Depression is one of the most common psychiatric diseases, and is often resistant to treatment. Its diagnose is based on clinical interview, but not objective examinations. Since there is no biomarkers for depression, we evaluated DNA methylation in SHATI/NAT8L promotor regions in patients with the illness, and examined the effect of medication. Methylation rates of SHATI/NAT8L promotor regions at the CpG site in peripheral blood from unmedicated patients were significantly greater compared to those of healthy subjects.  By contrast, medicated patients revealed significantly less rates compared to healthy subjects for the same measure of methylation. Since previous studies of DNA methylation were performed using samples from treated patients, the present results from untreated subjects provide valuable information on the role for methylation of SHATI/NAT8L promotor regions in the diagnosis of depression.