title: MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy.
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.
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Ziegler
authors.affiliation: Institute of Psychology, University of Greifswald, Greifswald, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Richter
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Mahr
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Gajewska
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.|Department of Biological Psychology, Clinical Psychology and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: M A
authors.initials: MA
authors.lastname: Schiele
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Gehrmann
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Schmidt
authors.affiliation: Division of Molecular Psychiatry, Department of Psychiatry, University of Würzburg, Würzburg, Germany.
authors.forename: K-P
authors.initials: KP
authors.lastname: Lesch
authors.affiliation: Christoph-Dornier-Foundation for Clinical Psychology, Bremen, Germany.|Outpatient Psychotherapy Treatment Center, University of Bremen, Bremen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Lang
authors.affiliation: Department of Clinical Psychology and Psychotherapy, University of Hamburg, Hamburg, Germany.|Department of Clinical Psychology and Psychotherapy, Technical University of Dresden, Dresden, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Helbig-Lang
authors.affiliation: Department of Biological Psychology, Clinical Psychology and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Pauli
authors.affiliation: Department of Psychiatry, Marburg University, Marburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kircher
authors.affiliation: Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe-University, Frankfurt, Germany.
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-0992-634X
authors.initials: A
authors.lastname: Reif
authors.affiliation: Section for Clinical Psychology and Psychotherapy, University of Marburg, Marburg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Rief
authors.affiliation: Institute of Psychology, University of Münster, Münster, Germany.
authors.forename: A N
authors.initials: AN
authors.lastname: Vossbeck-Elsebusch
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Arolt
authors.affiliation: Department of Clinical Psychology and Psychotherapy, Technical University of Dresden, Dresden, Germany.
authors.forename: H-U
authors.initials: HU
authors.lastname: Wittchen
authors.affiliation: Institute of Psychology, University of Greifswald, Greifswald, Germany.
authors.forename: A O
authors.initials: AO
authors.lastname: Hamm
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Deckert
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Domschke
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015928:Cognitive Behavioral Therapy; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008995:Monoamine Oxidase / Q000235:genetics*; D016584:Panic Disorder / Q000235:genetics* / Q000628:therapy; D017422:Sequence Analysis, DNA
chemical_list: D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human