The potential of SLC6A4 gene methylation analysis for the diagnosis and treatment of major depression

Satoshi Okada, Shigeru Morinobu, Manabu Fuchikami, Masahiro Segawa, Kana Yokomaku, Tsutomu Kataoka, Yasumasa Okamoto, Shigeto Yamawaki, Takeshi Inoue, Ichiro Kusumi, Tsukasa Koyama, Kounosuke Tsuchiyama, Takeshi Terao, Yosuke Kokubo, Masaru Mimura

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38 Citations (Scopus)

Abstract

We examined the utility of DNA methylation profiles at the CpG island of SLC6A4 (DMS) as a diagnostic biomarker for major depression (MD). In addition, the relationship between DMS and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) allele, the severity of symptoms, number of early adversities, and therapeutic responses to antidepressants were examined. Genomic DNA was extracted from peripheral blood of Japanese healthy controls and patients with MD before and after treatment. DMS was analyzed using a MassARRAY Compact System. The severity of depression was evaluated using the Hamilton Rating Scale for Depression, and early adversity was evaluated using the Early Trauma Inventory. We were unable to distinguish between and healthy controls, or between unmedicated patients and medicated patients using DMS. The 5-HTTLPR allele had no significant effect on DMS. The methylation rates for several CpGs differed significantly after treatment. Notably, the methylation rate of CpG 3 in patients with better therapeutic responses was significantly higher than that in patients with poorer responses. Although further studies examining the function of specific CpG units of SLC6A4 are required, these results suggest that the pre-treatment methylation rate of SLC6A4 is associated with therapeutic responses to antidepressants in unmedicated patients with MD.

Original languageEnglish
Pages (from-to)47-53
Number of pages7
JournalJournal of Psychiatric Research
Volume53
Issue number1
DOIs
Publication statusPublished - 2014

Keywords

  • Antidepressant
  • DNA methylation
  • Major depression
  • Serotonin transporter
  • Serotonin transporter-linked polymorphic region
  • Therapeutic response

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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    Okada, S., Morinobu, S., Fuchikami, M., Segawa, M., Yokomaku, K., Kataoka, T., Okamoto, Y., Yamawaki, S., Inoue, T., Kusumi, I., Koyama, T., Tsuchiyama, K., Terao, T., Kokubo, Y., & Mimura, M. (2014). The potential of SLC6A4 gene methylation analysis for the diagnosis and treatment of major depression. Journal of Psychiatric Research, 53(1), 47-53. https://doi.org/10.1016/j.jpsychires.2014.02.002