Serotonin transporter polymorphisms, microstructural white matter abnormalities and remission of geriatric depression.
| Publication Type | Academic Article |
| Authors | Alexopoulos G, Murphy C, Gunning-Dixon F, Glatt C, Latoussakis V, Kelly R, Kanellopoulos D, Klimstra S, Lim K, Young R, Hoptman M |
| Journal | J Affect Disord |
| Volume | 119 |
| Issue | 1-3 |
| Pagination | 132-41 |
| Date Published | 04/17/2009 |
| ISSN | 1573-2517 |
| Keywords | Brain, Depressive Disorder, Major, Polymorphism, Genetic, Serotonin Plasma Membrane Transport Proteins |
| Abstract | 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. |
| DOI | 10.1016/j.jad.2009.03.004 |
| PubMed ID | 19375170 |
| PubMed Central ID | PMC2796561 |