Mutations in the MTHFR gene lead to changes in the key enzymes that encode homocysteine and folate metabolism; Elevated homocysteine may lead to endothelial dysfunction, which in turn affects the development of cortical diffusion inhibition leading to migraine, and high homocysteine leads to impaired methylation of the central nervous system leading to depression. The gene discussed is MTHFR; the disease is depressive disorder.