Clarification of pathophysiology of autism related to single-incidence family and multiple-incidence families by combining brain imaging study and CNV analysis study

• Project/Area Number: 23390288
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Hirosaki University (2013); Hamamatsu University School of Medicine (2011-2012)
• Principal Investigator: NAKAMURA KAZUHIKO 弘前大学, 医学(系)研究科(研究院), 教授 (80263911)
• Co-Investigator(Kenkyū-buntansha): OUCHI Yasuomi 浜松医科大学, 学内共同利用施設等, 教授 (40436978) ; TSUZII Masatsugu 中京大学, 現代社会学部, 教授 (20257546) ; IWATA Yasuhide 浜松医科大学, 医学部附属病院, 講師 (10285025) ; SUZUKI Katsuaki 浜松医科大学, 学内共同利用施設等, 准教授 (00285040) ; MORI Norio 浜松医科大学, 医学部, 教授 (00174376) ; TAKEBAYASHI Kiyokazu 浜松医科大学, 医学部附属病院, 講師 (50397428) ; 吉原 雄二郎 浜松医科大学, 医学部, 研究員 (00529464)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 児童・思春期精神医学 / 自閉症 / CNV解析 / トリオサンプル / CNV

Research Abstract

Among the 203 trio autism families, 191 were simplex, while the remaining 12 were multiplex. The samplese were analyzed using Affymetrix Genome-Wide Human SNP Nsp/Sty 6.0 microarray. Among a total of 7305 CNVs detected in affected children after all QC corrections, 3728 were found to be affecting genes. 89.6% of these were confirmed to be inheited from parents. Among the remaining 378 CNVs, 17 novel/ultra-rare de novo events were identified.Novel deletions were observed in genes involved in neurodevelopmental pathways such as SHANK3 et al..

