalitĂ©. GlycogĂšne Synthase Kinase-3 Beta (GSK3B) est un enzyme cellulaire ubiquitaire qui a Ă©tĂ© dĂ©couvert pour son effet sur le mĂ©tabolisme glucidique. De plus, il a Ă©tĂ© montrĂ© sur divers modĂšles cellulaires et animaux quâil interagissait avec les protĂ©ines de lâhorloge biologique influençant ainsi les rythmes circadiens et par consĂ©quent le sommeil. GSK3B Ă©tant une protĂ©ine candidate dans les troubles de lâhumeur nous avons Ă©tudiĂ© lâassociation entre 5 polymorphismes nuclĂ©otidiques simples (SNP) de cette protĂ©ine, lâinsomnie et les facteurs de risque cardio-vasculaires durant lâEDC. MĂ©thodes : ce travail est basĂ© sur les donnĂ©es issues de la cohorte METADAP. Il sâagit dâune cohorte prospective de 624 patients en EDC dans le cadre dâun trouble dĂ©pressif caractĂ©risĂ© suivis sur 6 mois et Ă©valuĂ©s Ă 4 temps (M0, M1, M3, M6). Ces 4 temps ont permis la constitution dâune sĂ©roplasmathĂšque dont sont extraits nos 5 SNPs de GSK3B. Les patients avaient Ă©galement Ă©tĂ© Ă©valuĂ©s pour le syndrome mĂ©tabolique (objectif principal de lâĂ©tude METADAP). LâĂ©valuation clinique a permis dâextraire les donnĂ©es dâinsomnie Ă partir de lâĂ©chelle de dĂ©pression de Hamilton (HDRS). A partir de ces donnĂ©es, 2 marqueurs cliniques ont Ă©tĂ© confrontĂ©s Ă nos variables gĂ©nĂ©tiques et mĂ©taboliques : lâinsomnie totale et lâinsomnie sĂ©vĂšre. Ce travail a recherchĂ© des associations statistiques entre SNPs de GSK3B, insomnie et mĂ©tabolisme glucido-lipidique des patients. Puis, nous avons recherchĂ© un lien entre insomnie et mĂ©tabolisme glucido-lipidique Ă chacun des temps de lâĂ©tude. RĂ©sultats : 1) Nous avons retrouvĂ© une association entre le polymorphisme rs334558 (SNP du promoteur) et une plus grande frĂ©quence dâinsomnie sĂ©vĂšre pour les porteurs de lâallĂšle mineur (C+). 2) Il existe une amĂ©lioration de lâinsomnie significativement plus Ă©levĂ©e Ă M6 chez les patients porteurs de lâallĂšle mineur du polymorphisme rs334558. 3) LâĂ©tude de lâassociation des SNPs de GSK3B avec le mĂ©tabolisme glucido-lipidique nâa pas Ă©tĂ© concluante. 4) Nous retrouvons une association entre insomnie sĂ©vĂšre et triglycĂ©ridĂ©mie Ă jeun spĂ©cifiquement chez les femmes. 5) Nous retrouvons une association entre insomnie sĂ©vĂšre et syndrome mĂ©tabolique spĂ©cifiquement chez les femmes. Conclusion : Nos travaux ont permis de mieux caractĂ©riser les liens entre SNPs de GSK3B, insomnie et mĂ©tabolisme glucido-lipidique. En partant de dĂ©couvertes biologiques sur la protĂ©ine GSK3B, nous avons mis en Ă©vidence et dĂ©fini un marqueur clinique simple, lâinsomnie sĂ©vĂšre, qui pourrait rendre compte de risques cardiovasculaires particuliĂšrement importants chez les femmes en EDC. Ce marqueur est Ă©galement associĂ© Ă un polymorphisme gĂ©nĂ©tique particulier de GSK3B (rs334558) du fait quâil est situĂ© en rĂ©gion promotrice du gĂšne et pourrait avoir un effet sur la transcription de la protĂ©ine. Lâinsomnie sĂ©vĂšre pourrait servir de marqueur endophĂ©notypique dâintĂ©rĂȘt dans lâEDC. Lâanalyse de donnĂ©es de mĂ©tabolomique et de biologie cellulaire Ă disposition au sein de notre Ă©quipe pourrait permettre de rĂ©pliquer nos rĂ©sultats et dâaller plus loin dans les explications mĂ©canistiques de ces observations
Programmes de prévention et d'intervention dans les cas de dépression chez les étudiants.
