European Journal of Pediatrics

, Volume 167, Issue 10, pp 1091–1101 | Cite as

What’s new in autism?

Review

Abstract

This review on autism spectrum disorder (ASD) focusses on recent insights in the clinical picture, such as continuity of the phenotype and the concept of broader phenotype, on epidemiology and on clinical issues relevant to physicians, including new methods for early screening and diagnosis, psychiatric and somatic co-morbidity, and the expansion of so-called complementary and alternative treatments. ASD is a disorder with mainly genetic causes and recent insights show that a variety of genetic mechanisms may be involved, i.e. single gene disorders, copy number variations and polygenic mechanisms. Technological advances in genetics have lead to a number of promising findings, which, together with other lines of fundamental research, suggest that ASD may be a disorder of connectivity in the brain, at least in a subgroup of patients. It is possible that part of the genetic load in autism actually reflects gene–environment interaction, but there is no evidence for purely environmental causes in a substantial number of cases. Clinical research suggests that ASD may be a multi-system disorder in at least a subgroup of subjects, affecting the gastro-intestinal (GI) tract, the immune system and perhaps other systems. Behavioural treatments remain the cornerstone of management, and are mainly aimed at stimulation of the domains of impaired development and reducing secondary behaviours. These treatments are constantly being refined, but the main progress in this area may be the increase of research on effectiveness.

Keywords

Autism Review Autism spectrum disorders Pervasive developmental disorders 

Abbreviations

ADHD

Attention deficit and hyperactivity disorder

ASD

Autism spectrum disorder

BAP

Broader autism phenotype

CAM

Complementary and alternative medical treatments

CDD

Childhood disintegrative disorder

DSM-IV

Diagnostic and statistical manual of mental disorders, 4th edition

GERD

Gastro-oesophageal reflux disorder

LKS

Landau-Kleffner syndrome

MEG

Magnetoencephalography

MNS

Mirror neuron system

PECS

Picture exchange communication system

PDD

Pervasive developmental disorder

PDD-NOS

Pervasive developmental disorder not otherwise specified

NLD

Non-verbal learning disability

SLI

Specific language impairment

TEACCH

Treatment and Education of Autistic and related Communication-handicapped Children

