Epigenetic signature of MAOA and MAOB genes in mental disorders
Abstract
Epigenetic processes such as DNA methylation are considered key mechanisms at the crossroads between genetics and environment in the etiology of mental disorders. The monoamine oxidases A and B (MAOA/MAOB) are prime candidates for the investigation into the role of DNA methylation in mental disorders, given their pivotal role in the metabolism of monoamines and as pharmacological targets of potent antidepressant drugs such as tranylcypromine, phenelzine or moclobemide. The present mini-review aims at summarizing and critically discussing the growing body of the literature supporting a role of DNA methylation of the MAOA gene promoter/exon I/intron I region and its interaction with environmental factors in several mental disorders, i.e., anxiety disorders, depression, posttraumatic stress disorder, substance use disorder, conduct disorder/antisocial personality disorder, borderline personality disorder and schizophrenia, as well as some pilot data on MAOB methylation in smokers and patients with borderline personality disorder. Furthermore, first evidence for MAOA methylation to be involved in treatment response prediction and as a potential mechanistic correlate of fear extinction is presented. Altered MAOA gene DNA methylation emerges as a possible pathogenetically relevant epigenetic mechanism in mental disorders. Given robust replication and further functional characterization, MAOA methylation patterns might serve as a peripheral biomarker of disease risk and treatment response informing preventive and personalized therapeutic approaches in the future.
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Human MAOA methylation is positively correlated with the percentage of recently experienced positive life events, while relative hypomethylation is associated with the experience of negative life events and a number of mental disorders including panic disorder, depression and substance abuse.
“human MAOA methylation has been found to be positively correlated with the percentage of recently experienced positive life events, while relative hypomethylation has been associated with the experience of negative life events (Domschke et al., 2012) and a number of mental disorders including panic disorder, depression and substance abuse (for review, see Ziegler & Domschke, 2018).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Ziegler & Domschke, 2018
The effects of genes on behavior may also be modified by sex-specific factors such as the levels of testosterone and Y-chromosome genes.
“the effects of genes on behavior may also be modified by sex-specific factors such as the levels of testosterone and Y-chromosome genes [140, 141].”
From Genetics of child aggression, a systematic review (2024) · cites this paper as [141]
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Genetics of child aggression, a systematic review
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- Authors
- Ziegler, C., & Domschke, K.
- Affiliations
- University of Freiburg (DE)
- Corresponding author
- Domschke, Katharina
- Venue
- Journal of Neural Transmission
- Published
- 2018-09-21
- Volume
- 125
- Issue
- 11
- Pages
- 1581-1588
- ISSN
- 0300-9564 (ISSN-L)
- 1435-1463
- OpenAlex
- W2892238887
- Cited by
- 72
- References
- 38
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 6 · 2023: 13 · 2022: 14 · 2021: 16 · 2020: 9 · 2019: 2 · 2018: 1
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neural Transmission (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB-TRR-58, C02, SFB-TRR-58, Z02)
- German Ministry of Research and Education, BMBF (01EE1402F, PROTECT-AD, P5)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- monoamine oxidase A, monoamine oxidase B, monoamine oxidase, DNA methylation, epigenetics, mental illness, gene-environment interaction, anxiety disorders, depression, post-traumatic stress disorder, substance use disorders, conduct disorder, antisocial personality disorder, borderline personality disorder, schizophrenia, smoking, treatment response prediction, fear extinction, biomarkers
- MeSH terms
- Mental Disorders, Humans, Monoamine Oxidase, Promoter Regions, Genetic, DNA Methylation, Genetic Predisposition to Disease, Epigenesis, Genetic
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