早年心理创伤与促肾上腺皮质激素释放激素受体1型基因多态性对视觉空间记忆的影响

Effect of early psychological traumatic stress and corticotropin-releasing factor receptor 1 gene polymorphism on visual spatial memory

目的探讨早年创伤与促肾上腺皮质激素释放激素受体1型(CRHR1)基因多态性对工作记忆的影响。方法根据暴露于唐山大地震的情况将受试者分为婴儿期暴露组(n=176)、胎儿期暴露组(n=172)、对照组(n=187);胎儿期暴露组又分为孕早期(1~3个月,n=50)、孕中期(4~6个月,n=59)、孕晚期(7~9个月,n=63)。采用简易视觉空间记忆测验(BVMT-R)和霍普金斯词汇学习测验(HVLT-R)分析3组人群的工作记忆情况;提取受试者外周血中的DNA,采用荧光定量PCR方法分析CRHR1 rs242924和rs7209436基因多态性,采用两因素析因设计资料的方差分析方法分析影响工作记忆的因素(地震应激和基因分型)是否具有交互作用。结果胎儿期暴露组、婴儿期暴露组BVMT-R总分较对照组明显下降;CRHR1基因型分为A/T基因携带者和C基因携带者2组,C基因型携带者在婴儿期、胎儿期暴露组中的BVMT-R总分比对照组均明显降低[(22.5±8.1)分比(28.9±5.7)分,t=-4.231,P<0.01;(23.0±8.5)分比(28.9±5.7)分,t=-3.201,P<0.05];对照组C基因携带者的BVMT-R总分比A/T基因携带者升高[(28.9±5.7)分比(25.8±7.3)分,t=-2.215,P<0.05]。地震暴露组和基因型两因素交互作用于BVMT-R总分(F=4.028,P<0.05)。结论胎儿期和婴儿期遭受地震创伤对视觉空间记忆存在持续性的潜在影响;早年地震创伤与CRHR1易感基因型的交互作用可能是视觉空间记忆受损的主要原因。

Objective To explore the effects of early psychological trauma and corticotropin-releasing factor receptor 1(CRHR1) gene polymorphism on working memory. Methods 1 534 healthy adult volunteers were recruited and divided into 3 groups according to whether ever being exposed to the Tangshan earthquake in their early life: infant exposure group (IEG, n=176), fetal exposure group (FEG, n=172), and control group (n=182). The fetal exposure group was further divided into three subgroups: exposure in the first trimester (1~3months, n=50), exposure in the second trimester (4~6months, n=59), and exposure in the third trimester (7~9months, n=63). Brief Visuospatial Memory Test-Revised (BVMT-R) and Hopkins Verbal Learning Test-Revised (HVLT-R) were used to measure their working memory. The DNA extracted from the peripheral blood were analyzed to determine the CRHR1 rs242924 and rs7209436 gene polymorphism real-time PCR.The CRHR1 genotype was further divided into two groups: A/T gene carrier and C gene carrier. Possible interactions between psychological impact of the earthquake in early life time and the CRHR1 genotype were explored. Results The total scores of BVMT-R in the FEG and IEG groups were significantly lower than that in the control group;The total BVMT-R scores of the CRHR1 C gene carriers in the IEG and FEG groups were significantly lower than that in the control group (22.5±8.1 vs. 28.9±5.7;t=-4.231, P<0.01;23.0±8.5 vs. 28.9±5.7, t=-3.201, P<0.05);Within the control group, the BVMT-R total score of the C gene carriers was higher than that of the A/T gene carrier (28.9±5.7 vs. 25.8±7.3, t=2.215, P<0.05). The earthquake early exposure and the genotype of CRHR1 had interactive effect on the BVMT-R total score (F=4.028, P<0.05). There was no significant difference in the HVLT-R score among the three groups (P>0.05). Conclusions The early psychological traumatic stress after earthquake exposure may contribute to the adulthood visual spatial memory decline, which may be explained partly by the interaction of the early psychological stress with the CRHR1 vulnerable genotype.