Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Primer
  • Published:

Autism spectrum disorder

Nature Reviews Disease Primers volume 6, Article number: 5 (2020) Cite this article

Subjects

Abstract

Autism spectrum disorder is a construct used to describe individuals with a specific combination of impairments in social communication and repetitive behaviours, highly restricted interests and/or sensory behaviours beginning early in life. The worldwide prevalence of autism is just under 1%, but estimates are higher in high-income countries. Although gross brain pathology is not characteristic of autism, subtle anatomical and functional differences have been observed in post-mortem, neuroimaging and electrophysiological studies. Initially, it was hoped that accurate measurement of behavioural phenotypes would lead to specific genetic subtypes, but genetic findings have mainly applied to heterogeneous groups that are not specific to autism. Psychosocial interventions in children can improve specific behaviours, such as joint attention, language and social engagement, that may affect further development and could reduce symptom severity. However, further research is necessary to identify the long-term needs of people with autism, and treatments and the mechanisms behind them that could result in improved independence and quality of life over time. Families are often the major source of support for people with autism throughout much of life and need to be considered, along with the perspectives of autistic individuals, in both research and practice.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Theories and findings regarding autism mechanisms, outcomes and heterogeneity.
Fig. 2: Environmental risk factors for autism.
Fig. 3: Encoded proteins associated with autism risk.
Fig. 4: Longitudinal trajectories of total brain volume, surface area and cortical thickness in autism.
Fig. 5: Co-occurring disorders.
Fig. 6: Major parental milestones in advocating and supporting their child with autism.
Fig. 7: Changes in daily living scores as predicted by IQ scores and autistic symptoms.

Similar content being viewed by others

References

  1. Lord, C. et al. Autism from 2 to 9 years of age. Arch. Gen. Psychiatry 63, 694–701 (2006). This paper establishes that autism is a stable diagnosis (as a spectrum) beginning at least by 2 years of age. The paper also establishes parent interview and clinician observation as predictive of autism at 9 years of age. Finally, it is the first paper that shows that the specific DSM-IV-TR diagnoses is unstable across childhood but that the instability is almost all shifting across categories not outside the spectrum.

    Article  PubMed  Google Scholar 

  2. Risi, S. et al. Combining information from multiple sources in the diagnosis of autism spectrum disorders. J. Am. Acad. Child Adolesc. Psychiatry 45, 1094–1103 (2006).

    Article  PubMed  Google Scholar 

  3. Loomes, R., Hull, L. & Mandy, W. P. L. What is the male-to-female ratio in autism spectrum disorder? A systematic review and meta-analysis. J. Am. Acad. Child Adolesc. Psychiatry 56, 466–474 (2017).

    Article  PubMed  Google Scholar 

  4. Brugha, T. S. et al. Epidemiology of autism in adults across age groups and ability levels. Br. J. Psychiatry 209, 498–503 (2016). This paper uses active case-finding to provide representative estimates of the prevalence of autism and demonstrated that rates of autism in men and women are equivalent in adults with moderate-to-profound intellectual disability.

    Article  PubMed  Google Scholar 

  5. Brugha, T., Bankart, J., McManus, S. & Gullon-Scott, F. CDC autism rate: misplaced reliance on passive sampling? Lancet 392, 732–733 (2018).

    Article  PubMed  Google Scholar 

  6. Baxter, A. J. et al. The epidemiology and global burden of autism spectrum disorders. Psychol. Med. 45, 601–613 (2015).

    Article  CAS  PubMed  Google Scholar 

  7. Elsabbagh, M. et al. Global prevalence of autism and other pervasive developmental disorders. Autism Res. 5, 160–179 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Magnusson, C. et al. Migration and autism spectrum disorder: population-based study. Br. J. Psychiatry 201, 109–115 (2012).

    Article  PubMed  Google Scholar 

  9. Goodman, R. & Richards, H. Child and adolescent psychiatric presentations of second-generation Afro-Caribbeans in Britain. Br. J. Psychiatry 167, 362–369 (1995).

    Article  CAS  PubMed  Google Scholar 

  10. Dyches, T. T., Wilder, L. K., Sudweeks, R. R., Obiakor, F. E. & Algozzine, B. Multicultural issues in autism. J. Autism Dev. Disord. 34, 211–222 (2004).

    Article  PubMed  Google Scholar 

  11. Keen, D. V., Reid, F. D. & Arnone, D. Autism, ethnicity and maternal immigration. Br. J. Psychiatry 196, 274–281 (2010).

    Article  CAS  PubMed  Google Scholar 

  12. McManus, S., Bebbington, P., Jenkins, R. & Brugha, T. Adult Psychiatric Morbidity Survey: mental health and wellbeing in England, 2014. NHS https://digital.nhs.uk/data-and-information/publications/statistical/adult-psychiatric-morbidity-survey/adult-psychiatric-morbidity-survey-survey-of-mental-health-and-wellbeing-england-2014 (2016).

  13. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392, 1789–1858 (2018).

    Article  Google Scholar 

  14. Marcheselli, F. et al. Mental health of children and young people in England, 2017. NHS https://digital.nhs.uk/data-and-information/publications/statistical/mental-health-of-children-and-young-people-in-england/2017/2017 (2018).

  15. Brugha, T. C. et al. Autism Spectrum Disorder, Adult Psychiatric Morbidity Survey 2014. (2014).

  16. Lundstrom, S., Reichenberg, A., Anckarsater, H., Lichtenstein, P. & Gillberg, C. Autism phenotype versus registered diagnosis in Swedish children: prevalence trends over 10 years in general population samples. BMJ 350, h1961 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Tromans, S., Chester, V., Kiani, R., Alexander, R. & Brugha, T. The prevalence of autism spectrum disorders in adult psychiatric inpatients: a systematic review. Clin. Pract. Epidemiol. Ment. Health 14, 177–187 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Modabbernia, A., Velthorst, E. & Reichenberg, A. Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Mol. Autism 8, 13 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Wu, S. et al. Advanced parental age and autism risk in children: a systematic review and meta-analysis. Acta Psychiatr. Scand. 135, 29–41 (2017).

    Article  CAS  PubMed  Google Scholar 

  20. Taylor, L. E., Swerdfeger, A. L. & Eslick, G. D. Vaccines are not associated with autism: an evidence-based meta-analysis of case-control and cohort studies. Vaccine 32, 3623–3629 (2014).

    Article  CAS  PubMed  Google Scholar 

  21. Lai, M.-C., Lombardo, M. V. & Baron-Cohen, S. Autism. Lancet 383, 896–910 (2014).

    Article  PubMed  Google Scholar 

  22. Velikonja, T., Fett, A.-K. & Velthorst, E. Patterns of nonsocial and social cognitive functioning in adults with autism spectrum disorder: a systematic review and meta-analysis. JAMA Psychiatry 76, 135–151 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  23. McNally Keehn, R. H., Lincoln, A. J., Brown, M. Z. & Chavira, D. A. The coping cat program for children with anxiety and autism spectrum disorder: a pilot randomized controlled trial. J. Autism Dev. Disord. 43, 57–67 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Jones, E. J. H., Gliga, T., Bedford, R., Charman, T. & Johnson, M. H. Developmental pathways to autism: a review of prospective studies of infants at risk. Neurosci. Biobehav. Rev. 39, 1–33 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ozonoff, S. et al. Recurrence risk for autism spectrum disorders: a baby siblings research consortium study. Pediatrics 128, e488–e495 (2011).

