Association of DNA methylation with child abuse, suicidal behavior, and stage of illness in major depressive disorder

• Project/Area Number: 15K09809
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: The University of Tokushima
• Principal Investigator: NUMATA Shusuke 徳島大学, 大学院医歯薬学研究部(医学系), 准教授 (10403726)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: depression / DNA methylation / blood / child abuse / suicidal behavior / うつ病 / メチル化 / 末梢血 / 幼少期ストレス / 自殺 / ＤＮＡメチル化

Outline of Final Research Achievements

The main aim of the present study is to examine whether childhood abuse experiences and suicidal behaviors are involved in DNA methylation of peripheral leukocytes from major depressive disorder. Our results suggest that childhood abuse experiences are associated with methylation levels in the specific genes and suicidal behaviors are linked to altered methylation in the promoter region of the serotonin transporter gene.

Research Products

• [Journal Article] Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia. (2017)
  • Author(s): Kinoshita M, Numata S, Tajima A, Yamamori H, Yasuda Y, Fujimoto M, Watanabe S, Umehara H, Shimodera S, Nakazawa T, Kikuchi M, Nakaya A, Hashimoto H, Imoto I, Hashimoto R, Ohmori T.
  • Journal Title: Int J Mol Sci. Volume: 18 Issue: 3 Pages: 632-632
  • DOI: 10.3390/ijms18030632
  • NAID: 120006535029
  • Peer Reviewed / Open Access
• [Journal Article] De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity (2017)
  • Author(s): Nishi Akira、Numata Shusuke、Tajima Atsushi、Zhu Xiaolei、Ito Koki、Saito Atsushi、Kato Yusuke、Kinoshita Makoto、Shimodera Shinji、Ono Shinji、Ochi Shinichiro、Imamura Akira、Kurotaki Naohiro、Ueno Shu-ichi、Iwata Nakao、Fukui Kiyoshi、Imoto Issei、Kamiya Atsushi、Ohmori Tetsuro
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 2887-2887
  • DOI: 10.1038/s41598-017-02792-z
  • NAID: 120006309984
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Altered KYN/TRP, Gln/Glu, and Met/methionine sulfoxide ratios in the blood plasma of medication-free patients with major depressive disorder. (2017)
  • Author(s): Umehara H, Numata S, Watanabe SY, Hatakeyama Y, Kinoshita M, Tomioka Y, Nakahara K, Nikawa T, Ohmori T.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 4855-4855
  • DOI: 10.1038/s41598-017-05121-6
  • NAID: 120006324295
  • Peer Reviewed / Open Access
• [Journal Article] Gene expression-based biological test for major depressive disorder; an advanced study (2017)
  • Author(s): Watanabe S, Numata S, Iga J, Kinoshita M, Umehara H, Ishii K, Ohmori T
  • Journal Title: Neuropsychiatr Dis Treat. Volume: 13 Pages: 535-541
  • DOI: 10.2147/ndt.s120038
  • NAID: 120006999399
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 1H-magnetic resonance spectroscopy study of glutamate-related abnormality in bipolar disorder. (2017)
  • Author(s): Kubo H, Nakataki M, Sumitani S, Iga JI, Numata S, Kameoka N, Watanabe SY, Umehara H, Kinoshita M, Inoshita M, Tamaru M, Ohta M, Nakayama-Yamauchi C, Funakoshi Y, Harada M, Ohmori T.
  • Journal Title: J Affect Disord. Volume: 208 Pages: 139-144
  • DOI: 10.1016/j.jad.2016.08.046
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cumulative effect of the plasma total homocysteine-related genetic variants on schizophrenia risk. (2016)
  • Author(s): Kinoshita M, Numata S, Tajima A, Nishi A, Muraki S, Tsuchiya A, Umehara H, Watanabe SY, Imoto I, Ohmori T.
