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Genetische und hirnstrukturelle Anomalien bei Autismus-Spektrum-Störungen

Eine Brücke zum Verständnis der Ätiopathogenese?

Genetic and brain structure anomalies in autism spectrum disorders

Towards an understanding of the aetiopathogenesis?

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Zusammenfassung

Autismus-Spektrum-Störungen (ASD) sind tiefgreifende Entwicklungsstörungen mit hoher Heritabilität und bislang noch unbekannter Ätiopathogenese. Der molekulargenetischen Forschung ist es gelungen, mehrere Kandidatengene für die Erkrankung zu identifizieren, die funktionell in Verbindung zu Neurotransmission bzw. neuronaler Migration, kortikaler Organisation und synaptischer Plastizität stehen. Magnetresonanztomographische Studien konnten ein erhöhtes Hirnvolumen bei ASD-Patienten nachweisen. Vor allem die Frontal- und die Temporallappen waren im Volumen vergrößert. Am ausgeprägtesten war diese Volumenzunahme im frühen Kindesalter. Eine Kombination molekulargenetischer und strukturell-bildgebender Forschungsansätze erscheint als vielversprechend für die weitere Aufklärung der Ätiopathogenese der ASD.

Summary

Autism spectrum disorders (ASD) are pervasive development disorders with high heritability and an as yet unclear aetiology. So far molecular genetic research was able to identify several candidate genes for the disorder which are functionally linked to neurotransmission and neuronal migration, cortical organisation and synaptic plasticity. MRI studies repeatedly showed a higher total brain volume for ASD patients. The volume increase was most pronounced for the frontal and the temporal lobes and peaked in early childhood. A combination of molecular genetic and structural imaging research appears promising for a further characterization of ASD aetiology.

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Literatur

  1. Abell F, Krams M, Ashburner J et al (1999) The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans. Neuroreport 10(8):1647–1651

    Article  PubMed  CAS  Google Scholar 

  2. Abrahams BS, Tentler D, Perederiy JV et al (2007) Genome-wide analyses of human perisylvian cerebral cortical patterning. Proc Natl Acad Sci U S A 104(45):17849–17854

    Article  PubMed  CAS  Google Scholar 

  3. Abrahams BS, Geschwind DH (2008) Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 9(5):341–355

    Article  PubMed  CAS  Google Scholar 

  4. Alarcon M, Cantor LM, Liu J et al (2002) Evidence for a language quantitative trait locus on chromosome 7q in multiplex autism families. Am J Hum Genet 70(1):60–71

    Article  PubMed  CAS  Google Scholar 

  5. Alarcon M, Abrahams BS, Stone JL et al (2008) Linkage, association and gene-expression analyses identify CNTNAP2 as an autism susceptibility gene. Am J Hum Genet 82(1):150–159

    Article  PubMed  CAS  Google Scholar 

  6. Amir RE, Veyver IB van den, Wan M et al (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23(2):185–188

    Article  PubMed  CAS  Google Scholar 

  7. Arking DE, Cutler DJ, Brune CW et al (2008) A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. Am J Hum Genet 82(1):160–164

    Article  PubMed  CAS  Google Scholar 

  8. Autism Genome Project Consortium (2007) Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet 39(3):319–328

    Article  CAS  Google Scholar 

  9. Aylward EH, Minshew NJ, Goldstein G et al (1999) MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults. Neurology 53(9):2145–2150

    PubMed  CAS  Google Scholar 

  10. Bailey A, LeCouteur A, Gottesman I et al (1995) Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 25(1):63–77

    Article  PubMed  CAS  Google Scholar 

  11. Bakkaloglu B, O‘Roak BJ, Louvi A et al (2008) Molecular cytogenetic analysis and resequencing of contactin-associated protein-like 2 in autism spectrum disorders. Am J Hum Genet 82(1):165–173

    Article  PubMed  CAS  Google Scholar 

  12. Barnea-Goraly N, Kwon H, Menon V et al (2004) White matter structure in autism: preliminary evidence from diffusion tensor imaging. Biol Psychiatry 55(3):323–326

    Article  PubMed  Google Scholar 

  13. Bartholomeusz HH, Courchesne E, Karns CM (2002) Relationship between head circumference and brain volume in healthy normal toddlers, children and adults. Neuropediatrics 33(5):239–241