    PubMed  PubMed Central  Google Scholar 

  26. Jones, R. M. & Lord, C. Diagnosing autism in neurobiological research studies. Behav. Brain Res. 251, 113–124 (2013).

    Article  PubMed  Google Scholar 

  27. Johnson, M. H. Autism: demise of the innate social orienting hypothesis. Curr. Biol. 24, R30–R31 (2014).

    Article  CAS  PubMed  Google Scholar 

  28. Johnson, M. H., Jones, E. J. H. & Gliga, T. Brain adaptation and alternative developmental trajectories. Dev. Psychopathol. 27, 425–442 (2015).

    Article  PubMed  Google Scholar 

  29. The Lancet Psychiatry. Of mice and mental health. Lancet Psychiatry 6, 877 (2019).

    Article  CAS  PubMed  Google Scholar 

  30. Nelson, C. A. et al. An integrative, multidisciplinary approach to the study of brain-behavior relations in the context of typical and atypical development. Dev. Psychopathol. 14, 499–520 (2002).

    Article  PubMed  Google Scholar 

  31. Cross-Disorder Group of the Psychiatric Genomics Consortium et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat. Genet. 45, 984–994 (2013).

    Article  CAS  Google Scholar 

  32. Gaugler, T. et al. Most genetic risk for autism resides with common variation. Nat. Genet. 46, 881–885 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang, K., Gaitsch, H., Poon, H., Cox, N. J. & Rzhetsky, A. Classification of common human diseases derived from shared genetic and environmental determinants. Nat. Genet. 49, 1319–1325 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sanders, S. J. et al. Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron 87, 1215–1233 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Satterstrom, F. K. et al. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Preprint at https://doi.org/10.1101/484113 (2019).

  36. Sanders, S. J. et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485, 237–241 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Neale, B. M. et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 485, 242–245 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. O’Roak, B. J. et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 485, 246–250 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Sanders, S. J. et al. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 70, 863–885 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Levy, D. et al. Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron 70, 886–897 (2011).

    Article  CAS  PubMed  Google Scholar 

  41. Sebat, J. et al. Strong association of de novo copy number mutations with autism. Science 316, 445–449 (2007). This paper is the first to focus explicitly on simplex autism and show the importance of de novo CNVs in simplex cases, versus familial cases, versus controls.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Grove, J. et al. Identification of common genetic risk variants for autism spectrum disorder. Nat. Genet. 51, 431–444 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Willsey, J. et al. De novo coding variants are strongly associated with Tourette syndrome. Eur. Neuropsychopharmacol. 29, S737 (2019).

    Article  Google Scholar 

  44. Epi4K Consortium. Epi4K: gene discovery in 4,000 genomes. Epilepsia 53, 1457–1467 (2012).

    Article  Google Scholar 

  45. Jamain, S. et al. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat. Genet. 34, 27–29 (2003). This is the first paper to show a de novo loss-of-function mutation in a synaptic gene associated with non-syndromic autism and was a harbinger for many of the findings that came after.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Iossifov, I. et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature 515, 216–221 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. De Rubeis, S. et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 515, 209–215 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Sestan, N. & State, M. W. Lost in translation: traversing the complex path from genomics to therapeutics in autism spectrum disorder. Neuron 100, 406–423 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. State, M. W. & Sestan, N. The emerging biology of autism spectrum disorders. Science 337, 1301–1303 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427 (2014).

    Article  PubMed Central  CAS  Google Scholar 

  51. Devlin, B. & Scherer, S. W. Genetic architecture in autism spectrum disorder. Curr. Opin. Genet. Dev. 22, 229–237 (2012).

    Article  CAS  PubMed  Google Scholar 

  52. de la Torre-Ubieta, L., Won, H., Stein, J. L. & Geschwind, D. H. Advancing the understanding of autism disease mechanisms through genetics. Nat. Med. 22, 345–361 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. SFARI Gene Website. https://gene.sfari.org/ (2019).

  54. Parikshak, N. N. et al. Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism. Cell 155, 1008–1021 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ben-David, E. & Shifman, S. Combined analysis of exome sequencing points toward a major role for transcription regulation during brain development in autism. Mol. Psychiatry 18, 1054–1056 (2013).

    Article  CAS  PubMed  Google Scholar 

  56. Willsey, A. J. et al. Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell 155, 997–1007 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Pinto, D. et al. Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466, 368–372 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Gilman, S. R. et al. Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses. Neuron 70, 898–907 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Fuccillo, M. V. Striatal circuits as a common node for autism pathophysiology. Front. Neurosci. 10, 27 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Velmeshev, D. et al. Single-cell genomics identifies cell type-specific molecular changes in autism. Science 364, 685–689 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Mendell, J. R. et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N. Engl. J. Med. 377, 1713–1722 (2017).

    Article  CAS  PubMed  Google Scholar 

  62. Mercuri, E. et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N. Engl. J. Med. 378, 625–635 (2018).

    Article  CAS  PubMed  Google Scholar 

  63. Matharu, N. et al. CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency. Science 363, eaau0629 (2019).

    Article  CAS  PubMed  Google Scholar 

  64. Abudayyeh, O. O. et al. RNA targeting with CRISPR–cas13. Nature 550, 280–284 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Power, J. D. et al. Customized head molds reduce motion during resting state fMRI scans. NeuroImage 189, 141–149 (2019).

    Article  PubMed  Google Scholar 

  66. Solso, S. et al. Diffusion tensor imaging provides evidence of possible axonal overconnectivity in frontal lobes in autism spectrum disorder toddlers. Biol. Psychiatry 79, 676–684 (2016).

    Article  PubMed  Google Scholar 

  67. Clements, C. C. et al. Evaluation of the social motivation hypothesis of autism: a systematic review and meta-analysis. JAMA Psychiatry 75, 797–808 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Ecker, C. Brain anatomy and its relationship to behavior in adults with autism spectrum disorder: a multicenter magnetic resonance imaging study. Arch. Gen. Psychiatry 69, 195–209 (2012).

    Article  PubMed  Google Scholar 

  69. Langen, M. et al. Changes in the development of striatum are involved in repetitive behavior in autism. Biol. Psychiatry 76, 405–411 (2014).

    Article  PubMed  Google Scholar 

  70. Elsabbagh, M. & Johnson, M. H. Autism and the social brain: the first-year puzzle. Biol. Psychiatry 80, 94–99 (2016).

    Article  PubMed  Google Scholar 

  71. Courchesne, E. et al. Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology 57, 245–254 (2001).

    Article  CAS  PubMed  Google Scholar 

  72. Hazlett, H. C. et al. Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years. Arch. Gen. Psychiatry 62, 1366–1376 (2005).