TSC

Tuberous sclerosis complex

References

  1. 1.
    Alarcón M, Abrahams BS, Stone JL, Duvall JA, Perederiy JV, Bomar JM, Sebat J, Wigler M, Martin CL, Ledbetter DH, Nelson SF, Cantor RM, Geschwind DH (2008) Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am J Hum Genet 82:150–159PubMedCrossRefGoogle Scholar
  2. 2.
    American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. APA, Washington, DCGoogle Scholar
  3. 3.
    Anderson GM, Scahill L, McCracken JT, McDougle CJ, Aman MG, Tierney E, Arnold LE, Martin A, Katsovich L, Posey DJ, Shah B, Vitiello B (2007) Effects of short- and long-term risperidone treatment on prolactin levels in children with autism. Biol Psychiatry 61:545–550PubMedCrossRefGoogle Scholar
  4. 4.
    Antshel KM, Aneja A, Strunge L, Peebles J, Fremont WP, Stallone K, AbdulSabur N, Higgins AM, Shprintzen RJ, Kates WR (2007) Autistic spectrum disorders in velo-cardio facial syndrome (22q11.2 deletion). J Autism Dev Disord 37:1776–1786PubMedCrossRefGoogle Scholar
  5. 5.
    Arnold LE, Aman MG, Martin A, Collier-Crespin A, Vitiello B, Tierney E, Asarnow R, Bell-Bradshaw F, Freeman BJ, Gates-Ulanet P, Klin A, McCracken JT, McDougle CJ, McGough JJ, Posey DJ, Scahill L, Swiezy NB, Ritz L, Volkmar FR (2000) Assessment in multisite randomized clinical trials of patients with autistic disorder: the Autism RUPP Network. Research Units on Pediatric Psychopharmacology. J Autism Dev Disord 30:99–111PubMedCrossRefGoogle Scholar
  6. 6.
    Ashwood P, Van de Water J (2004) Is autism an autoimmune disease? Autoimmun Rev 3:557–562PubMedCrossRefGoogle Scholar
  7. 7.
    Asperger H (1944) “Autistic psychopathy” in childhood (translated and annotated). In: Frith U (ed) (1991) Autism and Asperger syndrome. Cambridge University Press, Cambridge UK, pp 37–92Google Scholar
  8. 8.
    Autism and Developmental Disabilities Monitoring Network Surveillance Year 2002 Principal Investigators; Centers for Disease Control and Prevention (2007) Prevalence of autism spectrum disorders—autism and developmental disabilities monitoring network, 14 sites, United States, 2002. MMWR Surveill Summ 56:12–28Google Scholar
  9. 9.
    Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M (1995) Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 25:63–77PubMedGoogle Scholar
  10. 10.
    Baird G, Charman T, Baron-Cohen S, Cox A, Swettenham J, Wheelwright S, Drew A (2000) A screening instrument for autism at 18 months of age: a 6-year follow-up study. J Am Acad Child Adolesc Psychiatry 39:694–702PubMedCrossRefGoogle Scholar
  11. 11.
    Baird G, Robinson RO, Boyd S, Charman T (2006) Sleep electroencephalograms in young children with autism with and without regression. Dev Med Child Neurol 48:604–608PubMedCrossRefGoogle Scholar
  12. 12.
    Baird G, Simonoff E, Pickles A, Chandler S, Loucas T, Meldrum D, Charman T (2006) Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP). Lancet 368:210–215PubMedCrossRefGoogle Scholar
  13. 13.
    Baron-Cohen S (2004) The cognitive neuroscience of autism. J Neurol Neurosurg Psychiatry 75:945–948PubMedCrossRefGoogle Scholar
  14. 14.
    Baron-Cohen S, Allen J, Gillberg C (1992) Can autism be detected at 18 months? The needle, the haystack, and the CHAT. Br J Psychiatry 161:839–843PubMedGoogle Scholar
  15. 15.
    Baron-Cohen S, Scahill VL, Izaguirre J, Hornsey H, Robertson MM (1999) The prevalence of Gilles de la Tourette syndrome in children and adolescents with autism: a large scale study. Psychol Med 29:1151–1159PubMedCrossRefGoogle Scholar
  16. 16.
    Battaglia A (2007) On the selection of patients with developmental delay/mental retardation and autism spectrum disorders for genetic studies. Am J Med Genet A 143:789–790Google Scholar
  17. 17.
    Battaglia A, Carey JC (2006) Etiologic yield of autistic spectrum disorders: a prospective study. Am J Med Genet C Semin Med Genet 142:3–7Google Scholar
  18. 18.
    Besag FM (2004) Behavioral aspects of pediatric epilepsy syndromes. Epilepsy Behav 5(Suppl 1):S3–S13PubMedCrossRefGoogle Scholar
  19. 19.
    Bethea TC, Sikich L (2007) Early pharmacological treatment of autism: a rationale for developmental treatment. Biol Psychiatry 61:521–537PubMedCrossRefGoogle Scholar
  20. 20.
