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


CONCLUSIONS
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.
Alexopoulos
George S
GS
Weill Cornell Medical College, Weill-Cornell Institute of Geriatric Psychiatry, United States. gsalexop@med.cornell.edu
Murphy
Christopher F
CF
Gunning-Dixon
Faith M
FM
Glatt
Charles E
CE
Latoussakis
Vassilios
V
Kelly
Robert E
RE
Kanellopoulos
Dora
D
Klimstra
Sibel
S
Lim
Kelvin O
KO
Young
Robert C
RC
Hoptman
Matthew J
MJ
D000368:Aged; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D015283:Citalopram / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011110:Polymorphism, Genetic; D012074:Remission Induction; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use
D015283:Citalopram; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors