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5,10-Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism is considered as a predisposition and promising genetic candidate to major depressive disorder (MDD), as it is associated with impaired one-carbon cycles, which may be involved in the pathogenesis of depression. Cortical thickness (CT) and subcortical structure volumes have been extensively studied in MDD and have been proposed as one of the phenotypes for MDD. We intend to discuss the association between CT, subcortical structure volume, and MTHFR C677T