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Transl Psychiatry. 2016 Apr 5;6:e773. doi: 10.1038/tp.2016.41.

MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy.

Author information

1
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
2
Institute of Psychology, University of Greifswald, Greifswald, Germany.
3
Department of Biological Psychology, Clinical Psychology and Psychotherapy, University of Würzburg, Würzburg, Germany.
4
Division of Molecular Psychiatry, Department of Psychiatry, University of Würzburg, Würzburg, Germany.
5
Christoph-Dornier-Foundation for Clinical Psychology, Bremen, Germany.
6
Outpatient Psychotherapy Treatment Center, University of Bremen, Bremen, Germany.
7
Department of Clinical Psychology and Psychotherapy, University of Hamburg, Hamburg, Germany.
8
Department of Clinical Psychology and Psychotherapy, Technical University of Dresden, Dresden, Germany.
9
Department of Psychiatry, Marburg University, Marburg, Germany.
10
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe-University, Frankfurt, Germany.
11
Section for Clinical Psychology and Psychotherapy, University of Marburg, Marburg, Germany.
12
Institute of Psychology, University of Münster, Münster, Germany.
13
Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.

Abstract

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.

PMID:
27045843
PMCID:
PMC4872399
DOI:
10.1038/tp.2016.41
[Indexed for MEDLINE]
Free PMC Article

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