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Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes

February 25, 2019 16:45 | CINP Office (Administrator)

Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271).

Michael G. Gottschalk, Jan Richter, Christiane Ziegler, Miriam A. Schiele, Julia Mann, Maximilian J. Geiger, Christoph Schartner, György A. Homola, Georg W. Alpers, Christian Büchel, Lydia Fehm, Thomas Fydrich, Alexander L. Gerlach, Andrew T. Gloster, Sylvia Helbig-Lang, Raffael Kalisch, Tilo Kircher, Thomas Lang, Tina B. Lonsdorf, Christiane A. Pané-Farré, Andreas Ströhle, Heike Weber, Peter Zwanzger, Volker Arolt, Marcel Romanos, Hans-Ulrich Wittchen, Alfons Hamm, Paul Pauli, Andreas Reif, Jürgen Deckert, Susanne Neufang, Michael Höfler & Katharina Domschke.

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