    Bondy AS, Frost LA (1998) The picture exchange communication system. Semin Speech Lang 19:373–388PubMedGoogle Scholar
  21. 21.
    Bondy A, Frost L (2001) The Picture Exchange Communication System. Behav Modif 25:725–744PubMedCrossRefGoogle Scholar
  22. 22.
    Buie T (2007) Gastrointestinal disorders and autism. In: Proceedings of the 6th International Meeting for Autism Research (IFMAR), Seattle, Washington, May 2007Google Scholar
  23. 23.
    Canitano R (2007) Epilepsy in autism spectrum disorders. Eur Child Adolesc Psychiatry 16:61–66PubMedCrossRefGoogle Scholar
  24. 24.
    Canitano R, Luchetti A, Zappella M (2005) Epilepsy, electroencephalographic abnormalities, and regression in children with autism. J Child Neurol 20:27–31PubMedCrossRefGoogle Scholar
  25. 25.
    Carr D, Felce J (2007) The effects of PECS teaching to Phase III on the communicative interactions between children with autism and their teachers. J Autism Dev Disord 37:724–737PubMedCrossRefGoogle Scholar
  26. 26.
    Castermans D, Wilquet V, Parthoens E, Huysmans C, Steyaert J, Swinnen L, Fryns JP, Van de Ven W, Devriendt K (2003) The neurobeachin gene is disrupted by a translocation in a patient with idiopathic autism. J Med Genet 40:352–356PubMedCrossRefGoogle Scholar
  27. 27.
    Castermans D, Wilquet V, Steyaert J, Van de Ven W, Fryns JP, Devriendt K (2004) Chromosomal anomalies in individuals with autism: a strategy towards the identification of genes involved in autism. Autism 8:141–161PubMedCrossRefGoogle Scholar
  28. 28.
    Castermans D, Vermeesch JR, Fryns JP, Steyaert JG, Van de Ven WJM, Creemers JWM, Devriendt K (2007) Identification and characterization of the TRIP8 and REEP3 genes on chromosome 10q21.3 as novel candidate genes for autism. Eur J Hum Genet 15:422–431PubMedCrossRefGoogle Scholar
  29. 29.
    Castermans D, Thienpont B, Volders K, Crepel A, Vermeesch JR, Schrander-Stumpel CT, Van de Ven WJ, Steyaert JG, Creemers JW, Devriendt K (2008) Position effect leading to haploinsufficiency in a mosaic ring chromosome 14 in a boy with autism. Eur J Hum Genet (in press)Google Scholar
  30. 30.
    Chakrabarti S, Fombonne E (2005) Pervasive developmental disorders in preschool children: confirmation of high prevalence. Am J Psychiatry 162:1133–1141PubMedCrossRefGoogle Scholar
  31. 31.
    Chawarska K, Klin A, Paul R, Volkmar FR (2007) Autism spectrum disorder in the second year: stability and change in syndrome expression. J Child Psychol Psychiatry 48:128–138PubMedCrossRefGoogle Scholar
  32. 32.
    Conciatori M, Stodgell CJ, Hyman SL, O’Bara M, Militerni R, Bravaccio C, Trillo S, Montecchi F, Schneider C, Melmed R, Elia M, Crawford L, Spence SJ, Muscarella L, Guarnieri V, D’Agruma L, Quattrone A, Zelante L, Rabinowitz D, Pascucci T, Puglisi-Allegra S, Reichelt KL, Rodier PM, Persico AM (2004) Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism. Biol Psychiatry 55:413–419PubMedCrossRefGoogle Scholar
  33. 33.
    Constantino JN, Lajonchere C, Lutz M, Gray T, Abbacchi A, McKenna K, Singh D, Todd RD (2006) Autistic social impairment in the siblings of children with pervasive developmental disorders. Am J Psychiatry 163:294–296PubMedCrossRefGoogle Scholar
  34. 34.
    Coonrod EE, Stone WL (2005) Screening for autism in young children. In: Volkmar FR, Paul R, Klin A, Cohen DJ (eds) Handbook of autism and pervasive developmental disorders, 3rd edn. Wiley, Hoboken, NJGoogle Scholar
  35. 35.
    Correll CU, Carlson HE (2006) Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. J Am Acad Child Adolesc Psychiatry 45:771–791PubMedGoogle Scholar
  36. 36.
    Courchesne E (2004) Brain development in autism: early overgrowth followed by premature arrest of growth. Ment Retard Dev Disabil Res Rev 10:106–111PubMedCrossRefGoogle Scholar
  37. 37.
    Courchesne E, Pierce K (2005) Brain overgrowth in autism during a critical time in development: implications for frontal pyramidal neuron and interneuron development and connectivity. Int J Dev Neurosci 23:153–170PubMedCrossRefGoogle Scholar
  38. 38.
    Courchesne E, Carper R, Akshoomoff N (2003) Evidence of brain overgrowth in the first year of life in autism. JAMA 290:337–344PubMedCrossRefGoogle Scholar
  39. 39.
