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

作者：Christiane Ziegler, Jan Richter, Marina Mahr, Agnieszka Gajewska, Miriam A. Schiele, Andrea Gehrmann, Brigitte Schmidt, K-P Lesch, Thomas G. Lang, Sylvia Helbig‐Lang, Paul Pauli, Tilo T. J. Kircher, Andreas Reif, Winfried Rief, Anna N. Voßbeck-Elsebusch, Volker Arolt, H-U Wittchen, Alfons O. Hamm, J. Deckert, Katharina Domschke · 发表于：Translational Psychiatry · 年份：2016 · DOI：10.1038/tp.2016.41 · 被引用次数：184 · 研究领域：Child and Adolescent Psychosocial and Emotional Development、Epigenetics and DNA Methylation、Identity, Memory, and Therapy

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 r...