    Article  PubMed  CAS  Google Scholar 

  14. Ben Bashat D, Kronfeld-Duenias V, Zachor DA et al (2007) Accelerated maturation of white matter in young children with autism: a high b value DWI study. Neuroimage 37(1):40–47

    Article  Google Scholar 

  15. Birchmeier C, Gherardi E (1998) Developmental roles of HGF/SF and its receptor, the c-Met tyrosine kinase. Trends Cell Biol 8(10):404–410

    Article  PubMed  CAS  Google Scholar 

  16. Bishop DV, Maybery M, Maley A et al (2004) Using self-report to identify the broad phenotype in parents of children with autistic spectrum disorders: a study using the Autism-Spectrum Quotient. J Child Psychol Psychiatry 45(8):1431–1436

    Article  PubMed  Google Scholar 

  17. Blasi F, Bacchelli E, Pesaresi G et al (2006) Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection. Am J Med Genet B Neuropsychiatr Genet 141B(3):220–221

    Article  PubMed  CAS  Google Scholar 

  18. Blomquist HK, Bohman M, Edvinsson SO et al (1985) Frequency of the fragile X syndrome in infantile autism. A Swedish multicenter study. Clin Genet 27(2):113–117

    Article  PubMed  CAS  Google Scholar 

  19. Bloss CS, Courchesne E (2007) MRI neuroanatomy in young girls: a preliminary study. J Am Acad Child Adolesc Psychiatry 46(4):515–523

    Article  PubMed  Google Scholar 

  20. Boeckers TM, Brockmann J, Kreutz MR et al (2002) ProSAP/SHANK proteins – a family of higher order organizing molecules of the postsynaptic density with an emerging role in human neurological disease. J Neurochem 81(5):903–910

    Article  PubMed  CAS  Google Scholar 

  21. Boger-Meggido I, Shaw DW, Friedman SD et al (2006) Corpus callosum morphometrics in young children with autism spectrum disorder. J Autism Dev Disord 36(6):733–739

    Article  Google Scholar 

  22. Bolton P, Macdonald H, Pickles A et al (1994) A case-control family history study of autism. J Child Psychol Psychiatry 35(2):311–322

    Article  PubMed  Google Scholar 

  23. Bonora E, Beyer KS, Lamb JA et al (2003) Analysis of reelin as a candidate gene for autism. Mol Psychiatry 8(10):885–892

    Article  PubMed  CAS  Google Scholar 

  24. Brambilla P, Hardan A, di Nemi SU et al (2003) Brain anatomy and development in autism: review of structural MRI studies. Brain Res Bull 61(6):557–569

    Article  PubMed  Google Scholar 

  25. Butler MG, Dasouki MJ, Zhou XP et al (2005) Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J Med Genet 42:318–321

    Article  PubMed  CAS  Google Scholar 

  26. Buxbaum JD, Silverman JM, Smith CJ et al (2002) Association between a GABARB3 polymorphism and autism. Mol Psychiatry 7(3):311–316

    Article  PubMed  CAS  Google Scholar 

  27. Buxbaum JD, Cai G, Chaste P et al (2007) Mutation screening of the PTEN gene in patients with autism spectrum disorders andmacrocephaly. Am J Med Genet B Neuropsychiatr Genet 144:484–491

    Google Scholar 

  28. Campbell DB, Sutcliffe JS, Ebert PJ et al (2006) A genetic variant that disrupts MET transcription is associated with autism. Proc Natl Acad Sci U S A 103(45):16834–16839

    Article  PubMed  CAS  Google Scholar 

  29. Campbell DB, D’Oronzio R, Garbett K et al (2007) Disruption of cerebral cortex MET signaling in autism spectrum disorder. Ann Neurol 62(3):243–250

    Article  PubMed  Google Scholar 

  30. Carper RA, Courchesne E (2000) Inverse correlation between frontal lobe and cerebellum sizes in children with autism. Brain 123:836–844

    Article  PubMed  Google Scholar 

  31. Carper RA, Moses P, Tigue ZD et al (2002) Cerebral lobes in autism: early hyperplasia and abnormal age effects. Neuroimage 16(4):1038–1051

    Article  PubMed  Google Scholar 

  32. Carper RA, Courchesne E (2005) Localized enlargement of the frontal cortex in autism. Biol Psychiatry 57(2):126–133

    Article  PubMed  Google Scholar 

  33. Chen GK, Kono N, Geschwind DH et al (2006) Quantitative trait locus analysis of nonverbal communication in autism spectrum disorder. Mol Psychiatry 11(2):214–220