    Article  PubMed  Google Scholar 

  73. Wolff, J. J. et al. Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. Am. J. Psychiatry 169, 589–600 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Hazlett, H. C. et al. Early brain development in infants at high risk for autism spectrum disorder. Nature 542, 348–351 (2017). This seminal paper, through careful recruitment and methodology, was the first to show significant early differences that may contribute to our understanding of developmental features in neural structure and circuits.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wolff, J. J. et al. Neural circuitry at age 6 months associated with later repetitive behavior and sensory responsiveness in autism. Mol. Autism 8, 8 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Emerson, R. W. et al. Functional neuroimaging of high-risk 6-month-old infants predicts a diagnosis of autism at 24 months of age. Sci. Transl. Med. 9, eaag2882 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Smith, E. et al. Cortical thickness change in autism during early childhood: CT in early childhood ASD. Hum. Brain Mapp. 37, 2616–2629 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Uddin, L. Q., Dajani, D. R., Voorhies, W., Bednarz, H. & Kana, R. K. Progress and roadblocks in the search for brain-based biomarkers of autism and attention-deficit/hyperactivity disorder. Transl. Psychiatry 7, e1218 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Herringshaw, A. J., Ammons, C. J., DeRamus, T. P. & Kana, R. K. Hemispheric differences in language processing in autism spectrum disorders: a meta-analysis of neuroimaging studies. Autism Res. 9, 1046–1057 (2016).

    Article  PubMed  Google Scholar 

  80. He, Y., Byrge, L. & Kennedy, D. P. Non-replication of functional connectivity differences in autism spectrum disorder across multiple sites and denoising strategies. Preprint at https://doi.org/10.1101/640797 (2019).

  81. Lawrence, K. E., Hernandez, L. M., Bookheimer, S. Y. & Dapretto, M. Atypical longitudinal development of functional connectivity in adolescents with autism spectrum disorder. Autism Res. 12, 53–65 (2019).

    Article  PubMed  Google Scholar 

  82. Plitt, M., Barnes, K. A., Wallace, G. L., Kenworthy, L. & Martin, A. Resting-state functional connectivity predicts longitudinal change in autistic traits and adaptive functioning in autism. Proc. Natl Acad. Sci. USA 112, E6699–E6706 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Di Martino, A. et al. The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism. Mol. Psychiatry 19, 659–667 (2014).

    Article  PubMed  Google Scholar 

  84. Doyle-Thomas, K. A. R. et al. Atypical functional brain connectivity during rest in autism spectrum disorders. Ann. Neurol. 77, 866–876 (2015).

    Article  PubMed  Google Scholar 

  85. Supekar, K. et al. Brain hyperconnectivity in children with autism and its links to social deficits. Cell Rep. 5, 738–747 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Dajani, D. R. & Uddin, L. Q. Local brain connectivity across development in autism spectrum disorder: a cross-sectional investigation. Autism Res. 9, 43–54 (2016).

    Article  PubMed  Google Scholar 

  87. Hull, J. V. et al. Resting-state functional connectivity in autism spectrum disorders: a review. Front. Psychiatry 7, 205 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Lombardo, M. V. et al. Different functional neural substrates for good and poor language outcome in autism. Neuron 86, 567–577 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Carlisi, C. O. et al. Disorder-specific and shared brain abnormalities during vigilance in autism and obsessive-compulsive disorder. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 2, 644–654 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Alaerts, K., Swinnen, S. P. & Wenderoth, N. Sex differences in autism: a resting-state fMRI investigation of functional brain connectivity in males and females. Soc. Cogn. Affect. Neurosci. 11, 1002–1016 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Kirkovski, M., Enticott, P. G., Hughes, M. E., Rossell, S. L. & Fitzgerald, P. B. Atypical neural activity in males but not females with autism spectrum disorder. J. Autism Dev. Disord. 46, 954–963 (2016).

    Article  PubMed  Google Scholar 

  92. Venkataraman, A. et al. Pivotal response treatment prompts a functional rewiring of the brain among individuals with autism spectrum disorder. NeuroReport 27, 1081–1085 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Levisohn, P. M. The autism-epilepsy connection. Epilepsia 48, 33–35 (2007).

    Article  PubMed  Google Scholar 

  94. Cantor, D. S., Thatcher, R. W., Hrybyk, M. & Kaye, H. Computerized EEG analyses of autistic children. J. Autism Dev. Disord. 16, 169–187 (1986).

    Article  CAS  PubMed  Google Scholar 

  95. Lefebvre, A. et al. Alpha waves as a neuromarker of autism spectrum disorder: the challenge of reproducibility and heterogeneity. Front. Neurosci. 12, 662 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Tierney, A. L., Gabard-Durnam, L., Vogel-Farley, V., Tager-Flusberg, H. & Nelson, C. A. Developmental trajectories of resting EEG power: an endophenotype of autism spectrum disorder. PLOS ONE 7, e39127 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Oberman, L. M. et al. EEG evidence for mirror neuron dysfunction in autism spectrum disorders. Cogn. Brain Res. 24, 190–198 (2005).

    Article  Google Scholar 

  98. Fan, Y.-T., Decety, J., Yang, C.-Y., Liu, J.-L. & Cheng, Y. Unbroken mirror neurons in autism spectrum disorders. J. Child Psychol. Psychiatry 51, 981–988 (2010).

    Article  PubMed  Google Scholar 

  99. Southgate, V. & Hamilton, A. F. Unbroken mirrors: challenging a theory of autism. Trends Cogn. Sci. 12, 225–229 (2008).

    Article  PubMed  Google Scholar 

  100. Bernier, R., Aaronson, B. & McPartland, J. The role of imitation in the observed heterogeneity in EEG mu rhythm in autism and typical development. Brain Cogn. 82, 69–75 (2013).

    Article  PubMed  Google Scholar 

  101. Raymaekers, R., Wiersema, J. R. & Roeyers, H. EEG study of the mirror neuron system in children with high functioning autism. Brain Res. 1304, 113–121 (2009).

    Article  CAS  PubMed  Google Scholar 

  102. Dumas, G., Soussignan, R., Hugueville, L., Martinerie, J. & Nadel, J. Revisiting mu suppression in autism spectrum disorder. Brain Res. 1585, 108–119 (2014). This paper replicates the mu suppression deficits in autism during action observation but questions, through high-density spectral analyses and source reconstruction, its previously drawn relation to the mirror neuron system.

    Article  CAS  PubMed  Google Scholar 

  103. Marco, E. J., Hinkley, L. B. N., Hill, S. S. & Nagarajan, S. S. Sensory processing in autism: a review of neurophysiologic findings. Pediatr. Res. 69, 48R–54R (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  104. Schwartz, S., Shinn-Cunningham, B. & Tager-Flusberg, H. Meta-analysis and systematic review of the literature characterizing auditory mismatch negativity in individuals with autism. Neurosci. Biobehav. Rev. 87, 106–117 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  105. Kang, E. et al. Atypicality of the N170 event-related potential in autism spectrum disorder: a meta-analysis. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 3, 657–666 (2018).

    Article  PubMed  Google Scholar 

  106. Bonnet-Brilhault, F. et al. GABA/glutamate synaptic pathways targeted by integrative genomic and electrophysiological explorations distinguish autism from intellectual disability. Mol. Psychiatry 21, 411–418 (2016).

