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., 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:
CreatorsEmailORCIDORCID Put Code
Ridderbusch, Isabelle C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Richter, JanUNSPECIFIEDorcid.org/0000-0002-7127-6990UNSPECIFIED
Yang, YunboUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoefler, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, HeikeUNSPECIFIEDorcid.org/0000-0002-9421-1292UNSPECIFIED
Reif, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamm, AlfonsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pane-Farre, Christiane A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerlach, Alexander L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stroehle, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfleiderer, BettinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arolt, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wittchen, Hans-UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gloster, AndrewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helbig-Lang, SylviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fehm, LydiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pauli, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kircher, TiloUNSPECIFIEDorcid.org/0000-0002-2514-2625UNSPECIFIED
Lueken, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Straube, BenjaminUNSPECIFIEDorcid.org/0000-0002-9837-0944UNSPECIFIED
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: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; DOMAIN CRITERIA RDOC; ANXIETY DISORDERS; NEURAL ORGANIZATION; BRAINMultiple languages
Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; PsychiatryMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13298

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