Psychotropic drug-induced genetic-epigenetic modulation of CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_7876169F9529
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Psychotropic drug-induced genetic-epigenetic modulation of CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients.
Journal
Clinical epigenetics
Author(s)
Delacrétaz A., Glatard A., Dubath C., Gholam-Rezaee M., Sanchez-Mut J.V., Gräff J., von Gunten A., Conus P., Eap C.B.
ISSN
1868-7083 (Electronic)
ISSN-L
1868-7075
Publication state
Published
Issued date
26/12/2019
Peer-reviewed
Oui
Volume
11
Number
1
Pages
198
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
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).
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.
Keywords
Adult, Age of Onset, Alleles, Case-Control Studies, CpG Islands/drug effects, DNA Methylation/drug effects, Epigenesis, Genetic, Female, Genetic Association Studies, Humans, Longitudinal Studies, Male, 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
Pubmed
Web of science
Open Access
Yes
Create date
03/01/2020 21:48
Last modification date
12/08/2020 5:22
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