    Dapretto M, Davies MS, Pfeifer JH, Scott AA, Sigman M, Bookheimer SY, Iacoboni M (2006) Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders. Nat Neurosci 9:28–30PubMedCrossRefGoogle Scholar
  40. 40.
    Dawson G, Webb S, Schellenberg GD, Dager S, Friedman S, Aylward E, Richards T (2002) Defining the broader phenotype of autism: genetic, brain, and behavioral perspectives. Dev Psychopathol 14:581–611PubMedCrossRefGoogle Scholar
  41. 41.
    Dawson G, Estes A, Munson J, Schellenberg G, Bernier R, Abbott R (2007) Quantitative assessment of autism symptom-related traits in probands and parents: Broader Phenotype Autism Symptom Scale. J Autism Dev Disord 37:523–536PubMedCrossRefGoogle Scholar
  42. 42.
    De Hert M, van Eyck D, De Nayer A (2006) Metabolic abnormalities associated with second generation antipsychotics: fact or fiction? Development of guidelines for screening and monitoring. Int Clin Psychopharmacol 21:S11–S15PubMedCrossRefGoogle Scholar
  43. 43.
    di Pellegrino G, Fadiga L, Fogassi L, Gallese V, Rizzolatti G (1992) Understanding motor events: a neurophysiological study. Exp Brain Res 91:176–180PubMedCrossRefGoogle Scholar
  44. 44.
    Doja A, Roberts W (2006) Immunizations and autism: a review of the literature. Can J Neurol Sci 33:341–346PubMedGoogle Scholar
  45. 45.
    Dziobek I, Fleck S, Rogers K, Wolf OT, Convit A (2006) The ‘amygdala theory of autism’ revisited: linking structure to behavior. Neuropsychologia 44:1891–1899PubMedCrossRefGoogle Scholar
  46. 46.
    Esch BE, Carr JE (2004) Secretin as a treatment for autism: a review of the evidence. J Autism Dev Disord 34:543–556PubMedCrossRefGoogle Scholar
  47. 47.
    Feasby T, Banwell B, Benstead T, Bril V, Brouwers M, Freedman M, Hahn A, Hume H, Freedman J, Pi D, Wadsworth L (2007) Guidelines on the use of intravenous immune globulin for neurologic conditions. Transfus Med Rev 21:S57–S107PubMedCrossRefGoogle Scholar
  48. 48.
    Findling RL (2005) Pharmacologic treatment of behavioral symptoms in autism and pervasive developmental disorders. J Clin Psychiatry 66(Suppl 10):26–31PubMedGoogle Scholar
  49. 49.
    Folstein SE, Rosen-Sheidley B (2001) Genetics of autism: complex aetiology for a heterogeneous disorder. Nat Rev Genet 2:943–955PubMedCrossRefGoogle Scholar
  50. 50.
    Folstein S, Rutter M (1977) Genetic influences and infantile autism. Nature 265:726–728PubMedCrossRefGoogle Scholar
  51. 51.
    Fombonne E (2005) Epidemiology of autistic disorder and other pervasive developmental disorders. J Clin Psychiatry 66(Suppl 10):3–8PubMedGoogle Scholar
  52. 52.
    Fombonne E, Zakarian R, Bennett A, Meng LY, McLean-Heywood D (2006) Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations. Pediatrics 118:E139–E150PubMedCrossRefGoogle Scholar
  53. 53.
    Freitag CM (2007) The genetics of autistic disorders and its clinical relevance: a review of the literature. Mol Psychiatry 12:2–22PubMedCrossRefGoogle Scholar
  54. 54.
    Gadow KD, DeVincent CJ, Pomeroy J, Azizian A (2004) Psychiatric symptoms in preschool children with PDD and clinic and comparison samples. J Autism Dev Disord 34:379–393PubMedCrossRefGoogle Scholar
  55. 55.
    Gallese V, Keysers C, Rizzolatti G (2004) A unifying view of the basis of social cognition. Trends Cogn Sci 8:396–403PubMedCrossRefGoogle Scholar
  56. 56.
    Georgiades S, Szatmari P, Zwaigenbaum L, Duku E, Bryson S, Roberts W, Goldberg J, Mahoney W (2007) Structure of the autism symptom phenotype: a proposed multidimensional model. J Am Acad Child Adolesc Psychiatry 46:188–196PubMedCrossRefGoogle Scholar
  57. 57.
    Geschwind DH, Levitt P (2007) Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol 17:103–111PubMedCrossRefGoogle Scholar
  58. 58.
    Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645PubMedCrossRefGoogle Scholar
  59. 59.
    Gupta S (2000) Immunological treatments for autism. J Autism Dev Disord 30:475–479PubMedCrossRefGoogle Scholar
  60. 60.
    Gupta AR, State MW (2007) Recent advances in the genetics of autism. Biol Psychiatry 61:429–437PubMedCrossRefGoogle Scholar
  61. 61.
    Hanson JE, Madison DV (2007) Presynaptic FMR1 genotype influences the degree of synaptic connectivity in a mosaic mouse model of fragile X syndrome. J Neurosci 27:4014–4018PubMedCrossRefGoogle Scholar