    Article  PubMed  CAS  Google Scholar 

  34. Christian SL, Brune CW, Sudi J et al (2008) Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. Biol Psychiatry 63(12):1111–1117

    Article  PubMed  CAS  Google Scholar 

  35. Comoletti D, De Jaco A, Jennings LL et al (2004) The Arg451Cys-neuroligin-3 mutation associated with autism reveals a defect in protein processing. J Neurosci 24(40):4889–4893

    Article  PubMed  CAS  Google Scholar 

  36. Cook EH Jr, Courchesne R, Lord C et al (1998) Linkage-disequilibrium mapping of autistic disorder, with 15q11–13 markers. Am J Hum Genet 62(5):1077–1083

    Article  PubMed  CAS  Google Scholar 

  37. Cook EH Jr, Scherer SW (2008) Copy-number variations associated with neuropsychiatric conditions. Nature 455(7215):919–923

    Article  PubMed  CAS  Google Scholar 

  38. Coon H (2006) Current perspectives on the genetic analysis of autism. Am J Med Genet C Semin Med Genet 142C(1):24–32

    Article  PubMed  Google Scholar 

  39. Courchesne E, Press GA, Yeung-Courchesne R (1993) Parietal lobe abnormalities detected with MR in patients with infantile autism. AJR Am J Roentgenol 160:387–393

    PubMed  CAS  Google Scholar 

  40. Courchesne E, Pierce K, Schumann CM et al (2007) Mapping early brain development in autism. Neuron 56(2):399–413

    Article  PubMed  CAS  Google Scholar 

  41. Devlin B, Bennett P, Dawson G et al (2004) Alleles of a reelin CGG repeat do not convey liability to autism in a sample from the CPEA network. Am J Med Genet B Neuropsychiatr Genet 126B(1):46–50

    Article  PubMed  Google Scholar 

  42. Domes G, Kumbier E, Herpertz-Dahlmann B et al (2008) Autismus und soziale Kognition. Nervenarzt 79(3):261–274

    Article  PubMed  CAS  Google Scholar 

  43. Durand CM, Betancur C, Boeckers TM et al (2007) Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 39(1):25–27

    Article  PubMed  CAS  Google Scholar 

  44. European Chromosome 16 Tuberous Sclerosis Consortium (1993) Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 75(7):1305–1315

    Article  Google Scholar 

  45. Fang P, Lev-Lehmann E, Tsai TF et al (1999) The spectrum of mutations in UBE3A causing Angelman syndrome. Hum Mol Genet 8(1):129–135

    Article  PubMed  CAS  Google Scholar 

  46. Fatemi SH, Snow AV, Stary JM et al (2005) Reelin signaling is impaired in autism. Biol Psychiatry 57(7):777–787

    Article  PubMed  CAS  Google Scholar 

  47. Feng J, Schroer R, Yan J et al (2006) High frequency of neurexin 1beta signal peptide structural variants in patients with autism. Neurosci Lett 409(1):10–13

    Article  PubMed  CAS  Google Scholar 

  48. Fombonne E, Tidmarsh L (2003) Epidemologic data on Asperger disorder. Child Adolesc Psychiatr Clin N Am 12:15–21

    Article  PubMed  Google Scholar 

  49. Fombonne E (2005) Epidemiology of autistic disorder and other pervasive development disorders. J Clin Psychiatry 66:3–8

    PubMed  Google Scholar 

  50. Forster E, Jossin Y, Zhao S et al (2006) Recent progress in understanding the role of Reelin in radial neuronal migration, with specific emphasis on the dentate gyrus. Eur J Neurosci 23(4):901–909

    Article  PubMed  Google Scholar 

  51. Gaffney GR, Kuperman S, Tsai LY et al (1987) Midsagittal magnetic resonance imaging of autism. Br J Psychiatry 151:831–835

    Article  PubMed  CAS  Google Scholar 

  52. Gaffney GR, Tsai LY, Kuperman S et al (1987) Cerebellar structure in autism. Am J Dis Child 141(12):1330–1332

    PubMed  CAS  Google Scholar 

  53. Gail Williams P, Sears LL, Allard A (2004) Sleep problems in children with autism. J Sleep Res 13(3):265–268

    Article  Google Scholar 

  54. Garber HJ, Ritvo ER (1992) Magnetic resonance imaging of the posterior fossa in autistic adults. Am J Psychiatry 149(2):245–247

