Effect Of Early Trauma And CRHR1 Gene Polymorphism On Working Memory

Objective:Early trauma is associated with persisting working memory deficits.However,the mechanism is unclear.The aim of the current study is to analyze the expression of corticotrophin releasing hormone receptor type 1(CRHR1)gene polymorphism and corticotrophin releasing hormone(CRH)protein,to explore whether CRHR1 genotype and early trauma regulate the function of working memory.It provides a basis for the pathogenesis that the early trauma effects on working memory.Methods:The sample of 535 subjects from nine mining areas,three communities and five other affiliated units in Kailuan Mining Group were investigated.There were divided into three groups according to the exposure to the Tangshan earthquake: infant exposure group(earthquake exposure after birth),fetal exposure group(maternal pregnancy experience earthquake),control group(without experiencing earthquake),the average age of the three groups was 40,39 and 38 respectively.There were 176 subjects in the infant exposure group,172 subjects in the fetal exposure group(50 subjects in the first trimester(1~3months),59 subjects in the second trimester(4~6months),63 subjects in the third trimester(7~9months)),187 subjects in the control group.Comparison of the three groups of general baseline situation and the maternal condition of the subjects exposed to earthquake trauma etc.Brief Visuospatial Memory Test-Revised(BVMT-R)and Hopkins Verbal Learning Test-Revised(HVLT-R)were used to measure the working memory of three groups of subjects.The plasma and DNA were extracted from the peripheral blood of the subjects,and the CRH level of the ELISA method and the CRHR1rs242924 and rs7209436 gene polymorphism were analyzed respectively.SPSS22.0 software was used for statistical analysis,the statistical difference is defined as P>0.05.Results:1.Comparison of the general conditions in fetal,infant exposure and control groupThere was significant difference in age(Z=397.404,P<0.01)in the three groups,there was no statistical significance in other aspects(P > 0.05).2.Comparison of the results of working memory test in fetal,infant exposure group and control groupThe BVMT-R score of the fetal exposure group 3rd test(9.74±2.781)is lower than that of control group(10.42±2.380),and the total score(24.67±7.792)is lower than that of control group(26.24±7.185),and the difference was statistically significant.The control group compared with infant exposure group,The BVMT-R score 2nd test(9.30±2.678 vs.8.55±3.144),3rd test(10.42±2.380 vs.9.65±2.763),and the total score(26.24±7.185 vs.24.18±8.435)are lower in the latter,and the difference was statistically significant.There was no statistically significant difference among the three groups in the score of HVLT-R(P>0.05).3.Comparison of the results of the working memory test between three subgroups of fetal exposure group and the control groupThe control group compared with the second trimester exposure group,the BVMT-R score 2nd test(9.30±2.678 vs.8.29±3.000),3rd test(10.42±2.380 vs.9.42±2.842),and the total score(26.24±7.185 vs.23.37±8.043),all statistically decreased in the latter.The BVMT-R score of the late pregnancy exposure group 3rd test(9.54±3.010)is lower than that of control group(10.42±2.380),and the difference was statistically significant.There was no significant difference between the BVMT-R score and the HVLT-R score among the three subgroups in the fetal exposure group(P>0.05).4.Comparison of working memory results in the fetal,infant exposure and control group according to the genotypic groupingThe CRHR1 gene was classified as the C gene carrier,there are significant differences in the total score of BVMT-R in three groups(F=7.343,P<0.01).The results show that the infant exposure group(22.48±8.123)was lower than that of the control group(28.51±5.800),the fetal exposure group(23.00±8.547)was lower than that of the control group(28.51±5.800).In the control group,the carrier of AT gene(25.67±7.396)was lower than that of the C gene carrier(28.51±5.800).There was no statistical difference in the total score of BVMT-R of the three groups of CRHR1 AT gene carriers.5.Comparison of CRH concentration(pg/ml)in the group of fetal,infant and control groups according to genotypic groupingCRHR1 genotype AT gene carriers,the concentration of CRH has significant differences in the three groups(F=7.343,P < 0.01).The fetal exposure group(1497.93±955.98)is lower than the infant exposure group(1943.19±1169.07)and the control group(1824.95±1300.50),respectively.There was no significant difference in the concentration of CRH in the three groups with C carriers(P > 0.05).6.Interaction effects of earthquake exposure groups and genotyping on working memoryThe CRH concentration was a covariate,earthquake exposure group and genotype interact on the total score of BVMT-R(P<0.05).When the CRHR1 genotype was at the level of C gene,the total score of BVMT-R in the infant exposure group and the fetal exposure group was lower than that in the control group,and the difference was statistically significant(P<0.05).Conclusions:1.Early trauma in fetal and infant stage is associated with impaired working memory of the offspring,the working memory deficits in the second trimester pregnancy who suffered from earthquake trauma is serious.2.The interaction between early trauma and CRHR1 vulnerable genotypes may be the main factor in working memory impairment.