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

J Affect Disord. 2007 Feb;98(1-2):137-42. doi: 10.1016/j.jad.2006.07.010. Epub 2006 Aug 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amygdala / anatomy & histology*
  • Amygdala / physiopathology
  • Caudate Nucleus / anatomy & histology*
  • Caudate Nucleus / physiopathology
  • DNA / genetics
  • DNA / isolation & purification
  • Depressive Disorder / genetics*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Promoter Regions, Genetic
  • Reference Values
  • Serotonin Plasma Membrane Transport Proteins / genetics*


  • Serotonin Plasma Membrane Transport Proteins
  • DNA