Antioxidant system and medical treatnment in social impairment of autism spectrum disprders

• Project/Area Number: 26461777
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kyoto University (2016-2017); Dokkyo Medical University (2015); Ashiya University (2014)
• Principal Investigator: Yui Kunio 京都大学, 医学研究科, 客員研究員 (90101352)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); 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)
• Keywords: 自閉症スペクトラム障害 / 社会性障害 / 酸化ストレス / 抗酸化能 / TAC / HEL / 8-OHdG / superoxide disnutase / 効果サイズ / 自閉スペクトラム / 抗酸化タンパク / セルロプラスミン / トランスフェリン / 臨床モデル / 結節性硬化症 / 難治性症状の改善 / 根治薬への架橋 / ceruloplasmine（Cp) / アラキドン酸 / 結節硬化症 / Cpの血漿濃度 / 病態と治療とCp / ＴＡＣ / ceruloplasmin

Outline of Final Research Achievements

Oxidant/antioxidant imbalance may contribute to the pathophysiology of autism spectrum disorder (ASD). The ASD group exhibited significantly lower urinary TAOC levels and significantly elevated urinary HEL levels than the control group. Urinary 8-OHdG levels and plasma SOD levels were not significantly different between the groups. Standardized regression coefficients revealed that TAOC levels had a larger effect size than HEL levels in urine. This study firstly reveals that an imbalance between urinary HEL and TAOC levels in favor of urinary TAOC levels may contribute to impaired social responsiveness in individuals with ASD.

