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:
CreatorsEmailORCIDORCID Put Code
Straube, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reif, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Richter, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lueken, U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arolt, V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jansen, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zwanzger, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Domschke, K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pauli, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Konrad, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerlach, A. L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fydrich, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alpers, G. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stroehle, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wittmann, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfleiderer, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wittchen, H-UUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamm, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deckert, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kircher, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; RECEPTOR GENE POLYMORPHISM; PANIC DISORDER; PSYCHOLOGICAL TREATMENT; C(-1019)G POLYMORPHISM; DEFENSIVE REACTIVITY; TREATMENT RESPONSE; MAJOR DEPRESSION; MICE LACKINGMultiple languages
PsychiatryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42290

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