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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 <jats:italic>MAOA<\/jats:italic> methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. <jats:italic>MAOA<\/jats:italic> methylation was compared between <jats:italic>N<\/jats:italic>=28 female Caucasian PD patients (discovery sample) and <jats:italic>N<\/jats:italic>=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. <jats:italic>MAOA<\/jats:italic> 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 (<jats:italic>N<\/jats:italic>=20). Patients exhibited lower <jats:italic>MAOA<\/jats:italic> methylation than healthy controls (<jats:italic>P<\/jats:italic>&lt;0.001), and baseline PD severity correlated negatively with <jats:italic>MAOA<\/jats:italic> methylation (<jats:italic>P<\/jats:italic>=0.01). In the discovery sample, <jats:italic>MAOA<\/jats:italic> methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0\u2013T1: +3.37\u00b12.17%), while non-responders further decreased in methylation (\u22122.00\u00b11.28%; <jats:italic>P<\/jats:italic>=0.001). In the replication sample, increases in <jats:italic>MAOA<\/jats:italic> methylation correlated with agoraphobic symptom reduction after CBT (<jats:italic>P<\/jats:italic>=0.02\u20130.03). The present results support previous evidence for <jats:italic>MAOA<\/jats:italic> hypomethylation as a PD risk marker and suggest reversibility of <jats:italic>MAOA<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/tp.2016.41","type":"journal-article","created":{"date-parts":[[2016,4,5]],"date-time":"2016-04-05T13:48:23Z","timestamp":1459864103000},"page":"e773-e773","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":167,"title":["MAOA gene hypomethylation in panic disorder\u2014reversibility of an epigenetic risk pattern by psychotherapy"],"prefix":"10.1038","volume":"6","author":[{"given":"C","family":"Ziegler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Mahr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Gajewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Schiele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Gehrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K-P","family":"Lesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Helbig-Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Pauli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Kircher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0992-634X","authenticated-orcid":false,"given":"A","family":"Reif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Rief","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A N","family":"Vossbeck-Elsebusch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Arolt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H-U","family":"Wittchen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A O","family":"Hamm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Deckert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Domschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,4,5]]},"reference":[{"key":"BFtp201641_CR1","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.euroneuro.2011.07.018","volume":"21","author":"HU Wittchen","year":"2011","unstructured":"Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, J\u00f6nsson B et al. 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