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1 17
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4 ADHD ADHD CBQ-R) ADHD Rating Scale- IV (ADHD-RS-IV) 163 ADHD 92 ADHD CBCL / ADHD
5 CPT NIRS Stop signal task WASH OUT MPH 5 CPT NIRS Stop signal task 5 CPT NIRS Stop signal task
6 MPH MPH MPH 2 MPH 5 Open 18mg Week 27mg Week 36mg Week 45mg 4 Weeks CPT check NIRS Stop signal task
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8 California PDD Early Intervention in Autism ADHD % 200
9
10 q
11 15q11-q13 Maternal Expression Domain MED) Imprinting Center (IC) GABA
12 Allele frequencies of 31 SNPs in autism patients and healthy controls in the MED (Maternal Expression Domain) and the IC (Imprinting Center) on 15q11 Alleles Minor allele frequency Chromosome SNP No. db SNP ID Location (Major/Minor) Autism* Control* position (bp) MED IC SNP SNRPN IC p = ) ATP10C MED 1 rs SNRPN T/C 0.54 (165) 0.49 (365) rs SNRPN A/G 0.17 (167) 0.15 (394) rs SNRPN T/A (167) (411) rs SNRPN T/G 0.13 (167) 0.11 (413) rs SNRPN C/T 0.11 (166) 0.11 (359) rs SNRPN T/C 0.37 (166) 0.32 (375) rs SNRPN T/C (166) (409) rs SNRPN A/G 0.38 (167) 0.46 (413) rs SNRPN T/G (166) (403) rs SNRPN A/G 0.16 (165) 0.12 (412) rs SNRPN G/A 0.14 (166) 0.15 (369) rs SNRPN T/C 0.26 (162) 0.28 (307) rs705 SNRPN/SNURF T/C 0.48 (166) 0.45 (404) rs SNRPN C/T 0.51 (166) 0.49 (416) rs SNRPN/PWCR1 C/T 0.52 (166) 0.49 (415) rs SNRPN/PWCR1 C/T 0.46 (165) 0.48 (409) rs SNRPN/PAR4 G/A (167) (415) rs UBE3A/SNRPN A/G 0.35 (166) 0.38 (397) rs UBE3A/SNRPN G/C 0.35 (163) 0.38 (395) rs ATP10C A/G 0.42 (166) 0.37 (412) rs ATP10C C/T (167) (414) rs ATP10C T/C 0.50 (166) 0.50 (367) rs ATP10C T/C 0.21 (165) 0.17 (411) rs ATP10C G/A 0.47 (165) 0.49 (361) rs ATP10C G/A 0.41 (166) 0.41 (376) rs ATP10C T/C 0.23 (166) 0.23 (415) rs ATP10C G/A 0.22 (165) 0.23 (394) rs ATP10C T/C 0.27 (165) 0.29 (411) rs ATP10C C/T 0.48 (166) 0.50 (372) rs ATP10C C/T 0.27 (164) 0.28 (415) rs ATP10C G/A 0.24 (166) 0.22 (416) SNRPN ; small nuclear ribonucleoprotein polypeptide N, SNURF ; SNRPN upstream reading frame, PWCR1 ; Prader-Willi syndrome chromosome region 1, PAR4 ; Prader-Willi/Angelman region gene 4, UBE3A ; ubiquitin-protein ligase E3A, ATP10C ; ATPase, Class V, type 10C * Number of genotyped individuals for each SNP is given in parenthesis.
13 ATP10C 4 SNPs haplotype permutation haplotype ACCT Estimated haplotype frequencies of the haplotype consisting of SNPs Frequency in all subjects* Frequency in males** SNP Autism Control Permutation Autism Control Permutation p value p value A C T T G C C C A C C T G C C T G T C T Haplotypes whose frequencies were estimated >1% were described. * global permutaion p value = , ** global permutation p value =
14 GABA Allelic frequencies of 11 SNPs in the GABR genes on15q11-q13 Alleles Minor allele frequency Chromosome SNPs db SNP ID Location (Major/Minor) Autism* Control* p value position (bp) SNP1 rs GABRB3 (3'-UTR) C/T (166) (397) SNP2 rs GABRB3 (intron 3) A/C 0.49 (164) 0.47 (409) SNP3 rs GABRB3 (intron 3) T/A 0.38 (166) 0.37 (407) SNP4 rs GABRB3 (intron 3) A/T 0.35 (160) 0.34 (358) SNP5 rs GABRB3 (intron 3) C/T 0.39 (166) 0.38 (399) SNP6 rs GABRB3 (5' upstream C/T 0.38 (165) 0.38 (407) SNP7 rs GABRA5 (exon 8) C/T 0.31 (166) 0.35 (406) SNP8 rs GABRA5 (exon 10) C/T 0.32 (166) 0.37 (409) SNP9 rs GABRG3 (intron 3) A/C 0.42 (166) 0.48 (411) SNP10 rs GABRG3 (intron 5) G/A 0.40 (165) 0.35 (348) SNP11 rs GABRG3 (intron 5) G/A 0.38 (164) 0.36 (409) * Number of genotyped individuals for each SNP is given in parenthesis.