  62. 62.
    Hanson E, Kalish LA, Bunce E, Curtis C, McDaniel S, Ware J, Petry J (2007) Use of complementary and alternative medicine among children diagnosed with autism spectrum disorder. J Autism Dev Disord 37:628–636PubMedCrossRefGoogle Scholar
  63. 63.
    Holtmann M, Bolte S, Poustka F (2007) Attention deficit hyperactivity disorder symptoms in pervasive developmental disorders: association with autistic behavior domains and coexisting psychopathology. Psychopathology 40:172–177PubMedCrossRefGoogle Scholar
  64. 64.
    Horvath K, Stefanatos G, Sokolski KN, Wachtel R, Nabors L, Tildon JT (1998) Improved social and language skills after secretin administration in patients with autistic spectrum disorders. J Assoc Acad Minor Phys 9:9–15PubMedGoogle Scholar
  65. 65.
    Howlin P, Goode S, Hutton J, Rutter M (2004) Adult outcome for children with autism. J Child Psychol Psychiatry 45:212–229PubMedCrossRefGoogle Scholar
  66. 66.
    Icasiano F, Hewson P, Machet P, Cooper C, Marshall A (2004) Childhood autism spectrum disorder in the Barwon region: a community based study. J Paediatr Child Health 40:696–701PubMedCrossRefGoogle Scholar
  67. 67.
    Ingersoll B, Schreibman L (2006) Teaching reciprocal imitation skills to young children with autism using a naturalistic behavioral approach: effects on language, pretend play, and joint attention. J Autism Dev Disord 36:487–505PubMedCrossRefGoogle Scholar
  68. 68.
    Jamain S, Quach H, Betancur C, Råstam M, Colineaux C, Gillberg IC, Soderstrom H, Giros B, Leboyer M, Gillberg C, Bourgeron T; Paris Autism Research International Sibpair Study (2003) Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34:27–29PubMedCrossRefGoogle Scholar
  69. 69.
    Jesner O, Aref-Adib M, Coren E (2007) Risperidone for autism spectrum disorder. Cochrane Database Syst Rev (1):CD005040Google Scholar
  70. 70.
    Johnson MH (2007) Developing a social brain. Acta Paediatr 96:3–5PubMedCrossRefGoogle Scholar
  71. 71.
    Johnson CP, Myers SM; American Academy of Pediatrics Council on Children With Disabilities (2007) Identification and evaluation of children with autism spectrum disorders. Pediatrics 120:1183–1215PubMedCrossRefGoogle Scholar
  72. 72.
    Johnson MH, Griffin R, Csibra G, Halit H, Farroni T, de Haan M, Tucker LA, Baron-Cohen S, Richards J (2005) The emergence of the social brain network: evidence from typical and atypical development. Dev Psychopathol 17:599–619PubMedCrossRefGoogle Scholar
  73. 73.
    Jyonouchi H, Geng L, Ruby A, Reddy C, Zimmerman-Bier B (2005) Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders. J Pediatr 146:605–610PubMedCrossRefGoogle Scholar
  74. 74.
    Kanner L (1943) Autistic disturbances of affective contact. Nerv Child 2:217–250Google Scholar
  75. 75.
    Keen D, Ward S (2004) Autistic spectrum disorder: a child population profile. Autism 8:39–48PubMedCrossRefGoogle Scholar
  76. 76.
    Kim HL, Donnelly JH, Tournay AE, Book TM, Filipek P (2006) Absence of seizures despite high prevalence of epileptiform EEG abnormalities in children with autism monitored in a tertiary care center. Epilepsia 47:394–398PubMedCrossRefGoogle Scholar
  77. 77.
    Kim HG, Kishikawa S, Higgins AW, Seong IS, Donovan DJ, Shen Y, Lally E, Weiss LA, Najm J, Kutsche K, Descartes M, Holt L, Braddock S, Troxell R, Kaplan L, Volkmar FR, Klin A, Tsatsanis K, Harris DJ, Noens I, Pauls DL, Daly MJ, MacDonald ME, Morton CC, Quade BJ, Gusella JF (2008) Disruption of neurexin 1 associated with autism spectrum disorder. Am J Hum Genet 82:199–207PubMedCrossRefGoogle Scholar
  78. 78.
    Klin A, Saulnier CA, Sparrow SS, Cicchetti DV, Volkmar FR, Lord C (2007) Social and communication abilities and disabilities in higher functioning individuals with autism spectrum disorders: the Vineland and the ADOS. J Autism Dev Disord 37:748–759PubMedCrossRefGoogle Scholar
  79. 79.
    Kolevzon A, Mathewson KA, Hollander E (2006) Selective serotonin reuptake inhibitors in autism: a review of efficacy and tolerability. J Clin Psychiatry 67:407–414PubMedGoogle Scholar
  80. 80.
    Kosinovsky B, Hermon S, Yoran-Hegesh R, Golomb A, Senecky Y, Goez H, Kramer U (2005) The yield of laboratory investigations in children with infantile autism. J Neural Transm 112:587–596PubMedCrossRefGoogle Scholar
