title: The potential of SLC6A4 gene methylation analysis for the diagnosis and treatment of major depression.
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.
authors.affiliation: Department of Psychiatry and Neurosciences, Applied Life Sciences Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okada
authors.affiliation: Department of Psychiatry and Neurosciences, Applied Life Sciences Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan; Department of Neuropsychiatry, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan. Electronic address: smorinob@kochi-u.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morinobu
authors.affiliation: Department of Psychiatry and Neurosciences, Applied Life Sciences Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fuchikami
authors.affiliation: Department of Psychiatry and Neurosciences, Applied Life Sciences Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Segawa
authors.affiliation: Department of Psychiatry and Neurosciences, Applied Life Sciences Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Yokomaku
authors.affiliation: Department of Psychiatry and Neurosciences, Applied Life Sciences Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kataoka
authors.affiliation: Department of Psychiatry and Neurosciences, Applied Life Sciences Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Psychiatry and Neurosciences, Applied Life Sciences Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Yamawaki
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kusumi
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Department of Neuropsychiatry, Oita University Faculty of Medicine, Yufu, Oita, Japan.
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Tsuchiyama
authors.affiliation: Department of Neuropsychiatry, Oita University Faculty of Medicine, Yufu, Oita, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Terao
authors.affiliation: Department of Psychiatry, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kokubo
authors.affiliation: Department of Psychiatry, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Mimura
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D018899:CpG Islands / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013223:Statistics as Topic
chemical_list: D000928:Antidepressive Agents; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: Antidepressant; DNA methylation; Major depression; Serotonin transporter; Serotonin transporter-linked polymorphic region; Therapeutic response