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

• Project/Area Number: 22390222
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: MORI Norio 浜松医科大学, 医学部, 教授 (00174376)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Katsuaki 浜松医科大学, 医学部, 准教授 (00285040) ; TSUCHIYA Kenji 浜松医科大学, 子どものこころの発達研究センター, 准教授 (20362189) ; MINOSHIMA Shinsei 浜松医科大学, メディカルフォトニクス研究センター, 教授 (90181966) ; 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) ; NAKAMURA Kazuhiko 弘前大学, 医学系研究科, 教授 (80263911)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2010: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
• Keywords: 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

Research Abstract

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.

Research Products

• [Journal Article] Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism (2013)
  • Author(s): 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
  • Journal Title: Mol Autism Volume: 4(1) Pages: 6-6
• [Journal Article] Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism. (2013)
  • Author(s): Shimmura C
  • Journal Title: Mol Autism Volume: 4 Pages: 6-6
  • DOI: 10.1186/2040-2392-4-6
  • Peer Reviewed
• [Journal Article] Microglial activation in young adults with autism spectrum disorder. (2013)
  • Author(s): Suzuki K
  • Journal Title: JAMA Psychiatry. Volume: 70 Pages: 49-5
  • DOI: 10.1001/jamapsychiatry.2013.272
  • Peer Reviewed
• [Journal Article] Downregulation of the Expression of Mitochondrial Electron Transport Complex Genes in Autism Brains. (2013)
  • Author(s): Anitha A, Nakamura K, Thanseem I, Matsuzaki H, Miyachi T, Tsujii M, Iwata Y, Suzuki K, Sugiyama T, Mori N.
  • Journal Title: Brain Pathology Volume: 23 Pages: 294-302
  • DOI: 10.1111/bpa.12002
  • Peer Reviewed
• [Journal Article] Protocadherin α (PCDHA) as a novel susceptibility gene for autism. (2013)
  • Author(s): Anitha A, Thanseem I, Nakamura K, Yamada K, Iwayama Y, Toyota T, Iwata Y, Suzuki K, Sugiyama T, Tsujii M, Yoshikawa T, Mori N.
  • Journal Title: J Psychiatry Neurosci Volume: 38 Pages: 192-198
  • DOI: 10.1503/jpn.120058
  • Peer Reviewed
• [Journal Article] Brain region-specific altered expression and association of mitochondria-related genes in autism (2012)
  • Author(s): Anitha A, Nakamura K, Thanseem I, Yamada K, Iwayama Y, Toyota T, Matsuzaki H, Miyachi T, Yamada S, Tsujii M, Tsuchiya KJ, Matsumoto K, Iwata Y, Suzuki K, Ichikawa H, Sugiyama T, Yoshikawa T, Mori N
  • Journal Title: Mol Autism. Volume: 3(1) Pages: 12-12
• [Journal Article] Elevated transcription factor specificity protein 1 in autistic brains alters the expression of autism candidate genes (2012)
  • Author(s): Thanseem I, Anitha A, Nakamura K, Suda S, Iwata K, Matsuzaki H, Ohtsubo M, Ueki T, Katayama T, Iwata Y, Suzuki K, Minoshima S, Mori N
  • Journal Title: Biol Psychiatry Volume: 71(5) Pages: 410-8
• [Journal Article] Brain-region specific altered expression, and association of mitochondria-related genes in autism. (2012)
  • Author(s): Anitha A
  • Journal Title: Mol Autism Volume: 3 Pages: 12-12
  • DOI: 10.1186/2040-2392-3-12
  • Peer Reviewed
• [Journal Article] Investigation of the serum levels of anterior pituitary hormones in male children with autism (2011)
  • Author(s): Iwata K, Matsuzaki H, Miyachi T, Shimmura C, Suda S, Tsuchiya KJ, Matsumoto K, Suzuki K, Iwata Y, Nakamura K, Tsujii M, Sugiyama T, Sato K, Mori N
  • Journal Title: Mol Autism Volume: 2 Pages: 16-16
• [Journal Article] Alteration of plasma glutamate and glutamine levels in children with high-functioning autism (2011)
  • Author(s): 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
  • Journal Title: PLoS One Volume: 6(10)
• [Journal Article] Association of transcription factor gene LMX1B with autism (2011)
  • Author(s): Thanseem I, Nakamura K, Anitha A, Suda S, Yamada K, Iwayama Y, Toyota T, Tsujii M, Iwata Y, Suzuki K, Matsuzaki H, Iwata K, Sugiyama T, Yoshikawa T, Mori N
  • Journal Title: PLoS One Volume: 6(8)
• [Journal Article] Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism (2011)
  • Author(s): Suda S, Iwata K, Shimmura C, Kameno Y, Anitha A, Thanseem I, Nakamura K, Matsuzaki H, Tsuchiya KJ, Sugihara G, Iwata Y, Suzuki K, Koizumi K, Higashida H, Takei N, Mori N
  • Journal Title: Mol Autism Volume: 2(1) Pages: 14-14