    PubMed  CAS  Google Scholar 

  55. Gauthier J, Bonnel A, St-Onge J et al (2005) NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population. Am J Med Genet B Neuropsychiatr Genet 132B(1):74–75

    Article  PubMed  Google Scholar 

  56. Goffin A, Hoefsloot LH, Bosgoed E et al (2001) PTEN mutation in a family with Cowden syndrome and autism. Am J Med Genet 105:521–524

    Article  PubMed  CAS  Google Scholar 

  57. Graf ER, Zhang X, Jin SX et al (2004) Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins Cell 119(7):1013–1026

  58. Hardan AY, Minshew NJ, Mallikarjuhn M et al (2001) Brain volume in autism. J Child Neurol 16(6):421–424

    PubMed  CAS  Google Scholar 

  59. Hazlett HC, Poe MD, Gerig G et al (2005) Magnetic resonance imaging and head circumference study of brain size and autism: birth through age 2 years. Arch Gen Psychiatry 62(12):1366–1376

    Article  PubMed  Google Scholar 

  60. Hazlett HC, Poe M, Gerig G et al (2006) Cortical white and grey brain tissue volume in adolescents and adults with autism. Biol Psychiatry 59(1):1–6

    Article  PubMed  Google Scholar 

  61. Haznedar MM, Buchsbaum MS, Wei TC et al (2000) Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging. Am J Psychiatry 152(12):1994–2001

    Article  Google Scholar 

  62. Holttum JR, Minshew NJ, Sanders RS et al (1992) Magnetic resonance imaging of the posterior fossa in autism. Biol Psychiatry 32(12):1091–1101

    Article  PubMed  CAS  Google Scholar 

  63. Howard MA, Cowell PE, Boucher J et al (2000) Convergent neuroanatomical and behavioural evidence of an amygdala hypothesis in autism. Neuroreport 11:2931–2935

    Article  PubMed  CAS  Google Scholar 

  64. Hrdlicka M (2008) Structural neuroimaging in autism. Neuro Endocrinol Lett 29(3):281–286

    PubMed  Google Scholar 

  65. Jamain S, Quach H, Betancur C et al (2003) Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34(1):27–29

    Article  PubMed  CAS  Google Scholar 

  66. Jorde LB, Hasstedt SJ, Ritvo ER et al (1991) Complex segregation analysis of autism. Am J Hum Genet 49(5):932–938

    PubMed  CAS  Google Scholar 

  67. Kanner L (1943) Autistic disturbances of affective contact. Nerv Child 2:217–250

    Google Scholar 

  68. Kates WR, Burnette CP, Eliez S et al (2004) Neuroanatomic variation in monozygotic twin pairs discordant for the narrow phenotype in autism. Am J Psychiatry 161(3):539–546

    Article  PubMed  Google Scholar 

  69. Kircher TT, Liddle PF, Brammer MJ et al (2001) Neural correlates of formal thought disorder in schizophrenia: preliminary findings from a functional magnetic resonance imaging study. Arch Gen Psychiatry 58(8):769–774

    Article  PubMed  CAS  Google Scholar 

  70. Krebs MO, Betancur C, Leroy S et al (2002) Absence of association between a polymorphic GGC repeat in the 5‘ untranslated region of the reelin gene and autism. Mol Psychiatry 7(7):801–804

    Article  PubMed  CAS  Google Scholar 

  71. Kumar RA, KaraMohamed S, Sudi J et al (2008) Recurrent 16p11.2 microdeletions in autism. Hum Mol Genet 17(4):628–638

    Article  PubMed  CAS  Google Scholar 

  72. Kwon CH, Zhu X, Zhang J et al (2001) PTEN regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease. Nat Genet 29:404–411

    Article  PubMed  CAS  Google Scholar 

  73. Lalande M, Calciano MA (2007) Molecular epigenetics of Angelman syndrome. Cell Mol Life Sci 64:947–960

    Article  PubMed  CAS  Google Scholar 

  74. Landa RJ, Holman KC, Garrett-Mayer E (2007) Social and communication development in toddlers with early and later diagnosis of autism spectrum disorders. Arch Gen Psychiatry 64(7):853–864

    Article  PubMed  Google Scholar 

  75. Landa RJ (2008) Diagnosis of autism spectrum disorders in the first 3 years of life. Nat Clin Pract Neurol 4(3):138–147

