Association analysis of the COMT/MTHFR genes and geriatric depression: An MRI study of the putamen

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, depressed subjects with MTHFR C/C, both the right and left putamen have smaller volumes as the number of COMT 158Val increase. The left putamen volumes of depressed subjects with COMT Met/Met are smaller as the number of MTHFR 677T increase 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.