Research Products

• [Journal Article] Therapeutic potential of everolimus on core autism symptoms and (2018)
  • Author(s): Yui k, Imataka G,Toru Okanishi T, Oka H,and Kawasaki Y
  • Journal Title: J Neonatal Pediatr Med Volume: 3 Issue: 01 Pages: 112-118
  • DOI: 10.4172/2572-4983.1000128
  • Peer Reviewed
• [Journal Article] The role of antioxidant proteins in improvement of autism core symptoms in two patients with tuberous sclerosis treated with mTOR inhibitor everolimus (2018)
  • Author(s): Yui K, Sasaki H, Imataka G, Okanishi T
  • Journal Title: Global Med Ther Volume: 1 Pages: 12-18
  • Peer Reviewed
• [Journal Article] The role of imbalance between urinary hexanoyl-lysine and total antioxidant capacity levels and its relation to plasma superoxide dismutase levels in autism spectrum disorder (2018)
  • Author(s): Yui K, Sasaki H, Tanuma N
  • Journal Title: Global Med Ther Volume: 1 Pages: 34-40
  • Peer Reviewed
• [Journal Article] Reduced endogenous urinary total antioxidant power and its relation of plasma antioxidant activity of superoxide dismutase in individuals with autism spectrum disorder. (2017)
  • Author(s): Yui K, Tanuma N, Yamada H, Kawasaki Y
  • Journal Title: Int J Dev Neurosci Volume: 60 Issue: 02 Pages: 70-77
  • DOI: 10.4172/2375-4494.1000e118
  • Peer Reviewed
• [Journal Article] Decreased total antioxidant capacity has a larger effect size than increased oxidant levels in urine in individuals with autism spectrum disorder. (2016)
  • Author(s): Yui K, Tanuma N, Yamada H, Kawasaki Y.
  • Journal Title: Environ Sci Pollut Res Int. Volume: 24 Issue: 10 Pages: 9635-9644
  • DOI: 10.1007/s11356-017-8595-3
  • Peer Reviewed
• [Journal Article] Reduced endogenous urinary total antioxidant power and its relation of plasma antioxidant activity of superoxide dismutase in individuals with autism spectrum disorder. (2016)
  • Author(s): Yui K, Tanuma N, Yamada H, Kawasaki Y.
  • Journal Title: Int J Dev Neurosci. Volume: 2016 Issue: 1 Pages: 0736-5748
  • DOI: 10.1016/j.ijdevneu.2016.08.003
  • Peer Reviewed
• [Journal Article] Psycho-Cognitive Intervention for ASD from Cross-Species Behavioral Analyses of Infants, Chicks and Common Marmosets. (2016)
  • Author(s): Koshiba M, Karino G, Mimura K, Nakamura S, Yui K, Kunikata T, Yamanouchi H.
  • Journal Title: CNS Neurol Disord Drug Targets. Volume: 15 Pages: 578-86
  • Peer Reviewed
• [Journal Article] Oxidative Stress and Nitric Oxide in Autism Spectrum Disorder and Other Neuropsychiatric Disorders. (2016)
  • Author(s): Yui K, Kawasaki Y, Yamada H, Ogawa S.
  • Journal Title: CNS Neurol Disord Drug Targets. Volume: 15 Pages: 587-96
  • Peer Reviewed
• [Journal Article] Increased ω-3 polyunsaturated fatty acid/arachidonic acid ratios and upregulation of signaling mediator in individuals with autism spectrum disorders. (2016)
  • Author(s): Yui K, Imataka G, Kawasaki Y.
  • Journal Title: Med Chem. Volume: 12 Pages: 318-27
  • Peer Reviewed
• [Journal Article] Down-regulation of a signaling mediator in association with lowered plasma arachidonic acid levels in individuals with autism spectrum disorders. (2016)
  • Author(s): Yui K, Imataka G, Kawasak Y, Yamada H.
  • Journal Title: Neurosci Lett. Volume: 1610 Pages: 223-8
  • Peer Reviewed
• [Journal Article] Mitochondrial Dysfunction and Its Relationship with mTOR Signaling and Oxidative Damage in Autism Spectrum Disorders. (2016)
  • Author(s): Yui K, Imataka G, Nakamura H, Ohara N, Naito Y.
  • Journal Title: Curr Neuropharmacol. Volume: 13 Pages: 776-85
  • Peer Reviewed
• [Journal Article] 自閉症スペクトラム障害の病態類型とバイオマーカー、治療方向性。 (2016)
  • Author(s): 油井邦雄
  • Journal Title: 日本生物学的精神医学会誌、26, 146-153, 2015 Volume: ２６ Pages: 143-152
  • NAID: 130005395607
  • Peer Reviewed
• [Journal Article] オメガー６脂肪酸アタキドン酸のシグナリング調整と自閉症スペクトラム障害の中核症状の改善 (2016)
  • Author(s): 油井邦雄、川崎洋平、山田浩
  • Journal Title: 日本生物学的精神医学会誌 Volume: 27 Pages: 41-47
