Sensorimotor Gating Depends on Polymorphisms of the Serotonin-2A Receptor and Catechol-O-Methyltransferase, but Not on Neuregulin-1 Arg38Gln Genotype: A Replication Study
Sensorimotor Gating Depends on Polymorphisms of the Serotonin-2A Receptor and Catechol-O-Methyltransferase, but Not on Neuregulin-1 Arg38Gln Genotype: A Replication Study
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DOI：
10.1016/j.biopsych.2009.05.007
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发表时间：
2009-09-15
影响因子：
10.6
通讯作者：
Kumari, Veena
中科院分区：
文献类型：
--
作者：
Quednow, Boris B.;Schmechtig, Anne;Kumari, Veena
背景资料：声惊吓反应（ASR）的前脉冲抑制（PPI）是一种感觉运动门控的操作措施，也是精神分裂症的一种有希望的内表型。我们最近发现，连锁5-羟色胺-2A受体（5-HT（2A）R）A-1438 G和T102 C多态性调节精神分裂症患者的PPI。此外，研究表明，儿茶酚-O-甲基转移酶（COMT）和神经调节蛋白-1（NRG-1）蛋白的遗传变异影响精神分裂症患者和健康志愿者的PIPI。因此，我们的目的是复制这些结果，并研究相关多态性对健康人类志愿者PPI的影响。方法：我们分析了5-HT（2A）RA-1438 G/T102 C（rs6311/rs6313）、COMT Val 158Met（rs4680）和NRG-1 Arg38Gln结果：5-HT（2A）R T102 C-T/A-1438 G-A等位基因纯合子受试者显示PPI水平升高。特别是，具有COMT Met 158 Met基因型的男性受试者也显示PPI升高。NRG-1 Arg 38 Gln基因型对PPI无显著影响。惊吓反应不受任何调查polymorphis.Conclusions：我们证实，在一个独立的健康志愿者的样本，PPI是由5-HT 2AR基因的遗传变异的影响。COMT Val 158 Met基因型对PPI的影响似乎具有性别特异性。这些结果强调了5-羟色胺和多巴胺系统在感觉运动门控调制中的重要性。
Background: Prepulse inhibition (PPI) of the acoustic startle response (ASR) is an operational measure of sensorimotor gating and a promising endophenotype of schizophrenia. We have recently shown that the linked serotonin-2A receptor (5-HT(2A)R) A-1438 G and T102C polymorphisms modulate PPI in schizophrenia patients. Moreover, it was shown that genetic variation in the catechol-O-methyltransferase (COMT) and the neuregulin-1 (NRG-1) proteins influences PIPI in schizophrenia patients and healthy volunteers. Therefore, we aimed to replicate these results and investigated the impact of the related polymorphisms on PPI in healthy human volunteers.Methods: We analyzed the 5-HT(2A)RA-1438 G/T102C (rs6311/rs6313), the COMT Val158Met (rs4680), and the NRG-1 Arg38Gln(rs3924999) polymorphisms, assessing startle reactivity, habituation, and PIPI of ASR in 107 healthy Caucasian volunteers.Results: Subjects homozygous for the 5-HT(2A)R T102C-T/A-1438 G-A allele showed increased PPI levels. In particular, male subjects with the COMT Met158Met-genotype also showed elevated PPI. The NRG-1 Arg38Gln genotype did not have a significant impact on PPI. Startle reactivity was not affected by any of the investigated polymorphisms.Conclusions: We confirmed in an independent sample of healthy volunteers that PPI is influenced by genetic variation in the 5-HT2AR gene. The influence of the COMT Val158Met genotype on PPI appears to be sex-specific. These results underscore the significance of the serotonin and dopamine systems in the modulation of sensorimotor gating.