Interactions Of The GABRG2 Polymorphisms And Childhood Trauma On Suicide Attempt,Impulsive-aggressive Traits And Cognitive Function In Depressed Patients

Part 1:Interactions of the GABRG2 polymorphisms and childhood trauma on suicide attempt and impulsive-aggressive traits in depressionBackgroundSuicide is a very important public health problem.The World Health Organization(WHO)found that nearly 1 million people died by suicide every year in the world,and 2 million people completed suicide attempts(SA).SA is the important factor of preventing suicide death,preventing the occurrence of SA is a key measure to prevent suicide death.Suicide is a disease with a very complex pathogenesis,which is related to biological,genetic and environmental factors.In recent years,studies have found that the interactions of polymorphisms with environmental factors(childhood or early trauma)can predict the risk of suicide.Our previous study found that γ-aminobutyric acid(GABA)system played an important role in the biological mechanism of suicide behavior,and the genetic polymorphism of gamma-aminobutyric acid type A receptor subunit gamma2(GABRG2)was related to suicide behavior.Therefore,this study would focus on the interaction of GABRG2 gene polymorphisms with childhood trauma(CT),and explore whether it affects certain traits(impulsivity and aggression)to lead to the risk of depression or SA.MethodsThe subjects of the study were inpatients or outpatients with depression in the Department of Psychiatry,Nanfang Hospital,Southern Medical University,including 94 depression patients with a history of SA,168 depression patients without a history of SA,and 100 healthy controls recruited during the same period.The general clinical data questionnaire was used to record the gender,age and other basic information of subjects.The Hamilton Depression Scale(HAMD-24)was used to assess the severity of depression in the subjects.The Childhood Trauma Questionnaire(CTQ)was used to assess the amount of stimuli in CT experiences,the Barratt Impulsiveness Scale-11(BIS-11)was used to assess impulsivity,and the Buss-Pretty Aggression Questionnaire(BPAQ)was used to assess aggression.5ml peripheral venous blood was drawn,and the whole genome DNA was extracted by the phenol-chloroform method.The GABRG2 gene single nucleotide polymorphism(SNP)was genotyped by Sanger sequencing.Haploview 4.2 was used to analyze linkage disequilibrium(LD)between SNPs and to determine haplotype regions,and SPSS 21.0 and "R" were used for statistical analysis.ResultsThe GABRG2 gene SNP rs211034 was associated with SA,and its A allele was a protective factor of SA(OR=0.50(0.32,0.80),p=0.003).the interaction of this allele with emotional neglect was associated with the risk of depression(OR=0.89(0.82,0.97),p=0.006).LD analysis revealed a haplotype region consisting of rs211035 and rs211034,which was in complete linkage disequilibrium(r2=0.698).Gene haplotype analysis found that haplotype GA(Frequency=7.3%)was a protective factor for SA(OR=0.26(0.10,0.67),p=0.006)with GG as reference(Frequency=68.1%).After controlling for age and gender factors,this study found that cognitive impulsivity(OR=1.38(1.24,1.55),p<0.001),nonplanning impulsivity(OR=1.18(1.10,1.25),p<0.001),anger(OR=1.13(1.07,1.19),p<0.001),BIS total score(OR=1.10(1.06,1.15),p<0.001),hostility(OR=1.10(1.04,1.15),p<0.001)and BPAQ total score(OR=1.05(1.03,1.07),p<0.001)were associated with depression;Despair(OR=2.18(1.56,3.04),p<0.001)and BIS total score(OR=1.05(1.02,1.08),p<0.001)were related to SA.ConclusionThe A allele of the GABRG2 gene SNP rs211034 was a protective factor for SA,and the allele may reverse the effects of emotional neglect on depression..Part 2:Interactions of SNP rs211034 between CT on attentional bias and processing speed in depressionBackgroundThe first part of the study found that the A allele of GABRG2 gene SNP rs211034 was associated with suicide behavior,and the interaction of this allele with emotional neglect was associated with the risk of depression.Another study found that cognitive changes were regarded as a susceptibility factor for suicide behavior and a potential endophenotype.Depressed patients with a history of SA showed a particular attentional bias towards suicidal cue-related words,,and depression had slower processing.CT was associated with altered cognitive function.The Stroop task test was considered to be the most effective and direct test tool for responding to cognitive regulation or executive control function,which was considered to simultaneously evaluate subjects’ processing speed and attention bias.The Suicide Stroop Task(SST)is often used to assess potential suicide risk and suicide-related attention bias.Therefore,this study intends to use the SST to explore whether the interaction of SNPrs211034 and CT affects attentional bias and processing speed to affect the risk of depression or SA.MethodsThe subjects of the study were inpatients or outpatients with depression in the Department of Psychiatry,Nanfang Hospital,Southern Medical University,including 52 depression patients with a history of SA,59 depression patients without a history of SA,and 90 healthy controls recruited during the same period.General clinical data questionnaires were used to record the gender,age and other basic information of subjects,HAMD-24 was used to assess the severity of depression,CTQ was used to assess the amount of stimuli in CT experiences.The performance of positive words,negative words,neutral words and suicide words was recorded by SST,then calculating the corresponding average Reaction Time(RT)and Interference Index(IF);5ml peripheral venous blood was drawn,and the whole genome DNA was extracted by the phenol-chloroform method.The GABRG2 gene SNP was genotyped by Sanger sequencing,and SPSS 21.0 and "R" were used for statistical analysis.ResultsAfter using age,gender,and education as covariates,the depression had longer RT for all emotional words(positive words,negative words,and suicide words)than the healthy control,and the depression had longer IF for positive words and negative words than in the healthy control.The GABRG2 gene SNP rs211034 was associated with processing speed.Among subjects without a history of Childhood Trauma Questionnaire Sexual Abuse(CSA),subjects who carried the A allele of SNPrs211034 had shorter positive words(β=-92.060,p=0.004),negative words β=-103.670,p=0.001),and suicidal words(β=-97.082,p=0.004)than those who did not carry this allele;In subjects with a history of CSA,it was not statistically different between subjects who carried the A allele of SNPrs211034 and those who not carried the A allele in positive words β=110.464,p=0.143),negative words(β=118.115,p=0.121),and suicide words β=118.039,p=0.121).ConclusionDepressed patients had a certain degree of cognitive dysfunction,and their information processing speed was slowed down.The GABRG2 gene SNP rs211034 was associated with processing speed,and a history of CSA may reverse the protective effect of the A allele.Since there are many influencing factors of SA,it is necessary to analyze more influencing factors in the follow-up study for analysis.