Objectives: According to the dopamine hypothesis, several studies on the gene for the dopamine receptor D2 (DRD2) have been conducted. However, no trait biomarkers on DRD2 are available. We examined whether the methylation rates in the upstream region of DRD2 in leukocytes are different in schizophrenia (SCZ) subjects compared to control subjects.Methods: We selected seven CpG sites in the upstream region of DRD2 that may theoretically bind major transcription factors. The methylation rates in these regions of 50 medicated and 18 drug-naive SCZ subjects were compared with those of age-matched control subjects.Results: The methylation rates were significantly lower in medicated (CpG2, P<0.0001; CpG4, P=0.013; CpG7, P<0.0001; and average: 12.91.8 vs. 14.1 +/- 2.2, P=0.005) and drug-naive SCZ subjects (CpG1, P=0.006; CpG2, P =0.001; CpG3, P=0.001; CpG5, P =0.02; CpG6, P=0.015; CpG7, P=0.027; and average: 9.86 +/- 0.9 vs. 11.2 +/- 1.3, P=0.002).Conclusions: We confirmed low methylation rates in the upstream region of DRD2 in both medicated and drug-naive SCZ subjects. Low methylation rates of DRD2 in leukocytes may be a trait biomarker for SCZ.