精神分裂症患者听觉惊跳反射抑制与儿茶酚-O-甲基转移酶基因Val158Met多态性的相关性

Correlation of catechol-O-methyl transferase Vall58Met polymorphism with prepulse inhibition of the auditorystartle reflex in patients with schizophrenia

目的:探讨精神分裂症患者儿茶酚-O-甲基转移酶(COMT)第158位密码子从缬氨酸到蛋氨酸的多态性(Vall58Met)与听觉惊跳反射抑制(PPI)的关系。方法:选取符合美国精神障碍诊断与统计手册第4版(DSM-IV)的精神分裂症患者178例,正常对照190例,使用SR-HLAB惊跳反射监控系统测查听觉惊跳反射,其分析指标包括:惊跳反射的反应波幅(SR);惊跳反射的适应性(HAB);时间间隔(LI)为30 ms、60 ms、120 ms时的听觉刺激惊跳反射弱刺激抑制(PPI30%、PPI60%、PPI120%);应用聚合酶链反应和限制性片段长度多态性的方法,分析精神分裂症组与对照组COMT Vall58Met基因型与等位基因分布频率。结果:精神分裂症组的波幅(SR)低于对照组[(563±460)mVvs.(695±447)m V,P<0.05],适应性(HAB)低于对照组[(32±46)vs.(48±33),P<0.01],差异有统计学意义;精神分裂症组与对照组之间PPI差异有统计学意义(F=7.15,P<0.05),组与时间间隔的交互作用差异有统计学意义(F=5.57,P<0.05),进一步分析发现精神分裂症组的%PPI120低于对照组[(27±5)vs.(35±3),P<0.05]。2组间COMT基因型和等位基因分布有统计学意义(χ~2=8.16、11.74,均P<0.05)。COMT三种基因型对HAB%的主效应有统计学意义(F=3.07,P<0.05);分组和COMT基因型对SR,HAB%,%PPI120的交互作用无统计学意义(F=1.64、2.87、2.26,均P>0.05)。结论:COMT基因Vall58Met多态性可能与精神分裂症的适应性有关,但与精神分裂症PPI缺陷可能无关。

Objective： To investigate the association between catechol-O-methyl transferase （COMT） Val158Met polymorphism and prepulse inhibition of the auditory startle reflex （PPI） in patients with schizophrenia. Methods： Totally 178 patients with schizophrenia and 190 healthy volunteers were recruited. The auditory startle reflex was detected by using SR-HLAB monitoring system. The indexed of the auditory startle reflex included the amplitude, habituation% and PPI30, PPI60, PPI120 （the lead interval was set 30 ms, 60 ms, 120 ms）.COMT Val158Met polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism （PCR-RELP）. The differences of PPI among COMT genotypes were compared. Results： Compared to the healthy volunteers, patients with schizophrenia had a significant lower the amplitude of auditory startle reflex [ （563 ± 460） mV vs （695 ±447） mV, P 〈 0. 05 ] and habituation% [ （ 32 ±46） vs （48 ±33）, P 〈 0. 01 ] as well as the % PPI120[ （27 ±5） vs （35 ±3）, P 〈 0.05]. The significant differences in COMT allelic and genotypic distribions were observed between patients with schizophrenia and healthy volunteers （χ^2= 8. 16, 11.74, Ps 〈 0. 05）. The significant main effect of COMT genotype on habituation% was observed （P 〈 0. 05） but no interaction genotype by diagnosis on the amplitude of auditory startle reflex, habituation% and % PPI120 was observed （Ps 〉 0. 05）. Conclusions： There may be a correlation between COMT genotype and adaptability, but not between COMT genotype and PPI deficit present in patients with schizophrenia.