    Article  CAS  PubMed  Google Scholar 

  107. Schilbach, L. Towards a second-person neuropsychiatry. Phil. Trans. R. Soc. B 371, 20150081 (2016). This review supports that psychiatric disorders are more commonly characterized by impairments of social interaction rather than social observation, and advocates for an interactive turn in neuropsychiatry.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Barraza, P. et al. Implementing EEG hyperscanning setups. MethodsX 6, 428–436 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Dumas, G., de Guzman, G. C., Tognoli, E. & Kelso, J. A. The human dynamic clamp as a paradigm for social interaction. Proc. Natl Acad. Sci. USA 111, E3726–E3734 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Jones, E. J. H. et al. Reduced engagement with social stimuli in 6-month-old infants with later autism spectrum disorder: a longitudinal prospective study of infants at high familial risk. J. Neurodev. Disord. 8, 7 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Ciarrusta, J. et al. Social brain functional maturation in newborn infants with and without a family history of autism spectrum disorder. JAMA Netw. Open 2, e191868 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Levin, A. R., Varcin, K. J., O’Leary, H. M., Tager-Flusberg, H. & Nelson, C. A. EEG power at 3 months in infants at high familial risk for autism. J. Neurodev. Disord. 9, 34 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Kolesnik, A. et al. Increased cortical reactivity to repeated tones at 8 months in infants with later ASD. Transl. Psychiatry 9, 46 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Rippon, G., Brock, J., Brown, C. & Boucher, J. Disordered connectivity in the autistic brain: challenges for the ‘new psychophysiology’. Int. J. Psychophysiol. 63, 164–172 (2007).

    Article  PubMed  Google Scholar 

  115. Rosenberg, A., Patterson, J. S. & Angelaki, D. E. A computational perspective on autism. Proc. Natl Acad. Sci. USA 112, 9158–9165 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Masuda, F. et al. Motor cortex excitability and inhibitory imbalance in autism spectrum disorder assessed with transcranial magnetic stimulation: a systematic review. Transl. Psychiatry 9, 110 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  117. O’Reilly, C., Lewis, J. D. & Elsabbagh, M. Is functional brain connectivity atypical in autism? A systematic review of EEG and MEG studies. PLOS ONE 12, e0175870 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Khan, S. et al. Somatosensory cortex functional connectivity abnormalities in autism show opposite trends, depending on direction and spatial scale. Brain 138, 1394–1409 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Chen, H., Nomi, J. S., Uddin, L. Q., Duan, X. & Chen, H. Intrinsic functional connectivity variance and state-specific under-connectivity in autism. Hum. Brain Mapp. 38, 5740–5755 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Catarino, A., Churches, O., Baron-Cohen, S., Andrade, A. & Ring, H. Atypical EEG complexity in autism spectrum conditions: a multiscale entropy analysis. Clin. Neurophysiol. 122, 2375–2383 (2011).

    Article  PubMed  Google Scholar 

  121. Engemann, D. A. et al. Robust EEG-based cross-site and cross-protocol classification of states of consciousness. Brain 141, 3179–3192 (2018).

    Article  PubMed  Google Scholar 

  122. Open Science Collaboration. Psychology. Estimating the reproducibility of psychological science. Science 349, aac4716 (2015).

    Article  CAS  Google Scholar 

  123. Lord, C. et al. Autism diagnostic observation schedule: ADOS-2 (Western Psychological Services, 2012).

  124. Regier, D. A. et al. DSM-5 field trials in the United States and Canada, part II: test-retest reliability of selected categorical diagnoses. Am. J. Psychiatry 170, 59–70 (2013).

    Article  PubMed  Google Scholar 

  125. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th Edn (American Psychiatric Association, 2013).

  126. World Health Organization. International classification of diseases for mortality and morbidity statistics (11th Revision). https://icd.who.int/browse11/l-m/en (WHO, 2018).

  127. Constantino, J. N. & Charman, T. Diagnosis of autism spectrum disorder: reconciling the syndrome, its diverse origins, and variation in expression. Lancet Neurol. 15, 279–291 (2016).

    Article  PubMed  Google Scholar 

  128. Lord, C. A multisite study of the clinical diagnosis of different autism spectrum disorders. Arch. Gen. Psychiatry 69, 306–313 (2012).

    Article  PubMed  Google Scholar 

  129. Miller, J. N. & Ozonoff, S. The external validity of Asperger disorder: lack of evidence from the domain of neuropsychology. J. Abnorm. Psychol. 109, 227–238 (2000).

    Article  CAS  PubMed  Google Scholar 

  130. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edn (American Psychiatric Association, 1994).

  131. Green, D., Chandler, S., Charman, T., Simonoff, E. & Baird, G. Brief report: DSM-5 sensory behaviours in children with and without an autism spectrum disorder. J. Autism Dev. Disord. 46, 3597–3606 (2016).

    Article  PubMed  Google Scholar 

  132. Ozonoff, S. et al. Diagnosis of autism spectrum disorder after age 5 in children evaluated longitudinally since infancy. J. Am. Acad. Child Adolesc. Psychiatry 57, 849–857.e2 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  133. Russell, G., Steer, C. & Golding, J. Social and demographic factors that influence the diagnosis of autistic spectrum disorders. Soc. Psychiatry Psychiatr. Epidemiol. 46, 1283–1293 (2011).

    Article  PubMed  Google Scholar 

  134. Charman, T. & Gotham, K. Measurement issues: screening and diagnostic instruments for autism spectrum disorders—lessons from research and practice. Child Adolesc. Ment. Health 18, 52–63 (2013).

    Article  PubMed  Google Scholar 

  135. Ashwood, K. L., Buitelaar, J., Murphy, D., Spooren, W. & Charman, T. European clinical network: autism spectrum disorder assessments and patient characterisation. Eur. Child Adolesc. Psychiatry 24, 985–995 (2015).

    Article  PubMed  Google Scholar 

  136. Rutter, M., LeCouteur, A. & Lord, C. Autism Diagnostic Interview-Revised (ADI-R). (Western Psychological Services, 2003).

  137. Durkin, M. S. et al. Autism screening and diagnosis in low resource settings: challenges and opportunities to enhance research and services worldwide. Autism Res. 8, 473–476 (2015). This position paper highlights the challenges to translating knowledge on better awareness, understanding, identification and diagnosis (and then treatments) from the past two decades of clinical research in high-income countries into low-income and middle-income countries.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Baird, G. et al. 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, 210–215 (2006).

    Article  PubMed  Google Scholar 

  139. Luyster, R. et al. The autism diagnostic observation schedule — toddler module: a new module of a standardized diagnostic measure for autism spectrum disorders. J. Autism Dev. Disord. 39, 1305–1320 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  140. de Vries, P. J. Thinking globally to meet local needs: autism spectrum disorders in Africa and other low-resource environments. Curr. Opin. Neurol. 29, 130–136 (2016).

    Article  PubMed  CAS  Google Scholar 

  141. Georgiades, S., Bishop, S. L. & Frazier, T. Editorial perspective: longitudinal research in autism—introducing the concept of ‘chronogeneity’. J. Child Psychol. Psychiatry 58, 634–636 (2017).

    Article  PubMed  Google Scholar 

  142. Fountain, C., Winter, A. S. & Bearman, P. S. Six developmental trajectories characterize children with autism. Pediatrics 129, e1112–e1120 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  143. Kim, S. H. et al. Variability in autism symptom trajectories using repeated observations from 14 to 36 months of age. J. Am. Acad. Child Adolesc. Psychiatry 57, 837–848.e2 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  144. Bussu, G. et al. Latent trajectories of adaptive behaviour in infants at high and low familial risk for autism spectrum disorder. Mol. Autism 10, 13 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  145. Zerbi, V. et al. Dysfunctional autism risk genes cause circuit-specific connectivity deficits with distinct developmental trajectories. Cereb. Cortex 28, 2495–2506 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  146. Fein, D. et al. Optimal outcome in individuals with a history of autism. J. Child Psychol. Psychiatry 54, 195–205 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  147. Anderson, D. K., Liang, J. W. & Lord, C. Predicting young adult outcome among more and less cognitively able individuals with autism spectrum disorders. J. Child Psychol. Psychiatry 55, 485–494 (2014).