    Article  PubMed  Google Scholar 

  76. Lang UE, Puls I, Muller DJ et al (2007) Molecular mechanisms of schizophrenia. Cell Physiol Biochem 20(6):687–702

    Article  PubMed  CAS  Google Scholar 

  77. Lauritsen MB, Pedersen CB, Mortensen PB (2005) Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study. J Child Psychol Psychiatry 46(9):963–971

    Article  PubMed  Google Scholar 

  78. Levitt JG, Blanton RE, Smalley S et al (2003) Cortical sulcal maps in autism. Cereb Cortex 13(7):728–735

    Article  PubMed  Google Scholar 

  79. Lonard DM, O‘Malley BW (2006) The expanding cosmos of nuclear receptor coactivators. Cell 125(3):411–414

    Article  PubMed  CAS  Google Scholar 

  80. Lossie AC, Whitney MM, Amidon D et al (2001) Distinct phenotypes distinguish the molecular classes of Angelman syndrome. J Med Genet 38(12):834–845

    Article  PubMed  CAS  Google Scholar 

  81. Malzac P, Webber H, Moncla A et al (1998) Mutation analysis of UBE3A in Angelman syndrome patients. Am J Hum Genet 62(6):1353–1360

    Article  PubMed  CAS  Google Scholar 

  82. Maier W, Zobel A, Rietschel M (2003) Genetics of schizophrenia and affective disorders. Pharmacopsychiatry 36:195–202

    Article  Google Scholar 

  83. Manning MA, Cassidy SB, Clericuzio C et al (2004) Terminal 22q deletion syndrome: a newly recognized cause of speech and language disability in the autism spectrum. Pediatrics 114:451–457

    Article  PubMed  Google Scholar 

  84. Marshall CR, Noor A, Vincent JB et al (2008) Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 82(2):477–488

    Article  PubMed  CAS  Google Scholar 

  85. Martin ER, Menold MM, Wolpert CM et al (2000) Analysis of linkage disequilibrium in gamma-aminobutyric acid receptor subunit genes in autistic disorder. Am J Med Genet 96(1):43–48

    Article  PubMed  Google Scholar 

  86. Menold MM, Shao Y, Wolpert CM et al (2001) Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder. J Neurogenet 15:245–259

    Article  PubMed  CAS  Google Scholar 

  87. Meyer G, Varoqueaux F, Neeb A et al (2004) The complexity of PDZ-domain-mediated interactions at glutamatergic synapses: a case study on neuroligin. Neuropharmacology 47(5):724–733

    Article  PubMed  CAS  Google Scholar 

  88. Moessner R, Marshall CR, Sutcliffe JS et al (2007) Contributions of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet 81(6):1289–1297

    Article  PubMed  CAS  Google Scholar 

  89. Nickl-Jockschat T, Rietschel M, Kircher T (2009) Korrelation zwischen Risikogenvarianten für Schizophrenie und Hirnstrukturanomalien. Nervenarzt 80(1):40–2, 44–48

    Article  PubMed  CAS  Google Scholar 

  90. Nowell MA, Hackney DB, Muraki AS et al (1990) Varied MR appearance in autism: fifty-three pediatric patients having the full autistic syndrome. Magn Reson Imaging 8(6):811–816

    Article  PubMed  CAS  Google Scholar 

  91. Nurmi EL, Bradford Y, Chen Y et al (2001) Linkage disequilibrium at the Angelman syndromegene UBE3A in autism families. Genomics 77:105–113

    Article  PubMed  CAS  Google Scholar 

  92. Palmen SJ, Hulshoff Pol HE, Kemner C et al (2005) Increased grey-matter volume in medication-naive high-functioning children with autism spectrum disorder. Psychol Med 35(4):561–570

    Article  PubMed  Google Scholar 

  93. Pardo CA, Eberhard CG (2007) The neurobiology of autism. Brain Pathol 17(4):434–447

    Article  PubMed  CAS  Google Scholar 

  94. Persico AM, D’Agruma L, Maiorano N et al (2001) Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder. Mol Psychiatry 6(2):150–159

    Article  PubMed  CAS  Google Scholar 

  95. Peters SU, Beaudet AL, Madduri N et al (2004) Autism in Angelman syndrome: implications for autism research. Clin Genet 66:530–536

