Risk alleles of the serotonin transporter polymorphism predict small hippocampal volumes in major depression

Abstract

Background. Functional polymorphisms of the serotonin (5-HT) transporter gene (SLC6A4) are associated with risk of major depressive disorder (MDD) and treatment response.  Methods.  We examined hippocampal volumes and triallelic polymorphisms of the 5-HT transporter in 50 patients with MDD and 50 healthy controls. Results. Our mean age of onset was 23.5 years.  In this patient population, patients with the functionally low 5HTTLPR genotypes (Lg/S or S/S) had significantly smaller hippocampal volume compared to healthy controls with the Lg/S or S/S genotype. No significant differences were found between patients and controls with the La/La or La/Lg + La/S genotypes.  There was a significant relation between reduced left and right HC volume and the La/S genotype in patients with MDD suggesting that the presence of the S allele was a stronger predictor of hippocampal volume in patients with MDD than the Lg allele. Conclusions. These findings provide important additional evidence that genetic variation in the 5HTTLPR contributes to the variation in hippocampal volume observed in patients with MDD.

1.Department of Psychiatry & Behavioural Neurosciences, McMaster University, Hamilton, ON, 2.  Brain-Body Institute, St. Joseph’s Healthcare, Hamilton, ON,  3.  Department of Psychiatry, University of Calgary, Calgary, AB, Canada