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DNA methylation may mediate psychotropic drug-induced metabolic side effects: results from a 1-month observational study

Published online by Cambridge University Press:  01 September 2022

C. Dubath ,
E. Porcu ,
A. Delacrétaz ,
C. Grosu ,
N. Laaboub ,
M. Piras ,
A. Von Gunten ,
P. Conus ,
K. Von Plessen  and
Z. Kutalik
...Show all authors
C. Dubath*
Affiliation:
Lausanne University Hospital, Psychiatry, Prilly, Switzerland
E. Porcu
Affiliation:
Swiss institute of bioinformatics, Bioinformatics, Lausanne, Switzerland
A. Delacrétaz
Affiliation:
Lausanne University Hospital, Psychiatry, Prilly, Switzerland
C. Grosu
Affiliation:
Lausanne University Hospital, Psychiatry, Prilly, Switzerland
N. Laaboub
Affiliation:
Lausanne University Hospital, Psychiatry, Prilly, Switzerland
M. Piras
Affiliation:
Lausanne University Hospital, Psychiatry, Prilly, Switzerland
A. Von Gunten
Affiliation:
Lausanne University Hospital, Psychiatry, Prilly, Switzerland
P. Conus
Affiliation:
Lausanne University Hospital, Psychiatry, Prilly, Switzerland
K. Von Plessen
Affiliation:
Lausanne University Hospital, Psychiatry, Prilly, Switzerland
Z. Kutalik
Affiliation:
Swiss institute of bioinformatics, Bioinformatics, Lausanne, Switzerland
C. Eap
Affiliation:
Lausanne University Hospital, Psychiatry, Prilly, Switzerland
*
*Corresponding author.

Abstract

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Introduction

Metabolic side effects of psychotropic medications are a major drawback to patients’ effective treatment. Among the mechanisms underlying their development, DNA methylation may be involved.

Objectives

The aim of this study was to estimate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and baseline DNA methylation or 1-month DNA methylation changes, using an epigenome-wide approach.

Methods

Seventy-nine psychiatric patients recruited as part of PsyMetab study, who started a treatment with either an antipsychotic, a mood stabilizer or mirtazapine were selected. Epigenome-wide DNA methylation was measured using the Illumina Methylation EPIC BeadChip at baseline and after one month of treatment.

Results

A global methylation increase was observed after 1 month of treatment, which was more pronounced in patients whose weight remained stable (i.e., <2.5% weight increase). Epigenome-wide significant methylation changes were observed at 52 loci in the whole cohort and at one site, namely cg12209987, located in an intergenic region within an enhancer, specifically in patients who underwent important early weight gain (i.e., ≥5% weight increase) during the same period of treatment (p<5*10-8). Multivariable analysis confirmed an association between an increase in methylation at this locus and weight gain in the whole cohort (p=0.004). Epigenome-wide association analyses failed to identify any significant link between other metabolic changes (e.g. glucose or lipid levels) and methylation data.

Conclusions

These findings give new insight into the mechanisms of psychotropic drug-induced weight gain. With improved understanding of the metabolic side effects, the use of precision medicine with epigenetics may become possible

Disclosure

No significant relationships.

Keywords

psychotropic drugsMetabolic side effectsPrecision Medicineepigenetics
Type
Abstract
Information
European Psychiatry , Volume 65 , Special Issue S1: Abstracts of the 30th European Congress of Psychiatry , June 2022 , pp. S98 - S99
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of the European Psychiatric Association
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