Research on the biological pathology and diagnosis, treatment of obsessive-compulsive disorder using brain imaging and analysis of gene polymorphism

• Project/Area Number: 25461732
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kyushu University
• Principal Investigator: Kawasaki Hiroaki 九州大学, 医学(系)研究科(研究院), 研究員 (50224762)
• Co-Investigator(Kenkyū-buntansha): NAKAO TOMOHIRO 九州大学, 大学病院, 講師 (50423554) ; MITUYASU HIROSHI 九州大学, 大学病院, 助教 (00533176) ; SANEMATSU HIROKUNI 九州大学, 大学病院, 共同研究員 (30588116) ; HIWATASHI AKIO 九州大学, 大学病院, 助教 (30444855) ; YOSHIURA TAKASHI 鹿児島大学, 医歯(薬)学総合研究科, 教授 (40322747)
• Co-Investigator(Renkei-kenkyūsha): KANBA SHIGENOBU 九州大学, 医学研究科, 教授 (50195187) ; NAKAGAWA AKIKO 千葉大学, 医学研究科, 教授 (70253424)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 臨床精神分子遺伝学 / 強迫性障害 / 遺伝子多型 / メチル化解析 / MRI脳画像 / 5-HTTLPR / メチル化 / MRI / 遺伝子

Outline of Final Research Achievements

95 obsessive and compulsive disorder (OCD) patients and 93 healthy controls (HCS) were genotyped with L- and s- types polymorphisms of 5HTT-LPR, 5HTT-VNTR, DAT-VNTR, D4-120、D4-48. As a result, any genetic polymorphisms were observed no significant difference between OCD patients and HCs. Magnetic resonance imaging examinations of 40 OCD patients and 40 HCs were carried out. As of genotype-diagnosis interaction, though no voxels survived multiple comparison, we observed a tendency that 5-HTTLPR polymorphism with OCD patients had stronger effects on the right frontal pole than those in HCs. Moreover, we investigated the differences in terms of DNA methylation profile of HTR2A gene and COMT gene between 48 OCD patients and 48 HCs.
We found a significant difference between the OCD patients and HCs in the percent methylation of the COMT gene.