    Article  PubMed  CAS  Google Scholar 

  96. Pilarski R, Eng C (2004) Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome. Neuron 30:79–89

    Google Scholar 

  97. Piven J, Arndt S (1995) The cerebellum and autism. Neurology 45(2):398–402

    PubMed  CAS  Google Scholar 

  98. Piven J, Arndt S, Bailey J et al (1996) Regional brain enlargement in autism: a magnetic resonance imaging study. J Am Acad Child Adolesc Psychiatry 35(4):530–536

    Article  PubMed  CAS  Google Scholar 

  99. Powell EM, Mars WM, Levitt P (2001) Hepatocyte growth factor/scatter factor is a motogen for interneurons migrating from the ventral to dorsal telencephalon. Neuron 30(1):79–89

    Article  PubMed  CAS  Google Scholar 

  100. Powell EM, Mühlfriedel S, Bolz J et al (2003) Differential regulation of thalamic and cortical axonal growth by hepatocyte growth factor/scatter factor. Dev Neurosci 25:197–206

    Article  PubMed  CAS  Google Scholar 

  101. Qin J, Jia M, Wang L et al (2009) Association study of SHANK3 gene polymorphisms with autism in Chinese Han population. BMC Med Genet 10:61

    Article  PubMed  CAS  Google Scholar 

  102. Radyushkin K, Hammerschmidt K, Boretius S et al (2009) Neuroligin-3-deficient mice: model of a monogenic heritable form of autism with an olfactory deficit. Genes Brain Behav 8(4):416–425

    Article  PubMed  CAS  Google Scholar 

  103. Ramocki MB, Zoghbi HY (2008) Failure of neuronal homeostasis results in common neuropsychiatric phenotypes. Nature 455(7215):912–918

    Article  PubMed  CAS  Google Scholar 

  104. Redcay E, Courchesne E (2005) When is the brain enlarged in autism? A meta-analysis of all brain size reports. Biol Psychiatry 58(1):1–9

    Article  PubMed  Google Scholar 

  105. Remschmidt H, Hebebrand J (2001) Das Asperger-Syndrom. Eine aktuelle Übersicht. Z Kinder Jugendpsychiatr Psychother 29:59–69

    Article  PubMed  CAS  Google Scholar 

  106. Remschmidt H, Kamp-Becker I (2007) Das Asperger-Syndrom – eine Autismus-Spektrum-Störung. Dtsch Ärztebl 104(13):A873–882

    Google Scholar 

  107. Remschmidt H (2008) Autismus. In: Herpertz-Dahlmann B, Resch F, Schulte-Markwort M (Hrsg) Entwicklungspsychiatrie. Biopsychologische Grundlagen und die Entwicklung psychischer Störungen. Schattauer, Stuttgart, S 373–396

  108. Rice SA, Bigler ED, Cleavinger HB et al (2005) Macrocephaly, corpus callosum morphology and autism. J Child Neurol 20(1):34–41

    Article  PubMed  Google Scholar 

  109. Richdale AL, Prior MR (1995) The sleep/wake rhythm in children with autism. Eur Child Adolesc Psychiatry 4(3):175–186

    Article  PubMed  CAS  Google Scholar 

  110. Rojas DC, Bawn SD, Benkers TL et al (2002) Smaller left hemisphere planum temporale in adults with autistic disorder. Neurosci Lett 328:237–240

    Article  PubMed  CAS  Google Scholar 

  111. Ronald A, Happe F, Bolton P et al (2006) Genetic heterogeneity between the three components of the autism spectrum: a twin study. J Am Acad Child Adolesc Psychiatry 45(6):691–696

    Article  PubMed  Google Scholar 

  112. Saitoh O, Karns CM, Courchesne E (2001) Development of the hippocampal formation from 2 to 42 years: MRI evidence of smaller area dentata in autism. Brain 124:1317–1324

    Article  PubMed  CAS  Google Scholar 

  113. Samaco RC, Hogart A, LeSalle JM (2005) Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Hum Mol Genet 14(4):483–492

    Article  PubMed  CAS  Google Scholar 

  114. Scheffner M, Huibregtse JM, Vierstra RD et al (1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75(3):495–505

    Article  PubMed  CAS  Google Scholar 

  115. Sebat J, Lakshmi B, Troge J et al (2004) Large-scale copy number polymorphism in the human genome. Science 305(5683):525–528

    Article  PubMed  CAS  Google Scholar 

  116. Sebat J, Lakshmi B, Malhotra D et al (2007) Strong association of de novo copy number mutations with autism. Science 316:445–449