  81. 81.
    Kumar RA, KaraMohamed S, Sudi J, Conrad DF, Brune C, Badner JA, Gilliam TC, Nowak NJ, Cook EH Jr, Dobyns WB, Christian SL (2008) Recurrent 16p11.2 microdeletions in autism. Hum Mol Genet 17:628–638PubMedCrossRefGoogle Scholar
  82. 82.
    Lainhart JE, Bigler ED, Bocian M, Coon H, Dinh E, Dawson G, Deutsch CK, Dunn M, Estes A, Tager-Flusberg H, Folstein S, Hepburn S, Hyman S, McMahon W, Minshew N, Munson J, Osann K, Ozonoff S, Rodier P, Rogers S, Sigman M, Spence MA, Stodgell CJ, Volkmar FR (2006) Head circumference and height in autism: a study by the Collaborative Program of Excellence in Autism. Am J Med Genet A 140:2257–2274PubMedGoogle Scholar
  83. 83.
    Le Couteur A, Bailey A, Goode S, Pickles A, Robertson S, Gottesman I, Rutter M (1996) A broader phenotype of autism: the clinical spectrum in twins. J Child Psychol Psychiatry 37:785–801PubMedCrossRefGoogle Scholar
  84. 84.
    Levy SE, Hyman SL (2005) Novel treatments for autistic spectrum disorders. Ment Retard Dev Disabil Res Rev 11:131–142PubMedCrossRefGoogle Scholar
  85. 85.
    Levy SE, Souders MC, Ittenbach RF, Giarelli E, Mulberg AE, Pinto-Martin JA (2007) Relationship of dietary intake to gastrointestinal symptoms in children with autistic spectrum disorders. Biol Psychiatry 61:492–497PubMedCrossRefGoogle Scholar
  86. 86.
    Lord C, Corsello C (2005) Diagnostic instruments in autistic spectrum disorders. In: Volkmar FR, Paul R, Klin A, Cohen DJ (eds) Handbook of autism and pervasive developmental disorders, 3rd edn. Wiley, Hoboken, NJGoogle Scholar
  87. 87.
    Lord C, Rutter M, Goode S, Heemsbergen J, Jordan H, Mawhood L, Schopler E (1989) Autism diagnostic observation schedule: a standardized observation of communicative and social behavior. J Autism Dev Disord 19:185–212PubMedCrossRefGoogle Scholar
  88. 88.
    Lord C, Rutter M, Le Couteur A (1994) Autism Diagnostic Interview—Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord. 24:659–685PubMedCrossRefGoogle Scholar
  89. 89.
    Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC, Pickles A, Rutter M (2000) The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord 30:205–223PubMedCrossRefGoogle Scholar
  90. 90.
    Lucarelli S, Frediani T, Zingoni AM, Ferruzzi F, Giardini O, Quintieri F, Barbato M, D’Eufemia P, Cardi E (1995) Food allergy and infantile autism. Panminerva Med 37:137–141PubMedGoogle Scholar
  91. 91.
    Marans WD, Rubin E, Laurent A (2005) Communication skills in individuals with high-functioning autism and Asperger syndrome. In: Volkmar FR, Paul R, Klin A, Cohen DJ (eds) Handbook of autism and pervasive developmental disorders, 3rd edn. Wiley, Hoboken, NJGoogle Scholar
  92. 92.
    McDonald BC (2002) Recent developments in the application of the nonverbal learning disabilities model. Curr Psychiatry Rep 4:323–330PubMedCrossRefGoogle Scholar
  93. 93.
    McDougle CJ, Scahill L, Aman MG, McCracken JT, Tierney E, Davies M, Arnold LE, Posey DJ, Martin A, Ghuman JK, Shah B, Chuang SZ, Swiezy NB, Gonzalez NM, Hollway J, Koenig K, McGough JJ, Ritz L, Vitiello B (2005) Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology. Am J Psychiatry 162:1142–1148PubMedCrossRefGoogle Scholar
  94. 94.
    McVicar KA, Shinnar S, Ballaban-Gil K, Rapin I, Moshe SL (2005) Clinical and EEG characteristics of children with language regression. Neurology 64:A433–A434Google Scholar
  95. 95.
    Muhle R, Trentacoste SV, Rapin I (2004) The genetics of autism. Pediatrics 113:e472–e486PubMedCrossRefGoogle Scholar
  96. 96.
    Myers SM, Johnson CP; American Academy of Pediatrics Council on Children With Disabilities (2007) Management of children with autism spectrum disorders. Pediatrics 120:1162–1182PubMedCrossRefGoogle Scholar
  97. 97.
    National Center for Health Statistics (2008) NCHS definitions. Health, United States. Centers for Disease ControlGoogle Scholar
  98. 98.
    National Research Council (NRC) Committee on Educational Interventions for Children with Autism (2001) Educating children with autism. National Academies Press, Washington, DCGoogle Scholar
  99. 99.