    Article  PubMed  Google Scholar 

  148. Chlebowski, C., Robins, D. L., Barton, M. L. & Fein, D. Large-scale use of the modified checklist for autism in low-risk toddlers. Pediatrics 131, e1121–e1127 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  149. Stenberg, N. et al. Identifying children with autism spectrum disorder at 18 months in a general population sample. Paediatr. Perinat. Epidemiol. 28, 255–262 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  150. Pierce, K., Courchesne, E. & Bacon, E. To screen or not to screen universally for autism is not the question: why the task force got it wrong. J. Pediatr. 176, 182–194 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Siu, A. L. et al. Screening for autism spectrum disorder in young children: US Preventive Services Task Force recommendation statement. JAMA 315, 691–696 (2016).

    Article  CAS  PubMed  Google Scholar 

  152. Øien, R. A. et al. Clinical features of children with autism who passed 18-month screening. Pediatrics 141, e20173596 (2018).

    Article  PubMed  Google Scholar 

  153. Sánchez-García, A. B., Galindo-Villardón, P., Nieto-Librero, A. B., Martín-Rodero, H. & Robins, D. L. Toddler screening for autism spectrum disorder: a meta-analysis of diagnostic accuracy. J. Autism Dev. Disord. 49, 1837–1852 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  154. Marlow, M., Servili, C. & Tomlinson, M. A review of screening tools for the identification of autism spectrum disorders and developmental delay in infants and young children: recommendations for use in low- and middle-income countries. Autism Res. 12, 176–199 (2019).

    Article  PubMed  Google Scholar 

  155. Raza, S. et al. Brief report: evaluation of the short quantitative checklist for autism in toddlers (Q-CHAT-10) as a brief screen for autism spectrum disorder in a high-risk sibling cohort. J. Autism Dev. Disord. 49, 2210–2218 (2019).

    Article  PubMed  Google Scholar 

  156. Charman, T. et al. Testing two screening instruments for autism spectrum disorder in UK community child health services. Dev. Med. Child Neurol. 58, 369–375 (2016).

    Article  PubMed  Google Scholar 

  157. Brett, D., Warnell, F., McConachie, H. & Parr, J. R. Factors affecting age at ASD diagnosis in UK: no evidence that diagnosis age has decreased between 2004 and 2014. J. Autism Dev. Disord. 46, 1974–1984 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  158. Zuckerman, K. E., Lindly, O. J. & Sinche, B. K. Parental concerns, provider response, and timeliness of autism spectrum disorder diagnosis. J. Pediatr. 166, 1431–1439.e1 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  159. Boterberg, S., Charman, T., Marschik, P. B., Bölte, S. & Roeyers, H. Regression in autism spectrum disorder: a critical overview of retrospective findings and recommendations for future research. Neurosci. Biobehav. Rev. 102, 24–55 (2019).

    Article  PubMed  Google Scholar 

  160. Pearson, N., Charman, T., Happé, F., Bolton, P. F. & McEwen, F. S. Regression in autism spectrum disorder: reconciling findings from retrospective and prospective research. Autism Res. 11, 1602–1620 (2018).

    Article  PubMed  Google Scholar 

  161. Ozonoff, S. & Iosif, A.-M. Changing conceptualizations of regression: what prospective studies reveal about the onset of autism spectrum disorder. Neurosci. Biobehav. Rev. 100, 296–304 (2019). Despite its potential importance as a biological marker and/or subgroup of ASD, developmental regression has remained very poorly understood. This paper outlines recent data and reconceptualization about patterns of onset (and loss) that chime with a more contemporaneous understanding of ASD as a heterogeneous condition in terms of its manifestation both within and across individuals.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Brugha, T. S. et al. Validating two survey methods for identifying cases of autism spectrum disorder among adults in the community. Psychol. Med. 42, 647–656 (2012).

    Article  CAS  PubMed  Google Scholar 

  163. Brugha, T. S. The Psychiatry of Adult Autism and Asperger Syndrome: a Practical Guide (Oxford Univ. Press, 2018).

  164. Epstein, J., Johnson, D. E. & Conners, C. K. Conners Adult ADHD Diagnostic Interview for DSM-IV (CAADID) (MHS, 2001).

  165. Lai, M.-C. et al. Prevalence of co-occurring mental health diagnoses in the autism population: a systematic review and meta-analysis. Lancet Psychiatry 6, 819–829 (2019).

    Article  PubMed  Google Scholar 

  166. Havdahl, A. & Bishop, S. Heterogeneity in prevalence of co-occurring psychiatric conditions in autism. Lancet Psychiatry 6, 794–795 (2019).

    Article  PubMed  Google Scholar 

  167. Croen, L. A. et al. The health status of adults on the autism spectrum. Autism 19, 814–823 (2015).

    Article  PubMed  Google Scholar 

  168. Mannion, A., Leader, G. & Healy, O. An investigation of comorbid psychological disorders, sleep problems, gastrointestinal symptoms and epilepsy in children and adolescents with autism spectrum disorder. Res. Autism Spectr. Disord. 7, 35–42 (2013).

    Article  Google Scholar 

  169. Soke, G. N., Maenner, M. J., Christensen, D., Kurzius-Spencer, M. & Schieve, L. A. Prevalence of co-occurring medical and behavioral conditions/symptoms among 4- and 8-year-old children with autism spectrum disorder in selected areas of the United States in 2010. J. Autism Dev. Disord. 48, 2663–2676 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Chandler, S. et al. Emotional and behavioural problems in young children with autism spectrum disorder. Dev. Med. Child Neurol. 58, 202–208 (2016).

    Article  PubMed  Google Scholar 

  171. Pezzimenti, F., Han, G. T., Vasa, R. A. & Gotham, K. Depression in youth with autism spectrum disorder. Child Adolesc. Psychiatr. Clin. N. Am. 28, 397–409 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  172. Hwang, Y. I. J., Srasuebkul, P., Foley, K. R., Arnold, S. & Trollor, J. N. Mortality and cause of death of Australians on the autism spectrum. Autism Res. 12, 806–815 (2019).

    Article  CAS  PubMed  Google Scholar 

  173. Hirvikoski, T. et al. Premature mortality in autism spectrum disorder. Br. J. Psychiatry 208, 232–238 (2016).

    Article  PubMed  Google Scholar 

  174. Havdahl, K. A. et al. Multidimensional influences on autism symptom measures: implications for use in etiological research. J. Am. Acad. Child Adolesc. Psychiatry 55, 1054–1063.e3 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  175. Nicolaidis, C. et al. Comparison of healthcare experiences in autistic and non-autistic adults: a cross-sectional online survey facilitated by an academic-community partnership. J. Gen. Intern. Med. 28, 761–769 (2013).

