難治性統合失調症における塩酸ミノサイクリンの有効性とその機序に関する研究

• 研究課題/領域番号: 23591673
• 研究種目: 基盤研究(C)
• 配分区分: 基金
• 応募区分: 一般
• 研究分野: 精神神経科学
• 研究機関: 島根大学
• 研究代表者: 宮岡 剛 島根大学, 医学部, 准教授 (50284047)
• 研究期間 (年度): 2011 – 2013
• 研究課題ステータス: 完了 (2013年度)
• 配分額: 5,200千円 (直接経費: 4,000千円、間接経費: 1,200千円); 2013年度: 1,040千円 (直接経費: 800千円、間接経費: 240千円); 2012年度: 1,950千円 (直接経費: 1,500千円、間接経費: 450千円); 2011年度: 2,210千円 (直接経費: 1,700千円、間接経費: 510千円)
• キーワード: 統合失調症 / 神経炎症 / 難治性 / ミノサイクリン / モデル動物

研究概要

難治性統合失調症における塩酸ミノサイクリンの有効性の特徴とその奏功機序について、臨床研究およびモデル動物を用いいた基礎研究により明らかにした。塩酸ミノサイクリンの統合失調治療薬としての有用性を検討し、塩酸ミノサイクリンがいかなる精神症状に有効であるかを明確にしたい。また塩酸ミノサイクリンの治療効果機序の解明のため治療前後での血清グルタミン酸代謝やミクログリアの活性変化を明らかにした。

研究成果

• [雑誌論文] Efficacy and safety of yokukansan in treatment-resistant schizophrenia : a randomized,double-blind,placebo-controlled trial(a Positive and Negative Syndrome Scale, five-faotor analisis) (2014)
  • 著者名/発表者名: Miyaoka T, Furuya M, Horiguchi J, Wake R, Hashioka S, Tohyama M, Mori N, Minabe Y, Iyo M, Ueno S, Ezoe S, Murotani K, Hoshino S, Seno H
  • 雑誌名: Psychopharmacology(Berl) 巻: (in press)
• [雑誌論文] The Effects of combine treatment of memantine and donepezil on Alzheimer's Disease patients and its relationship with cerebral blood flow in the prefrontal area (2014)
  • 著者名/発表者名: Araki T, Wake R, Miyaoka T, Kawakami K, Nagahama M, Furuya M, Limoa E, Liaury K, Hashioka S, Murotani K, Horiguchi J
  • 雑誌名: Int J Geriatr Psychiatry 巻: (in press)
• [雑誌論文] The Effects of Aging on Changes in Regional Cerebral Blood Flow in Schizophrenia (2014)
  • 著者名/発表者名: Kawakami K, Wake R, Miyaoka T, Furuya M, Liaury K, Horiguchi J
  • 雑誌名: Neuropsychobiology 巻: 69(4) ページ: 202-209
  • 査読あり
• [雑誌論文] Minocycline improves recognition memory and attenuates microglial activation in Gunn rat : a possible hyperbilirubinemia-induced model of schizophrenia (2014)
  • 著者名/発表者名: Liaury K, Miyaoka T, Tsumori T, Furuya M, Hashioka S, Wake R, Tsuchie K, Fukushima M, Limoa E, Tanra AJ, Horiguchi J
  • 雑誌名: Prog Neuropsychopharmacol Biol Psychiatry 巻: 50 ページ: 184-190
  • 査読あり
• [雑誌論文] The effects of combine treatment of memantine and donepezil on Alzheimer’s Disease patients and its relationship with cerebral blood flow in the prefrontal area. (2014)
  • 著者名/発表者名: Araki T, Wake R, Miyaoka T, Kawakami K, Nagahama M, Furuya M, Limoa E, Liaury K, Hashioka S, Murotani K, Horiguchi J
  • 雑誌名: Int J Geriatr Psychiatry 巻: 10 ページ: 4074-4074
  • 査読あり
• [雑誌論文] Minocycline improves recognition memory and attenuates microglial activation in Gunn rat:a possible hyperbilirubilirubinemia-induced animal model of schizophrenia. (2014)
  • 著者名/発表者名: Liaury K, Miyaoka T, Tsumori T, Furuya M, Hashioka S, Wake R, Tsuchie K, Fukushima M, Limoa E, Tanra AJ, Horiguchi J
  • 雑誌名: Prog Neuropsychopharmacol Biol Psychiatry 巻: 50 ページ: 184-190
  • 査読あり
• [雑誌論文] Yokukansan promotes hippocampal neurogenesis associated with the suppression of activated microglia in Gunn rat (2013)
  • 著者名/発表者名: Furuya M, Miyaoka T, Tsumori T, Liaury K, Hashioka S, Wake R, Tsuchie K, Fukushima M, Ezoe S and Horiguchi J
  • 雑誌名: JOURNAL OF NEUROINFLAMMATION 巻: 10 ページ: 145-145
  • 査読あり
• [雑誌論文] Yokukansan (TJ-54) forIrritability Associated with Pervasive Developmental Disorder in Children and Adolescents : A 12-Week Prospective, Open-Label Study (2013)
