BRAIN and NERVE－神経研究の進歩64巻2号

2012年02月発行

特集 生物学的精神医学の進歩

発達期精神障害―発達障害を中心に

著者： 久島周¹ 岡田俊² 尾崎紀夫¹²

所属機関： ¹名古屋大学大学院医学系研究科精神医学分野 ²名古屋大学大学院医学系研究科親と子どもの心療学分野

ページ範囲：P.139 - P.147

文献概要

はじめに

　DSM-IV-TR（Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision）では，発達期精神障害，すなわち幼児期，小児期，青年期に初めて診断される障害として，知的障害，学習障害，運動能力障害，コミュニケーション障害，広汎性発達障害，注意欠如・多動性障害（attention-deficit hyperactivity disorder：ADHD）および破壊的行動障害，幼児期または小児期早期の哺育・摂食障害，チック障害，排泄障害，幼児期・小児期・青年期のその他の障害が含まれる。診断される時期に基づいてカテゴリー化されているため多様な障害を含むが，有病率の高さからすれば，現在，発達障害と総称されている障害が主要なものである。

　発達障害には明確な定義はないが，脳機能の相違によって認知・行動面の偏りを生じ，そのために日常生活に困難をきたす状態をいう。発症因としては，多因子疾患の中では遺伝因子が比較的高いが，胎生期，周産期，出生後早期などの環境因子の関与も示されている。遺伝因子と環境因子の相互作用の分子基盤として，遺伝子のエピジェネティックな変化が発達障害の発症に寄与していることを示唆する知見も，近年報告されている。

　本稿では，発達障害の診断とその病態上の位置づけについて述べたうえで，遺伝子研究，画像研究の最新の知見を展望し，今後の研究の方向性について論じることとする。

参考文献

1) Gillberg C, Billstedt E: Autism and Asperger syndrome: coexistence with other clinical disorders. Acta Psychiatr Scand 102: 321-330, 2000

2) Reiersen AM, Constantino JN, Todd RD: Co-occurrence of motor problems and autistic symptoms in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 47: 662-672, 2008

3) Reiersen AM, Constantino JN, Grimmer M, Martin NG, Todd RD: Evidence for shared genetic influences on self-reported ADHD and autistic symptoms in young adult Australian twins. Twin Res Hum Genet 11: 579-585, 2008

4) Lichtenstein P, Carlstrom E, Rastam M, Gillberg C, Anckarsater H: The genetics of autism spectrum disorders and related neuropsychiatric disorders in childhood. Am J Psychiatry 167: 1357-1363, 2010

5) Biederman J, Mick E, Faraone SV: Age-dependent decline of symptoms of attention deficit hyperactivity disorder: impact of remission definition and symptom type. Am J Psychiatry 157: 816-818, 2000

6) Rapoport J, Chavez A, Greenstein D, Addington A, Gogtay N. Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited. J Am Acad Child Adolesc Psychiatry 48: 10-18, 2009

7) Kim-Cohen J, Caspi A, Moffitt TE, Harrington H, Milne BJ, et al: Prior juvenile diagnoses in adults with mental disorder: developmental follow-back of a prospective-longitudinal cohort. Arch Gen Psychiatry 60: 709-717, 2003

8) Biederman J, Petty CR, Evans M, Small J, Faraone SV: How persistent is ADHD? A controlled 10-year follow-up study of boys with ADHD. Psychiatry Res 177: 299-304, 2010

9) Colman I, Murray J, Abbott RA, Maughan B, Kuh D, et al: Outcomes of conduct problems in adolescence: 40 year follow-up of national cohort. BMJ 338: a2981, 2009

10) Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, et al: Global variation in copy number in the human genome. Nature 444: 444-454, 2006

11) Lupski JR: Genomic rearrangements and sporadic disease. Nat Genet 39: S43-S47, 2007

12) Bruder CE, Piotrowski A, Gijsbers AA, Andersson R, Erickson S, et al: Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. Am J Hum Genet 82: 763-771, 2008

13) Piotrowski A, Bruder CE, Andersson R, Diaz de Ståhl T, Menzel U, et al: Somatic mosaicism for copy number variation in differentiated human tissues. Hum Mutat 29: 1118-1124, 2008

14) Gejman PV, Sanders AR, Kendler KS: Genetics of schizophrenia: new findings and challenges. Annu Rev Genomics Hum Genet 12: 127-144, 2011

15) Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, et al: Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 459: 569-573, 2009

16) Elia J, Gai X, Xie HM, Perin JC, Geiger E, et al: Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes. Mol Psychiatry 15: 637-646, 2010

17) Williams NM, Zaharieva I, Martin A, Langley K, Mantripragada K, et al: Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet 376: 1401-1408, 2010

18) Wallace GL, Eric Schmitt J, Lenroot R, Viding E, Ordaz S, et al: A pediatric twin study of brain morphometry. J Child Psychol Psychiatry 47: 987-993, 2006

19) Lenroot RK, Gogtay N, Greenstein DK, Wells EM, Wallace GL, et al: Sexual dimorphism of brain developmental trajectories during childhood and adolescence. Neuroimage 36: 1065-1073, 2007

20) Giedd JN, Rapoport JL: Structural MRI of pediatric brain development: what have we learned and where are we going? Neuron 67: 728-734, 2010

21) Shaw P, Greenstein D, Lerch J, Clasen L, Lenroot R, et al: Intellectual ability and cortical development in children and adolescents. Nature 440: 676-679, 2006

22) Shaw P, Gogtay N, Rapoport J: Childhood psychiatric disorders as anomalies in neurodevelopmental trajectories. Hum Brain Mapp 31: 917-925, 2010

23) Mills RE, Pittard WS, Mullaney JM, Farooq U, Creasy TH, et al: Natural genetic variation caused by small insertions and deletions in the human genome. Genome Res 21: 830-839, 2011

24) Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, et al: Finding the missing heritability of complex diseases. Nature 461: 747-753, 2009

25) Brennand KJ, Simone A, Jou J, Gelboin-Burkhart C, Tran N, et al: Modelling schizophrenia using human induced pluripotent stem cells. Nature 473: 221-225, 2011

26) Sigurdsson T, Stark KL, Karayiorgou M, Gogos JA, Gordon JA: Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia. Nature 464: 763-767, 2010

27) Nakatani J, Tamada K, Hatanaka F, Ise S, Ohta H, et al: Abnormal behavior in a chromosome-engineered mouse model for human 15q11-13 duplication seen in autism. Cell 137: 1235-1246, 2009

28) Sasaki E, Suemizu H, Shimada A, Hanazawa K, Oiwa R, et al: Generation of transgenic non-human primates with germline transmission. Nature 459: 523-527, 2009