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Sensorimotor gating and D2 receptor signalling: evidence from a molecular genetic approach


Völter, C; Riedel, M; Aichert, D S; Lobo, S; Costa, A; Schmechtig, A; Collier, D A; Hartmann, A M; Giegling, I; Möller, H J; Quednow, Boris B; Rujescu, D; Kumari, V; Ettinger, U (2012). Sensorimotor gating and D2 receptor signalling: evidence from a molecular genetic approach. International Journal of Neuropsychopharmacology, 15(10):1427-1440.

Abstract

Converging evidence from pharmacological investigations, genetic association studies and schizophrenia research indicates an important influence of the dopamine system on sensorimotor gating as measured by prepulse inhibition (PPI) of the acoustic startle response. In particular, D2 receptor agonists have been shown to disrupt PPI in humans and rodents. In the present study, we investigated the associations of two functional DRD2 related single nucleotide polymorphisms (rs4648317 and rs1800497, the latter also known as DRD2/ANKK1 Taq1A) with PPI in two independent healthy human samples (overall n=197; Munich n=101; London n=96). Taq1A is a prominent marker of striatal D2 receptor signalling and was therefore hypothesized to impact on PPI. In line with our hypothesis, we report here reduced PPI levels in individuals with higher striatal D2 receptor signalling as indicated by the Taq1A genotype. Meta-analysis across both samples confirmed this finding. In contrast, an association between rs4648317 and PPI found in the Munich sample could not be confirmed in the London sample. Overall, the present study helps to bridge the gap between pharmacological manipulations of PPI and molecular genetics of the dopaminergic system.

Abstract

Converging evidence from pharmacological investigations, genetic association studies and schizophrenia research indicates an important influence of the dopamine system on sensorimotor gating as measured by prepulse inhibition (PPI) of the acoustic startle response. In particular, D2 receptor agonists have been shown to disrupt PPI in humans and rodents. In the present study, we investigated the associations of two functional DRD2 related single nucleotide polymorphisms (rs4648317 and rs1800497, the latter also known as DRD2/ANKK1 Taq1A) with PPI in two independent healthy human samples (overall n=197; Munich n=101; London n=96). Taq1A is a prominent marker of striatal D2 receptor signalling and was therefore hypothesized to impact on PPI. In line with our hypothesis, we report here reduced PPI levels in individuals with higher striatal D2 receptor signalling as indicated by the Taq1A genotype. Meta-analysis across both samples confirmed this finding. In contrast, an association between rs4648317 and PPI found in the Munich sample could not be confirmed in the London sample. Overall, the present study helps to bridge the gap between pharmacological manipulations of PPI and molecular genetics of the dopaminergic system.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:November 2012
Deposited On:20 Dec 2012 09:28
Last Modified:17 Feb 2018 00:21
Publisher:Cambridge University Press
ISSN:1461-1457
Additional Information:Copyright: Cambridge University Press
OA Status:Gold
Publisher DOI:https://doi.org/10.1017/S1461145711001787
PubMed ID:22244514

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