  • Journal Title: Psychiatry Res. Volume: 246 Pages: 833-837
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Calcium signaling pathway is associated with the long-term clinical response to selective serotonin reuptake inhibitors (SSRI) and SSRI with antipsychotics in patients with obsessive-compulsive disorder. (2016)
  • Author(s): Umehara H, Numata S, Tajima A, Nishi A, Nakataki M, Imoto I, Sumitani S, Ohmori T.
  • Journal Title: PLoS One Volume: 11 Issue: 6 Pages: e0157232-e0157232
  • DOI: 10.1371/journal.pone.0157232
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Low methylation rates of dopamine receptor D2 gene promoter sites in Japanese schizophrenia subjects. (2016)
  • Author(s): Yoshino Y, Kawabe K, Mori T, Mori Y, Yamazaki K, Numata S, Nakata S, Yoshida T, Iga J, Ohmori T, Ueno S.
  • Journal Title: World J Biol Psychiatry Volume: 17 Issue: 6 Pages: 449-456
  • DOI: 10.1080/15622975.2016.1197424
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders. (2016)
  • Author(s): Nakazawa T, Hashimoto R, Sakoori K, Sugaya Y, Tanimura A, Hashimotodani Y, Ohi K, Yamamori H, Yasuda Y, Umeda-Yano S, Kiyama Y, Konno K, Inoue T, Yokoyama K, Inoue T, Numata S, Ohnuma T, Iwata N, Ozaki N, Hashimoto H, Watanabe M, Manabe T, Yamamoto T, Takeda M, Kano M.
  • Journal Title: Nat Communications Volume: 7 Issue: 1 Pages: 10594-10594
  • DOI: 10.1038/ncomms10594
  • NAID: 120006535052
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] No association between BDNF Val66Met polymorphism and treatment response in obsessive-compulsive disorder in the Japanese population (2016)
  • Author(s): Umehara H, Numata S*, Kinoshita M, Watanabe S, Nakaaki S, Sumitani S, Ohmori T
  • Journal Title: Neuropsychiatric Disease and Treatment Volume: 12 Pages: 611-615
  • DOI: 10.2147/ndt.s102100
  • NAID: 120006999400
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TREM2 mRNA Expression in Leukocytes Is Increased in Alzheimer's Disease and Schizophrenia (2015)
  • Author(s): Mori Y, Yoshino Y, Ochi S, Yamazaki K, Kawabe K, Abe M, Kitano T, Ozaki Y, Yoshida T, Numata S, Mori T, Iga J, Kuroda N, Ohmori T, Ueno S
  • Journal Title: PLoS One. Volume: 10 Issue: 9 Pages: e0136835-e0136835
  • DOI: 10.1371/journal.pone.0136835
  • NAID: 120006871195
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of an association between plasma total homocysteine and schizophrenia by a Mendelian randomization analysis (2015)
  • Author(s): Numata S, Kinoshita M, Tajima A, Nishi A, Imoto I, Ohmori T
  • Journal Title: BMC Med Genet Volume: 16 Issue: 1 Pages: 54-54
  • DOI: 10.1186/s12881-015-0197-7
  • NAID: 120006859997
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sex differences of leukocytes DNA methylation adjusted for estimated cellular proportions. (2015)
  • Author(s): Inoshita M, Numata S, Tajima A, Kinoshita M, Umehara H, Yamamori H, Hashimoto R, Imoto I, Ohmori T.
  • Journal Title: Biol Sex Differ. Volume: 6 Issue: 1 Pages: 11-11
  • DOI: 10.1186/s13293-015-0029-7
  • NAID: 120005646687
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] No association between the COMT Val158Met polymorphism and the long-term clinical response in obsessive-compulsive disorder in the Japanese population. (2015)
  • Author(s): Umehara H, Numata S*, Tajima A, Kinoshita M, Nakaaki S, Imoto I, Sumitani S, Ohmori T.