    Article  PubMed  Google Scholar 

  176. Schreibman, L. et al. Naturalistic developmental behavioral interventions: empirically validated treatments for autism spectrum disorder. J. Autism Dev. Disord. 45, 2411–2428 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  177. Tomlinson, M. et al. Setting global research priorities for developmental disabilities, including intellectual disabilities and autism: setting research priorities for developmental disabilities. J. Intellect. Disabil. Res. 58, 1121–1130 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Rahman, A. et al. Effectiveness of the parent-mediated intervention for children with autism spectrum disorder in South Asia in India and Pakistan (PASS): a randomised controlled trial. Lancet Psychiatry 3, 128–136 (2016).

    Article  PubMed  Google Scholar 

  179. Lovaas, O. I. Behavioral treatment and normal educational and intellectual functioning in young autistic children. J. Consult. Clin. Psychol. 55, 3–9 (1987).

    Article  CAS  PubMed  Google Scholar 

  180. Nevill, R. E., Lecavalier, L. & Stratis, E. A. Meta-analysis of parent-mediated interventions for young children with autism spectrum disorder. Autism 22, 84–98 (2018).

    Article  PubMed  Google Scholar 

  181. Kasari, C. et al. Randomized controlled trial of parental responsiveness intervention for toddlers at high risk for autism. Infant Behav. Dev. 37, 711–721 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  182. Shire, S. Y. et al. Hybrid implementation model of community-partnered early intervention for toddlers with autism: a randomized trial. J. Child Psychol. Psychiatry 58, 612–622 (2017).

    Article  PubMed  Google Scholar 

  183. Siller, M., Hutman, T. & Sigman, M. A parent-mediated intervention to increase responsive parental behaviors and child communication in children with ASD: a randomized clinical trial. J. Autism Dev. Disord. 43, 540–555 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  184. Rogers, S. J. et al. Effects of a brief early start denver model (ESDM)-based parent intervention on toddlers at risk for autism spectrum disorders: a randomized controlled trial. J. Am. Acad. Child Adolesc. Psychiatry 51, 1052–1065 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  185. Green, J. et al. Parent-mediated communication-focused treatment in children with autism (PACT): a randomised controlled trial. Lancet 375, 2152–2160 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  186. Pickles, A. et al. Parent-mediated social communication therapy for young children with autism (PACT): long-term follow-up of a randomised controlled trial. Lancet 388, 2501–2509 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  187. Dawson, G. et al. Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics 125, e17–e23 (2010).

    Article  PubMed  Google Scholar 

  188. Charman, T. Editorial: trials and tribulations in early autism intervention research. J. Am. Acad. Child Adolesc. Psychiatry 58, 846–848 (2019).

    Article  PubMed  Google Scholar 

  189. Rogers, S. J. et al. A multisite randomized controlled two-phase trial of the early start denver model compared to treatment as usual. J. Am. Acad. Child Adolesc. Psychiatry 58, 853–865 (2019).

    Article  PubMed  Google Scholar 

  190. Dawson, G. et al. Early behavioral intervention is associated with normalized brain activity in young children with autism. J. Am. Acad. Child Adolesc. Psychiatry 51, 1150–1159 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  191. Myers, S. M., Johnson, C. P. & The Council on Children With Disabilities. Management of children with autism spectrum disorders. Pediatrics 120, 1162–1182 (2007).

    Article  PubMed  Google Scholar 

  192. Laugeson, E. A., Frankel, F., Gantman, A., Dillon, A. R. & Mogil, C. Evidence-based social skills training for adolescents with autism spectrum disorders: the UCLA PEERS program. J. Autism Dev. Disord. 42, 1025–1036 (2012).

    Article  PubMed  Google Scholar 

  193. Reichow, B., Servili, C., Yasamy, M. T., Barbui, C. & Saxena, S. Non-specialist psychosocial interventions for children and adolescents with intellectual disability or lower-functioning autism spectrum disorders: a systematic review. PLOS Med. 10, e1001572 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  194. Brignell, A. et al. Communication interventions for autism spectrum disorder in minimally verbal children. Cochrane Database Syst. Rev. 11, CD012324 (2018).

    PubMed  Google Scholar 

  195. Tarver, J. et al. Child and parent outcomes following parent interventions for child emotional and behavioral problems in autism spectrum disorders: a systematic review and meta-analysis. Autism 23, 1630–1644 (2019).

    Article  PubMed  Google Scholar 

  196. Keefer, A. et al. Exploring relationships between negative cognitions and anxiety symptoms in youth with autism spectrum disorder. Behav. Ther. 49, 730–740 (2018).

    Article  PubMed  Google Scholar 

  197. Bearss, K. et al. Effect of parent training vs parent education on behavioral problems in children with autism spectrum disorder: a randomized clinical trial. JAMA 313, 1524–1533 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Da Paz, N. S. & Wallander, J. L. Interventions that target improvements in mental health for parents of children with autism spectrum disorders: a narrative review. Clin. Psychol. Rev. 51, 1–14 (2017).

    Article  PubMed  Google Scholar 

  199. Kasari, C. et al. Children with autism spectrum disorder and social skills groups at school: a randomized trial comparing intervention approach and peer composition. J. Child Psychol. Psychiatry 57, 171–179 (2016).

    Article  PubMed  Google Scholar 

  200. Marshall, D. et al. Social stories in mainstream schools for children with autism spectrum disorder: a feasibility randomised controlled trial. BMJ Open 6, e011748 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  201. Taylor, J. L. et al. A systematic review of vocational interventions for young adults with autism spectrum disorders. Pediatrics 130, 531–538 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  202. Pallathra, A. A., Cordero, L., Wong, K. & Brodkin, E. S. Psychosocial interventions targeting social functioning in adults on the autism spectrum: a literature review. Curr. Psychiatry Rep. 21, 5 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  203. White, S. W. et al. Psychosocial treatments targeting anxiety and depression in adolescents and adults on the autism spectrum: review of the latest research and recommended future directions. Curr. Psychiatry Rep. 20, 82 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  204. Shattuck, P. T., Wagner, M., Narendorf, S., Sterzing, P. & Hensley, M. Post-high school service use among young adults with an autism spectrum disorder. Arch. Pediatr. Adolesc. Med. 165, 141–146 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  205. Wehman, P. et al. Effects of an employer-based intervention on employment outcomes for youth with significant support needs due to autism. Autism 21, 276–290 (2017).

    Article  PubMed  Google Scholar 

  206. McCracken, J. T. et al. Risperidone in children with autism and serious behavioral problems. N. Engl. J. Med. 347, 314–321 (2002).

    Article  CAS  PubMed  Google Scholar 

  207. Owen, R. et al. Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics 124, 1533–1540 (2009).

    Article  PubMed  Google Scholar 

  208. McPheeters, M. L. et al. A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics 127, e1312–e1321 (2011).

    Article  PubMed  Google Scholar 

  209. Anagnostou, E. et al. Metformin for treatment of overweight induced by atypical antipsychotic medication in young people with autism spectrum disorder: a randomized clinical trial. JAMA Psychiatry 73, 928–937 (2016).

    Article  PubMed  Google Scholar 

  210. Research Units on Pediatric Psychopharmacology Autism Network. Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Arch. Gen. Psychiatry 62, 1266–1274 (2005).