    Newcomer JW (2007) Antipsychotic medications: metabolic and cardiovascular risk. J Clin Psychiatry 68:8–13PubMedCrossRefGoogle Scholar
  100. 100.
    Newschaffer CJ, Falb MD, Gurney JG (2005) National autism prevalence trends from United States special education data. Pediatrics 115:e277–e282PubMedCrossRefGoogle Scholar
  101. 101.
    Palmen SJ, Durston S, Nederveen H, Van Engeland H (2006) No evidence for preferential involvement of medial temporal lobe structures in high-functioning autism. Psychol Med 36:827–834PubMedCrossRefGoogle Scholar
  102. 102.
    Persico AM, Bourgeron T (2006) Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends Neurosci 29:349–358PubMedCrossRefGoogle Scholar
  103. 103.
    Pickles A, Starr E, Kazak S, Bolton P, Papanikolaou K, Bailey A, Goodman R, Rutter M (2000) Variable expression of the autism broader phenotype: findings from extended pedigrees. J Child Psychol Psychiatry 41:491–502PubMedCrossRefGoogle Scholar
  104. 104.
    Piven J, Palmer P, Jacobi D, Childress D, Arndt S (1997) Broader autism phenotype: evidence from a family history study of multiple-incidence autism families. Am J Psychiatry 154:185–190PubMedGoogle Scholar
  105. 105.
    Prizant BM, Wetherby AM (2005) Critical issues in enhancing communication abilities for persons with autism spectrum disorders. In: Volkmar FR, Paul R, Klin A, Cohen DJ (eds) Handbook of autism and pervasive developmental disorders, 3rd edn. Wiley, Hoboken, NJGoogle Scholar
  106. 106.
    Rogers SJ (2004) Developmental regression in autism spectrum disorders. Ment Retard Dev Disabil Res Rev 10:139–143PubMedCrossRefGoogle Scholar
  107. 107.
    Ronald A, Happé F, Bolton P, Butcher LM, Price TS, Wheelwright S, Baron-Cohen S, Plomin R (2006) Genetic heterogeneity between the three components of the autism spectrum: a twin study. J Am Acad Child Adolesc Psychiatry 45:691–699PubMedCrossRefGoogle Scholar
  108. 108.
    Rourke BP (1998) Symposium: Asperger, Williams, and velocardiofacial syndromes: the NLD connection. Clin Neuropsychol 12:266Google Scholar
  109. 109.
    Rourke BP, Fuerst DR (1992) Psychological dimensions of learning disability subtypes: neuropsychological studies in the windsor laboratory. School Psych Rev 21:361–374Google Scholar
  110. 110.
    Scahill L, Martin A (2005) Psychopharmacology. In: Volkmar FR, Paul R, Klin A, Cohen DJ (eds) Handbook of autism and pervasive developmental disorders, 3rd edn. Wiley, Hoboken, NJGoogle Scholar
  111. 111.
    Scambler DJ, Hepburn SL, Rogers SJ (2006) A two-year follow-up on risk status identified by the checklist for autism in toddlers. J Dev Behav Pediatr 27:S104–S110PubMedCrossRefGoogle Scholar
  112. 112.
    Schaefer GB, Mendelsohn NJ (2008) Clinical genetics evaluation in identifying the etiology of autism spectrum disorders. Genet Med 10:301–305PubMedGoogle Scholar
  113. 113.
    Schreibman L, Ingersoll B (2005) Behavioral interventions to promote learning in individuals with autism. In: Volkmar FR, Paul R, Klin A, Cohen DJ (eds) Handbook of autism and pervasive developmental disorders, 3rd edn. Wiley, Hoboken, NJ, pp 882–896Google Scholar
  114. 114.
    Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimäki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M (2007) Strong association of de novo copy number mutations with autism. Science 316:445–449PubMedCrossRefGoogle Scholar
  115. 115.
    Shaffer D, Fisher P, Lucas CP, Dulcan MK, Schwab-Stone ME (2000) NIMH Diagnostic Interview Schedule for Children Version IV (NIMH DISC-IV): description, differences from previous versions, and reliability of some common diagnoses. J Am Acad Child Adolesc Psychiatry 39:28–38PubMedCrossRefGoogle Scholar
  116. 116.
    Shattuck PT (2006) The contribution of diagnostic substitution to the growing administrative prevalence of autism in US special education. Pediatrics 117:1028–1037PubMedCrossRefGoogle Scholar
  117. 117.
    Singh J, Hallmayer J, Illes J (2007) Interacting and paradoxical forces in neuroscience and society. Nat Rev Neurosci 8:153–160PubMedCrossRefGoogle Scholar
  118. 118.
    Skuse D, Warrington R, Bishop D, Chowdhury U, Lau J, Mandy W, Place M (2004) The developmental, dimensional and diagnostic interview (3di): a novel computerized assessment for autism spectrum disorders. J Am Acad Child Adolesc Psychiatry 43:548–558PubMedCrossRefGoogle Scholar