International audienc
Psychological distress among outpatient physicians in private practice linked to COVID-19 and related mental health during the second lockdown
International audienceBackground: Outpatient physicians in private practice, as inpatient physicians, are on the frontline of the COVID-19 pandemic. Mental-health consequences of the pandemic on hospital staff have been published, but the psychological distress among outpatient physicians in private practice due to COVID-19 has never been specifically assessed.Methods: A French national online cross-sectional survey assessed declared psychological distress among outpatient physicians in private practice linked to COVID-19, sociodemographic and work conditions, mental health (Copenhagen Burn-out Inventory, Hospital Anxiety and Depression Scale, and the Insomnia severity Index), consequences on alcohol, tobacco, and illegal substance misuse, and sick leave during the 2nd COVID-19 wave.Findings: Among the 1,992 physicians who answered the survey, 1,529 (76.8%) declared psychological distress linked to COVID-19. Outpatient physicians who declared psychological distress linked to COVID-19 had higher rates of insomnia (OR = 1.4; CI95 [1.1-1.7], p = 0.003), burnout (OR = 2.7; CI95 [2.1; 3.2], p < 0.001), anxiety and depressive symptoms (OR = 2.4; CI95 [1.9-3.0], p < 0.001 and OR = 1.7; CI95 [1.3-2.3], p < 0.001) as compared to physicians who did not. They also had higher psychotropic drug use in the last twelve months, or increased alcohol or tobacco consumption due to work-related stress and were more frequently general practitioners.Interpretation: The feeling of being in psychological distress due to COVID-19 is highly frequent among outpatient physicians in private practice and is associated with mental health impairment. There is a need to assess specific interventions dedicated to outpatient physicians working in private practice
Cerebrospinal fluid levels of monoamines among suicide attempters: A systematic review and random-effects meta-analysis
International audienceBackground: It remains unclear whether the dopaminergic and noradrenergic systems may be implied in suicide attempt risk. In addition, although the serotonergic system has been extensively studied, no formal meta-analysis has been performed to examine its association with suicide attempt.Methods: Using PRISMA methodology, we performed a systematic literature review and random-effects meta-analyses of the differences in cerebrospinal fluid (CSF) levels of 5-HIAA, HVA and MHPG between suicide attempters and individuals who never attempted suicide.Results: We identified 30 studies including 937 suicide attempters and 1128 non-attempters; 29 of them measured CSF levels of 5-HIAA, 22 measured CSF levels of HVA and 14 measured CSF levels of MHPG. CSF levels of 5-HIAA and HVA were significantly lower in suicide attempters than in non-attempters [SMD = -0.43 (95% CI: -0.71 to -0.15; p < 0.01) and SMD = -0.45 (95% CI: -0.72 to -0.19; p < 0.01), respectively]. We did not find a significant association between CSF MHPG levels and suicide attempt.Limitations: Our analyses relied on a limited number of studies of good quality and most studies included small sample sizes.Conclusion: Both serotonin and dopamine systems may play a role in suicide attempt risk. Our findings suggest that a silo approach to biomarkers should be phased out in favor of the study of multiple systems in parallel and in the same populations to progress in the identification of the biological components independently associated with suicide risk, with the goal of identifying new treatment targets and improving suicide risk prediction
Severe insomnia is associated with metabolic syndrome in women over 50 years with major depression treated in psychiatry settings: a METADAP report
Glycogen synthase kinase-3ÎČ genetic polymorphisms and insomnia in depressed patients: A prospective study
International audienc