Serotonin transporter gene status predicts caudate nucleus but not amygdala or hippocampal volumes in older persons with major depression

Background: Although the short allele of the serotonin transporter promoter polymorphism (5-HTT) has been linked to increased risk of major depression in early adult life, its relationships with late-life depression and to changes in subcortical nuclei remain unclear. Methods: 5-HTT genotypes (SS, SL, LL) were determined for 45 older persons with major depression (mean age = 52.0, sd = 12.8) and 16 healthy controls (mean age = 55.8, sd = 10.3). MRI-derived volumes of the amygdala, hippocampus, caudate and putamen were determined by reliable tracing techniques. Results: In those with depression, the short allele of 5-HTT was associated with smaller caudate nucleus volumes. Although hippocampal and amygdala volumes were smaller in those with depression as compared with control subjects, 5-HTT gene status did not predict this reduction in size. Limitations: The findings are limited by the number of clinical and control participants. Conclusions: Reduced caudate nucleus volume in older patients with major depression was associated with the short allele of the 5-HTT gene. This regional brain change may be a consequence of early developmental expression as well as later vascular or degenerative effects of this genotype.