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Metabolic syndrome in psychiatry: clinical, genetic and pharmacogenetic studies

English title Metabolic syndrome in psychiatry: clinical, genetic and pharmacogenetic studies
Applicant Eap Chin Bin
Number 173211
Funding scheme Project funding
Research institution
Biochimie et Psychopharmacologie clinique Centre de Neurosciences Psychiatriques Département de Psychiatrie - CHUV
Pharmacogenetique Psychopharmacologie clin. Centre de Neurosciences Psychiatriques Département de Psychiatrie - CHUV
Institution of higher education University of Lausanne - LA
Main discipline Neurology, Psychiatry
Start/End 01.04.2017 - 31.05.2021
Approved amount 732'898.00
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All Disciplines (3)

Discipline
Neurology, Psychiatry
Clinical Pharmacology
Metabolic Disorders

Keywords (11)

psychiatry; Genetics; weight gain; metabolic syndrome; pharmacogenetics; antipsychotics; psychotropic drugs; Personnalized medicine; dyslipidemia; hypertension; diabetes

Lay Summary (French)

Lead
La prise de poids et les complications métaboliques (augmentation du cholestérol et des triglycérides, hypertension, diabète, obésité abdominale) sont des effets indésirables majeurs de plusieurs médicaments psychotropes. Ces effets métaboliques contribuent fortement à l’augmentation de la morbidité et de la mortalité observée dans la population psychiatrique. Il existe une variabilité dans la susceptibilité à ces effets indésirables entre les patients expliquée par des facteurs cliniques, génétiques et environnementaux. Le projet contribue à la compréhension de ces facteurs.
Lay summary

Contenu et objectif du travail de recherche

Certains patients peuvent développer rapidement un surpoids voir une obésité sous médication psychotrope, alors que d’autres semblent être protégés. Durant ces dernières années, notre groupe a mis en évidence l’implication de nombreux facteurs cliniques et génétiques dans la prise de poids induite par  la médication. La connaissance de ces facteurs est importante pour le suivi clinique des patients en psychiatrie car il permet de mieux identifier les patients qui sont à risque et éventuellement d’adapter le traitement. L’objectif de ce projet est de continuer la recherche sur les causes génétiques, cliniques et environnementales sous-jacentes aux problèmes métaboliques, en étendant notamment les analyses sur les problèmes de dyslipidémie, d’hypertension et de diabète.

Contexte scientifique et social du projet de recherche

Les troubles métaboliques sont un problème de santé publique dans la population psychiatrique. Notre travail contribuera à une meilleure compréhension des mécanismes impliqués dans l’apparition d’une prise de poids importante et/ou d’autres symptômes du syndrome métabolique lors de la prescription de psychotropes. Ceci devrait permettre de mieux prévoir et prévenir ces effets et contribuer à une médecine personnalisée en psychiatrie.