  • 著者名/発表者名: Wake R, MD, Miyaoka T, Inagaki T, MD, Furuya M, Ieda M, MD, Liaury K, MD, Kishi K, Horiguchi J
  • 雑誌名: JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY 巻: 23(5) ページ: 329-336
  • 査読あり
• [雑誌論文] Evaluation of autonomic nervous system by salivary alpha-amylase level and heart rate variability in patients with schizophrenia (2013)
  • 著者名/発表者名: Ieda M, Miyaoka T, Wake R, Liaury K, Tsuchie K, Fukushima M, Araki T, Ezoe S, Inagaki T, Horiguchi J
  • 雑誌名: Eur Arch Psychiatry Clin Neurosci
  • 査読あり
• [雑誌論文] Glia : An Important Target for Anti-Inflammatory and Antidepressant Activity (2013)
  • 著者名/発表者名: Hashioka S, Miyaoka T, Wake R, Furuya M and Horiguchi J
  • 雑誌名: Current Drug Targets 巻: 14(11) ページ: 1322-1328
  • NAID: 120006863742
  • 査読あり
• [雑誌論文] Yokukansan(TJ-54) for treatment of very-late-onset schizophrenia-like psychosis : An open-label study (2013)
  • 著者名/発表者名: Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, Tsuchie K, Fukushima M, Ishihara K, Araki T, Hashioka S, Horiguchi J
  • 雑誌名: Phytomedicine 巻: 20(7) ページ: 654-658
  • 査読あり
• [雑誌論文] The effects of antipsychotics on behavioral abnormalities of the Gunn rat (unconjugated hyperbilirubinemia rat), a rat model of schizophrenia (2013)
  • 著者名/発表者名: Tsuchie K, Miyaoka T, Furuya M, Liaury K, Ieda M, Wake R, Horiguchi J, Takechi M
  • 雑誌名: Asian Journal of Psychiatry 巻: 6(2) ページ: 119-123
  • 査読あり
• [雑誌論文] Possibility of early withdrawal of benzodiazepine hypnotics by combination with ramelteon for the treatment of insomnia : A pilot study (2013)
  • 著者名/発表者名: Furuya M, Miyaoka T, Wake R, Nagahama M, Kawano K, Yamashita S, Ieda M, Ezoe S and Horiguchi J
  • 雑誌名: Sleep and Biological Rhythms 巻: 11(1) ページ: 55-61
  • 査読あり
• [雑誌論文] Yokukansan prometes hippocampal neurogenesis associated with the suppression of activated microglia in Gunn rat. (2013)
  • 著者名/発表者名: Furuya M, Miyaoka T, Tsumori T, Liaury K, Hashioka S, Wake R, Tsuchie K, Fukushima M, Ezoe S, Horiguchi J
  • 雑誌名: J Neuroinflammation 巻: 10 ページ: 145-145
  • 査読あり
• [雑誌論文] Possibility of early withdrawal of benzodiazepine hypnotics by combination with ramelteon for the treatment of insomnia: A pilot study. (2013)
  • 著者名/発表者名: Furuya M, Miyaoka T, Wake R, Nagahama M, Kawano K, Yamashita S, Ieda M, Ezoe S and Horiguchi J
  • 雑誌名: Sleep and Biological Rhythms 巻: 11（1） ページ: 55-61
  • 査読あり
• [雑誌論文] Yokukansan(TJ-54)for treatment of very-late-onset schizophrenia-like psychosis: An open-label study. (2013)
  • 著者名/発表者名: Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, Tsuchie K, Fukushima M, Ishihara K, Araki T, Hashioka S, Horiguchi J
  • 雑誌名: Phytomedicine 巻: 20(7) ページ: 654-658
  • 査読あり
• [雑誌論文] Glia: An Important Target for Anti-Inflammatory and Antidepressant Activity. (2013)
  • 著者名/発表者名: Hashioka S, Miyaoka T, Wake R, Furuya M and Horiguchi J
  • 雑誌名: Current Drug Targets 巻: 14(11) ページ: 1322-1328
  • NAID: 120006863742
  • 査読あり
• [雑誌論文] Yokukansan(TJ-54) for Irritability Associated with Pervasive Developmental Disorder in Children and Adolescents: A 12-Week Prospective,Open-Label Study. (2013)
  • 著者名/発表者名: Wake R, Miyaoka T, Inagaki T, Furuya M, Ieda M, Liaury K, Kishi K and Horiguchi J
  • 雑誌名: JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY 巻: 23(5) ページ: 329-336
  • 査読あり
