TY  - JOUR
A1  - Lueken, U
A1  - Kuhn, M
A1  - Yang, Y
A1  - Straube, B
A1  - Kircher, T
A1  - Wittchen, H-U
A1  - Pfleiderer, B
A1  - Arolt, V
A1  - Wittmann, A
A1  - Ströhle, A
A1  - Weber, H
A1  - Reif, A
A1  - Domschke, K
A1  - Deckert, J
A1  - Lonsdorf, TB
T1  - Modulation of defensive reactivity by GLRB allelic variation: converging evidence from an intermediate phenotype approach
T2  - Translational Psychiatry
N2  - Representing a phylogenetically old and very basic mechanism of inhibitory neurotransmission, glycine receptors have been implicated in the modulation of behavioral components underlying defensive responding toward threat. As one of the first findings being confirmed by genome-wide association studies for the phenotype of panic disorder and agoraphobia, allelic variation in a gene coding for the glycine receptor beta subunit (GLRB) has recently been associated with increased neural fear network activation and enhanced acoustic startle reflexes. On the basis of two independent healthy control samples, we here aimed to further explore the functional significance of the GLRB genotype (rs7688285) by employing an intermediate phenotype approach. We focused on the phenotype of defensive system reactivity across the levels of brain function, structure, and physiology. Converging evidence across both samples was found for increased neurofunctional activation in the (anterior) insular cortex in GLRB risk allele carriers and altered fear conditioning as a function of genotype. The robustness of GLRB effects is demonstrated by consistent findings across different experimental fear conditioning paradigms and recording sites. Altogether, findings provide translational evidence for glycine neurotransmission as a modulator of the brain’s evolutionary old dynamic defensive system and provide further support for a strong, biologically plausible candidate intermediate phenotype of defensive reactivity. As such, glycine-dependent neurotransmission may open up new avenues for mechanistic research on the etiopathogenesis of fear and anxiety disorders.
KW  - glycine receptor beta subunit
KW  - neural fear network activation
KW  - intermediate phenotype approach
KW  - defensive system reactivity
Y1  - 2017
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/18238
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-182381
VL  - 7
IS  - e1227
ER  -