Interaction of the 5-HTTLPR and childhood trauma influences memory bias in healthy individuals

- Memory bias is a risk factor for depression and a stable depression trait.
- The SS, SLg and LgLg genotypes of the serotonin transporter gene are related to depression risk.
- Gene-environment interactions are associated with memory bias as an intermediate phenotype.
- Less positive memory bias was found in SS, SLg or LgLg individuals who experienced childhood trauma.
- Genetic susceptibility factors may depend on the interaction with environmental factors.

The tendency to recall more negative and less positive information has been frequently related to the genetic susceptibility to depression. This memory bias may be associated with depression candidate genes especially in individuals who experienced stressful childhood events. The serotonin transporter gene, SLC6A4/5-HTT, regulates the reuptake of serotonin. The 5-HTTLPR polymorphism in the gene's promoter region has a short (S) and a long (L) allele, of which L contains a further SNP (rs25531), resulting in a triallelic polymorphism: La, Lg, and S.Both S and Lg result in increased serotonin signaling (to simplify, we refer to both alleles as 'S'), which in turn appears associated with depression vulnerability, specifically in individuals with stressful events.In non-depressed individuals (N=1083), we examined the interaction between the 5-HTTLPR genotype (LaLa, SLa, and SS) and stressful childhood events in association with explicit verbal memory bias (positive, negative). Two types of stressful childhood events were studied, namely childhood adverse events (e.g. parental loss) and interpersonal traumatic childhood events (e.g. abuse).Less positive memory bias was found for individuals with the SS genotype who had experienced interpersonal childhood traumatic events. No general association of genotype with memory bias was found, nor was there a significant interaction between genotype and childhood adverse events.Our results suggest that the depression-susceptibility genotype of the 5-HTTLPR is associated with depressive information processing styles when occurring in combination with traumatic childhood events. Tailoring treatment to specific risk profiles based on genetic susceptibility and childhood stress could be promising.