Kouter K, Šalamon Arčan I, Videtič Paska A. Epigenetics in psychiatry: Beyond DNA methylation. World J Psychiatry 2023; 13(6): 319-330 [PMID: 37383287 DOI: 10.5498/wjp.v13.i6.319]
Corresponding Author of This Article
Alja Videtič Paska, PhD, Associate Professor, Faculty of Medicine, Institute of Biochemistry and Molecular Genetics, University of Ljubljana, Vrazov trg 2, Ljubljana 1000, Slovenia. alja.videtic@mf.uni-lj.si
Research Domain of This Article
Psychiatry
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Psychiatry. Jun 19, 2023; 13(6): 319-330 Published online Jun 19, 2023. doi: 10.5498/wjp.v13.i6.319
Epigenetics in psychiatry: Beyond DNA methylation
Katarina Kouter, Iris Šalamon Arčan, Alja Videtič Paska
Katarina Kouter, Faculty of Medicine, Institute of Microbiology and Immunology, University of Ljubljana, Ljubljana 1000, Slovenia
Iris Šalamon Arčan, Alja Videtič Paska, Faculty of Medicine, Institute of Biochemistry and Molecular Genetics, University of Ljubljana, Ljubljana 1000, Slovenia
Author contributions: Kouter K, Šalamon Arčan I and Videtič Paska A organized and planned the manuscript; Šalamon Arčan I wrote Introduction, DNA hydroxymethylation and schizophrenia, bipolar disorder; Kouter K wrote Epigenetics of psychiatric disorders, Methods for DNA hydroxymethylation detection, DNA hydroxymethylation and suicidal behavior; Videtič Paska A wrote DNA hydroxymethylation and depression and obsessive-compulsive disorder, Conclusion; all authors reviewed and edited the manuscript; and all authors approved the final version of the manuscript.
Supported bySlovenian Research Agency, Young Researcher Grant to Šalamon Arčan I, No. P1-0390, J3-4533, Z3-2653.
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, Faculty of Medicine, Institute of Biochemistry and Molecular Genetics, University of Ljubljana, Vrazov trg 2, Ljubljana 1000, Slovenia. alja.videtic@mf.uni-lj.si
Received: December 27, 2022 Peer-review started: December 27, 2022 First decision: January 17, 2023 Revised: January 31, 2023 Accepted: April 25, 2023 Article in press: April 25, 2023 Published online: June 19, 2023
Abstract
The global burden of psychopathologies appears to be underestimated, since the global psychiatric disorder burden is exceeding other medical burdens. To be able to address this problem more effectively, we need to better understand the etiology of psychiatric disorders. One of the hallmarks of psychiatric disorders appears to be epigenetic dysregulation. While some epigenetic modifications (such as DNA methylation) are well known and studied, the roles of others have been investigated much less. DNA hydroxymethylation is a rarely studied epigenetic modification, which as well as being an intermediate stage in the DNA demethylation cycle is also an independent steady cell state involved in neurodevelopment and plasticity. In contrast to DNA methylation, DNA hydroxymethylation appears to be related to an increase in gene expression and subsequent protein expression. Although no particular gene or genetic locus can be at this point linked to changes in DNA hydroxymethylation in psychiatric disorders, the epigenetic marks present good potential for biomarker identification because the epigenetic landscape is a result of the interplay between genes and environment, which both influence the development of psychiatric disorders, and because hydoxymethylation changes are particularly enriched in the brain and in synapse-related genes.
Core Tip: DNA hydroxymethylation is one of the least investigated epigenetic mechanisms but based on currently available results it is abundant in the brain, thus potentially influencing the development of psychiatric disorders through modulation of gene expression. Currently no particular genetic locus or gene can be linked to hydroxymethylation in psychiatric disorders. However, the dynamics in gene expression of the ten-eleven translocation enzymes that catalyze hydroxymethylation have been demonstrated, and changes in hydroxymethylation levels when comparing healthy subjects with psychiatric disorders can be determined using genome-wide and candidate gene approaches.
