Serotonin transporter gene moderates associations between mood, memory and hippocampal volume

The short (S) allele of the serotonin transporter gene (5-HTTLPR) is associated with reduced serotonin turnover compared to the long (L) allele in Caucasians. Few studies have examined its impact on memory and brain structure in healthy young adults.

Participants included 51 healthy young adults (25 female; ages 18-25). Multiple regressions examined the independent contribution of 5-HTTLPR biomarker genotype and its interactions with gender and sub-clinical depressive symptoms on hippocampal volumes and memory.

The 5-HTTLPR genotype significantly interacted with gender in predicting larger left hippocampal volumes in S-carrying females and smaller hippocampal volumes in males (p<.03). Gender also moderated the impact of the 5-HTTLPR on neurocognition. In females, S allele carriers had poorer visual recall compared to L carriers (p<.05). A three-way interaction between 5-HTTLPR, gender, and depressive symptoms was also observed (p<.04). In females, larger left hippocampal volumes were associated with increased depressive symptoms while the opposite was seen in males. Finally, in male and female S carriers, increased depressive symptoms were marginally associated with poorer verbal memory (p<.09).

In females, the 5-HTTLPR S allele was associated with poorer memory performance, increased depressive symptoms and larger hippocampal volumes. In males, the S allele predicted smaller hippocampal volumes and increased depressive symptoms. The opposite morphometric patterns likely reflect gender differences in adolescent hippocampal development. Larger longitudinal studies are needed to examine whether the impact of 5-HTTLPR genotype on neurocognition across development differs according to extent of mood symptoms and gender.