title: Sensorimotor gating and D2 receptor signalling: evidence from a molecular genetic approach.
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.
authors.affiliation: Department of Psychology, University of Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Völter
authors.forename: Michael
authors.initials: M
authors.lastname: Riedel
authors.forename: Nicola
authors.initials: N
authors.lastname: Wöstmann
authors.forename: Désirée S
authors.initials: DS
authors.lastname: Aichert
authors.forename: Sarah
authors.initials: S
authors.lastname: Lobo
authors.forename: Anna
authors.initials: A
authors.lastname: Costa
authors.forename: Anne
authors.initials: A
authors.lastname: Schmechtig
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.forename: Annette M
authors.initials: AM
authors.lastname: Hartmann
authors.forename: Ina
authors.initials: I
authors.lastname: Giegling
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.forename: Boris B
authors.initials: BB
authors.lastname: Quednow
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: Veena
authors.initials: V
authors.lastname: Kumari
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ettinger
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods*; D000328:Adult; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D055139:Sensory Gating / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D055815:Young Adult
chemical_list: D017448:Receptors, Dopamine D2