多様化した気分障害患者に関する画像・分子薬理学的研究

2010 Fiscal Year Annual Research Report

• Project/Area Number: 21591494
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: 中村 純 産業医科大学, 医学部, 教授 (40148804)
• Keywords: うつ病 / MRI / DTI / 脳由来栄養因子(BDNF) / 血漿中MHPG / 血漿中HVA / NOx濃度 / γ-アミノ酪酸(GABA)

Research Abstract

本研究は、多様化したうつ病の急性期とその6ヶ月後とで、MRI画像、拡散テンソル画像、血中MHPG、HVA、BDNF、BDNFおよび5-HTTP遺伝子多型、認知機能評価(BACS、Iowa Gambling Task)を比較検討し、うつ病の病態解明をすることを目的としている。対象患者は産業医科大学病院神経・精神科の外来通院、あるいは入院している20歳から60歳までの患者でDSM-IV-TRの診断基準で大うつ病性障害を満たした患者である。治療開始時に、性格傾向をみるためにNeo FFI、Early Trauma Inventoryを実施した。治療開始時にコルチゾールと血中MHPG、HVA、BDNF、BDNFおよび5-HTTP遺伝子多型を検討するための採血や認知機能検査(BACS、Iowa Gambling Task)、さらに治療開始時・8週後、6ヶ月後にMHPG、HVA、BDNFを測定するための採血を施行した。2011年3月現在、患者29例、健常者15例を本研究に導入した。患者は13例、健常対象群14例が全過程を終了、残り2例が、現在進行中である。健常者は、3例が脱落し、2例が全過程を終了、残り10例が現在進行中である。今年度、健常者11例を導入予定である。現在までのところ、認知機能検査であるBACSを施行した6名のうつ病患者では、研究導入時と6か月後では、言語性記憶、ワーキング記憶、運動機能、言語流暢性、注意と処理能力、遂行機能等どの項目においても有意な差は認めなかった。6ヶ月後に寛解していた患者と回復していない患者による違いや治療初期の重症度等さまざなデータのバラツキが考えれるが、今後症例数を増やし、MRI撮像による海馬体積の変化、拡散テンソル画像、さらに血液から得られたデータと組み合わせてさまざまなうつ状態の病態を明らかにして、新たなテーラーメイド医療に結びつく治療戦略を立てたいと考えている。

Research Products

• [Journal Article] うつ病患者の社会復帰に関するSocial Adaptation Self-evaluation Scale(SASS)日本語版の臨床的有用性 (2011)
  • Author(s): 中野英樹, 上田展久, 中野和歌子, 杉田篤子, 吉村玲児, 中村純
  • Journal Title: 精神医学 Volume: 53 Pages: 185-190
  • Peer Reviewed
• [Journal Article] Predictive factors for responding to sertraline treatment : views fromPlasma catecholamine metabolites and serotonin transporter polymorphism. (2010)
  • Author(s): Umene-Nakano W., Yoshimura R, Ueda N, Suzuki A, Ikenouchi-Sugita A, Hori H, Otani K, Nakamura J
  • Journal Title: Journal of Psychopharmacology Volume: 24 Pages: 1764-1771
  • Peer Reviewed
• [Journal Article] Identification of novel candidate genes for treatment response to risperidone and susceptibility for schizophrenia : integrated analysis among pharmacogenomics, mouse expression, and genetic case-control association approaches. (2010)
  • Author(s): Ikeda M, Yasuyuki T, Mouri A, Koga M, Okochi T, Yoshimura R, Yamanouchi Y, Kinoshita Y, Hashimoto R, Williams HJ, Takeda M, Nakamura J, et al.
  • Journal Title: Biolological Psychiatry Volume: 67 Pages: 263-269
  • Peer Reviewed
• [Journal Article] Nonadherence to paroxetine : a study based on monitoring plasmaparoxetine levels. (2010)
  • Author(s): Yoshimura R, Sugita A, Nakano W, Hori H, Ueda N, Nakamura J.
  • Journal Title: J Clin Psychopharmacol Volume: 30(1) Pages: 82-83
  • Peer Reviewed
• [Journal Article] Association between plasma nitric oxide metabolites levels and negative symptoms of schizophrenia : a pilot study. (2010)
  • Author(s): Nakano Y, Yoshimura R, Nakano H, Sugita A, Hori H, Nakano W, Ueda N, Nakamura, J
  • Journal Title: Human Psychopharmacology Clinical and Experimental Volume: 25 Pages: 139-144
  • Peer Reviewed
• [Journal Article] Gray and white matter volumetric and diffusion tensor imaging (DTI)analyses in the early stage of first-episode schizophrenia. (2010)
  • Author(s): Moriya J, Kakeda S, Abe O, Goto N, Yoshimura R, Hori H, Ohnari N, Sato T, Aoki S, Ohtomo K, Nakamura J, Korogi Y.
  • Journal Title: Schizophrenia Research Volume: 116 Pages: 196-203
  • Peer Reviewed
• [Journal Article] Different patterns of longitudinal changes in plasma levels of catecholamine metabolites and brain-derived neurotrophic factor after administration of atypical antipsychotics in first episode untreated schizophrenic patients. (2010)
  • Author(s): Yoshimura R, Ueda N, Hori H, Sugita A, Nakano W, Nakamura J
  • Journal Title: World Journal of Biological Psychiatry Volume: 11 Pages: 256-261
  • Peer Reviewed
• [Journal Article] Varenichne does not increase serum BDNF levels in patients with nicotine dependence. (2010)
  • Author(s): Nakano W, Yoshimura R, Yoshii C, Hoshuyama T, Hayashi K, Hori H, Katsuki A, Sugita A, Nakamura J
  • Journal Title: Human Psychopharmacology Clinical and Experimental Volume: 25 Pages: 276-279
  • Peer Reviewed
• [Journal Article] Adding a low dose atypical antipsychotic drug to an antidepressant induced a rapid increase of plasma brain-derived neurotrophic factor levels inpatients with treatment-resistant depression. (2010)
  • Author(s): Yoshimura R, Sugita A, Hori H, Nakano W, Katsuki A, Hayashi K, Ueda N, Nakamura J
  • Journal Title: Progress in Nero-Psychopharmacology and Biological Psychiatry Volume: 34 Pages: 308-312
  • Peer Reviewed
• [Journal Article] Serum brain-derived neurotrophic factor levels as a novel biological marker for the activities of psychiatric symptoms in systemic lupus erythematosus. (2010)
  • Author(s): Ikenouchi-Sugita A, Yoshimura R, Okamoto T, Umene-Nakano W, Ueda N, Hori H, Katsuki A, Saito K, Tanaka Y, Nakamura J
  • Journal Title: World Journal of Biological Psychiatry Volume: 11 Pages: 121-128PMID20109107
  • Peer Reviewed
• [Journal Article] Association analysis of SIGMAR1 with major depressive disorder and SSRI response. (2010)
  • Author(s): Kishi T, Yoshimura R, Okochi T, Fukuo Y, Kitajima T, Okumura T, Nakano W., Naitoh H, Nakamura J, Ozaki N, Iwata N
  • Journal Title: Neuropharmacology Volume: 58 Pages: 1168-1173
  • Peer Reviewed
• [Journal Article] Storage of GABA in chromaffin granules and not in synaptic-like microvesicles in rat adrenal medullary cells. (2010)
  • Author(s): Harada K, Matsuoka H, Nakamura J, Fukuda M, Inoue M
  • Journal Title: J Neurochem Volume: 114(2) Pages: 617-626
  • Peer Reviewed
• [Journal Article] Serotonin 6 receptor gene and mood disorders : case-control study and meta-analysis. (2010)
  • Author(s): Fukuo Y, Kishi T, Yoshimura R, Kitajima T, Okochi T, Yamanouchi Y, Kinoshita Y, Kawashima K, Naitoh H, Nakano W, Inada T, Kunugi H, Kato T, Yoshikawa T, Ujike H, Nakamura J, Ozaki N, Iwata N
  • Journal Title: Neuroscience Research Volume: 67 Pages: 250-255
  • Peer Reviewed
• [Journal Article] Pharmacogenetic study of serotonin 6 receptor gene with antidepressant response in major depressive disorder in the Japanese population. (2010)
  • Author(s): Kishi T, Fukuo Y, Yoshimura R, Okochi T, Kitajima T, Naitoh H, Nakano W, Nakamura J, Ozaki N, Iwata, N
  • Journal Title: Human Psychopharmacology Clinical and Experimental Volume: 25 Pages: 481-486
  • Peer Reviewed
• [Journal Article] No difference in adherence to paroxetine between depressed patients with early remission and those with late remission based on monitoring of plasma paroxetine concentrations. (2010)
  • Author(s): Yoshimura R, Nakano W, Ueda N, Sugita A, Hori H, Katsuki A, Hayashi K, Miyamoto K, Kodama Y, Nakamura J.
  • Journal Title: Human Psychopharmacology Clinical and Experimental Volume: 25 Pages: 487-490
  • Peer Reviewed
• [Journal Article] HTR2A is associated with SSRI response in major depressive disorder in a Japanese cohort. (2010)
  • Author(s): Kishi T, Yoshimura R, Kitajima T, Okochi T, Okumura T, Tsunoka T, Yamanouchi Y, Kinoshita Y, Kawashima K, Naitoh H, Nakamura J, Ozaki N, Iwata N.
  • Journal Title: Neuromolecular Medicine Volume: 12 Pages: 237-242
  • Peer Reviewed
• [Journal Article] Lack of association between MAGEL2 and schizophrenia and mood disorders in the Japanese population. (2010)
  • Author(s): Fukuo Y, Kishi T, Okochi T, Kitajima T, Tsunoka T, Okumura T, Kinoshita Y, Kawashima K, Yamanouchi Y, Nakano W, Naitoh H, Inada T, Yoshimura R, Nakamura J, Ozaki N, Iwata N
  • Journal Title: Neuromelecular Medicine Volume: 12 Pages: 285-291
  • Peer Reviewed
• [Journal Article] SIRT1 gene is associated with major depressive disorder in the Japanese population. (2010)
  • Author(s): Kishi T, Yoshimura R, Kitajima T, Okochi T, Okumura T, Tsunoka T, Yamanouchi Y, Kinoshita Y, Kawashima K, Fukuo Y, Naitoh H, Umene-Nakano W, Inada T, Nakamura J, Ozaki N, Iwata N
  • Journal Title: Journal of Affective Disorder Volume: 126 Pages: 167-173
  • Peer Reviewed
• [Journal Article] Critical examination of a correlation between brain gamma- aminobutyricacid(GABA)concentrations and a personality trait of extroversion in healthy volunteers as measured by a 3Tesla proton magnetic resonance spectroscopy study. (2010)
  • Author(s): Goto N, Yoshimura R, Moriya J, Kakeda S, Hayashi K, Ueda N, Sugita, A, Nakano W, Ohnari N, Korogi Y, Nakamura J
  • Journal Title: Psychiatry Research Volume: 182 Pages: 53-57
  • Peer Reviewed
• [Journal Article] Relationships between stress, social adoptation, personality traits, brain-derived neurotrophic factor and 3-methoxy-4-hydroxyphenylglycol plasma concentrations in employees at a publishing company in Japan. (2010)
  • Author(s): Okuno K, Yoshimura R, Ueda N, Ikenouchi-Sugita A, Umene-Nakano W, Hori H, Hayashi K, Katsuki A, Chen HI, Nakamura J
  • Journal Title: Psychiatry Research Volume: Sep 8(Pubmed ahead of print)
  • Peer Reviewed
• [Journal Article] No alteratios of brain GABA after 6 months treatment with atypical antipsychotic drugs in early-stage first-episode schizophrenia. (2010)
  • Author(s): Goto N, Yoshimura R, Kakeda S, Moriya J, Hori H, Hayashi K, Ikenouchi-Sugita A, Nakano-Umene W, Katsuki A, Nishimura J, Korogi Y, Nakamura J
  • Journal Title: Progress in Neuro-Psychopharmacology and Biological Psychiatry Volume: 34 Pages: 1480-1483
  • Peer Reviewed
• [Journal Article] Plasma levels of brain-derived neurotrophic factor and interleukin-6 in patients with dysthymic disorder : comparison with age-and sex-matched major depressed patients and healthy controls. (2010)
  • Author(s): Yoshimura R, Umene-Nakano W, Hoshuyama T, Atsuko Ikenouchi-Sugita, Hikaru Hori, Asuka Katsuki, Kenji Hayashi, Kiyokazu Atake, Jun Nakamura
  • Journal Title: Human Psychycopharmacology Clinical and Experimental Volume: In Press
  • Peer Reviewed
• [Presentation] 精神疾患の生物学的マーカー-われわれの教室の研究から- (2010)
  • Author(s): 中村純
  • Organizer: 第32回日本生物学的精神医学会
  • Place of Presentation: 北九州市(リーガロイヤルホテル小倉)(会長講演)
  • Year and Date: 2010-10-08
• [Presentation] Plasma homovanillic acid levels and 5-HTTLPR gene polymorphism are predictive factors for sertraline in Japanese depressed patients. (2010)
  • Author(s): Nakano W, Yoshimura R, Ueda N, Suzuki A, Ikenouchi-Sugita A, Hori H, Otani K, Nakamura J
  • Organizer: 23rd European Neuro-psychopharmacologicum Congress
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre THE NETHERLAND
  • Year and Date: 2010-09-01
• [Presentation] Effects of mirtazapine on brain-derived neurotrophic factor (BDNF) and catecholamine metabolites. (2010)
  • Author(s): Katsuki A, Yoshimura R, Sugita A, Hori H, Nakano W, Hayashi K, Nakamura J
  • Organizer: 23rd European Neuro-psychopharmacologicum Congress
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre THE NETHERLAND
  • Year and Date: 2010-09-01
• [Presentation] Cognitive functions and dosage of antipsychotic drugs in Japanese schizophrenia patients. (2010)
  • Author(s): Hori H, Yoshimura R, Katsuki A, Hayashi K, Sugita A, Nakano W, Nakamura J
  • Organizer: 23rd European Neuro-psychopharmacologicum Congress
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre THE NETHERLAND
  • Year and Date: 2010-09-01
• [Presentation] The characteristics of pharmacotherapy for inpatients with schizophrenia : amulticentre comparitive study in Asia. (2010)
  • Author(s): Nakano W, Yoshimura R, Yang N, Shinfuku N, Fujii S, Hoshuyama T, Sim K, Chong M, Tan C, Nakamura J
  • Organizer: 23rd European Neuro-psychopharmacologicum Congress
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre THE NETHERLAND
  • Year and Date: 2010-09-01
• [Presentation] Three polymorphisms of endothelial nitric oxide synthase (eNOS) gene andplasma N03 levels. (2010)
  • Author(s): Ikenouchi-Sugita A, Yoshimura R, Tishi T, Umene-Nakano W, Hori H, Hayashi K, Katsuki A, Iwata N, Nakamura J
  • Organizer: 23rd European Neuro-psychopharmacologicum
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre THE NETHERLAND
  • Year and Date: 2010-08-31
• [Presentation] Nonadherence to paroxetine ; comparison between early-remitters and late-remitters. (2010)
  • Author(s): Nakamura J, Yoshimura R, Ikenouchi-Sugita A, Hori H, Umene-Nakano W, Katsuki A, Ueda N
  • Organizer: 23rd European Neuro-psychopharmacologicum Congress
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre THE NETHERLAND
  • Year and Date: 2010-08-31
• [Presentation] Adding an atypical antipsychotic drug induced a rapid increase of plasma BDNF levels in refractory depression., 2010 (2010)
  • Author(s): Yoshimura R, Ikenouchi-Sugita A, Hori H, Umene-Nakano W, Katsuki A, Hayashi K, Nakamura J
  • Organizer: 23rd European Neuro-psychopharmacologicum Congress
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre THE NETHERLAND
  • Year and Date: 2010-08-31
• [Presentation] Higher plasma interleukin-6(IL-6)level is associated with SSRI- orSNRI-refractory depression. (2010)
  • Author(s): Yoshimura R, Hori H, Sugita A, Nakano W, Hayashi K, Katsuki A, Nakamura J
  • Organizer: 27th Collegium Internationale Neuro-psychopharmacologicum Congress
  • Place of Presentation: Hong Kong, Convention and Exhibition Centre CHINA
  • Year and Date: 2010-06-06
• [Presentation] Nonadherence to SSRI ; a study based on monitoring plasma levels of antidepressant. (2010)
  • Author(s): Nakamura J, Yoshimura R, Sugita A, Hori H, Nakano W
  • Organizer: 27th Collegium Internationale Neuro-psychopharmacologicum Congress
  • Place of Presentation: Hong Kong, Convention and Exhibition Centre CHINA
  • Year and Date: 2010-06-06
• [Presentation] Plasma homovanillic acid levels and 5-HTTLPR gene polymorphism are predictive factors for sertraline in Japanese depressed patients. (2010)
  • Author(s): Chen HI, Shinkai T, Sakata S, Utsunomiya K, Yamada K, Ohmori O, Nakamura J
  • Organizer: 27th Collegium Internationale Neuro-psychopharmacologicum Congress
  • Place of Presentation: Hong Kong, Convention and Exhibition Centre CHINA
  • Year and Date: 2010-06-06
• [Remarks]
  • URL: http://www.uoeh-u.ac.jp/kouza/seisin/homepage/m_gyouseki.html