Serotonin transporter polymorphisms, microstructural white matter abnormalities and remission of geriatric depression

George S. Alexopoulos, Christopher F. Murphy, Faith M. Gunning-Dixon, Charles E. Glatt, Vassilios Latoussakis, Robert E. Kelly, Dora Kanellopoulos, Sibel Klimstra, Kelvin O. Lim, Robert C. Young, Matthew J. Hoptman

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62 Scopus citations


Objective: This study compared microstructural abnormalities in depressed elders and controls and studied the association of the serotonin transporter gene status to white matter abnormalities and to remission of depression. Methods: The subjects were Caucasians with non-psychotic major depression and normal elders. Depressed subjects received escitalopram 10 mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed and voxel-based analysis of fractional anisotropy (FA) was conducted using age and mean diffusivity as covariates. Results: Depressed elders (N = 27) had lower FA than controls (N = 27) in several frontolimbic areas. Depressed elderly S-allele carriers also had lower FA than L homozygotes in frontolimbic brain areas, including the dorsal and rostral anterior cingulate, posterior cingulate, dorsolateral prefrontal and medial prefrontal regions, thalamus, and in other regions. S-allele carriers had a lower remission rate than L homozygotes. Limitations: Small number of subjects, lack of random sampling, fixed antidepressant dose, short follow-up. Conclusions: Lower FA was observed in several frontolimbic and other regions in depressed elders compared to controls. Depressed S-allele carriers had both microstructural white matter abnormalities in frontolimbic networks and a low remission rate. It remains unclear whether the risk for chronicity of geriatric depression in S-allele carriers is mediated by frontolimbic compromise. However, these observations set the stage for studies aiming to identify the relationship of S allele to impairment in specific frontolimbic functions interfering with response of geriatric depression to antidepressants.

Original languageEnglish (US)
Pages (from-to)132-141
Number of pages10
JournalJournal of Affective Disorders
Issue number1-3
StatePublished - Jan 2009

Bibliographical note

Funding Information:
Personnel and imaging cost of this work was supported by NIMH grants R01 MH65653, P030 MH68638, T32 MH019132 (GSA), K23 MH067702 (CFM), K23 MH74818 (FGD), the Sanchez Foundation, and TRU Foundation. Escitalopram and placebo were provided free of cost by Forest Pharmaceuticals, Inc.


  • Geriatric depression
  • Serotonin transporter
  • White matter abnormalities

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