  119. 119.
    Steyaert J, Fryns JP (2002) Psychiatric genetics: the case of single gene disorders. Eur Child Adolesc Psychiatry 11:201–209PubMedCrossRefGoogle Scholar
  120. 120.
    Szatmari P, Maziade M, Zwaigenbaum L, Mérette C, Roy MA, Joober R, Palmour R (2007) Informative phenotypes for genetic studies of psychiatric disorders. Am J Med Genet B Neuropsychiatr Genet 144B:581–588PubMedCrossRefGoogle Scholar
  121. 121.
    Tidmarsh L, Volkmar FR (2003) Diagnosis and epidemiology of autism spectrum disorders. Can J Psychiatry 48:517–525PubMedGoogle Scholar
  122. 122.
    Trevathan E (2004) Seizures and epilepsy among children with language regression and autistic spectrum disorders. J Child Neurol 19(Suppl 1):S49–S57PubMedGoogle Scholar
  123. 123.
    Valicenti-McDermott M, McVicar K, Rapin I, Wershil BK, Cohen H, Shinnar S (2006) Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease. J Dev Behav Pediatr 27:S128–S136PubMedCrossRefGoogle Scholar
  124. 124.
    Volkmar FR, Cohen DJ (1986) Current concepts: infantile autism and the pervasive developmental disorders. J Dev Behav Pediatr 7:324–329PubMedCrossRefGoogle Scholar
  125. 125.
    Vorstman JAS, Morcus MEJ, Duijff SN, Klaassen PWJ, Heineman-de Boer JA, Beemer FA, Swaab H, Kahn RS, van Engeland H (2006) The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J Am Acad Child Adolesc Psychiatry 45:1104–1113PubMedCrossRefGoogle Scholar
  126. 126.
    Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A, Davies SE, Walker-Smith JA (1998) Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 351:637–641PubMedCrossRefGoogle Scholar
  127. 127.
    Walkup JT, Labellarte MJ, Riddle MA, Pine DS, Greenhill L, Klein R, Davies M, Sweeney M, Abikoff H, Hack S, Klee B, McCracken J, Bergman L, Piacentini J, March J, Compton S, Robinson J, O’Hara T, Baker S, Vitiello B, Ritz LA, Roper M (2001) Fluvoxamine for the treatment of anxiety disorders in children and adolescents. N Engl J Med 344:1279–1285CrossRefGoogle Scholar
  128. 128.
    Weiss LA, Shen Y, Korn JM, Arking DE, Miller DT, Fossdal R, Saemundsen E, Stefansson H, Ferreira MA, Green T, Platt OS, Ruderfer DM, Walsh CA, Altshuler D, Chakravarti A, Tanzi RE, Stefansson K, Santangelo SL, Gusella JF, Sklar P, Wu BL, Daly MJ (2008) Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med 358:667–675PubMedCrossRefGoogle Scholar
  129. 129.
    Wijsman E (2007) Statistical genetic approaches for analysis of autism and autism endophenotypes. In: Proceedings of the 6th International Meeting for Autism Research (IFMAR), Seattle, Washington, May 2007Google Scholar
  130. 130.
    Wing L, Potter D (2002) The epidemiology of autistic spectrum disorders: is the prevalence rising? Ment Retard Dev Disabil Res Rev 8:151–161PubMedCrossRefGoogle Scholar
  131. 131.
    Wing L, Yeates SR, Brierley LM, Gould J (1976) The prevalence of early childhood autism: comparison of administrative and epidemiological studies. Psychol Med 6:89–100PubMedCrossRefGoogle Scholar
  132. 132.
    World Health Organization (WHO) (1992) The ICD-10 Classification of Mental and Behavioural Disorders. WHO, GenevaGoogle Scholar
  133. 133.
    Yeargin-Allsopp M, Rice C, Karapurkar T, Doernberg N, Boyle C, Murphy C (2003) Prevalence of autism in a US metropolitan area. JAMA 289:49–55PubMedCrossRefGoogle Scholar
  134. 134.
    Zhao X, Leotta A, Kustanovich V, Lajonchere C, Geschwind DH, Law K, Law P, Qiu S, Lord C, Sebat J, Ye K, Wigler M (2007) A unified genetic theory for sporadic and inherited autism. Proc Natl Acad Sci U S A 104:12831–12836PubMedCrossRefGoogle Scholar
  135. 135.
    Zwaigenbaum L, Thurm A, Stone W, Baranek G, Bryson S, Iverson J, Kau A, Klin A, Lord C, Landa R, Rogers S, Sigman M (2007) Studying the emergence of autism spectrum disorders in high-risk infants: methodological and practical issues. J Autism Dev Disord 37:466–480PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Department of Child and Adolescent PsychiatryKatholieke Universiteit Leuven (UZ Leuven)LeuvenBelgium
  2. 2.Department of Clinical GeneticsUniversity Hospital of MaastrichtMaastrichtThe Netherlands

Personalised recommendations