Relationship between genetic variations in serotonin transporter, brain activity, and depression.

The effect of life stress on depression is moderated by a repeat length variation in the transcriptional control region of the serotonin transporter gene, which renders carriers of the short variant vulnerable for depression. Canli et al. have investigated the underlying neural mechanisms of these epigenetic processes in individuals with no history of psychopathology by using multimodal magnetic resonance-based imaging, genotyping, and self-reported life stress and rumination. Based on functional MRI and perfusion data, They found support for a model in which life stress interacts with the effect of serotonin transporter genotype on amygdala and hippocampal resting activation, two regions involved in depression and stress. Life stress also differentially affected, as a function of serotonin transporter genotype, functional connectivity of the amygdala and hippocampus with a wide network of other regions, as well as gray matter structural features, and affected individuals' level of rumination. They suggest that these interactions may constitute a neural mechanism for vulnerability toward, or protection against, depression.