Research Products

• [Journal Article] Zinc finger protein 804A (ZNF804A) and verbal deficits in individuals with autism (2014)
  • Author(s): Anitha A, Thanseem I, Nakamura K, Vasu MM, Yamada K, Ueki T, Iwayama Y, Toyota T, Tsuchiya KJ, Iwata Y, Suzuki K, Sugiyama T, Tsujii M, Yoshikawa T, Mori N
  • Journal Title: J Psychiatry Neurosci Volume: 39 Pages: 130126-130126
  • Peer Reviewed
• [Journal Article] N-ethylmaleimide-sensitive factor interacts with the serotonin transporter and modulates its trafficking: implications for pathophysiology in autism (2014)
  • Author(s): Iwata K, Matsuzaki H, Tachibana T, Ohno K, Yoshimura S, Takamura H, Yamada K, Matsuzaki S, Nakamura K, Tsuchiya KJ, Matsumoto K, Tsujii M, Sugiyama T, Katayama T, Mori N
  • Journal Title: Mol Autism 2014 10 Volume: 5 Pages: 33-33
  • Peer Reviewed
• [Journal Article] Serum levels of soluble platelet endothelial cell adhesion molecule-1 and vascular cell adhesion molecule-1 are decreased in subjects with autism spectrum disorder (2013)
  • Author(s): Kameno Y, Iwata K, Matsuzaki H, Miyachi T, Tsuchiya KJ, Matsumoto K, Iwata Y, Suzuki K, Nakamura K, Maekawa M, Tsujii M, Sugiyama T, Mori N
  • Journal Title: Mol Autism. 2013 17 Volume: 4 Pages: 19-19
  • Peer Reviewed
• [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.2013 26 Volume: 4 Pages: 6-6
  • Peer Reviewed
• [Journal Article] Microglial activation in young adults with autism spectrum disorder (2013)
  • Author(s): Suzuki K, Sugihara G, Ouchi Y, Nakamura K, Futatsubashi M, Takebayashi K, Yoshihara Y, Omata K, Matsumoto K, Tsuchiya KJ, Iwata Y, Tsujii M, Sugiyama T, Mori N
  • Journal Title: JAMA Psychiatry Volume: 70 Pages: 49-58
  • 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 Pathol Volume: 23 Pages: 294-302
  • Peer Reviewed
• [Journal Article] Protocadherin α (PCDHA) a novel susceptibilitygeneforautism (2013)
  • Author(s): A(as) nitha 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: 192-8
  • Peer Reviewed
• [Journal Article] Serum levels of soluble platelet endothelial cell adhesion molecule-1 and vascular cell adhesion molecule-1 are decreased in subjects with autism spectrum disorder. (2013)
  • Author(s): Kameno Y, Iwata K, Matsuzaki H, Miyachi T, Tsuchiya KJ, Matsumoto K, Iwata Y, Suzuki K, Nakamura K, Maekawa M, Tsujii M, Sugiyama T, Mori N.
  • Journal Title: Mol Autism Volume: 4 Issue: 1 Pages: 19-19
  • DOI: 10.1186/2040-2392-4-19
  • Peer Reviewed
• [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: Molecular Autism Volume: 4 Issue: 1 Pages: 6-6
  • DOI: 10.1186/2040-2392-4-6
  • 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 Pathol. Volume: 23 Issue: 3 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 Issue: 3 Pages: 192-198
  • DOI: 10.1503/jpn.120058
  • Peer Reviewed
• [Journal Article] Microglial activation in young adults with autism spectrum disorder (2013)
  • Author(s): Suzuki K
  • Journal Title: JAMA Psychiatry Volume: 70 Issue: 1 Pages: 49-58
  • DOI: 10.1001/jamapsychiatry.2013.272
  • 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. 2012 1 Volume: 3 Pages: 12-12
• [Journal Article] Vldlr overexpression hyperactivity in rats (2012)
  • Author(s): Iwata K, Izumo NMatsuzaki H, Manabe T, Ishibashi Y, Ichitani Y, Yamada K, Thanseem I, Anitha A, Vasu MM, Shimmura C, Wakuda T, Kameno Y, Takahashi T, Iwata Y, Suzuki K, ,(causes) Nakamura K, Mori N
  • Journal Title: Mol Autism Volume: 3 Pages: 11-11
  • Peer Reviewed
• [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 Pages: 410-8
  • Peer Reviewed
• [Journal Article] Brain region-specific altered expression and association of mitochondria-related genes in autism (2012)
  • Author(s): Anitha A
  • Journal Title: Molecular Autism Volume: 3 Issue: 1 Pages: 12-12
  • DOI: 10.1186/2040-2392-3-12
  • Peer Reviewed
• [Journal Article] Elevated transcription factor specificity protein 1 in autistic brains alters the expression of autism candidate genes. (2012)
  • Author(s): Thanseem I
  • Journal Title: Biol Psychiatry Volume: 71 Issue: 5 Pages: 410-8
  • DOI: 10.1016/j.biopsych.2011.09.020
  • Peer Reviewed
• [Journal Article] Vldlr overexpression causes hyperactivity in rats. (2012)
  • Author(s): Iwata K
  • Journal Title: Mol Autism. Volume: 3 Issue: 1 Pages: 11-11
  • DOI: 10.1186/2040-2392-3-11
