MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	Alexopoulos, 2009 PubMed
Full Info	Alexopoulos, G.S., Murphy, C.F., Gunning-Dixon, F.M., Glatt, C.E., Latoussakis, V., Kelly, R.E., Jr., Kanellopoulos, D., Klimstra, S., Lim, K.O., Young, R.C. et al. (2009) Serotonin transporter polymorphisms, microstructural white matter abnormalities and remission of geriatric depression. J Affect Disord, 119, 132-141.

Study

Hypothesis or Background	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.
Sample Information	The subjects were Caucasians with non-psychotic major depression and normal elders.
Method Detail	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.
Method Keywords	diffusion tensor imaging (DTI)
Result	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	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.
Remark	LIMITATIONS: Small number of subjects, lack of random sampling, fixed antidepressant dose, short follow-up.

Relationships reported by Alexopoulos, 2009

Component A Approved Name (Name in Paper)	Component A Type	Component B Approved Name (Name in Paper)	Component B Type	Statistical Result	Relationship Description	Result Category (Positive/Negative))
MDD	syndrome	SLC6A4 (serotonin transporter gene)	gene		Depressed elderly S-allele carriers also had lower FA (fractional anisotropy) than L homozygotes in frontolimbic brain areas,	Positive
MDD	syndrome	White matter (white matter)	brain morphology and function		Depressed elders (N=27) had lower FA (fractional anisotropy) than controls (N=27) in several frontolimbic areas.	Positive
White matter (white matter)	brain morphology and function	SLC6A4 (serotonin transporter gene)	gene		Depressed elderly S-allele carriers also had lower FA (fractional anisotropy) than L homozygotes in frontolimbic brain areas,	Positive
MDD	syndrome	Posterior cingulate cortex (posterior cingulate)	brain morphology and function		Depressed elders (N=27) had lower FA (fractional anisotropy) than controls (N=27) in several frontolimbic areas, including the posterior cingulate,	Positive
MDD	syndrome	Thalamus (thalamus)	brain morphology and function		Depressed elders (N=27) had lower FA (fractional anisotropy) than controls (N=27) in several frontolimbic areas, including the thalamus	Positive
MDD	syndrome	Anterior cingulate cortex (anterior cingulate)	brain morphology and function		Depressed elders (N=27) had lower FA (fractional anisotropy) than controls (N=27) in several frontolimbic areas, including the dorsal and rostral anterior cingulate,	Positive
MDD	syndrome	medial prefrontal cortex (MPFC) (medial prefrontal regions)	brain morphology and function		Depressed elders (N=27) had lower FA (fractional anisotropy) than controls (N=27) in several frontolimbic areas, including the medial prefrontal regions	Positive
MDD	syndrome	Dorsolateral prefrontal cortex (dorsolateral prefrontal regions)	brain morphology and function		Depressed elders (N=27) had lower FA (fractional anisotropy) than controls (N=27) in several frontolimbic areas, including the dorsolateral prefrontal regions.	Positive