MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy
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Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0-T1: +3.37±2.17%), while non-responders further decreased in methylation (-2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02-0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.
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In 28 female patients with panic disorder in comparison to matched healthy controls, DNA methylation in a region spanning exon 1/intron 1 of the MAOA gene was shown to significantly increase in treatment responders following a six-week exposure-based CBT, whereas methylation levels remained unchanged or even decreased in non-responders.
“In 28 female patients with panic disorder in comparison to matched healthy controls, DNA methylation in a region spanning exon 1/intron 1 of the MAOA gene was shown to significantly increase in treatment responders following a six-week exposure-based CBT, whereas methylation levels remained unchanged or even decreased in non-responders.”
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 et al., 2016
Following therapy DNA methylation levels in CBT responders no longer differed from those in healthy controls.
“Of note, following therapy DNA methylation levels in CBT responders no longer differed from those in healthy controls (Ziegler et al., 2016).”
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 et al., 2016
MAOA methylation is increased in responders post-CBT.
“↑ Methylation in responders (n=11) post-CBT”
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 et al., 2016
In candidate gene studies in anxiety disorders, the evidence points at a pattern of MAO-A hypomethylation, as shown in acrophobia and OCD.
“in candidate gene studies in anxiety disorders, the evidence points at a pattern of hypomethylation (Ziegler et al., 2016) as shown in acrophobia (Schiele et al., 2018) and obsessive compulsive disorder (OCD) (Domschke et al., 2012).”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Ziegler et al., 2016
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References 38 · Cited by 183
- Authors
- Ziegler, C., Richter, J., Mahr, M., Gajewska, A., Schiele, M. A., Gehrmann, A., Schmidt, B., Lesch, K.-P., Lang, T., Helbig-Lang, S., Pauli, P., Kircher, T., Reif, A., Rief, W., Vossbeck-Elsebusch, A. N., Arolt, V, Wittchen, H.-U., Hamm, A. O., Deckert, J., & Domschke, K.
- Affiliations
- University of Würzburg (DE)
- Universität Greifswald (DE)
- Philipps University of Marburg (DE)
- Goethe University Frankfurt (DE)
- University of Münster (DE)
- Corresponding author
- Domschke, K
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2016-04-05
- Volume
- 6
- Issue
- 4
- Pages
- e773-e773
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC4872399
- OpenAlex
- W2328700233
- Cited by
- 183
- References
- 38
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 17 · 2023: 15 · 2022: 13 · 2021: 19 · 2020: 30 · 2019: 22 · 2018: 26 · 2017: 18 · 2016: 10
- FWCI
- 13.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (TRR‐58, SFB TRR 58)
- Bundesministerium für Bildung und Forschung (01EE1402A, 01GV0614)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- panic disorder, MAOA gene, DNA methylation, epigenetics, exposure-based cognitive behavioral therapy, fear extinction, treatment response, agoraphobia, epigenetic biomarkers, monoamine oxidase A
- MeSH terms
- Adult, Female, Humans, Monoamine Oxidase, Cognitive Behavioral Therapy, Case-Control Studies, Panic Disorder, Sequence Analysis, DNA, DNA Methylation, Epigenesis, Genetic
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