  • Journal Title: Hum Psychopharmacol. Volume: 30 Issue: 5 Pages: 372-376
  • DOI: 10.1002/hup.2485
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Polymorphism in the promoter of the gene for the serotonin transporter affects the age of onset of major depressive disorder in the Japanese population. (2015)
  • Author(s): Watanabe SY, Iga J, Numata S, Umehara H, Nishi A, Kinoshita M, Inoshita M, Ohmori T.
  • Journal Title: J Affect Disord Volume: 183 Pages: 156-158
  • DOI: 10.1016/j.jad.2015.05.009
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Biological tests for major depressive disorder that involve leukocyte gene expression assays. (2015)
  • Author(s): Watanabe SY, Iga JI, Ishii K, Numata S, Shimodera S, Fujita H, Ohmori T.
  • Journal Title: J Psychiatr Res Volume: 66 Pages: 1-6
  • DOI: 10.1016/j.jpsychires.2015.03.004
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 治療抵抗性統合失調症治療薬クロザピン；治療反応関連因子と増強療法 (2017)
  • Author(s): 沼田周助
  • Organizer: 第12回日本統合失調症学会
  • Place of Presentation: 米子コンベンションセンター（鳥取県米子市）
  • Year and Date: 2017-03-24
• [Presentation] Blood Diagnostic Biomarkers for Major Depressive Disorder using Multiplex DNA Methylation Profiles (2017)
  • Author(s): 沼田周助
  • Organizer: 13th world congress of biological psychiatry
  • Int'l Joint Research
• [Presentation] DNA methylation of the serotonin transporter gene in obsessive-compulsive disorder (2017)
  • Author(s): 沼田周助
  • Organizer: 第39回日本生物学的精神医学会
• [Presentation] 縦断研究から同定したうつ病の血漿バイオマーカー (2017)
  • Author(s): 沼田周助
  • Organizer: 第10回脳表現型の分子メカニズム研究会
• [Presentation] うつ病の血漿バイオマーカー (2017)
  • Author(s): 沼田周助
  • Organizer: cocoroうつ病客観的診断基準meeting
• [Presentation] 治療抵抗性統合失調症におけるips細胞を用いたクロザピン反応性のDNAメチル化解析 (2016)
  • Author(s): 沼田周助、菊地正隆、中澤敬信、橋本亮太
  • Organizer: 第26回日本臨床精神神経薬理学会
  • Place of Presentation: ホルトホール大分（大分県大分市）
  • Year and Date: 2016-11-17
• [Presentation] De novo single-nucleotide variants in sporadic schizophrenia (2016)
  • Author(s): 沼田周助
  • Organizer: 第38回日本生物学的精神医学会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2016-09-08
• [Presentation] DNAメチル化修飾を利用したうつ病の診断マーカー開発の取り組み (2016)
  • Author(s): 沼田周助
  • Organizer: 第13回日本うつ病学会総会
  • Place of Presentation: ウインクあいち（愛知県名古屋市）
  • Year and Date: 2016-08-05
• [Presentation] うつ病の診断および治療反応性予測マーカーの検討 (2016)
  • Author(s): 沼田周助
  • Organizer: 第112回日本精神神経学会学術総会
  • Place of Presentation: 幕張メッセ （千葉県千葉市）
  • Year and Date: 2016-06-02
• [Presentation] Trio-based exome sequencing identified de novo non-synonymous missense mutations in schizophrenia (2015)
  • Author(s): NISHI A, NUMATA S, TAJIMA A, KINOSHITA M, SHIMODERA S, ONO S, OCHI S, KUROTAKI N, IMAMURA A, UENO S, IMOTO I, OHMORI T
  • Organizer: society for neuroscience
  • Place of Presentation: McCormick Place（アメリカ）
  • Year and Date: 2015-10-17
• [Presentation] Genome-wide association study of plasma total homocysisteine in schizophrenia (2015)
  • Author(s): KINOSHITA M, NUMATA S, TAJIMA A, NISHI A, IMOTO I, OHMORI T.
