Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Investigating DNA Methylation of SHATI/NAT8L Promoter Sites in Blood of Unmedicated Patients with Major Depressive Disorder
Hajime MiyanishiKyosuke UnoMina IwataYuu KikuchiHidenaga YamamoriYuka YasudaKazutaka OhiRyota HashimotoKotaro HattoriSumiko YoshidaYu-ichi GotoTomiki SumiyoshiAtsumi Nitta
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2020 Volume 43 Issue 7 Pages 1067-1072

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Abstract

Major depressive disorder (MDD) is one of the most common psychiatric diseases. However, early detection and diagnosis of MDD is difficult, largely because there is no known biomarker or objective diagnostic examination, and its diagnosis is instead based on a clinical interview. The aim of this study was to develop a novel diagnostic tool using DNA methylation as a blood biomarker. We sought to determine whether unmedicated patients with MDD showed significant differences in DNA methylation in the promoter region of the SHATI/N-acetyltransferase 8 like (SHATI/NAT8L) gene compared to healthy controls. Sixty participants with MDD were recruited from all over Japan. They were diagnosed and assessed by at least two trained psychiatrists according to DSM-5 criteria. DNA was extracted from peripheral blood. We then assessed DNA methylation of the SHATI/NAT8L promoter regions in patients with MDD by pyrosequencing. Methylation levels of the SHATI/NAT8L promoter region at CpG sites in peripheral blood from unmedicated patients were significantly higher than in healthy controls. In contrast, medicated patients with MDD showed significantly lower methylation levels in the same region compared to healthy controls. Since previous studies of DNA methylation in MDD only assessed medicated patients, the methylation status of the SHATI/NAT8L promoter region in unmedicated patients presented herein may prove useful for the diagnosis of MDD. To our knowledge, this is the first attempt to measure methylation of the SHATI/NAT8L gene in drug-naïve patients with psychiatric diseases. Based on our findings, methylation of SHATI/NAT8L DNA might be a diagnostic biomarker of MDD.

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© 2020 The Pharmaceutical Society of Japan
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