Direct link to Lay Summary Last update: 03.05.2017

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Valproate is associated with early decrease of high‐density lipoprotein cholesterol levels in the psychiatric population
Delacrétaz Aurélie, Glatard Anaïs, Dubath Céline, Gholam Mehdi, Gamma Franziska, van Gunten Armin, Conus Philippe, Eap Chin B. (2021), Valproate is associated with early decrease of high‐density lipoprotein cholesterol levels in the psychiatric population, in Basic & Clinical Pharmacology & Toxicology, 129(1), 26-35.
Psychological trauma occurring during adolescence is associated with an increased risk of greater waist circumference in Early Psychosis patients treated with psychotropic medication
Alameda Luis, Levier Axel, Gholam-Rezaee Mehdi, Golay Philippe, Vandenberghe Frederik, Delacretaz Aurélie, Baumann Philipp, Glatard Anaïs, Dubath Céline, Herane-Vives Andres, Rodriguez Victoria, Solida Alessandra, Do Kim Q., Eap Chin B., Conus Philippe (2020), Psychological trauma occurring during adolescence is associated with an increased risk of greater waist circumference in Early Psychosis patients treated with psychotropic medication, in PLOS ONE, 15(12), e0242569.
Amisulpride: Real-World Evidence of Dose Adaptation and Effect on Prolactin Concentrations and Body Weight Gain by Pharmacokinetic/Pharmacodynamic Analyses
Glatard Anaïs, Guidi Monia, Delacrétaz Aurélie, Dubath Céline, Grosu Claire, Laaboub Nermine, von Gunten Armin, Conus Philippe, Csajka Chantal, Eap Chin B. (2020), Amisulpride: Real-World Evidence of Dose Adaptation and Effect on Prolactin Concentrations and Body Weight Gain by Pharmacokinetic/Pharmacodynamic Analyses, in Clinical Pharmacokinetics, 59(3), 371-382.
Evaluation of Cardiometabolic Risk in a Large Psychiatric Cohort and Comparison With a Population-Based Sample in Switzerland
Dubath Céline, Delacrétaz Aurélie, Glatard Anaïs, Vollenweider Peter, Preisig Martin, Richard-Lepouriel Hélène, Hasler Roland, Gamma Franziska, Solida Alessandra, Thonney Jacques, Fassassi Sylfa, von Gunten Armin, Conus Philippe, Eap Chin B. (2020), Evaluation of Cardiometabolic Risk in a Large Psychiatric Cohort and Comparison With a Population-Based Sample in Switzerland, in The Journal of Clinical Psychiatry, 81(3), 19m12796.
Psychotropic drug-induced genetic-epigenetic modulation of CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients
Delacrétaz Aurélie, Glatard Anaïs, Dubath Céline, Gholam-Rezaee Mehdi, Sanchez-Mut Jose Vicente, Gräff Johannes, von Gunten Armin, Conus Philippe, Eap Chin B. (2019), Psychotropic drug-induced genetic-epigenetic modulation of CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients, in Clinical Epigenetics, 11(1), 198.
Genetic and clinic predictors of new onset diabetes mellitus after transplantation
Saigi-Morgui Núria, Quteineh Lina, Bochud Pierre-Yves, Crettol Severine, Kutalik Zoltán, Mueller Nicolas J., Binet Isabelle, Van Delden Christian, Steiger Jürg, Mohacsi Paul, Dufour Jean-francois, Soccal Paola M., Pascual Manuel, Eap Chin B. (2019), Genetic and clinic predictors of new onset diabetes mellitus after transplantation, in The Pharmacogenomics Journal, 19(1), 53-64.
Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients
Quteineh Lina, Wójtowicz Agnieszka, Bochud Pierre-Yves, Crettol Severine, Vandenberghe Frederik, Venetz Jean-Pierre, Manuel Oriol, Golshayan Dela, Lehmann Roger, Mueller Nicolas J., Binet Isabelle, van Delden Christian, Steiger Jürg, Mohacsi Paul, Dufour Jean-Francois, Soccal Paola M., Kutalik Zoltan, Marques-Vidal Pedro, Vollenweider Peter, Recher Mike, Hess Christoph, Pascual Manuel, Eap Chin B. (2019), Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients, in American Journal of Transplantation, 19(1), 238-246.
Lipid Disturbances in Adolescents Treated With Second-Generation Antipsychotics Clinical Determinants of Plasma Lipid Worsening and New-Onset Hypercholesterolemia
Delacrétaz Aurélie, Vandenberghe Frederik, Glatard Anaïs, Dubath Céline, Levier Axel, Gholam-Rezaee Mehdi, Holzer Laurent, Ambresin Anne-Emmanuelle, Conus Philippe, Eap Chin B. (2019), Lipid Disturbances in Adolescents Treated With Second-Generation Antipsychotics Clinical Determinants of Plasma Lipid Worsening and New-Onset Hypercholesterolemia, in The Journal of Clinical Psychiatry, 80(3), e1-e9.
Prevalence of ECG abnormalities and risk factors for QTc interval prolongation in hospitalized psychiatric patients
AnsermotNicolas, BochatayMeredith, SchläpferJürg, GholamMehdi, GonthierAriane, ConusPhilippe, EapChin B (2019), Prevalence of ECG abnormalities and risk factors for QTc interval prolongation in hospitalized psychiatric patients, in Therapeutic Advances in Psychopharmacology, 9, 1-13.
Association Between Plasma Caffeine and Other Methylxanthines and Metabolic Parameters in a Psychiatric Population Treated With Psychotropic Drugs Inducing Metabolic Disturbances
Delacrétaz Aurélie, Vandenberghe Frederik, Glatard Anaïs, Levier Axel, Dubath Céline, Ansermot Nicolas, Crettol Séverine, Gholam-Rezaee Mehdi, Guessous Idris, Bochud Murielle, von Gunten Armin, Conus Philippe, Eap Chin B. (2018), Association Between Plasma Caffeine and Other Methylxanthines and Metabolic Parameters in a Psychiatric Population Treated With Psychotropic Drugs Inducing Metabolic Disturbances, in Frontiers in Psychiatry, 9, 573.
Second-Generation Antipsychotics in Adolescent Psychiatric Patients: Metabolic Effects and Impact of an Early Weight Change to Predict Longer Term Weight Gain
Vandenberghe Frederik, Najar-Giroud Alexandra, Holzer Laurent, Conus Philippe, Eap Chin B., Ambresin Anne-Emmanuelle (2018), Second-Generation Antipsychotics in Adolescent Psychiatric Patients: Metabolic Effects and Impact of an Early Weight Change to Predict Longer Term Weight Gain, in Journal of Child and Adolescent Psychopharmacology, 28(4), 258-265.
Early changes of blood lipid levels during psychotropic drug treatment as predictors of long-term lipid changes and of new onset dyslipidemia
Delacrétaz Aurélie, Vandenberghe Frederik, Gholam-Rezaee Mehdi, Saigi Morgui Nuria, Glatard Anais, Thonney Jacques, Solida-Tozzi Alessandra, Kolly Stephane, Gallo Sylfa Fassassi, Baumann Philipp, Berney Sylvie, Zulauff Sandrine Valloton, Aubry Jean-Michel, Hasler Roland, Ebbing Karsten, von Gunten Armin, Conus Philippe, Eap Chin B (2018), Early changes of blood lipid levels during psychotropic drug treatment as predictors of long-term lipid changes and of new onset dyslipidemia, in Journal of Clinical Lipidology, 12(1), 219-229.
Influence of polygenic risk scores on lipid levels and dyslipidemia in a psychiatric population receiving weight gain-inducing psychotropic drugs
Delacrétaz Aurélie, Lagares Santos Patricia, Saigi Morgui Nuria, Vandenberghe Frederik, Glatard Anaïs, Gholam-Rezaee Mehdi, von Gunten Armin, Conus Philippe, Eap Chin B (2017), Influence of polygenic risk scores on lipid levels and dyslipidemia in a psychiatric population receiving weight gain-inducing psychotropic drugs, in Pharmacogenetics and genomics, 27(12), 464-472.
Association of variants in SH2B1 and RABEP1 with worsening of low-density lipoprotein and glucose parameters in patients treated with psychotropic drugs
Delacrétaz Aurélie, Zdralovic Adna, Vandenberghe Frederik, Saigi-Morgui Nuria, Glatard Anaïs, Quteineh Lina, Gholam-Rezaee Mehdi, Raffoul Wassim, Applegate Lee Ann, Jafari Paris, Gamma Franziska, von Gunten Armin, Conus Philippe, Eap Chin B (2017), Association of variants in SH2B1 and RABEP1 with worsening of low-density lipoprotein and glucose parameters in patients treated with psychotropic drugs, in Gene, 628, 8-15.