Research Products

• [Journal Article] Biological heterogeneity of obsessive-compulsive disorder: A voxel-based morphometric study based on dimensional assessment. (2014)
  • Author(s): Okada K, Nakao T, Sanematsu H, Murayama K, Honda S, Tomita M, Togao O, Yoshiura T, Kanba S.
  • Journal Title: Psychiatry Clin Neurosci. Volume: 印刷中 Issue: 7 Pages: 411-421
  • DOI: 10.1111/pcn.12269
  • Peer Reviewed / Open Access
• [Journal Article] Neurobiological model of obsessive-compulsive disorder: evidence from recent neuropsychological and neuroimaging findings. (2014)
  • Author(s): Nakao T, Okada K, Kanba S.
  • Journal Title: Psychiatry Clin Neurosci. Volume: 68(8) Issue: 8 Pages: 587-605
  • DOI: 10.1111/pcn.12195
  • Peer Reviewed / Open Access
• [Journal Article] 強迫性障害の長期予後 (2014)
  • Author(s): 實松寛晋
  • Journal Title: 臨床精神医学 Volume: 43 Pages: 1445-1450
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Comparative efficacy and tolerability of pharmacological treatments in the maintenance treatment of bipolar disorder: a systematic review and network meta-analysis (2014)
  • Author(s): Tomofumi Miura, Hisashi Noma, Toshi A Furukawa, Hiroshi Mitsuyasu, Shiro Tanaka, Sarah Stockton, Georgia Salanti, Keisuke Motomura, Satomi Shimano-Katsuki, Stefan Leucht, Andrea Cipriani, John R Geddes, Shigenobu Kanba
  • Journal Title: The Lancet Psychiatry Volume: 1 Issue: 5 Pages: 351-359
  • DOI: 10.1016/s2215-0366(14)70314-1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 双極Ⅱ型およびソフト双極Ⅱ型障害に対する長期薬物療法のエビデンスと治療の終結の工夫 (2014)
  • Author(s): 光安 博志, 三浦 智史, 川嵜 弘詔
  • Journal Title: 臨床精神薬理 Volume: 17 Pages: 477-488
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Neural bases of antisocial behavior: a voxel-based meta-analysis. (2013)
  • Author(s): Aoki Y, Inokuchi R, Nakao T, Yamasue H
  • Journal Title: Soc Cogn Affect Neurosci Volume: ahead of print
  • Peer Reviewed
• [Journal Article] 躁状態の治療とリチウム －第2世代抗精神病薬との比較、併用を含む－ (2013)
  • Author(s): 光安博志, 川嵜弘詔
  • Journal Title: 臨床精神医学 Volume: 42 Pages: 1363-1369
• [Presentation] A morphometric study into the pathophysiology of obsessive- compulsive disorder. Basic and Clinical Neuroscience Collaboration Symposium: Uncovering pathophysioology of psychiatric symptoms with multimodal MRIs and their clinical applications. (2015)
  • Author(s): Nakao T, Okada K
  • Organizer: The 38th Annual Meeting of the Japan Neuroscience Society.
  • Place of Presentation: Kobe
  • Year and Date: 2015-07-28
  • Int'l Joint Research
• [Presentation] Neurobiological heterogeneities of OCD. Symposium: Biological approaches toward clarifying heterogeneities of obsessive-compulsive disorder. (2015)
  • Author(s): Nakao T
  • Organizer: 12th WFSBP
  • Place of Presentation: Athens, Greece.
  • Year and Date: 2015-06-14
  • Int'l Joint Research
• [Presentation] The association of serotonin and/or dopamine system genes and gray matter volume in OCD. (2015)
  • Author(s): Honda S, Nakao T, Mitsuyasu H
  • Organizer: WPA REGIONAL CONGRESS OSAKA JAPAN 2015.
  • Place of Presentation: Osaka
  • Year and Date: 2015-06-04
  • Int'l Joint Research
• [Presentation] 退院前訪問を繰り返し、居住スペースを 確保し、退院となったためこみ症の一例 (2014)
  • Author(s): 安達利昭, 桑野真澄, 山田聖, 實松寛晋, 宮崎恭輔, 神庭重信
  • Organizer: 第67回九州精神神経学会
  • Place of Presentation: 福岡
  • Year and Date: 2014-12-05
• [Presentation] White Matter Structural Changes of Obsessive Compulsive disorder -from the aspects of Diffusion Tensor Imaging (2014)
  • Author(s): Kayo Okada, Tomohiro Nakao, Hirokuni Sanematsu, Keitaro Murayama, Shinichi Honda, Shigenobu Kanba
  • Organizer: 第36回日本生物学的精神医学会年会
  • Place of Presentation: 奈良市
  • Year and Date: 2014-09-29 – 2014-10-01
• [Presentation] The association of serotonin and/or dopamine system genes and gray matter volume in OCD (2014)
  • Author(s): Shinichi Honda, Tomohiro Nakao, Hiroshi Mitsuyasu
  • Organizer: 第36回日本生物学的精神医学会年会
  • Place of Presentation: 奈良市
  • Year and Date: 2014-09-29 – 2014-10-01
• [Presentation] Brain activity in drug-free patients with obsessive-compulsive disorder during visual working memory task: an fMRI study (2014)
  • Author(s): K. Murayama, T. Nakao , M. Tomita, H. Sanematu, K. Okada, S. Honda, K. Ikari, M. Kuwano, A. Nakagawa, S. Kanba
