The bioenergetic dysfunction in ASD focusing on free radicals

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K21754
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 9:Education and related fields
• Research Institution: University of Fukui
• Principal Investigator: MATSUZAKI HIDEO 福井大学, 子どものこころの発達研究センター, 教授 (00334970)
• Co-Investigator(Kenkyū-buntansha): 平山 暁 筑波技術大学, 保健科学部, 教授 (20323298)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 自閉症 / 酸化ストレス / 社会性 / フリーラジカル

Outline of Final Research Achievements

We assessed oxidative stress alterations in autism spectrum disorder (ASD) by the MULTIS method, an electron spin resonance-based technique measuring multiple free radical scavenging activities simultaneously. Serum samples of 39 children with ASD and 58 age-matched children with typical development were analyzed.
The ASD group showed decreased hydroxyl radical and singlet oxygen scavenging activity with increased serum coenzyme Q10 oxidation rate, indicating a prooxidative tendency in ASD. By contrast, scavenging activities against superoxide and alkoxyl radical were increased in the ASD group suggesting antioxidative shifts. In the subgroup analysis of 6-year-olds or younger, the combination of hydroxyl radical, superoxide, and alkoxyl radical scavenging activities predicted ASD with high odds ratio, positive likelihood, and percentage of correct classification (87.0%). MULTIS measurements may serve as a very powerful non-behavioral tool for the diagnosis of ASD in children.

Free Research Field

分子精神医学

Academic Significance and Societal Importance of the Research Achievements

自閉スペクトラム症（ASD）は社会性・コミュニケーションの障害、興味対象の制限を臨床的特徴とする発達障害であるが、病態機序が不明で、ASDの早期診断に資するバイオマーカーは未だ存在しない（Uddin et al Transl Psychiatry 2017）。本研究で採用するフリーラジカル消去活性をふくむ多変量解析とコホートの組み合わせはASD研究の方法論としてこれまでに例がなく、この手法で特異度、敏感度、再現性の高いASD早期診断マーカーが確立できた場合、世界初の血液によるASD早期診断ツールの開発、予測に基づく早期介入が可能になる。ひいてはASD者の社会適応の促進につながる点も有益である。