Orexin in the anxiety spectrum
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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. / Gottschalk, Michael G; Richter, Jan; Ziegler, Christiane; Schiele, Miriam A; Mann, Julia; Geiger, Maximilian J; Schartner, Christoph; Homola, György A; Alpers, Georg W; Büchel, Christian; Fehm, Lydia; Fydrich, Thomas; Gerlach, Alexander L; Gloster, Andrew T; Helbig-Lang, Sylvia; Kalisch, Raffael; Kircher, Tilo; Lang, Thomas; Lonsdorf, Tina B; Pané-Farré, Christiane A; Ströhle, Andreas; Weber, Heike; Zwanzger, Peter; Arolt, Volker; Romanos, Marcel; Wittchen, Hans-Ulrich; Hamm, Alfons; Pauli, Paul; Reif, Andreas; Deckert, Jürgen; Neufang, Susanne; Höfler, Michael; Domschke, Katharina.
in: TRANSL PSYCHIAT, Jahrgang 9, Nr. 1, 04.02.2019, S. 75.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Orexin in the anxiety spectrum
T2 - association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes
AU - Gottschalk, Michael G
AU - Richter, Jan
AU - Ziegler, Christiane
AU - Schiele, Miriam A
AU - Mann, Julia
AU - Geiger, Maximilian J
AU - Schartner, Christoph
AU - Homola, György A
AU - Alpers, Georg W
AU - Büchel, Christian
AU - Fehm, Lydia
AU - Fydrich, Thomas
AU - Gerlach, Alexander L
AU - Gloster, Andrew T
AU - Helbig-Lang, Sylvia
AU - Kalisch, Raffael
AU - Kircher, Tilo
AU - Lang, Thomas
AU - Lonsdorf, Tina B
AU - Pané-Farré, Christiane A
AU - Ströhle, Andreas
AU - Weber, Heike
AU - Zwanzger, Peter
AU - Arolt, Volker
AU - Romanos, Marcel
AU - Wittchen, Hans-Ulrich
AU - Hamm, Alfons
AU - Pauli, Paul
AU - Reif, Andreas
AU - Deckert, Jürgen
AU - Neufang, Susanne
AU - Höfler, Michael
AU - Domschke, Katharina
PY - 2019/2/4
Y1 - 2019/2/4
N2 - 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). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10-7), particularly in the female subsample (p = 9.8 × 10-9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10-4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.
AB - 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). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10-7), particularly in the female subsample (p = 9.8 × 10-9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10-4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.
U2 - 10.1038/s41398-019-0415-8
DO - 10.1038/s41398-019-0415-8
M3 - SCORING: Journal article
C2 - 30718541
VL - 9
SP - 75
JO - TRANSL PSYCHIAT
JF - TRANSL PSYCHIAT
SN - 2158-3188
IS - 1
ER -
