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Association analysis of the COMT/MTHFR genes and geriatric depression: An MRI study of the putamen
Author(s) -
Pan ChihChuan,
McQuoid Douglas R.,
Taylor Warren D.,
Payne Martha E.,
AshleyKoch Allison,
Steffens David C.
Publication year - 2009
Publication title -
international journal of geriatric psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 129
eISSN - 1099-1166
pISSN - 0885-6230
DOI - 10.1002/gps.2206
Subject(s) - methylenetetrahydrofolate reductase , putamen , psychology , medicine , depression (economics) , basal ganglia , endocrinology , genotype , genetics , central nervous system , biology , macroeconomics , gene , economics
Objective Catechol‐O‐Methyltransferase (COMT) and Methylenetetrahydrofolate reductase (MTHFR) had been reported to relate to depression but with inconsistent results. The basal ganglia are also important in the pathophysiology of affective disorder via connections with limbic system and prefrontal cortex. The authors examined the relationship between an interaction of COMT/MTHFR polymorphisms and volumes of putamen in depressed and nondepressed elders. Methods Participants included 170 depressed and 83 nondepressed subjects aged 60 years or older. Subjects completed cross‐sectional assessments, including clinical evaluation, brain magnetic resonance imaging (MRI) scan, and COMT Val158Met and MTHFR C677T genotyping. Putamen volumes were measured using 1.5‐Tesla whole‐body MRI system. Statistical models examined the relationship between COMT/MTHFR genotype, proportional volumes of putamen and depression while controlling for age and sex. Results After controlling for covariates, among depressed subjects with MTHFR C/C, both the right and left putamen had smaller volumes as the number of COMT 158Val increased. The left putamen volumes of depressed subjects with COMT Met/Met were smaller as the number of MTHFR 677T increased compared to nondepressed subjects. Conclusions Our findings do not support a major role for COMT or MTHFR alone. However, an epigenetic interaction of COMT Val158Met and MTHFR C677T polymorphisms may contribute to putamen volumes differences between depressed and nondepressed subjects. Further studies with a larger sample size are necessary to support a genetically based role for basal ganglia structures in the etiopathogenesis of depression. Copyright © 2009 John Wiley & Sons, Ltd.