  • Organizer: World Psychiatric Association International Congress
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2014-09-15 – 2014-09-19
• [Presentation] The association of serotonin and/or dopamine system genes and gray matter volume in OCD (2014)
  • Author(s): Shinichi Honda, Tomohiro Nakao, Hiroshi Mitsuyasu, Kayo Okada, Leo Gotoh, Mayumi Tomita, Hirokuni Sanematsu, Keitaro Murayama, Keisuke Ikari, Masumi Kuwano, Takashi Yoshiura, Hiroaki Kawasaki, Shigenobu Kanba
  • Organizer: World Psychiatric Association International Congress
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2014-09-15 – 2014-09-19
• [Presentation] Alterations of the brain activation during N-back task in patients with OCD after 12weeks treatments. (2014)
  • Author(s): K. Murayama, T. Nakao , M. Tomita, A. Nakagawa E. Nakatani, M. Nabeyama, C. Yoshizato, H. Sanematu, K. Okada, S. Honda, K. Ikari, M. Kuwano, S. Kanba
  • Organizer: Europian Association for Behavioural and Cognitive Therapies
  • Place of Presentation: The Hague, The Kingdom of the Netherlands.
  • Year and Date: 2014-08-29 – 2014-09-01
• [Presentation] Neurobiological model of obsessive-compulsive disorder: Evidence from recent neuroimaging findings (2013)
  • Author(s): Nakao T
  • Organizer: 11th World congress of biological psychiatry
  • Place of Presentation: 京都
• [Presentation] Grey matter abnormality in Checking-based Obsessive-Compulsive Disorder. (2013)
  • Author(s): Okada K, Nakao T, Yoshiura T, Sanematsu H, Murayama K, Honda S, Tomita M, Kanba S
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: 京都
• [Presentation] White Matter Structural Changes of Obsessive-Compulsive disorder~ from the aspect of Diffusion Tensor Imaging. (2013)
  • Author(s): Okada K, Nakao T, Sanematsu H, Murayama K, Honda S, Kanba S
  • Organizer: 43rd Annual Congress of European Association for Behavioral and Cognitive Therapies
  • Place of Presentation: Marrakech
• [Presentation] 口腔癌患者の術後せん妄の危険因子の検討 (2013)
  • Author(s): 光安博志, 光安岳志, 川嵜弘詔, 松尾裕美, 中村誠司, 神庭重信
  • Organizer: 第26回日本総合病院精神医学会総会
  • Place of Presentation: 京都
• [Presentation] 強迫性障害におけるセロトニントランスポーター遺伝子多型（5HTT-LPR）と脳の形態画像による脳体積との関連解析
  • Author(s): 本田慎一
  • Organizer: 第46回精神神経系薬物治療研究報告会
  • Place of Presentation: 千里ライフ サイエンスセンター
• [Presentation] Involvement of the medial habenula-interpeduncular nucleus pathway in adaptation and social memory.
  • Author(s): KOBAYASHI Y, OBA-ASAKA A, KOGO N, YASUDA K, HAYASHI Y, KAWASAKI H, ITOHARA S
  • Organizer: Involvement of the medial habenula-interpeduncular nucleus pathway in adaptation and social memory.
  • Place of Presentation: San Diego, U.S.A.
• [Book] 強迫性障害の生物学的側面ー森田学説との関連. 北西憲二・久保田幹子編; 森田療法で読む強迫性障害. (2015)
  • Author(s): 黒木俊秀, 中尾智博
  • Total Pages: 17
  • Publisher: 白揚社
• [Book] 溜め込み癖に関する疫学調査および治療的介入の試み. (2015)
  • Author(s): 中尾智博, 實松寛晋, 村山桂太郎, 岡田佳代, 本田慎一, 猪狩圭介, 桑野真澄, 富田真弓
  • Total Pages: 4
  • Publisher: メンタルヘルス岡本記念財団 2014年度研究助成報告集
• [Book] 強迫性障害.山脇成人, 西条寿夫編;情動の仕組みとその異常. (2015)
  • Author(s): 中尾智博
  • Total Pages: 1
  • Publisher: 朝倉書店
• [Book] 強迫性障害の早期徴候と治療・対応. 水野雅文編; 重症化させないための精神疾患の診方と対応 (2014)
  • Author(s): 中尾智博
  • Total Pages: 9
  • Publisher: 医学書院
• [Book] Hoarding（ため込み）と児童思春期に発症する精神疾患の関連についての疫学的研究. 明治安田こころの健康財団 研究助成論文集 (2014)
  • Author(s): 中尾智博, 桑野真澄, 實松寛晋, 村山桂太郎, 岡田佳代, 本田慎一, 猪狩圭介, 富田真弓
  • Total Pages: 6
  • Publisher: 明治安田こころの健康財団
• [Book] 強迫症／強迫性障害. 神庭重信、三村将編；DSM-5を読み解く ４ 不安症群, 強迫症および関連症群, 心的外傷およびストレス因関連障害群, 解離症群，身体症状症および関連症群 (2014)
  • Author(s): 中尾智博
  • Total Pages: 9
  • Publisher: 中山書店
• [Book] 他の医学的疾患による強迫症および関連症／他の医学的疾患による強迫性障害および関連障害, 他の特定される強迫症および関連症／他の特定される強迫性障害および関連障害, 特定不能の強迫症および関連症／特定不能の強迫性障害および関連障害. DSM-5を読み解く４ (2014)
  • Author(s): 實松寛晋
  • Total Pages: 4
  • Publisher: 中山書店
• [Book] NMDA受容体機能調整作用を有する新たな強迫症治療薬への期待. 臨床精神医学 (2014)
  • Author(s): 村山桂太郎, 中尾智博
  • Total Pages: 9
  • Publisher: アークメディア
• [Book] 不安障害診療のすべて (2013)
  • Author(s): 中尾智博
  • Publisher: 医学書院
• [Book] 強迫性障害の神経回路障害と治療による修復 (2013)
  • Author(s): 中尾智博
  • Publisher: メディカルフロント社
• [Book] III 抗精神病薬. 精神・神経の治療薬事典2014-15 (2013)
  • Author(s): 中尾智博, 猪狩圭介
  • Publisher: 総合医学社
• [Book] 精神疾患の歴史と病名・診断名 (2013)
  • Author(s): 岡田佳代, 中尾智博, 神庭重信
  • Publisher: 南江堂
• [Book] 日本総合病院精神医学会治療指針６, 生体臓器移植ドナーの意思確認に関する指針 (2013)
  • Author(s): 川嵜弘詔，光安博志，南里幸一郎
  • Publisher: 星和書店