Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes
| Autor: | Andreas Ströhle, Jan Richter, Lydia Fehm, Thomas Lang, Michael Höfler, Peter Zwanzger, Jürgen Deckert, Christiane A. Pané-Farré, Julia Mann, Tina B. Lonsdorf, Andrew T. Gloster, Tilo Kircher, Marcel Romanos, Susanne Neufang, Christoph Schartner, György A. Homola, Katharina Domschke, Georg W. Alpers, Sylvia Helbig-Lang, Alfons O. Hamm, Andreas Reif, Volker Arolt, Raffael Kalisch, Christian Büchel, Heike Weber, Maximilian J. Geiger, Alexander L. Gerlach, Michael G. Gottschalk, Paul Pauli, Thomas Fydrich, Miriam A. Schiele, Hans-Ulrich Wittchen, Christiane Ziegler |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology medicine.medical_specialty Hamilton Anxiety Rating Scale medicine.medical_treatment behavioral disciplines and activities Article Arousal lcsh:RC321-571 Young Adult 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Orexin Receptors Internal medicine Outcome Assessment Health Care Avoidance Learning medicine Humans ddc:610 Allele Agoraphobia Cerebrum lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry Cognitive Behavioral Therapy business.industry Panic disorder Case-control study Fear Middle Aged medicine.disease Magnetic Resonance Imaging Cognitive behavioral therapy Psychiatry and Mental health Phenotype 030104 developmental biology Case-Control Studies Panic Disorder Anxiety Female medicine.symptom business Personalized medicine Human behaviour Predictive markers Molecular neuroscience Psychiatric disorders 030217 neurology & neurosurgery |
| Zdroj: | Translational Psychiatry, Vol 9, Iss 1, Pp 1-13 (2019) Translational Psychiatry Translational Psychiatry, 1(9):75 |
| ISSN: | 2158-3188 |
| DOI: | 10.1038/s41398-019-0415-8 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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