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精神分裂症患者的感觉运动门控受5-HT2A受体基因多态性的影响。

Sensorimotor gating of schizophrenia patients is influenced by 5-HT2A receptor polymorphisms.

作者信息

Quednow Boris B, Kühn Kai-Uwe, Mössner Rainald, Schwab Sibylle G, Schuhmacher Anna, Maier Wolfgang, Wagner Michael

机构信息

Department of Psychiatry, University of Bonn, Germany.

出版信息

Biol Psychiatry. 2008 Sep 1;64(5):434-7. doi: 10.1016/j.biopsych.2008.02.019. Epub 2008 Apr 16.

DOI:10.1016/j.biopsych.2008.02.019
PMID:18420180
Abstract

BACKGROUND

Schizophrenia patients exhibit impairment in prepulse inhibition (PPI) of the acoustic startle response (ASR), suggesting a sensorimotor gating deficit. The serotonin-2A receptor (5-HT(2A)R) has been implicated in both the pathogenesis of schizophrenia and the PPI deficits of schizophrenia patients. Moreover, both schizophrenia and PPI are thought to be inheritable. We investigated the impact of three 5-HT(2A)R polymorphisms (A-1438G, T102C, H452Y) on PPI in schizophrenia patients.

METHODS

We analyzed the 5-HT(2A)R A-1438G, T102C, and H452Y polymorphisms and assessed startle reactivity, habituation, and PPI of ASR in 68 Caucasian schizophrenia inpatients. Patients were also examined with the Positive and Negative Syndrome Scale.

RESULTS

The 5-HT(2A)R A-1438G and T102C polymorphisms were in complete linkage disequilibrium. Patients carrying the T102C TT and the A-1438G AA allele show significantly higher PPI levels and a faster early habituation compared with all other variants. 5-HT(2A)R A-1438G and T102C genotype explained approximately 11% of the PPI and early habituation variance. In contrast, the 5-HT(2A)R H452Y polymorphism did not affect startle parameters.

CONCLUSIONS

Our findings suggest that PPI and habituation are modulated by 5-HT(2A)R A-1438G and T102C genotype in schizophrenia. Consequently, alterations within brain 5-HT(2A)Rs may contribute to the PPI deficits in schizophrenia.

摘要

背景

精神分裂症患者在听觉惊吓反应（ASR）的前脉冲抑制（PPI）方面表现出损伤，提示感觉运动门控缺陷。血清素-2A受体（5-HT(2A)R）与精神分裂症的发病机制以及精神分裂症患者的PPI缺陷均有关联。此外，精神分裂症和PPI都被认为具有遗传性。我们研究了三种5-HT(2A)R多态性（A-1438G、T102C、H452Y）对精神分裂症患者PPI的影响。

方法

我们分析了68名白种人精神分裂症住院患者的5-HT(2A)R A-1438G、T102C和H452Y多态性，并评估了惊吓反应性、习惯化以及ASR的PPI。患者还接受了阳性和阴性症状量表检查。

结果

5-HT(2A)R A-1438G和T102C多态性处于完全连锁不平衡状态。与所有其他变体相比，携带T102C TT和A-1438G AA等位基因的患者表现出显著更高的PPI水平和更快的早期习惯化。5-HT(2A)R A-1438G和T102C基因型解释了约11%的PPI和早期习惯化变异。相比之下，5-HT(2A)R H452Y多态性不影响惊吓参数。

结论

我们的研究结果表明，精神分裂症患者的PPI和习惯化受5-HT(2A)R A-1438G和T102C基因型的调节。因此，脑内5-HT(2A)Rs的改变可能导致精神分裂症患者的PPI缺陷。

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