Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-11436 Wissenschaftlicher Artikel Straube, B.; Reif, A.; Richter, J.; Lueken, U.; Weber, H.; Arolt, V.; Jansen, A.; Zwanzger, P.; Domschke, K.; Pauli, P.; Konrad, C.; Gerlach, A. L.; Lang, T.; Fydrich, T.; Alpers, G. W.; Stroehle, A.; Wittmann, A.; Pfleiderer, B.; Wittchen, H.-U.; Hamm, A.; Deckert, J.; Kircher, T. The functional - 1019C/G HTR1A polymorphism and mechanisms of fear Serotonin receptor 1A gene (HTR1A) knockout mice show pronounced defensive behaviour and increased fear conditioning to ambiguous conditioned stimuli. Such behaviour is a hallmark of pathological human anxiety, as observed in panic disorder with agoraphobia (PD/AG). Thus, variations in HTR1A might contribute to neurophysiological differences within subgroups of PD/AG patients. Here, we tested this hypothesis by combining genetic with behavioural techniques and neuroimaging. In a clinical multicentre trial, patients with PD/AG received 12 sessions of manualized cognitive-behavioural therapy (CBT) and were genotyped for HTR1A rs6295. In four subsamples of this multicentre trial, exposure behaviour (n = 185), defensive reactivity measured using a behavioural avoidance test (BAT; before CBT: n = 245; after CBT: n = 171) and functional magnetic resonance imaging (fMRI) data during fear conditioning were acquired before and after CBT (n = 39). HTR1A risk genotype (GG) carriers more often escaped during the BAT before treatment. Exploratory fMRI results suggest increased activation of the amygdala in response to threat as well as safety cues before and after treatment in GG carriers. Furthermore, GG carriers demonstrated reduced effects of CBT on differential conditioning in regions including the bilateral insulae and the anterior cingulate cortex. Finally, risk genotype carriers demonstrated reduced self-initiated exposure behaviour to aversive situations. This study demonstrates the effect of HTR1A variation on defensive behaviour, amygdala activity, CBT-induced neural plasticity and normalization of defence behaviour in PD/AG. Our results, therefore, translate evidence from animal studies to humans and suggest a central role for HTR1A in differentiating subgroups of patients with anxiety disorders. 2014 e490 Translational Psychiatry 4 urn:nbn:de:bvb:20-opus-114369 10.1038/tp.2014.130 Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie OPUS4-16442 Wissenschaftlicher Artikel Ziegler, C.; Richter, J.; Mahr, M.; Gajewska, A.; Schiele, M.A.; Gehrmann, A.; Schmidt, B.; Lesch, K.-P.; Lang, T.; Helbig-Lang, S.; Pauli, P.; Kircher, T.; Reif, A.; Rief, W.; Vossbeck-Elsebusch, A.N.; Arolt, V.; Wittchen, H.-U.; Hamm, A.O.; Deckert, J.; Domschke, K. MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy 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. 2016 e773 Translational Psychiatry 6 urn:nbn:de:bvb:20-opus-164422 10.1038/tp.2016.41 Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie