Effects of psychotropic drugs on the amino acid system in the brain: psychopharmacological application of high magnetic field MRS.

• Project/Area Number: 26461719
• 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: OHMORI Tetsuro 徳島大学, 大学院医歯薬学研究部(医学系), 教授 (00221135)
• Co-Investigator(Kenkyū-buntansha): 住谷 さつき 徳島大学, 大学院医歯薬学研究部(総合支援), 教授 (90346594)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 精神薬理学 / 脳画像解析 / グルタミン酸 / GABA

Outline of Final Research Achievements

Glutamate (Glu) and Glutamine (Gln) were separated and quantitated for bipolar disorder patients and healthy control subjects using high magnetic field MRS. Pearson 's correlation analysis revealed a significant positive correlation between the lithium carbonate blood concentration and the Gln / Glu ratio in the left basal ganglia, the valproate blood concentration and Glu in the anterior cingulate gyrus. Considering the influence of these drugs, the ratio of Gln / Glu was increased in the anterior cingulate gyrus in patients with bipolar disorder. The separation and quantification of GABA was also performed, but no clear drug effect was observed.

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] 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] Prefrontal cortex activation during neuropsychological tasks might predict response to pharmacotherapy in patients with obsessive-compulsive disorder. (2017)
  • Author(s): Takeda T, Sumitani S, Hamatani S, Yokose Y, Shikata M, Ohmori T.
  • Journal Title: Neuropsychiatr Dis Treat. Volume: 13 Pages: 577-583
  • DOI: 10.2147/ndt.s127752
  • NAID: 120006772555
  • Peer Reviewed / Open Access
• [Journal Article] Influence of cognitive function on quality of life in anorexia nervosa patients. (2017)
  • Author(s): Hamatani S, Tomotake M, Takeda T, Kameoka N, Kawabata M, Kubo H, Tada Y, Tomioka Y, Watanabe S, Inoshita M, Kinoshita M, Ohta M, Ohmori T.
  • Journal Title: Psychiatry Clin Neurosci. Volume: 印刷中 Issue: 5 Pages: 328-335
  • DOI: 10.1111/pcn.12491
  • Peer Reviewed / Open Access
• [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
  • DOI: 10.1016/j.psychres.2016.10.017
  • Peer Reviewed / Open Access
• [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] 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] Association study of polymorphism in the serotonin transporter gene promoter, methylation profiles, and expression in patients with major depressive disorder. (2016)
  • Author(s): Iga J, Watanabe SY, Numata S, Umehara H, Nishi A, Kinoshita M, Inoshita M, Shimodera S, Fujita H, Ohmori T.
  • Journal Title: Hum Psychopharmacol. Volume: 31(3) Issue: 3 Pages: 193-199
  • DOI: 10.1002/hup.2527
  • Peer Reviewed / Open Access
• [Journal Article] Impaired social cognition in anorexia nervosa patients. (2016)
  • Author(s): Hamatani S, Tomotake M, Takeda T, Kameoka N, Kawabata M, Kubo H, Tada Y, Tomioka Y, Watanabe S, Ohmori T.
  • Journal Title: Neuropsychiatr Dis Treat. Volume: 12 Pages: 2527-2531
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between Cognitive Function and Employment in Japanese Schizophrenia Patients. (2016)
  • Author(s): Takeda, T., Tomotake, M., Ueoka, Y., Tanaka, T., Tominaga, T., Kaneda, Y. and Ohmori, T.
  • Journal Title: Open Journal of Psychiatry Volume: 6 Issue: 01 Pages: 65-70
  • DOI: 10.4236/ojpsych.2016.61007
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Correlates Associated with Basic Ability of Social Life in Schizophrenia Inpatients. (2016)
  • Author(s): Chiba, S., Tomotake, M., Aono, M., Toshimitsu, H. and Ohmori, T.
  • Journal Title: Open Journal of Psychiatry Volume: 6 Issue: 01 Pages: 71-75
  • DOI: 10.4236/ojpsych.2016.61008
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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
• [Journal Article] Prefrontal activation during two Japanese Stroop tasks revealed with multi-channel near-infrared spectroscopy (2015)
  • Author(s): Watanabe Y, Sumitani S, Hosokawa M, Ohmori T.
  • Journal Title: The Journal of Medical Investigation Volume: 62 Issue: 1.2 Pages: 51-55
  • DOI: 10.2152/jmi.62.51
  • NAID: 130005129686
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Blood Diagnostic Biomarkers for Major Depressive Disorder using Multiplex DNA Methylation Profiles: Discovery and Validation. (2015)
  • Author(s): Shusuke Numata, Kazuo Ishii, Atsushi Tajima, Jun-Ichi Iga, Makoto Kinoshita, Shinya Watanabe, Hidehiro Umehara, Manabu Fuchikami, Satoshi Okada, Shuken Boku, Akitoyo Hishimoto, Shinji Shimodera, Issei Imoto, Shigeru Morinobu, Tetsuro Ohmori
  • Journal Title: Epigenetics Volume: 10(2) Issue: 2 Pages: 135-141
  • DOI: 10.1080/15592294.2014.1003743
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association of autism tendency and hemodynamic changes in the prefrontal cortex during facial expression stimuli measured by multi-channel near-infrared spectroscopy. (2015)
  • Author(s): Hosokawa M, Nakadoi Y, Watanabe Y, Sumitani S, Ohmori T.
  • Journal Title: Psychiatry Clin Neurosci. Volume: 69(3) Issue: 3 Pages: 145-152
  • DOI: 10.1111/pcn.12240
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Changes in plasma D-serine, L-serine, and glycine levels in treatment-resistant schizophrenia before and after clozapine treatment. (2014)
  • Author(s): Yamamori H, Hashimoto R, Fujita Y, Numata S, Yasuda Y, Fujimoto M, Ohi K, Umeda-Yano S, Ito A, Ohmori T, Hashimoto K, Takeda M.
  • Journal Title: Neurosci Lett. Volume: 582 Pages: 93-8
  • DOI: 10.1016/j.neulet.2014.08.052
  • Peer Reviewed
• [Journal Article] Aberrant DNA methylation of blood in schizophrenia by adjusting for estimated cellular proportions (2014)
  • Author(s): Kinoshita M, Numata S, Tajima A, Ohi K, Hashimoto R, Shimodera S, Imoto I, Takeda M, Ohmori T
  • Journal Title: NeuroMolecular Medicine Volume: 16 Issue: 4 Pages: 697-703
  • DOI: 10.1007/s12017-014-8319-5
  • Peer Reviewed
• [Journal Article] Neuropsychological and psychiatric assessments following bilateral deep brain stimulation of the subthalamic nucleus in Japanese patients with Parkinson's disease. (2014)
  • Author(s): Aono M, Iga J, Ueno S, Agawa M, Tsuda T, Ohmori T.
  • Journal Title: J Clin Neurosci. Volume: 21(9) Issue: 9 Pages: 1595-1598
  • DOI: 10.1016/j.jocn.2013.12.020
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Microarray analysis of global gene expression in leukocytes following lithium treatment. (2014)
  • Author(s): Watanabe S, Iga J, Nishi A, Numata S, Kinoshita M, Kikuchi K, Nakataki M, Ohmori T.
  • Journal Title: Hum Psychopharmacol. Volume: 29 Issue: 2 Pages: 190-198
  • DOI: 10.1002/hup.2381
  • Peer Reviewed
• [Presentation] MRSを用いた気分安定薬服用中の双極性障害患者におけるグルタミン酸神経伝達の異常 (2016)
  • Author(s): 久保弘子、中瀧理仁、住谷さつき、原田雅史、大森哲郎
  • 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] DNA methylation changes in leukocytes by clozapine treatment in patients with treatment-resistant schizophrenia. (2016)
  • Author(s): Kinoshita M, Numata S, Tajima A, Yamamori H, Yasuda Y, Fujimoto M, Imoto I, Hashimoto R, Ohmori T.
  • Organizer: Society for Neuroscience 2016 annual Meeting
  • Place of Presentation: San Diego（USA）
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] 統合失調症における血漿CRP濃度のDNAメチル化修飾への影響検討研究 (2016)
  • Author(s): 木下 誠, 沼田 周助, 井下 真利, 大森 哲郎
  • 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] Structural and functional brain alterations in schizophrenia patients treated with D-cycloserine: a combination of VBM and resting-state functional connectivity study. (2016)
  • Author(s): Masashi Ohta, Yasuhiro Funakoshi, Masafumi Harada, Jun-ichi Iga, Hiroko Kubo, Masahito Nakataki, Chiaki Nakayama, Toru Nishikawa, Shusuke Numata, Tetsuro Ohmori, Satsuki Sumitani, Mai Tamaru, Akihito Uezato.
  • Organizer: CINP2016
  • Place of Presentation: Seoul（Republic of Korea）
  • Year and Date: 2016-07-03
  • Int'l Joint Research
• [Presentation] Alterd Serotonin transporter mRNA expression in the peripheral leukocytes of obsessive-compulsive disorder. (2016)
  • Author(s): Hidehiro Umehara, Shusuke Numata, Shinya Watanabe, Satsuki Sumitani, and Tetsuro Ohmori.
  • Organizer: CINP2016
  • Place of Presentation: Seoul（Republic of Korea）
  • Year and Date: 2016-07-03
  • Int'l Joint Research
• [Presentation] 演題：抗精神病薬のリスクとベネフィット、シンポジウムタイトル：神経精神薬理学教育講座：神経精神薬理の基礎と臨床の最新のエビデンスの紹介 (2016)
  • Author(s): 大森哲郎
  • Organizer: 第46回日本神経精神薬理学会
  • Place of Presentation: Seoul（Republic of Korea）
  • Year and Date: 2016-07-02
• [Presentation] D-サイクロセリンにより治療された統合失調症患者における内側前頭前皮質の機能的結合 安静時fMRI研究 (2016)
  • Author(s): 大田将史、中瀧理仁、田丸麻衣、久保弘子、中山千明、船越康宏、上里彰仁、沼田周助、伊賀淳一、住谷さつき、原田雅史、西川徹、大森哲郎
  • Organizer: 第46回日本神経精神薬理学会
  • Place of Presentation: Seoul（Republic of Korea）
  • Year and Date: 2016-07-02
  • Invited
• [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: Neuroscience 2015
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [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: Neuroscience 2015
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [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: Neuroscience 2015
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [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: Neuroscience 2015
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] 日本人におけるセロトニントランスポータ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] 強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] 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] 統合失調症患者におけるNasu-Hakola病関連遺伝子の相関解析及び末梢血白血球の発現解析研究 (2015)
  • Author(s): 森蓉子, 吉野祐太, 越智紳一郎, 山崎聖弘, 安倍賢郎, 尾崎優樹, 北野知地, 沼田周助, 伊賀淳一, 大森哲郎, 上野修一
  • 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] Stroopおよび言語流暢性検査を用いた強迫性障害患者の脳血流変化の検討 (2015)
  • Author(s): 武田知也，住谷さつき，濱谷沙世，横瀬洋輔，四方めぐみ，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] MRSによる双極性障害におけるリチウムの作用の検討 (2014)
  • Author(s): 久保弘子, 中瀧理仁, 住谷さつき, 大森哲郎
  • Organizer: 第24回日本臨床精神神経薬理学会
  • Place of Presentation: 名古屋国際会議場, 愛知県名古屋市
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] Blood diagnostic biomarkers for major depressive disorder using DNA methylation profiles. (2014)
  • Author(s): Shusuke Numata, Ishii Kazuo, Atsushi Tajima, Junichi Iga, Makoto Kinoshita, Shinya Watanabe, Hidehiro Umehara, Fuchikami Manabu, Okada Satoshi, Shimodera Shinji, Issei Imoto, Morinobu Shigeru and Tetsuro Ohmori.
  • Organizer: Neuroscience
  • Place of Presentation: Washington Convention Center,USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Association between the COMT Val158Met polymorphism and the clinical response to SSRI or SSRI with antipsychotics in obsessive-compulsive disorder. (2014)
  • Author(s): Hidehiro Umehara, Shusuke Numata, Atsushi Tajima, Makoto Kinoshita, Nakaaki Shutaro, Issei Imoto, Satsuki Sumitani and Tetsuro Ohmori.
  • Organizer: Neuroscience
  • Place of Presentation: Washington Convention Center,USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Blood homocysteine and schizophrenia evaluated by a Mendelian randomization analysis. (2014)
  • Author(s): Makoto Kinoshita, Shusuke Numata, Atsushi Tajima, Nishi Akira, Issei Imoto and Tetsuro Ohmori.
  • Organizer: Neuroscience
  • Place of Presentation: Washington Convention Center,USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Sex differences of blood in DNA methylation. (2014)
  • Author(s): Inoshita Masatoshi, Shusuke Numata, Atsushi Tajima, Makoto Kinoshita, Issei Imoto and Tetsuro Ohmori.
  • Organizer: Neuroscience
  • Place of Presentation: Washington Convention Center,USA
  • Year and Date: 2014-11-15 – 2014-11-19