Universität zu Köln

Straube, B., Reif, A., Richter, J., Lueken, U., Weber, H., Arolt, V., Jansen, A., Zwanzger, P., Domschke, K., Pauli, P., Konrad, C., Gerlach, A. L., Lang, T., Fydrich, T., Alpers, G. W., Stroehle, A., Wittmann, A., Pfleiderer, B., Wittchen, H-U, Hamm, A., Deckert, J. and Kircher, T. (2014). The functional-1019C/G HTR1A polymorphism and mechanisms of fear. Transl. Psychiatr., 4. NEW YORK: NATURE PUBLISHING GROUP. ISSN 2158-3188

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Abstract

Serotonin receptor 1A gene (HTR1A) knockout mice show pronounced defensive behaviour and increased fear conditioning to ambiguous conditioned stimuli. Such behaviour is a hallmark of pathological human anxiety, as observed in panic disorder with agoraphobia (PD/AG). Thus, variations in HTR1A might contribute to neurophysiological differences within subgroups of PD/AG patients. Here, we tested this hypothesis by combining genetic with behavioural techniques and neuroimaging. In a clinical multicentre trial, patients with PD/AG received 12 sessions of manualized cognitive-behavioural therapy (CBT) and were genotyped for HTR1A rs6295. In four subsamples of this multicentre trial, exposure behaviour (n = 185), defensive reactivity measured using a behavioural avoidance test (BAT; before CBT: n = 245; after CBT: n = 171) and functional magnetic resonance imaging (fMRI) data during fear conditioning were acquired before and after CBT (n = 39). HTR1A risk genotype (GG) carriers more often escaped during the BAT before treatment. Exploratory fMRI results suggest increased activation of the amygdala in response to threat as well as safety cues before and after treatment in GG carriers. Furthermore, GG carriers demonstrated reduced effects of CBT on differential conditioning in regions including the bilateral insulae and the anterior cingulate cortex. Finally, risk genotype carriers demonstrated reduced self-initiated exposure behaviour to aversive situations. This study demonstrates the effect of HTR1A variation on defensive behaviour, amygdala activity, CBT-induced neural plasticity and normalization of defence behaviour in PD/AG. Our results, therefore, translate evidence from animal studies to humans and suggest a central role for HTR1A in differentiating subgroups of patients with anxiety disorders.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Straube, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reif, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Richter, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lueken, U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Arolt, V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jansen, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zwanzger, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Domschke, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pauli, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Konrad, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerlach, A. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lang, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fydrich, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Alpers, G. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stroehle, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittmann, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfleiderer, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittchen, H-U UNSPECIFIED UNSPECIFIED UNSPECIFIED Hamm, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Deckert, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kircher, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-422904
DOI:	10.1038/tp.2014.130
Journal or Publication Title:	Transl. Psychiatr.
Volume:	4
Date:	2014
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	2158-3188
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; RECEPTOR GENE POLYMORPHISM; PANIC DISORDER; PSYCHOLOGICAL TREATMENT; C(-1019)G POLYMORPHISM; DEFENSIVE REACTIVITY; TREATMENT RESPONSE; MAJOR DEPRESSION; MICE LACKING Multiple languages Psychiatry Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42290