Collaboration

Group / person Country
Types of collaboration
Laboratory of Neuroepigenetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Service de médecine interne, CHUV Switzerland (Europe)
- Publication
Unité Fonctionnelle de Toxicologie Centre de Biologie-Pathologie - CHU de Lille France (Europe)
- Publication
- Research Infrastructure
Centre d’épidémiologie psychiatrique et de psychopathologie Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Centre Universitaire Romand de Médecine Légale Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Swiss Transplant Cohort Study (University Lausanne, Geneva, Basel, Bern, Zurich) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Institut de Microbiologie, CHUV Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Congrès Français de psychiatrie Talk given at a conference Déterminants cliniques, génétiques et épigénétiques de la prise de poids et/ou du syndrome métabolique induits par les psychotropes 25.11.2020 Strasbourg, France Eap Chin Bin;
Formation postgraduée du Département de santé mentale et de psychiatrie des Hôpitaux universitaires de Genève Individual talk Psychotropes et risques métaboliques: facteurs de risque cliniques et génétiques 14.12.2019 Genève, Switzerland Eap Chin Bin;
14th world congress of Biological Psychiatry (WFSBP) Talk given at a conference Cardiometabolic health: where do we stand? Evaluation of risk in a large psychiatric cohort and comparison with a population-based sample in Switzerland. 02.06.2019 Vancouver, Canada Dubath Celine;
27th European Congress of Psychiatry. Chair of the symposium: Metabolic syndrome in psychiatry: recognition and management of psychotropic drug induced side-effects PLUS oral presentation Talk given at a conference Clinical determinant of the metabolic syndrome induced by psychot 06.04.2019 Warsaw, Poland Eap Chin Bin;
13ème symposium de la société Suisse des troubles bipolaires. Individual talk Effets secondaires et suivi métabolique lors du traitement des troubles bipolaires. 15.11.2018 Genève, Switzerland Eap Chin Bin;
Spring Meeting of the Swiss Society of General Internal Medicine Talk given at a conference Weight gain and worsening of other metabolic parameters induced by psychotropic drugs: genetic and clinical data 30.05.2018 Basel, Switzerland Eap Chin Bin;
Formation médicale continue du Département de Santé Mentale et de Psychiatrie des HUG Individual talk Psychotropes et risques métaboliques : facteurs de risque cliniques et génétiques 17.05.2018 Genève, Switzerland Eap Chin Bin;
Annual meeting of the American Psychiatric Association (APA). Chair of the workshop Psychotropic drug induced weight gain and/or metabolic syndrome: recognition and management PLUS oral presentation Talk given at a conference Clinical and genetic determinant of metabolic syndrome 05.05.2018 New York, United States of America Eap Chin Bin;
Séminaire du service d’Endocrinologie, Diabétologie et Métabolisme du CHUV Individual talk Psychotropes et risques métaboliques : facteurs de risque cliniques et génétiques 24.04.2018 CHUV, Switzerland Eap Chin Bin;
13th World congress of Biological psychiatry (WFSBP) Talk given at a conference Importance of early changes of blood lipid levels to predict long-term dyslipidemia during psychotropic drug treatment 18.06.2017 Copenhagen, Denmark Delacretaz Aurélie;


