TOPポスター発表
 
自閉症
P1-63
自閉症スペクトラム症における感覚過敏についての研究
安田 由華1,橋本 亮太1,2,中江 文3,康 紅玲3,大井 一高1,山森 英長1,4,藤本 美智子1,萩平 哲3,武田 雅俊1
大阪大院・医・精神医学1,大阪大院・連合小児発達学・子どものこころ2,大阪大院・医・麻酔・集中治療医学3,大阪大院・医・分子精神神経学(大日本住友製薬)寄付講座4

背景:自閉スペクトラム症(ASD:Autism Spectrum Disorder)は、社会性の障害、常同性を主とする神経発達障害である。新たに米国精神医学会の精神疾患診断基準(DSM-5)に、感覚過敏や感覚鈍麻などの感覚症状が加えられた。感覚症状は、ASD患者の80%に認められるとも言われる重要な症状である。しかし、一定の客観的な測定方法はなく科学的知見に乏しい。我々は、温痛覚刺激を用い、ASD患者の刺激に対する感覚過敏を検討した。
方法:年齢と性別がマッチしたASD患者と健常者各24名に対し、温冷痛覚刺激装置(PTHWAY:Medoc)を用いて痛み刺激を与えて、暖かさと冷たさを検出する最少閾値温度、暖かさと冷たさを痛みと感じる温度、暖かさと冷たさを痛くて我慢できなくなる最大耐性温度について測定した。統計はMann-Whitney's U testを行い、有意水準はp<0.05とした。
結果:ASD群では、健常群と比較して、暖かさと冷たさを検出する最少閾値温度、暖かさと冷たさを痛みと感じる温度、暖かさと冷たさを痛くて我慢できなくなる最大耐性温度の値については、有意差は認められなかった。
結論:ASD患者では、感覚症状が認められ、DSM-5においては新たな診断基準の一つとして取り入られたが、今回の検討では、それを検出することはできなかった。今後、さらなる検討を加えて、検出する方法を開発したいと考えている。
P1-64
自閉症スペクトラム障害とHPC-1/syntaxin1A遺伝子発現異常の関連性の検討
小藤 剛史1,林 優子2,藤原 智徳3,真田 ますみ3,田丸 政男4,赤川 公朗3
杏林大学医学部共研RI部門1,県立広島大学保健福祉学部付属診療センター小児科2,杏林大学医学部細胞生理学3,県立広島大学保健福祉学部作業療法学科4

HPC-1/syntaxin1A(STX1A)is thought to regulate the secretion of neurotransmitters or neuromodulaters as neuronal SNARE. STX1A gene knock-out(KO)mice we generated normally developed and showed normal synaptic transmission of glutamate or GABA. However, the secretion of monoamine, such as serotonin or dopamine, was reduced in STX1A-KO mice. Furthermore, STX1A-KO mice exhibited abnormal behavioral profiles in latent inhibition test, social interaction test and novel object recognition test, and showed hypersensitivity in pain and auditory sensation. These abnormal behaviors resemble to human autistic behavioral profiles. In this study, we examined if STX1A gene expression is correlated with autism spectrum disorder(ASD)using blood samples from ASD patients. Informed consents were obtained from all the participants. We examined known SNPs in STX1A gene by direct sequencing of genome DNA. There was no difference between ASD patients and control group. We measured STX1A mRNA amounts in lymphocytes by quantitative RT-PCR. There was a wide variation of STX1A mRNA expression in the patients compared to control group, and mean STX1A mRNA amount in all the patients was higher than that in control group. Especially, mean STX1A mRNA amount was also higher in asperger's syndrome(Asp)patients, one of subgroups in ASD by DSM-IV. STX1A mRNA expression in other ASD patients(high functioning autism, Kanner and PDD-NOS)was not different from that in control group. Furthermore, we found that in Asp patients communication ability was lowered in accordance with lowering STX1A mRNA expression. Hyperactivity was observed in Asp patients showing higher STX1A mRNA expression. These data suggest that regulation of STX1A gene expression may be disturbed in a part of ASD patients.
P1-65
CD157ノックアウトマウスの社会的行動回避と不安に対する、オキシトシンおよび新規合成類似薬の与える影響
Stanislav Cherepanov1,2,あくだーる しりん2,あざむ えーけーえむふぁくるる2,水野 彰3,菊地 裕介3,吉原 亨2,石原 克彦4,周東 智3,東田 陽博2
大阪大院大阪大学・金沢大学・浜松医科大学・千葉大学・福井大学 連合小児発達学研究科 金沢校1,金沢大学子どものこころの発達研究センター2,北海道大学大学院薬学研究院創薬科学分野3,川崎医科大学基礎医学免疫学4

Autism is developmental disorder characterized by core deficits in sociability and communication skills, repetitive behavior and restricted interests. Now, one of the most perspective fields of research of autism therapy is nanopeptide oxytocin(OT). Today we have a lot of proofs about role of oxytocin in the social interactions and social recognition. Now oxytocin is used intranasaly like experimental drug for treatment in social disturbance in patients with autism and schizophrenia. To ensure such roles, an analog with long-lasting and effective blood-brain barrier penetration properties should have a benefit, if we intend to use it as a therapeutic drug. To assess this, we designed and synthesized a new oxytocin analog, lipo-oxytocin-1(LOT-1), which conjugates two palmitoyl groups at the amino group of the cysteine(the 9th amino acid)and the phenolic hydroxyl group of the tyrosine(the 8th amino acid)in the OT molecule. We investigated OT and LOT-1 on sociability of CD157-/- mice in open field test. CD157-/- mice is a novel rodent model of non-motor symptoms of Parkinson Disease. In the open field test without object CD157-/- male mice demonstrate less in exploratory behavior in the inside zone, than wild-type males. In test with non-social and social object demonstrate to the less time in inside zone compare the wild type mice. Generally, CD157-/- mice show high anxiety and social avoidance. In the case of treatment of OT or LOT-1, 30 minutes after introperitoneal injection CD157-/- male mice demonstrate recovery of sociability. But after 24h mice treated by LOT-1 demonstrate more high recovery of sociability than mice treated by OT. The results suggest that LOT-1 has a functional advantage for recovery of social behavioral impairment.