  • Peer Reviewed
• [Journal Article] Elevated transcription factor specificity protein 1 in autistic brains alters the expression of autism candidate genes (2012)
  • Author(s): Thanseem I
  • Journal Title: Biol Psychiatry Volume: 71 Pages: 410-418
  • 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
  • Peer Reviewed
• [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
  • Peer Reviewed
• [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
  • Peer Reviewed
• [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 Pages: 14-14
  • 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, 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
  • Peer Reviewed
• [Journal Article] Reduced acetylcholinesterase activity in the fusiform gyrus in adults with autism spectrum disorders (2011)
  • Author(s): Suzuki K, Sugihara G, Ouchi Y, Nakamura K, Tsujii M, Futatsubashi M, Iwata Y, Tsuchiya KJ, Matsumoto K, Takebayashi K, Wakuda T, Yoshihara Y, Suda S, Kikuchi M, Takei N, Sugiyama T, Irie T, Mori N
  • Journal Title: Arch Gen Psychiatry Volume: 68 Pages: 306-13
  • Peer Reviewed
• [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, Yoshikawa T, Mori N
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 35(2) Pages: 454-8
  • Peer Reviewed
• [Journal Article] Investigation of the serum levels of anterior pituitary hormones in male children with autism (2011)
  • Author(s): Iwata K
  • Journal Title: Mol Autism Volume: 2 Pages: 16-16
  • Peer Reviewed
• [Journal Article] Alteration of plasma glutamate and glutamine levels in children with high-functioning autism (2011)
  • Author(s): Shimmura C
  • Journal Title: PloS One Volume: 6
  • Peer Reviewed
• [Journal Article] Association of transcription factor gene LMX1B with autism (2011)
  • Author(s): Thanseem I
  • Journal Title: PloS One Volume: 6
  • Peer Reviewed
• [Journal Article] Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism (2011)
  • Author(s): Suda S
  • Journal Title: Mol Autism Volume: 2 Pages: 14-14
  • Peer Reviewed
• [Journal Article] Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders (2011)
  • Author(s): Suzuki K
  • Journal Title: PloS One Volume: 6
  • Peer Reviewed
• [Journal Article] Reduced acetylcholinesterase activity in the fusiform gyrus in adults with autism spectrum disorders (2011)
  • Author(s): Suzuki K
  • Journal Title: Arch Gen Psychiatry Volume: 68 Pages: 306-313
  • Peer Reviewed
• [Presentation] Microglial activation in adults with Autism Spectrum Disorders (2012)
  • Author(s): Nakamura K, Suzuki K , Ouchi Y, Tsujii M, Sugihara G, Iwata Y, Matsumoto K, Takebayashi K, Wakuda T, Sugiyama T, Yoshihara Y, Mori N
  • Organizer: 11th Annual International Meeting For Autism Research
  • Place of Presentation: Toronto
• [Presentation] Glutanate dysfunction in the basal ganglia of Autism Spectrum Disorders:an MRS study (2012)
  • Author(s): Yoshihara Y, Sugihara G, Ishizuka A, Yogo H, Nakamura K, Sugiyama T, Matsumoto K, Tsuchiya KJ, Suzuki K , Takei N, Tsujii M, Mori N
  • Organizer: 11th Annual International Meeting For Autism Research
  • Place of Presentation: Toronto
• [Presentation] Microglial activation in young adults with autism spectrum disorder. (2012)
  • Author(s): Nakamura K
  • Organizer: IMFAR
  • Place of Presentation: Toronto
• [Presentation] 自閉症の生物学的研究について:PET画像研究他 (2011)
  • Author(s): 中村和彦
  • Organizer: 第52回日本児童青年精神医学会総会
  • Place of Presentation: 徳島市
  • Year and Date: 2011-11-10
• [Presentation] 自閉症の生物学的研究について(PET他) (2011)
  • Author(s): 中村和彦
  • Organizer: 第16回グリア研究会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-22
• [Presentation] 自閉症の生物学的研究について(PET他) (2011)
  • Author(s): 中村和彦
  • Organizer: 第16回グリア研究会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-22
• [Presentation] Reduced Acetylcolinesterase Activity In the Fusiform Gyrus In Adults Spectrum Disorders (2011)
  • Author(s): Nakamura K, Suzuki K , Sugihara G, Ouchi Y, Tsujii M, Sugihara Y, Iwata Y, Matsumoto K, Takebayashi K, Wakuda T, Yoshihara Y, Suda S, Kikuchi M, Takei N, Sugiyama T, Mori N
  • Organizer: 10th Annual International Meeting For Autism Research
  • Place of Presentation: San Diego
• [Presentation] 自閉症の生物学的研究について:PET画像研究他 (2011)
  • Author(s): 中村和彦
  • Organizer: 第52回日本児童青年精神医学会総会
  • Place of Presentation: 徳島