• [雑誌論文] Yokukansan (TJ-54) for treatment of pervasive developmental disorder not otherwise specified and Asperger's disorder : a 12-week prospective, open-label stury (2012)
  • 著者名/発表者名: Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, Tsuchie K, Inagaki T and Horiguchi J
  • 雑誌名: BMC Psychiatry 巻: 12 ページ: 215-215
  • 査読あり
• [雑誌論文] Minocycline for Schizophrenia : A critical review (2012)
  • 著者名/発表者名: Miyaoka T
  • 雑誌名: Open Journal of Psychiatry 巻: 2 ページ: 399-406
  • 査読あり
• [雑誌論文] Yokukansan(TJ-54)for treatment of very-late-onset Schizophrenia-like psychosis.An open-Label Study Authors. (2012)
  • 著者名/発表者名: Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, Tsuchie K, Fukushima M, Ishihara K, Araki T, Hashioka S, Horiguchi J
  • 雑誌名: Phytomedicine 巻: 20(7) ページ: 654-8
  • 査読あり
• [雑誌論文] Yokukansan(TJ-54)for Treatment of Pervasive Developmental Disorder Not Otherwise Specified and Asperger’s Disorder. (2012)
  • 著者名/発表者名: Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, Tsuchie K, Inagaki T and Horiguchi J
  • 雑誌名: BMC Psychiatry 巻: 12(1) ページ: 215-215
  • 査読あり
• [雑誌論文] Minocycline as adjunctive therapy for patients with unipolar psychoatic depression: An open-label study (2012)
  • 著者名/発表者名: Tsuyoshi Miyaoka et al.
  • 雑誌名: Progress in Neuro-Psychopharmacology & Biological Psychiatry 巻: 37 ページ: 222-226
  • 査読あり
• [雑誌論文] Morphological features of microglial cells in the hippocampal dentate gyrus of Gunn rat: a possible schizophrenia animal model (2012)
  • 著者名/発表者名: Kristian Liaury, Tsyuyoshi Miyaoka
  • 雑誌名: Journal of Neuroinflammation 巻: 9 号: 1 ページ: 56-56
  • DOI: 10.1186/1742-2094-9-56
  • 査読あり
• [学会発表] Efficacy and safety of yokukansan (TJ-54) for treatment-resistant schizophrenia : a randomised placebo-controlled trial (2013)
  • 著者名/発表者名: Miyaoka T, Furuya M, Horiguchi J, Wake R, Hayashida S, Toyama M, Daimon T, Mori N, Minabe Y, Iyo M
  • 学会等名: 26th ECNP
  • 発表場所: Barcelona, Spain
• [学会発表] Comorbidity between Neuroinflammatory Disorders and Depression (2013)
  • 著者名/発表者名: Miyaoka T
  • 学会等名: The 4th World Congress of Asian Psychiatry
  • 発表場所: Bangkok, Thailand
• [学会発表] The correlation between psychiatric symptoms and regional cerebral blood flow in first episode schizophrenia patients (2013)
  • 著者名/発表者名: Wake R, Miyaoka T, Kawakami K, Furuya M, Liaury K, Hashioka S, Horiguchi J
  • 学会等名: 11th World Congress of Biological Psychiatry
  • 発表場所: Kyoto
• [学会発表] The correlation between psychiatric symptoms and regional cerebral blood flow in first episode schizophrenia patients (2013)
  • 著者名/発表者名: Wake R, Miyaoka T, Kawakami K, Furuya M, Liaury K, Hashioka S, Horiguchi J
  • 学会等名: 11th World Congress of Biological Psychiatry
  • 発表場所: (Kyoto) Japan
• [学会発表] Anti-inflammatory treatments of unipolar depression and bipolar desorder (2013)
  • 著者名/発表者名: Miyaoka T
  • 学会等名: 11th World Congress of Biological Psychiatry
  • 発表場所: Kyoto
• [学会発表] Comorbidity of depression with neuro-inflammatory disorders (2013)
  • 著者名/発表者名: Miyaoka T
  • 学会等名: 11th World Congress of Biological Psychiatry
  • 発表場所: Kyoto
• [学会発表] The Effects of Minocycline on Microglial Cells in The Dentate Gyrus of Gunn Rat―A Possible Animal Model of Schizophrenia― (2013)
  • 著者名/発表者名: Liaury K, Miyaoka T, Tsumori T, Wake R, Furuya M, Ieda M, Tsuchie K, Fukushima M, A J Tanra, Horiguchi J