    Article  Google Scholar 

  211. Handen, B. L. et al. Atomoxetine, parent training, and their combination in children with autism spectrum disorder and attention-deficit/hyperactivity disorder. J. Am. Acad. Child Adolesc. Psychiatry 54, 905–915 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  212. Scahill, L. et al. Extended-release guanfacine for hyperactivity in children with autism spectrum disorder. Am. J. Psychiatry 172, 1197–1206 (2015).

    Article  PubMed  Google Scholar 

  213. Hollander, E. et al. A double-blind placebo-controlled trial of fluoxetine for repetitive behaviors and global severity in adult autism spectrum disorders. Am. J. Psychiatry 169, 292–299 (2012).

    Article  PubMed  Google Scholar 

  214. King, B. H. et al. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Arch. Gen. Psychiatry 66, 583–590 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Anagnostou, E. et al. Intranasal oxytocin in the treatment of autism spectrum disorders: a review of literature and early safety and efficacy data in youth. Brain Res. 1580, 188–198 (2014).

    Article  CAS  PubMed  Google Scholar 

  216. Guastella, A. J. et al. The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial. J. Child Psychol. Psychiatry 56, 444–452 (2015).

    Article  PubMed  Google Scholar 

  217. Parker, K. J. et al. A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism. Sci. Transl. Med. 11, eaau7356 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Bolognani, F. et al. A phase 2 clinical trial of a vasopressin V1a receptor antagonist shows improved adaptive behaviors in men with autism spectrum disorder. Sci. Transl. Med. 11, eaat7838 (2019).

    Article  CAS  PubMed  Google Scholar 

  219. Rubenstein, J. L. R. & Merzenich, M. M. Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes Brain Behav. 2, 255–267 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Veenstra-VanderWeele, J. et al. Arbaclofen in children and adolescents with autism spectrum disorder: a randomized, controlled, phase 2 trial. Neuropsychopharmacology 42, 1390–1398 (2017).

    Article  CAS  PubMed  Google Scholar 

  221. Berry-Kravis, E. et al. Mavoglurant in fragile X syndrome: results of two randomized, double-blind, placebo-controlled trials. Sci. Transl. Med. 8, 321ra5 (2016).

    Article  PubMed  CAS  Google Scholar 

  222. Krueger, D. A. et al. Everolimus for treatment of tuberous sclerosis complex-associated neuropsychiatric disorders. Ann. Clin. Transl. Neurol. 4, 877–887 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Georgiades, S. & Kasari, C. Reframing optimal outcomes in autism. JAMA Pediatr. 172, 716–717 (2018).

    Article  PubMed  Google Scholar 

  224. Bishop-Fitzpatrick, L. et al. Characterizing objective quality of life and normative outcomes in adults with autism spectrum disorder: an exploratory latent class analysis. J. Autism Dev. Disord. 46, 2707–2719 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  225. The WHOQOL Group. Development of the World Health Organization WHOQOL-BREF quality of life assessment. Psychol. Med. 28, 551–558 (1998).

    Article  Google Scholar 

  226. Gotham, K. et al. Characterizing the daily life, needs, and priorities of adults with autism spectrum disorder from interactive autism network data. Autism 19, 794–804 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  227. Taylor, J. L. & Seltzer, M. M. Employment and post-secondary educational activities for young adults with autism spectrum disorders during the transition to adulthood. J. Autism Dev. Disord. 41, 566–574 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  228. Orsmond, G. I., Shattuck, P. T., Cooper, B. P., Sterzing, P. R. & Anderson, K. A. Social participation among young adults with an autism spectrum disorder. J. Autism Dev. Disord. 43, 2710–2719 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  229. Henninger, N. A. & Taylor, J. L. Outcomes in adults with autism spectrum disorders: a historical perspective. Autism 17, 103–116 (2013).

    Article  PubMed  Google Scholar 

  230. Howlin, P. & Moss, P. Adults with autism spectrum disorders. Can. J. Psychiatry 57, 275–283 (2012).

    Article  PubMed  Google Scholar 

  231. Farley, M. A. et al. Twenty-year outcome for individuals with autism and average or near-average cognitive abilities. Autism Res. 2, 109–118 (2009).

    Article  PubMed  Google Scholar 

  232. Taylor, J. L., Henninger, N. A. & Mailick, M. R. Longitudinal patterns of employment and postsecondary education for adults with autism and average-range IQ. Autism 19, 785–793 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  233. Lai, M.-C. et al. Quantifying and exploring camouflaging in men and women with autism. Autism 21, 690–702 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  234. van Heijst, B. F. & Geurts, H. M. Quality of life in autism across the lifespan: a meta-analysis. Autism 19, 158–167 (2015).

    Article  PubMed  Google Scholar 

  235. Moss, P., Mandy, W. & Howlin, P. Child and adult factors related to quality of life in adults with autism. J. Autism Dev. Disord. 47, 1830–1837 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  236. Bishop-Fitzpatrick, L., Mazefsky, C. A. & Eack, S. M. The combined impact of social support and perceived stress on quality of life in adults with autism spectrum disorder and without intellectual disability. Autism 22, 703–711 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  237. Kamio, Y., Inada, N. & Koyama, T. A nationwide survey on quality of life and associated factors of adults with high-functioning autism spectrum disorders. Autism 17, 15–26 (2013).

    Article  PubMed  Google Scholar 

  238. Mason, D. et al. Predictors of quality of life for autistic adults. Autism Res. 11, 1138–1147 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  239. Autistica. Your questions shaping future autism research. https://www.autistica.org.uk/downloads/files/Autism-Top-10-Your-Priorities-for-Autism-Research.pdf (2016).

  240. Ontario Brain Institute. Community priorities for research on neurodevelopmental disorders. http://braininstitute.ca/img/JLA-NDD-Final-Report.pdf (2018).

  241. den Houting, J. Neurodiversity: an insider’s perspective. Autism 23, 271–273 (2018).

    Article  Google Scholar 

  242. Szatmari, P. Risk and resilience in autism spectrum disorder: a missed translational opportunity? Dev. Med. Child Neurol. 60, 225–229 (2018).

    Article  PubMed  Google Scholar 

  243. Markowitz, L. A. et al. Development and psychometric evaluation of a psychosocial quality-of-life questionnaire for individuals with autism and related developmental disorders. Autism 20, 832–844 (2016).

    Article  PubMed  Google Scholar 

  244. Ryan, S. & Cole, K. R. From advocate to activist? Mapping the experiences of mothers of children on the autism spectrum. J. Appl. Res. Intellect. Disabil. 22, 43–53 (2009).

    Article  Google Scholar 

  245. McCann, D., Bull, R. & Winzenberg, T. The daily patterns of time use for parents of children with complex needs: a systematic review. J. Child Health Care 16, 26–52 (2012).

    Article  PubMed  Google Scholar 

  246. Karst, J. S. & Van Hecke, A. V. Parent and family impact of autism spectrum disorders: a review and proposed model for intervention evaluation. Clin. Child Fam. Psychol. Rev. 15, 247–277 (2012).

    Article  PubMed  Google Scholar 

  247. Lounds, J., Seltzer, M. M., Greenberg, J. S. & Shattuck, P. T. Transition and change in adolescents and young adults with autism: longitudinal effects on maternal well-being. Am. J. Ment. Retard. 112, 401–417 (2007).