15 acgh 15q Breakpoint
16 TSC1,2 OXTR AVPR1A BDNF SLC6A11 GRIK3 PDE2A HTR2C, 7 DAB1 ARX SLC6A4 DRD1,2,5 GABRA4,B1,B3 GRIN2A GRM7 MAOA, B COMT SEMA5A NLGN4X ITGB3 OXTR CREB1 FZD5 FGF12 GRIA2 DISC1 GRM8 PEG3 NFKB1 HOXB genes GNAL GNAS
17 chr.2 chr.7 chr
18 p= p= A / B / (p<0.05)
19 2,7,
20
21 NIRS Control (N=10) PDD (N=10) Kuwabara et al., Behav Brain Res, 2006
22 um 5-5 um 5 Right PDD 0 (high functioning) Sibling 0 oxyhb deoxyhb Children N=14 N=12 2 channel NIRS machine Probes: Fp1, Fp2 (international 10/20) Left ID Right Adults N=13 N=12 Left NC -5 um 5 0 N=14 N= sec sec sec sec n.s. PDD < NC
23 Spatial attention in autism Posner s model Engagement: thalamus Disengagement: parietal cortex Attention shift: superior colliculus Lack of flexibility; monotonous, repetitive behavior; overselection of stimulus?
24 Subjects n M,F mean age mean IQ CARS score Autism 16(11,5) Mental retardation 17(12,5) Normal control 14(6,8) Gap-overlap task Peripheral stimulus Central stimulus Overlap
25 Saccade-locked ERP Saccade onset NC gap overlap Autism gap overlap MR gap overlap (µV) 0 (ms) Kawakubo et al., Clin Neurophysiol, 2007
26 MRI A) B) C)
27 0.55 Total gray matter volume / ICV Female Male Individual variability in cooperativeness (Yamasue et al., Cerebral Cortex, 2008)
28 Fig. 3 y= 62 mm y= 60 mm y= 58 mm y= 56 mm y= 52 mm Correlates of Cooperativeness in Female T value 4.44 y= 24 mm y= 20 mm y= 16 mm y= 14 mm y= 12 mm 2.66 y= 8 mm y= 6 mm y= 4 mm y= 0 mm y= -4 mm in Male 3.38 y= -8 mm y= -12 mm y=-16 mm y=-20 mm y=-22 mm 2.63 y=-24 mm y= -28 mm y= -32 mm y= -36 mm y= -40 mm L R (Yamasue et al., Cerebral Cortex, 2008)
29 ASD MNS 44 ASD MNS 44
30
31 ASD MNS Yamasaki et al.,
32 44 CARS items L44 L45 R44 R45 Social Communication(SC) Social Interaction(SI) Stereotypies and Sensory Abnormalities(SSA) Emotional Regulation(ER) Yamasaki et al.,
論文の内容の要旨 日本人サンプルを用いた 15 番染色体長腕領域における 自閉症感性候補遺伝子の検討 指導教員 笠井清登教授 東京大学大学院医学系研究科 平成 13 年 4 月入学 医学博士課程 脳神経医学専攻 加藤千枝子 はじめに 自閉症は (1 ) 社会的な相互交渉の質的な障害 (2 ) コミュ
論文の内容の要旨 日本人サンプルを用いた 15 番染色体長腕領域における 自閉症感性候補遺伝子の検討 指導教員 笠井清登教授 東京大学大学院医学系研究科 平成 13 年 4 月入学 医学博士課程 脳神経医学専攻 加藤千枝子 はじめに 自閉症は (1 ) 社会的な相互交渉の質的な障害 (2 ) コミュニケーション機 能の質的な障害 (3 ) 活動と興味の範囲の著しい限局性の 3 つを主な特徴 とする脳の発達障害である
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Management with Consideration for the Special Characteristics of Patients with Autistic Disorder in the Dental Setting Hiroshi NAKAGAWA Management of patients with autistic disorder (AD) can be difficult,
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