• [Journal Article] Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders (2011)
  • Author(s): Suzuki K, Matsuzaki H, Iwata K, Kameno Y, Shimmura C, Kawai S, Yoshihara Y, Wakuda T, Takebayashi K, Takagai S, Matsumoto K, Tsuchiya KJ, Iwata Y, Nakamura K, Tsujii M, Sugiyama T, Mori N.
  • Journal Title: PLoS One Volume: 6(5)
• [Journal Article] Replication study of Japanese cohorts supports the role of STX1A in autism susceptibility (2011)
  • Author(s): Nakamura K, Iwata Y, Anitha A, Miyachi T, Toyota T, Yamada S, Tsujii M, Tsuchiya KJ, Iwayama Y, Yamada K, Hattori E, Matsuzaki H, Matsumoto K, Suzuki K, Suda S, Takebayashi K, Takei N, Ichikawa H, Sugiyama T, YoshikawaT, Mori N
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 35(2) Pages: 454-8
• [Journal Article] The HBC Study Team. Age-specific 3-month cumulative incidence of postpartum depression: The Hamamatsu Birth Cohort (HBC) Study. (2011)
  • Author(s): Matsumoto K, Tsuchiya KJ, Itoh H, Kanayama N, Suda S, Matsuzaki H, Iwata Y, Suzuki K, Nakamura K, Mori N, Takei N; The HBC Study Team
  • Journal Title: J Affect Disord Volume: 133 Pages: 607-610
  • DOI: 10.1016/j.jad.2011.04.024
  • Peer Reviewed
• [Journal Article] Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders (2011)
  • Author(s): Suzuki K, Matsuzaki H, Iwata K, Kameno Y, Shinmura C, Kawai S, Yoshihara Y, Wakuda T, Takebayashi K, Takagai S, Matsumoto K, Tsuchiya KJ, Iwata Y, Nakamura K, Tsujii M, Sugiyama S, Mori N
  • Journal Title: PLoS One Volume: 6(5)
  • DOI: 10.1371/journal.pone.0020470
  • Peer Reviewed
• [Journal Article] Further evidence for the role of MET in autism susceptibility (2010)
  • Author(s): Thanseem I, Nakamura K, Miyachi T, Toyota T, Yamada S, Tsujii M, Tsuchiya KJ, AnithaA, Iwayama Y, Yamada K, Hattori E, Matsuzaki H, Matsumoto K, Iwata Y, Suzuki K, Suda S, Kawai M, Sugihara G, Takebayashi K, Takei N, Ichikawa H, Sugiyama T, Yoshikawa T, Mori N
  • Journal Title: Neurosci Res Volume: 68(2) Pages: 137-41
• [Journal Article] Decreased serum levels ofadiponectin in subjects with autism (2010)
  • Author(s): Fujita-Shimizu A, Suzuki K, Nakamura K, Miyachi T, Matsuzaki H, Kajizuka M,Shinmura C, Iwata Y, Suda S, Tsuchiya KJ, Matsumoto K, Sugihara G, Iwata K,Yamamoto S, Tsujii M, Sugiyama T, Takei N, Mori N.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 34(3) Pages: 455-8
• [Journal Article] Decreased serum levels of adiponectin in subjects with autism. (2010)
  • Author(s): Fujita-Shimizu A, Suzuki K, Nakamura K, Miyachi T, Matsuzaki H, Kajizuka M, Shinmura C, Iwata Y, Suda S, Tsuchiva KJ, Matsumoto K, Sugihara G, Iwata K, Yamamoto S, Tsujii M, Sugiyama T, Takei N, Mori N.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 34(3) Pages: 455-458
  • Peer Reviewed
• [Journal Article] Two genetic variants of CD38 in subjects with autism spectrum disorder and controls. (2010)
  • Author(s): Munesue T, Yokoyama S, Nakamura K, Anitha A, Yamada K, Hayashi K, Asaka T, Liu HX, Jin D, Koizumi K, Islam MS, Huang JJ, Ma WJ, Kim UH, Kim SJ, Park K, Kim D, Kikuchi M, Ono Y, Nakatani H, Suda S, Miyachi T, Hirai H, Salmina A, Pichugina YA, Soumarokov AA, Takei N, Mori N, et al.
  • Journal Title: Neurosci Res Volume: 67(2) Pages: 181-191
  • Peer Reviewed
• [Journal Article] Further evidence for the role of MET in autism susceptibility. (2010)
  • Author(s): Thanseem I, Nakamura K, Miyachi T, Toyota T, Yamada S, Tsujii M, Tsuchiya KJ, Anitha A, Iwayama Y, Yamada K, Hattori E, Matsuzaki H, Matsumoto K, Iwata Y, Suzuki K, Suda S, Kawai M, Sugihara G, Takebayashi K, Takei N, Ichikawa H, Sugiyama T, Yoshikawa T, Mori N.
  • Journal Title: Neurosci Res Volume: 68(2) Pages: 137-141
  • Peer Reviewed
• [Presentation] 自閉症死後脳縫線核メチル化状態の網羅的解析 (2012)
  • Author(s): 岩田圭子, 中林一彦, 松崎秀夫, 中村和彦, 秦健一郎, 森則夫
  • Organizer: 第39回日本脳科学会.
  • Place of Presentation: 北九州市
  • Year and Date: 2012-10-06
• [Presentation] 自閉症死後脳縫線核メチル化状態の網羅的解析 (2012)
  • Author(s): 岩田 圭子, 中林 一彦, 松崎 秀夫, 中村 和彦, 秦 健一郎, 森 則夫
  • Organizer: 第39回日本脳科学会
  • Place of Presentation: 北九州市
• [Presentation] 「精神障害の予防は可能か?」-自閉症・統合失調症の早期診断と早期介入- (2011)
  • Author(s): 森則夫
  • Organizer: 第106回日本小児精神神経学会
  • Place of Presentation: 浜松
  • Year and Date: 2011-11-26
• [Presentation] バイオマーカーからみた自閉症スペクトラム障害 (2010)
  • Author(s): 鈴木勝昭
  • Organizer: 第104回小児精神神経学会
  • Place of Presentation: 徳島
  • Year and Date: 2010-11-14