Homocysteine levels, MTHFR C677T genotype, and MRI hyperintensities in late-onset major depressive disorder

Objective: Epidemiological studies suggest that elevated plasma homocysteine is associated with an increased risk of depression and cerebrovascular disease. There are no published reports of homocysteine levels and methylenetetrahydrofolate reductase (MTHFR) C677T genotype in clinical samples of patients with late-onset major depressive disorder (MDD). The purpose of this study was to examine the association of homocysteine levels or MTHFR C677T genotype and late-onset MDD and assess whether this may be affected by brain magnetic resonance imaging (MRI) hyperintensities. Methods: Authors recruited 39 elderly patients with MDD with first episode occurring after age 50 and 20 comparison subjects and assessed total plasma homocysteine levels, MTHFR genotype, and brain MRIs. Results: Plasma total homocysteine levels were higher in elderly patients with late-onset MDD versus comparison subjects. The association did not change after controlling for MRI hyperintensities, and the distribution of MTHFR C677T genotype was not different between the groups. Conclusions: In this exploratory study, elevated homocysteine levels were associated with late-onset MDD, and the association did not appear to be mediated by vascular pathology as identified by brain MRI hyperintensities.