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

Christoph Voelter; Michael Riedel; Nicola Woestmann; Desiree S. Aichert; Sarah Lobo; Anna Costa; Anne Schmechtig; David A. Collier; Annette M. Hartmann; Ina Giegling; Hans-Juergen Moeller; Boris B. Quednow; Dan Rujescu; Veena Kumari; Ulrich Ettinger

doi:10.1017/S1461145711001787

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

Christoph Voelter, Michael Riedel, Nicola Woestmann, Desiree S. Aichert, Sarah Lobo, Anna Costa, Anne Schmechtig, David A. Collier, Annette M. Hartmann, Ina Giegling, Hans-Juergen Moeller, Boris B. Quednow, Dan Rujescu, Veena Kumari, Ulrich Ettinger

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14 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1427-1440
Number of pages	14
Journal	International Journal of Neuropsychopharmacology
Volume	15
Issue number	10
Early online date	16 Jan 2012
DOIs	https://doi.org/10.1017/S1461145711001787
Publication status	Published - Nov 2012

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Voelter, C., Riedel, M., Woestmann, N., Aichert, D. S., Lobo, S., Costa, A., Schmechtig, A., Collier, D. A., Hartmann, A. M., Giegling, I., Moeller, H.-J., Quednow, B. 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. https://doi.org/10.1017/S1461145711001787

@article{7f6aef91870d4b238de900b716a0c2e7,

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.",

author = "Christoph Voelter and Michael Riedel and Nicola Woestmann and Aichert, {Desiree S.} and Sarah Lobo and Anna Costa and Anne Schmechtig and Collier, {David A.} and Hartmann, {Annette M.} and Ina Giegling and Hans-Juergen Moeller and Quednow, {Boris B.} and Dan Rujescu and Veena Kumari and Ulrich Ettinger",

year = "2012",

month = nov,

doi = "10.1017/S1461145711001787",

language = "English",

volume = "15",

pages = "1427--1440",

journal = "International Journal of Neuropsychopharmacology ",

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Voelter, C, Riedel, M, Woestmann, N, Aichert, DS, Lobo, S, Costa, A, Schmechtig, A , Collier, DA, Hartmann, AM, Giegling, I, Moeller, H-J, Quednow, BB, Rujescu, D, Kumari, V & Ettinger, U 2012, 'Sensorimotor gating and D2 receptor signalling: evidence from a molecular genetic approach', International Journal of Neuropsychopharmacology , vol. 15, no. 10, pp. 1427-1440. https://doi.org/10.1017/S1461145711001787

TY - JOUR

T1 - Sensorimotor gating and D2 receptor signalling

T2 - evidence from a molecular genetic approach

AU - Voelter, Christoph

AU - Riedel, Michael

AU - Woestmann, Nicola

AU - Aichert, Desiree S.

AU - Lobo, Sarah

AU - Costa, Anna

AU - Schmechtig, Anne

AU - Collier, David A.

AU - Hartmann, Annette M.

AU - Giegling, Ina

AU - Moeller, Hans-Juergen

AU - Quednow, Boris B.

AU - Rujescu, Dan

AU - Kumari, Veena

AU - Ettinger, Ulrich

PY - 2012/11

Y1 - 2012/11

N2 - 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.

AB - 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.

U2 - 10.1017/S1461145711001787

DO - 10.1017/S1461145711001787

M3 - Article

C2 - 22244514

SN - 1461-1457

VL - 15

SP - 1427

EP - 1440

JO - International Journal of Neuropsychopharmacology

JF - International Journal of Neuropsychopharmacology

IS - 10

ER -

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

Abstract

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