  • Peer Reviewed
• [Journal Article] 自閉症スペクトラム障害の病態類型とバイオマーカー、治療方向性 (2016)
  • Author(s): 油井邦雄
  • Journal Title: 日本生物学的精神医学会誌 Volume: 26 Pages: 146-153
  • NAID: 130005395607
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Down-regulation of a signaling mediator in association with lowered plasma arachidonic acid levels in individuals with autism spectrum disorders. (2016)
  • Author(s): Yui K, Imataka G, Kawasaki Y, Yamada H.
  • Journal Title: eurosci Lett Volume: 610 Pages: 223-228
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased ω-3 polyunsaturated fatty acid/arachidonic acid ratios and upregulation of signaling mediator in individuals with autism spectrum disorders (2016)
  • Author(s): Yui K, Imataka G, Kawasak Y, Yamada H
  • Journal Title: Life Sci Volume: 145 Pages: 205-212
  • Peer Reviewed / Open Access
• [Journal Article] Mitochondrial Dysfunction and Its relation to mTOR signaling, and oxidative damege in autism spectrum disprders (2015)
  • Author(s): Yui K, Berk M
  • Journal Title: Mini Rev Med Chem. Volume: 15 Pages: 373-389
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Eicosanoids Derived From Arachidonic Acid and Their Family Prostaglandins and Cyclooxygenase in Psychiatric Disorders. (2015)
  • Author(s): Yui K, Imataka G, Nakamura H, Ohara N, Naito Y
  • Journal Title: Curr Neuropharmacol. Volume: 13
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 自閉症スペクトラム障害の病態類型とバイオマーカー、治療方向性 (2015)
  • Author(s): 油井邦雄
  • Journal Title: 日本生物精神医学会誌 Volume: 26
  • NAID: 130005395607
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mitochondrial Dysfunction and its Relationship with mTOR Signaling and Oxidative Damage in Autism Spectrum Disorders (2015)
  • Author(s): Kunio Yui, Atsushi Sato, George Imataka
  • Journal Title: MiniReview Medicinal Chemistry Volume: 15 Issue: 5 Pages: 373-378
  • DOI: 10.2174/1389557515666150324122930
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Eicosanoids Derived From Arachidonic Acid and Their Family Prostaglandins and Cyclooxygnase in Psychiatric Disorders (2015)
  • Author(s): Kunio Yui1, George Imataka, Hiroyuki Nakamura, Naoki Ohara, Yukiko Naito
  • Journal Title: Current Neuropharmacology Volume: 14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 脳ペプタイドに関わる精神神経疾患の病態と治療的展望：ミトコンドリアの機能障害との関連 (2014)
  • Author(s): 油井邦雄
  • Journal Title: 日本生物精神医学会誌 Volume: 25 Pages: 85-89
  • NAID: 130005395535
  • Peer Reviewed
• [Presentation] 精神神経疾患の新しい治療薬の展望 (2016)
  • Author(s): 油井邦雄
  • Organizer: 第３６回日本生物学的精神医学会
  • Place of Presentation: 東京都船堀
  • Year and Date: 2016-10-12
  • Invited
• [Presentation] 自閉症スペクトラム障害における情報伝達タンパクの機能不全の修復 による治療効果 (2016)
  • Author(s): 油井邦雄
  • Organizer: 第１１２回日本精神神経学会
  • Place of Presentation: 千葉県幕張メッセ
  • Year and Date: 2016-09-29
  • Invited
• [Presentation] 精神疾患の病態検索とそれにもとづく治療の効果 (2016)
  • Author(s): 油井邦雄
  • Organizer: 第112回日本精神神経学会
  • Place of Presentation: 東京都
  • Year and Date: 2016-06-01
  • Invited
• [Presentation] Omega－６脂肪酸によるシグナリング調整と自閉症スペクトラム障害の治療 (2015)
  • Author(s): 油井邦雄
  • Organizer: 第45回日本神経精神薬理学会ｍ第37回日本生物精神医学会、シンポジウム
  • Place of Presentation: 東京都
  • Year and Date: 2015-09-24 – 2015-09-26
• [Presentation] 精神疾患における新規シグナル伝達経路と治療的展開 (2015)
  • Author(s): 油井邦雄
  • Organizer: 第37回日本生物学的精神医学会
  • Place of Presentation: 東京都
  • Year and Date: 2015-09-24
  • Invited
• [Presentation] 自閉症スペクトラム障害の抗酸化能と治療的展開 (2014)
  • Author(s): 油井邦雄
  • Organizer: 第44回日本神経精神薬理学会、第24回日本臨床精神神経薬理学会、シンポジウム
  • Place of Presentation: 名古屋市
  • Year and Date: 2014-11-21
• [Presentation] アラキドン酸による自閉症スペクトラム障害の治療効果 (2014)
  • Author(s): 油井邦雄
  • Organizer: 第36回生物学的精神医学会、シンポジウム
  • Place of Presentation: 奈良市
  • Year and Date: 2014-09-30
• [Presentation] アラキドン酸を主としたomega-６/DHAを主としたomega-３の含有比が4：1の製品の社会性障害の著名改善 (2014)
  • Author(s): 油井邦雄
  • Organizer: 第110回日本精神神経学会 シンポジウム
  • Place of Presentation: 横浜市
  • Year and Date: 2014-06-27