Universität zu Köln

Ridderbusch, Isabelle C., Richter, Jan ORCID: 0000-0002-7127-6990, Yang, Yunbo, Hoefler, Michael, Weber, Heike ORCID: 0000-0002-9421-1292, Reif, Andreas, Hamm, Alfons, Pane-Farre, Christiane A., Gerlach, Alexander L. ORCID: 0000-0001-6794-5349, Stroehle, Andreas, Pfleiderer, Bettina, Arolt, Volker, Wittchen, Hans-Ulrich, Gloster, Andrew, Lang, Thomas, Helbig-Lang, Sylvia, Fehm, Lydia, Pauli, Paul, Kircher, Tilo ORCID: 0000-0002-2514-2625, Lueken, Ulrike and Straube, Benjamin ORCID: 0000-0002-9837-0944 (2019). Association of rs7688285 allelic variation coding for GLRB with fear reactivity and exposure-based therapy in patients with panic disorder and agoraphobia. Eur. Neuropsychopharmacol., 29 (10). S. 1138 - 1152. AMSTERDAM: ELSEVIER. ISSN 1873-7862

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Abstract

The gene coding for glycine receptor beta subunits (GLRB) has been found to be related to panic disorder and agoraphobia (PD/AG) and to be associated with altered insular BOLD activation during fear conditioning, as an intermediate phenotype of defensive system reactivity in healthy subjects. In a multicenter clinical trial on PD/AG patients we investigated in three sub-samples whether GLRB allelic variation (A/G; A-allele identified as risk) in the single nucleotide polymorphism rs7688285 was associated with autonomic (behavioral avoidance test BAT; n = 267 patients) and neural (differential fear conditioning; n = 49 patients, n = 38 controls) measures, and furthermore with responding towards exposure-based cognitive behavioral therapy (CBT, n = 184 patients). An interaction of genotype with current PD/AG diagnosis (PD/AG vs. controls; fMRI data only) and their modification after CBT was tested as well. Exploratory fMRI results prior to CBT, revealed A-allele carriers irrespective of diagnostic status to show overall higher BOLD activation in the hippocampus, motor cortex (MC) and insula. Differential activation in the MC, anterior cingulate cortex (ACC) and insula was found in the interaction genotype X diagnosis. Differential activation in ACC and hippocampus was present in differential fear learning. ACC activation was modified after treatment, while no overall rs7688285 dependent effect on clinical outcomes was found. On the behavioral level, A-allele carriers showed pronounced fear reactivity prior to CBT which partially normalized afterwards. In sum, rs7688285 variation interacts in a complex manner with PD/AG on a functional systems level and might be involved in the development of PD/AG but not in their treatment. (C) 2019 Elsevier B.V. and ECNP. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ridderbusch, Isabelle C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Richter, Jan UNSPECIFIED orcid.org/0000-0002-7127-6990 UNSPECIFIED Yang, Yunbo UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoefler, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Heike UNSPECIFIED orcid.org/0000-0002-9421-1292 UNSPECIFIED Reif, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hamm, Alfons UNSPECIFIED UNSPECIFIED UNSPECIFIED Pane-Farre, Christiane A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerlach, Alexander L. UNSPECIFIED orcid.org/0000-0001-6794-5349 UNSPECIFIED Stroehle, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfleiderer, Bettina UNSPECIFIED UNSPECIFIED UNSPECIFIED Arolt, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittchen, Hans-Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Gloster, Andrew UNSPECIFIED UNSPECIFIED UNSPECIFIED Lang, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Helbig-Lang, Sylvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Fehm, Lydia UNSPECIFIED UNSPECIFIED UNSPECIFIED Pauli, Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Kircher, Tilo UNSPECIFIED orcid.org/0000-0002-2514-2625 UNSPECIFIED Lueken, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Straube, Benjamin UNSPECIFIED orcid.org/0000-0002-9837-0944 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-132985
DOI:	10.1016/j.euroneuro.2019.07.133
Journal or Publication Title:	Eur. Neuropsychopharmacol.
Volume:	29
Number:	10
Page Range:	S. 1138 - 1152
Date:	2019
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1873-7862
Language:	English
Faculty:	Faculty of Human Sciences
Divisions:	Faculty of Human Sciences > Department Psychologie
Subjects:	Psychology
Uncontrolled Keywords:	Keywords Language COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; DOMAIN CRITERIA RDOC; ANXIETY DISORDERS; NEURAL ORGANIZATION; BRAIN Multiple languages Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13298