    Article  PubMed  CAS  Google Scholar 

  117. Serajee FJ, Zhong H, Mahbubul Hug AH (2006) Association of Reelin gene polymorphisms with autism. Genomics 87(1):75–83

    Article  PubMed  CAS  Google Scholar 

  118. Skaar DA, Shao Y, Haines JL et al (2005) Analysis of the RELN gene as a genetic risk factor for autism. Mol Psychiatry 10(6):563–571

    Article  PubMed  CAS  Google Scholar 

  119. Skuse DH (2007) Rethinking the nature of genetic vulnerability to autism spectrum disorders. Trends Genetic 23(8):387–395

    Article  CAS  Google Scholar 

  120. Slavotinek AM (2008) Novel microdeletion syndromes detected by chromosome microarrays. Hum Genet 124(1):1–17

    Article  PubMed  CAS  Google Scholar 

  121. Sparks BF, Friedman SD, Shaw DW et al (2002) Brain structural abnormalities in young children with autism spectrum disorder. Neurology 59(2):184–192

    PubMed  CAS  Google Scholar 

  122. Stanfield AC, McIntosh AM, Spencer MD et al (2008) Towards a neuroanatomy of autism: a systematic review and meta-analysis of structural magnetic resonance imaging studies. Eur Psychiatry 23(4):289–299

    Article  PubMed  Google Scholar 

  123. Steffenburg S, Gillberg C, Hellgren L et al (1989) A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry 30(3):405–416

    Article  PubMed  CAS  Google Scholar 

  124. Sykes DH (2007) Rethinking the nature of genetic vulnerability to autism spectrum disorders. Trends Genetic 23(8):387–395

    Article  CAS  Google Scholar 

  125. Szatmari P, Paterson AD, Zwaigenbaum L et al (2007) Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet 39(3):319–328

    Article  PubMed  CAS  Google Scholar 

  126. Tidmarsh L, Volkmar FR (2003) Diagnosis and epidemiology of autism spectrum disorders. Can J Psychiatry 48:517–525

    PubMed  Google Scholar 

  127. Varoqueaux F, Aramuni G, Rawson RL et al (2006) Neuroligins determine synapse maturation and function. Neuron 51(6):741–754

    Article  PubMed  CAS  Google Scholar 

  128. Vincent JB, Kolozsvari D, Roberts WS et al (2004) Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands. Am J Med Genet B Neuropsychiatr Genet 129B(1):82–84

    Article  PubMed  Google Scholar 

  129. Volkmar FR, Nelson DS (1990) Seizure disorders in autism. J Am Acad Child Adolesc Psychiatry 29(1):127–129

    Article  PubMed  CAS  Google Scholar 

  130. Vorstman JA, Staal WG, Daalen E van et al (2006) Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism. Mol Psychiatry 11(1):18–28

    Article  CAS  Google Scholar 

  131. Weiss LA, Shen Y, Korn JM et al (2008) Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med 358(7):667–675

    Article  PubMed  CAS  Google Scholar 

  132. Wilson HL, Crolla JA, Walker D et al (2008) Intersitial 22q13 deletions: genes other than SHANK3 have major effects on cognitive and language development. Eur J Hum Genet 2008 16(11):1301–1310

    Article  CAS  Google Scholar 

  133. Yan J, Oliveira G, Coutinho A et al (2005) Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients. Mol Psychiatry 10(4):329–332

    Article  PubMed  CAS  Google Scholar 

  134. Zhang H, Liu X, Zhang C et al (2002) Reelin gene alleles and susceptibility to autism spectrum disorders. Mol Psychiatry 7(9):1012–1017

    Article  PubMed  CAS  Google Scholar 

  135. Zhao X, Leotta A, Kustanovich V et al (2007) A unified genetic theory for sporadic and inherited autism. Proc Natl Acad Sci U S A 104:12831–12836

    Article  PubMed  CAS  Google Scholar 

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  1. Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Aachen, Pauwelsstraße 30, 2074, Aachen, Deutschland

    T. Nickl-Jockschat & T.M. Michel

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  1. T. Nickl-Jockschat
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  2. T.M. Michel
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Nickl-Jockschat, T., Michel, T. Genetische und hirnstrukturelle Anomalien bei Autismus-Spektrum-Störungen. Nervenarzt 82, 618–627 (2011). https://doi.org/10.1007/s00115-010-2989-5

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