Journal
TRANSLATIONAL PSYCHIATRY
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/tp.2016.41
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Funding
- German Research Foundation (DFG)
- Collaborative Research Centre 'Fear, Anxiety, Anxiety Disorders' [SFB-TRR-58]
- German Ministry of Research and Education (BMBF) [01EE1402A, 01GV0614]
- BMBF Psychotherapy Research Funding Initiative Improving the Treatment of Panic Disorder
- coordinating center for clinical studies in Dresden (KKS Dresden): Marko Kappler
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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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