  • Organizer: society for neuroscience
  • Place of Presentation: McCormick Place（アメリカ）
  • Year and Date: 2015-10-17
• [Presentation] The effect of blood cellular heterogeneity on DNA methylation in schizophrenia (2015)
  • Author(s): NUMATA S, KINOSHITA M, TAJIMA A,OHI K, HASHIMOTO R, SHIMODERA S, IMOTO I, TAKEDA M, OHMORI T
  • Organizer: society for neuroscience
  • Place of Presentation: McCormick Place（アメリカ）
  • Year and Date: 2015-10-17
• [Presentation] A genome-wide association study of the long-term clinical response to SSRI or SSRI with antipsychotics in obsessive-compulsive disorder in the Japanese population (2015)
  • Author(s): UMEHARA H, NUMATA S, TAJIMA A, NISHI A, IMOTO I, SUMITANI S, OHMORI T.
  • Organizer: society for neuroscience
  • Place of Presentation: McCormick Place（アメリカ）
  • Year and Date: 2015-10-17
• [Presentation] 細胞異種性を考慮した末梢血白血球のDNAメチル化の性差の検討 (2015)
  • Author(s): 井下真利、沼田周助、田嶋敦、木下誠、梅原英裕、山森英長、橋本亮太、井本逸勢、大森哲郎
  • Organizer: 第37回日本生物学的精神医学会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-09-24
• [Presentation] 迫性障害の治療反応性とセロトニントランスポータ遺伝子多型との関連 (2015)
  • Author(s): 梅原英裕,沼田周助、住谷さつき、大森哲郎
  • Organizer: 第37回日本生物学的精神医学会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-09-24
• [Presentation] 日本人におけるセロトニントランスポー多型とうつ病との関連研究 (2015)
  • Author(s): 渡部真也、伊賀淳一、梅原英裕,沼田周助、大森哲郎
  • Organizer: 第37回日本生物学的精神医学会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-09-24
• [Presentation] 気分障害の診断バイオマーカーの探索 (2015)
  • Author(s): 沼田周助、石井一夫、大森哲郎
  • Organizer: 第111回日本精神神経学会学術総会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-06-04
• [Presentation] One-Carbon Metabolismに着目した統合失調症の病態解明と治療法開発 (2015)
  • Author(s): 沼田周助、木下誠、大森哲郎
  • Organizer: 第111回日本精神神経学会学術総会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-06-04
• [Book] 双極性障害の生物学的マーカー (2017)
  • Author(s): 沼田周助、大森哲郎
  • Total Pages: 4
  • Publisher: カレントテラピー
• [Book] うつ病のメチレーションバイオマーカー (2017)
  • Author(s): 沼田周助、大森哲郎
  • Total Pages: 7
  • Publisher: 先端医学社
• [Book] うつ病の血液バイオマーカー (2017)
  • Author(s): 沼田周助、大森哲郎
  • Total Pages: 6
  • Publisher: 日本臨牀
• [Book] Depression Frintier2 (2016)
  • Author(s): 沼田周助、伊賀淳一、大森哲郎
  • Publisher: 医薬ジャーナル社
• [Book] 精神科外来処方navi (2016)
  • Author(s): 沼田周助
  • Publisher: 中外医学社
• [Book] 統合失調症のDNAメチル化修飾異常 (2015)
  • Author(s): 沼田周助、木下誠、大森哲郎
  • Total Pages: 8
  • Publisher: 日本生物学的精神医学会誌
• [Book] ここまでわかった統合失調症の病態メカニズム (2015)
  • Author(s): 沼田周助、木下誠
  • Total Pages: 7
  • Publisher: メジカルビュー社
• [Book] うつ病のエピゲノム研究 (2015)
  • Author(s): 沼田周助、大森哲郎
  • Total Pages: 14
  • Publisher: 医薬ジャーナル社