Influence of the GABA Receptor Subunit Gene Polymorphism and Childhood Sexual Abuse on Processing Speed in Major Depression and Suicide Attempt

Abstract

Background: Suicide is moderately heritable and also more common in those who report childhood abuse. Previously, it was found that allele A of GABRG2 (GABA A receptor subunit gamma2) polymorphism rs211034 was protective in a suicide attempt (SA). Hence, it was proposed that rs211034 may interact with childhood trauma to influence cognitive deficits related to SA or depression risk. Genetic variants may predict the benefits of certain cognitive treatments. Methods: A total of 52 individuals who had attempted suicide, 59 individuals with major depressive disorder (MDD) or bipolar depression who had not previously attempted suicide, and 90 healthy volunteers were subjected to the modified Suicide Stroop task and were clinically assessed using the Childhood Trauma Questionnaire (CTQ) and Hamilton Depression Scale-24 items (HAMD-24). rs211034 was genotyped using Sanger sequencing. Results: After correcting for covariates, depressed participants displayed longer reaction times for all emotional conditions, including suicide-related words, compared with healthy controls. Depressed suicide attempters displayed longer reaction times for negative words than depressed non-attempters. Depressed non-attempters displayed higher interference scores for negative words compared with healthy controls. There was an interaction between rs211034 risk allele and the effects of reported childhood sexual abuse (CSA) on reaction time for all emotional words and suicide-related words. Carriers of the rs211034 risk allele A exhibited shorter reaction times, but the protective effects of this allele were eliminated in those exposed to reported CSA. Conclusion: Only limited results were found regarding effects of a past suicide attempt on response times to emotional and suicide-related words, but there was an overall effect of major depression on slower response time. Protective genetic effects of the rs211034 A allele on this slowing were eliminated in those with a history of sexual abuse during childhood. Further research is needed to better characterize the mechanisms underlying the effects of childhood trauma on these genetic effects.