Psychotropic drug-induced genetic-epigenetic modulation of CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients
| Autor: | Delacrétaz A, Glatard A, Dubath C, Gholam-Rezaee M, Jv, Sanchez-Mut, Gräff J, Armin von Gunten, Conus P, Cb, Eap |
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| Předmět: |
Adult
Male Age of Onset Alleles Case-Control Studies CpG Islands/drug effects DNA Methylation/drug effects Epigenesis Genetic Female Genetic Association Studies Humans Longitudinal Studies Middle Aged Obesity/chemically induced Obesity/genetics Polymorphism Single Nucleotide Prospective Studies Psychotropic Drugs/adverse effects Psychotropic Drugs/pharmacology Transcription Factors/genetics Weight Gain/genetics CRTC1 Early weight gain Methylation Psychiatric population Psychotropic drugs body-mass index epigenome-wide Weight Gain metabolic syndrome insulin-resistance Obesity bipolar disorder Psychotropic Drugs Research DNA Methylation schizophrenia mood stabilizers antipsychotics depression CpG Islands Transcription Factors |
| Zdroj: | Europe PubMed Central Clinical Epigenetics Clinical epigenetics, vol. 11, no. 1, pp. 198 |
| Popis: | Background: Metabolic side effects induced by psychotropic drugs represent a major health issue in psychiatry. CREB-regulated transcription coactivator 1 (CRTC1) gene plays a major role in the regulation of energy homeostasis and epigenetic mechanisms may explain its association with obesity features previously described in psychiatric patients. This prospective study included 78 patients receiving psychotropic drugs that induce metabolic disturbances, with weight and other metabolic parameters monitored regularly. Methylation levels in 76 CRTC1 probes were assessed before and after 1 month of psychotropic treatment in blood samples. Results: Significant methylation changes were observed in three CRTC1 CpG sites (i.e., cg07015183, cg12034943, and cg 17006757) in patients with early and important weight gain (i.e., equal or higher than 5% after 1 month; FDR p value = 0.02). Multivariable models showed that methylation decrease in cg12034943 was more important in patients with early weight gain (>= 5%) than in those who did not gain weight (p = 0.01). Further analyses combining genetic and methylation data showed that cg12034943 was significantly associated with early weight gain in patients carrying the G allele of rs4808844A>G (p = 0.03), a SNP associated with this methylation site (p = 0.03). Conclusions: These findings give new insights on psychotropic-induced weight gain and underline the need of future larger prospective epigenetic studies to better understand the complex pathways involved in psychotropic-induced metabolic side effects. |
| Databáze: | OpenAIRE |
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