Awards

Title Year
Swiss Transplant Society award 2019 Award attributed to Dr L Quteineh for her work on the gene/environment interaction for SP110 (whose polymorphism is associated with diabetes both in transplant recipients and in psychiatric patients treated with weight gain inducing psychotropic drugs) 2019
Prix de Faculté Faculté de Biologie et Médecine 2018 2018

Associated projects

Number Title Start Funding scheme
200602 Metabolic syndrome in psychiatry: human microbiome transplantation in germ-free mice and brain imaging, telomeres, metabolomic and GWAS analysis in psychiatric patients 01.06.2021 Project funding
120686 Clinical and pharmacogenetic study on side effect induced by atypical antipsychotics 01.04.2008 Project funding
153320 Understanding the relations between psychosis an urban milieus: an experience-based approach 01.10.2014 Interdisciplinary projects
156874 Quantitative characterization of the connectome in the progression of psychosis 01.05.2015 Project funding
146166 Biomarkers of serotonin metabolism: Diagnostic, monitoring and pharmacogenetic interest 01.04.2013 Project funding
158776 NCCR SYNAPSY: The synaptic bases of mental diseases (phase II) 01.10.2014 National Centres of Competence in Research (NCCRs)

Abstract

This SNF project constitutes the continuation of our two previous SNF projects (320030-120686 and 324730-144064). Weight gain (WG) and metabolic complications are major side effects induced by some psychotropic drugs, and increase the risk of cardiovascular events and long term morbidity and mortality in psychiatric populations. >1460 patients were included and a very large data base with variables from the metabolic syndrome has been collected. Very interesting clinical as well as genetic results have been published in high impact journals thanks to the previous SNF project. A prize (Lundbeck Psychiatry award 2014) was awarded to Dr Choong for her paper published in JAMA Psychiatry (2013) and results have been accepted for oral presentations in 3 international congresses.The primary aims of the present project are to continue the analysis on the extensive clinical and genetic data presently collected, in particular on the following topics:- To continue the analysis of associations between genetic factors and metabolic symptoms. Thus, until now, mostly WG has been investigated. Analyses will be extended to hyperglycaemia and/or type 2 diabetes (T2D), hypercholesterolemia, hypertriglyceridemia and hypertension.- To extend (+540 patients) the number of included patients (adult and old age) to further increase the power of the study and to use the additional patients as a replication cohort for some genetic markers- To determine possible changes of DNA methylation induced by antipsychotic drugs and to determine the potential influence of such changes on metabolic parametersThe secondary aims are:- To extend PK-POP and PK-PD analysis to other psychotropic drugs of interest- To analyze changes during treatment of endogenous compounds in plasma using metabolomic approachesBecause of the experience acquired during the previous project, the feasibility of the present project appears optimal. Very large data sets from the presently included patients are already available. To further increase the number of patients, the number of sites of inclusion has been recently extended. To determine whether positive associations detected in psychiatric cohorts are also valid in the general populations, collaborations with investigators from very large consortia of populations based cohorts (i.e. GIANT, MAGIC, UK-Biobank, Genome Wide Associations Scans for Total Cholesterol, HDL-C, LDL-C and triglycerides) will be continued, thus widening the implication of our findings.
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