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World J Psychiatry. Sep 19, 2022; 12(9): 1150-1168
Published online Sep 19, 2022. doi: 10.5498/wjp.v12.i9.1150
Depressive disorder and antidepressants from an epigenetic point of view
Iris Šalamon Arčan, Katarina Kouter, Alja Videtič Paska
Iris Šalamon Arčan, Katarina Kouter, Alja Videtič Paska, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana SI-1000, Slovenia
Author contributions: Videtič Paska A and Šalamon Arčan I organized and planned the manuscript; Šalamon Arčan I wrote the first draft of the manuscript; Kouter K and Videtič Paska A reviewed and edited the manuscript; All authors approved the final version of the manuscript.
Supported by Slovenina Reserach Agency, Young Researcher Grant to IŠ, No. P1-0390.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Alja Videtič Paska, PhD, Associate Professor, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov Trg 2, Ljubljana SI-1000, Slovenia. alja.videtic@mf.uni-lj.si
Received: March 25, 2022
Peer-review started: March 25, 2022
First decision: May 11, 2022
Revised: May 27, 2022
Accepted: August 6, 2022
Article in press: August 6, 2022
Published online: September 19, 2022
Processing time: 178 Days and 15.2 Hours
Abstract

Depressive disorder is a complex, heterogeneous disease that affects approximately 280 million people worldwide. Environmental, genetic, and neurobiological factors contribute to the depressive state. Since the nervous system is susceptible to shifts in activity of epigenetic modifiers, these allow for significant plasticity and response to rapid changes in the environment. Among the most studied epigenetic modifications in depressive disorder is DNA methylation, with findings centered on the brain-derived neurotrophic factor gene, the glucocorticoid receptor gene, and the serotonin transporter gene. In order to identify biomarkers that would be useful in clinical settings, for diagnosis and for treatment response, further research on antidepressants and alterations they cause in the epigenetic landscape throughout the genome is needed. Studies on cornerstone antidepressants, such as selective serotonin reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors, norepinephrine, and dopamine reuptake inhibitors and their effects on depressive disorder are available, but systematic conclusions on their effects are still hard to draw due to the highly heterogeneous nature of the studies. In addition, two novel drugs, ketamine and esketamine, are being investigated particularly in association with treatment of resistant depression, which is one of the hot topics of contemporary research and the field of precision psychiatry.

Keywords: Epigenetics, Depression, DNA methylation, Histone tail modification, microRNA, Antidepressants

Core Tip: Deeper knowledge on the biological background of depressive disorder could be achieved through understanding of epigenetic mechanisms that alter the response of cells to environmental stimuli. Antidepressants are of particular interest since it has been shown that they affect DNA methylation, histone modifications, and microRNA expression. As not all patients respond to prescribed antidepressants, it is of interest to discover specific biomarkers that could be used in a clinical setting.