  • 学会等名: 第28回日本老年精神医学会
  • 発表場所: 大阪
• [学会発表] Efficacy and Safety of Yokukansan (TJ-54) for Treatment-Resistant Schizophrenia : A Randomized, Multi-centre, Double-blind, Placebo-controlled Trial (2013)
  • 著者名/発表者名: Miyaoka T, Furuya M, Horiguchi J, Wake R, Hashioka J, Toyama M, Daimon T, Mori N, Minabe Y, Iyo M, Ueno S, Ezoe S, Hoshino S, Seno H
  • 学会等名: Society of Biological Psychiatry 68th Annual Meeting
  • 発表場所: (San Francisco) California
• [学会発表] Yokukansan (TJ-54) for Irritability Associated with Pervasive Developmental Disorder in Children and Adolescents A 12-week Prospective, Open-label Study (2013)
  • 著者名/発表者名: Wake R, Miyaoka T, Inagaki T, Furuya M, Ieda M, Liaury K, Kishi K, Horiguchi J
  • 学会等名: The 7th Annual Scientific Meeting Hong Kong Society of Biological Psychiatry
  • 発表場所: Hong Kong
• [学会発表] Yokukansan (TJ-54)For Treatment Of Very-Late-Onset Schizophrenia-Like Psychosis : An Open-Label Study (2013)
  • 著者名/発表者名: Miyaoka T
  • 学会等名: The 3rd ASIAN CONGRESS ON SCHIZOPHRENIA RESEARCH(ACSR2013)
  • 発表場所: Sanur, Bali, Indonesia
• [学会発表] Yokukansan Promote Hippocampal Neurogenesis Through The Inhibition of Microglial Activation in Rodents with Hyperbillirubinemia : a neuroinflammational animal model of schizophrenia (2013)
  • 著者名/発表者名: Furuya M, Miyaoka T, Tsumori T, Hashioka S, Wake R, Liaury K, Ieda M, Ishihara K, Tsuchie K, Fukushima M, Araki T, Ezoe S, Horiguchi J
  • 学会等名: The 3rd ASIAN CONGRESS ON SCHIZOPHRENIA RESEARCH(ACSR2013)
  • 発表場所: Sanur, Bali, Indonesia
• [学会発表] Yokukansan(TJ-54)for Irritability Associated with Pervasive Developmental Disorder in Children and Adolescents A 12-week Prospective, Open-Label Study. (2013)
  • 著者名/発表者名: Wake R, Miyaoka T, Inagaki T, Furuya M, Ieda M, Liaury K, Kishi K, Horiguchi J
  • 学会等名: The 7th Annual Scientific Meeting Hong Kong Society of Biological Psychiatry.
  • 発表場所: (Hong Kong) Eaton
  • 招待講演
• [学会発表] Efficacy and Safety of Yokukansan(TJ-54) for Treatment-Resistant Schizoohrenia: A Randmized,Multi-centre, Double-blind, Placebo-controlledTrial. (2013)
  • 著者名/発表者名: Miyaoka T, Furuya M, Horiguchi J, Wake R, Hashioka S, Toyama M, Daimon T, Mori N, Minabe Y, Iyo M, Ueno S, Ezoe S, Hoshino S, Seno H
  • 学会等名: Society of Biological Osychiatry 68th Annual Meeting
  • 発表場所: (San Francisco California) Hilton Union Square
• [学会発表] Comorbidity between Neuroinflammatory Disorders and Depression. (2013)
  • 著者名/発表者名: Miyaoka T
  • 学会等名: The 4th World Conressof Asian Psychiatry
  • 発表場所: (Bangkok Thailand) Centara Grand at Central Worid
  • 招待講演
• [学会発表] Efficacy and safety of yokukansan(TJ-54) for treatment-resistant schizophrenia:a randmised placebo-controlled trial. (2013)
  • 著者名/発表者名: Miyaoka T, Furuya M, Horiguchi J, Wake R, Hayashida M, Toyama M, Daimon T, Mori N, Minabe Y, Iyo M
  • 学会等名: 26th ECNP
  • 発表場所: (Barcelona Spain) Catalunya Paul
• [学会発表] Yokukansan(TJ-54)for treatment of very-late onset shizophrenia-like psychosis:an open-label study. (2012)
  • 著者名/発表者名: Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, Tsuchie K, Fukushima M, Ishihara K, Araki T, Hashioka S, Horiguchi J
  • 学会等名: 12th Annual Meeting of the International College of Geriatric Psychoneuropharmacology
  • 発表場所: Spain(Sevilia)