A study on the development of biological "veryearly"diagnosis of autism

自闭症生物学“常年”诊断的进展研究

• 批准号: 22390222
• 负责人: MORI Norio
• 金额: $ 12.31万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390222/
• 关键词: 児童・思春期精神医学; 自閉症; バイオマーカー; サイトカイン; コホート研究; Copy number variation

The aim of the study was to explore biological markers in peripheral plasmasamples from non-medicated subjects with high-functioning ASD.(Experiment 1) A multiplex assay for cytokines and chemokines was applied to plasma samples frommale subjects with high-functioning ASD (n = 28) and matched controls (n = 28). Among a total of 48 analytes examined, theplasma concentrations of IL-1β, IL-1RA, IL-5, IL-8, IL-12(p70), IL-13, IL-17 and GRO-αwere significantly higher in subjects withASD compared with the corresponding values of matched controls after correction for multiple comparisons.(Experiment 2) Plasma levels of 25 amino acids in male children (n= 23) with ASDand matchedcontrols (n= 22) were determined using high-performance liquid chromatography. Compared with controls, subjects with ASD showed higher levels of plasmaglutamate and lower levels of plasma glutamine. Using discriminantanalysis with logistic regression, the two values of plasma glutamate and glutamine were shown to differentiate theASDgroup from the control group; the rate of correct classification was 91%.Theseresults suggest that abnormal immune responses as assessed by multiplex analysis and plasma glutamate and glutamine levelsmay serve as the biological markers for ASD.

本研究的目的是探索来自未接受药物治疗的高功能 ASD 受试者的外周血浆样本中的生物标志物。（实验 1）对来自患有高功能 ASD 的男性受试者 (n = 28) 和匹配对照 (n = 28) 的血浆样本应用细胞因子和趋化因子的多重检测。在总共检测的 48 种分析物中，经多重比较校正后，自闭症患者血浆中 IL-1β、IL-1RA、IL-5、IL-8、IL-12(p70)、IL-13、IL-17 和 GRO-α 的浓度显着高于匹配对照的相应值。（实验 2）患有自闭症谱系障碍的男孩（n=23）的 25 种氨基酸的血浆水平 使用高效液相色谱法测定 ASD 和匹配对照 (n = 22)。与对照组相比，自闭症谱系障碍患者的血浆谷氨酸水平较高，而血浆谷氨酰胺水平较低。使用逻辑回归判别分析，血浆谷氨酸和谷氨酰胺的两个值被证明可以区分 ASD 组和对照组；正确分类率为91%。这些结果表明，通过多重分析和血浆谷氨酸和谷氨酰胺水平评估的异常免疫反应可以作为自闭症谱系障碍的生物标志物。

项目成果

Alteration of plasma glutamate and glutamine levels in children with high-functioning autism.

• DOI: 10.1371/journal.pone.0025340
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Shimmura C;Suda S;Tsuchiya KJ;Hashimoto K;Ohno K;Matsuzaki H;Iwata K;Matsumoto K;Wakuda T;Kameno Y;Suzuki K;Tsujii M;Nakamura K;Takei N;Mori N
• 通讯作者: Mori N

Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism.

• DOI: 10.1186/2040-2392-4-6
• 发表时间: 2013-03-26
• 期刊: Molecular autism
• 影响因子: 6.2
• 作者: Shimmura C;Suzuki K;Iwata Y;Tsuchiya KJ;Ohno K;Matsuzaki H;Iwata K;Kameno Y;Takahashi T;Wakuda T;Nakamura K;Hashimoto K;Mori N
• 通讯作者: Mori N

Microglial Activation in Young Adults With Autism Spectrum Disorder

• DOI: 10.1001/jamapsychiatry.2013.272
• 发表时间: 2013-01-01
• 期刊: JAMA PSYCHIATRY
• 影响因子: 25.8
• 作者: Suzuki, Katsuaki;Sugihara, Genichi;Mori, Norio
• 通讯作者: Mori, Norio

Elevated Transcription Factor Specificity Protein 1 in Autistic Brains Alters the Expression of Autism Candidate Genes

• DOI: 10.1016/j.biopsych.2011.09.020
• 发表时间: 2012-03-01
• 期刊: BIOLOGICAL PSYCHIATRY
• 影响因子: 10.6
• 作者: Thanseem, Ismail;Anitha, Ayyappan;Mori, Norio
• 通讯作者: Mori, Norio

自閉症死後脳縫線核メチル化状態の網羅的解析

自闭症死后脑中缝核甲基化状态综合分析

• 发表时间: 2016
• 作者: 松﨑秀夫;岩田圭子;中林一彦;中村和彦;秦健一郎;森則夫
• 通讯作者: 森則夫