Clinical, genetic and environmental influences on weight gain and metabolic disorders induced by psychotropic drugs

Abstract

Introduction Weight gain and obesity are important health problems associated with psychiatric disorders and/or with psychotropic drug treatments. There is a high inter-individual variability in the susceptibility to drug induced weight gain and/or other cardiometabolic disorders. Objectives To study the genetic and environmental risk factors for weight gain and onset of metabolic syndrome during psychotropic treatment Methods Analysis in PsyMetab, a large (n>3000) ongoing longitudinal prospective cohort study investigating cardiometabolic disorders in psychiatric patients. Results Aside from well-known clinical risk factors for metabolic worsening (e.g. young age, first episode status, rapid weight gain during the first month of treatment and/or low initial BMI), additional risk factors have been recently identified. We showed an inverse association between socio-economic status (SES) and worsening of cardiometabolic parameters, adult patients with a low SES having a three-fold higher risk of developing metabolic syndrome over one year versus patients with a high SES (n=366). In addition, a causal inverse effect of educational attainment on BMI was revealed using Mendelian randomization in the UKBiobank (n=30’069). Results from an epigenome-wide association study (EWAS) performed in 78 patients before and after one month of treatment and from a genome-wide association study (GWAS) in 1924 patients will also be presented. Conclusions Differences in clinical, genetic and environmental factors contribute to the differences in weight gain and metabolic disorders induced by psychotropic drugs. When starting a psychotropic drug at risk, a prospective monitoring of clinical (e.g. weight and blood pressure) and biochemical (fasting glucose, lipid levels) parameters is essential. Disclosure Prof. Eap received honoraria for conferences or teaching CME courses from Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Vifor-Pharma, and Zeller in the past 3 years. The other authors report no potential conflicts of interest. This work has

Keywords

• Genetics
• metabolic syndrome
• psychotropic drugs
• epigenetics