Sensorimotor gating and D2 receptor signalling: evidence from a molecular genetic approach.
Sensorimotor gating and D2 receptor signalling: evidence from a molecular genetic approach.
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DOI：
10.1017/s1461145711001787
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发表时间：
2012-11
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影响因子：
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通讯作者：
C. Völter;M. Riedel;N. Wöstmann;D. Aichert;S. Lobo;Anna Costa;A. Schmechtig;D. Collier;A. Hartmann;I. Giegling;H. Möller;B. Quednow;D. Rujescu;V. Kumari;U. Ettinger
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文献类型：
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作者：
C. Völter;M. Riedel;N. Wöstmann;D. Aichert;S. Lobo;Anna Costa;A. Schmechtig;D. Collier;A. Hartmann;I. Giegling;H. Möller;B. Quednow;D. Rujescu;V. Kumari;U. Ettinger
从药理学调查，遗传关联研究和精神分裂症研究的证据表明，多巴胺系统对感觉运动门控的重要影响，通过声惊吓反应的前脉冲抑制（PPI）来测量。特别是，D2受体激动剂已被证明会破坏人类和啮齿动物的PPI。在本研究中，我们在两个独立的健康人样本（总体n=197;慕尼黑n=101;伦敦n=96）中调查了两个功能性DRD 2相关单核苷酸多态性（rs 4648317和rs 1800497，后者也称为DRD 2/ANKK 1 Taq 1A）与PPI的相关性。Taq 1A是纹状体D2受体信号传导的重要标志物，因此被假设影响PPI。与我们的假设一致，我们在这里报告降低PPI水平的个体具有较高的纹状体D2受体信号，如Taq 1A基因型所示。两个样本的荟萃分析证实了这一发现。相反，在慕尼黑样本中发现的rs 4648317与PPI之间的关联在伦敦样本中无法得到证实。总之，本研究有助于弥合PPI的药理学操作和多巴胺能系统的分子遗传学之间的差距。
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.