    Article  PubMed  Google Scholar 

  248. Burke, M. & Heller, T. Individual, parent and social-environmental correlates of caregiving experiences among parents of adults with autism spectrum disorder. J. Intellect. Disabil. Res. 60, 401–411 (2016).

    Article  CAS  PubMed  Google Scholar 

  249. Kim, S. H., Bal, V. H. & Lord, C. Longitudinal follow-up of academic achievement in children with autism from age 2 to 18. J. Child Psychol. Psychiatry 59, 258–267 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  250. Lord, C., Bishop, S. & Anderson, D. Developmental trajectories as autism phenotypes. Am. J. Med. Genet. C Semin. Med. Genet. 169, 198–208 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  251. Global Research on Developmental Disabilities Collaborators. Developmental disabilities among children younger than 5 years in 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancel Glob. Health 6, e1100–e1121 (2018).

  252. Kahn, R. S. et al. Schizophrenia. Nat. Rev. Dis. Primers 1, 15067 (2015).

    Article  PubMed  Google Scholar 

  253. Patel, V. et al. Addressing the burden of mental, neurological, and substance use disorders: key messages from Disease Control Priorities, 3rd edition. Lancet 387, 1672–1685 (2016).

    Article  PubMed  Google Scholar 

  254. Franz, L., Chambers, N., von Isenburg, M. & de Vries, P. J. Autism spectrum disorder in sub-Saharan Africa: a comprehensive scoping review. Autism Res. 10, 723–749 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  255. World Health Organization. Training parents to transform children’s lives. https://www.who.int/mental_health/maternal-child/PST/en/ (WHO, 2019).

  256. Naslund, J. A. et al. Digital innovations for global mental health: opportunities for data science, task sharing, and early intervention. Curr. Treat. Options Psychiatry https://doi.org/10.1007/s40501-019-00186-8 (2019).

  257. Sadowsky, J., Donvan, J. & Zucker, C. In a different key: the story of autism. J. Hist. Behav. Sci. 54, 66–67 (2018). This paper presents a different, broad overview of the changes in perspective about autism and ASD over the years.

    Article  Google Scholar 

  258. Rutter, M., Greenfeld, D. & Lockyer, L. A five to fifteen year follow-up study of infantile psychosis. II. Social and behavioural outcome. Br. J. Psychiatry 113, 1183–1199 (1967).

    Article  CAS  PubMed  Google Scholar 

  259. Hermelin, B. & O’Connor, N. Psychological Experiments with Autistic Children (Pergamon Press, 1970).

  260. Rimland, B. Infantile Autism: the Syndrome and its Implications for a Neural Theory of Behaviour (Meredith Publishing Company, 1964).

  261. Frith, U. Studies in pattern detection in normal and autistic children: I. Immediate recall of auditory sequences. J. Abnorm. Psychol. 76, 413–420 (1970).

    Article  CAS  PubMed  Google Scholar 

  262. Folstein, S. & Rutter, M. in Autism (eds. Rutter M. & Schopler E.) 219–241 (Springer, 1978).

  263. Mundy, P., Sigman, M. & Kasari, C. A longitudinal study of joint attention and language development in autistic children. J. Autism Dev. Disord. 20, 115–128 (1990).

    Article  CAS  PubMed  Google Scholar 

  264. Schopler, E. & Reichler, R. J. Parents as cotherapists in the treatment of psychotic children. J. Autism Child. Schizophr. 1, 87–102 (1971).

    Article  CAS  PubMed  Google Scholar 

  265. Sinclair, J. Don’t mourn for us. Autism Network International http://www.autreat.com/dont_mourn.html (1993).

  266. Wing, L. & Gould, J. Severe impairments of social interaction and associated abnormalities in children: epidemiology and classification. J. Autism Dev. Disord. 9, 11–29 (1979).

    Article  CAS  PubMed  Google Scholar 

  267. Chawner, S. et al. A genetic first approach to dissecting the heterogeneity of autism: phenotypic comparison of autism risk copy number variants. Eur. Neuropsychopharmacol. 29 (Suppl. 3), S783–S784 (2019).

    Article  Google Scholar 

  268. Modabbernia, A., Mollon, J., Boffetta, P. & Reichenberg, A. Impaired gas exchange at birth and risk of intellectual disability and autism: a meta-analysis. J. Autism Dev. Disord. 46, 1847–1859 (2016).

    Article  PubMed  Google Scholar 

  269. Christensen, J. et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA 309, 1696–1703 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  270. Xie, F., Peltier, M. & Getahun, D. Is the risk of autism in younger siblings of affected children moderated by sex, race/ethnicity, or gestational age? J. Dev. Behav. Pediatr. 37, 603–609 (2016).

    Article  PubMed  Google Scholar 

  271. Guy, A. et al. Infants born late/moderately preterm are at increased risk for a positive autism screen at 2 years of age. J. Pediatr. 166, 269–275.e3 (2015).

    Article  PubMed  Google Scholar 

  272. Schendel, D. & Bhasin, T. K. Birth weight and gestational age characteristics of children with autism, including a comparison with other developmental disabilities. Pediatrics 121, 1155–1164 (2008).

    Article  PubMed  Google Scholar 

  273. Windham, G. C. et al. Maternal pre-pregnancy body mass index and gestational weight gain in relation to autism spectrum disorder and other developmental disorders in offspring. Autism Res. 12, 316–327 (2019).

    Article  PubMed  Google Scholar 

  274. Schmidt, R. J. et al. Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Am. J. Clin. Nutr. 96, 80–89 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  275. Conde-Agudelo, A., Rosas-Bermudez, A. & Norton, M. H. Birth spacing and risk of autism and other neurodevelopmental disabilities: a systematic review. Pediatrics 137, e20153482 (2016).

    Article  PubMed  Google Scholar 

  276. Lyall, K. et al. The changing epidemiology of autism spectrum disorders. Annu. Rev. Public Health 38, 81–102 (2017).

    Article  PubMed  Google Scholar 

  277. Cheslack-Postava, K., Liu, K. & Bearman, P. S. Closely spaced pregnancies are associated with increased odds of autism in California sibling births. Pediatrics 127, 246–253 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  278. Conti, E., Mazzotti, S., Calderoni, S., Saviozzi, I. & Guzzetta, A. Are children born after assisted reproductive technology at increased risk of autism spectrum disorders? A systematic review. Hum. Reprod. 28, 3316–3327 (2013).

    Article  CAS  PubMed  Google Scholar 

  279. Lehti, V. et al. Autism spectrum disorders in IVF children: a national case-control study in Finland. Hum. Reprod. 28, 812–818 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  280. Rossignol, D. A., Genuis, S. J. & Frye, R. E. Environmental toxicants and autism spectrum disorders: a systematic review. Transl. Psychiatry 4, e360 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  281. Curran, E. A. et al. Research review: birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. J. Child Psychol. Psychiatry 56, 500–508 (2015).

    Article  PubMed  Google Scholar 

  282. Chandler, S., Howlin, P., Simonoff, E., Kennedy, J. & Baird, G. Comparison of parental estimate of developmental age with measured IQ in children with neurodevelopmental disorders. Child Care Health Dev. 42, 486–493 (2016).

    Article  CAS  PubMed  Google Scholar 

  283. Charman, T. et al. IQ in children with autism spectrum disorders: data from the Special Needs and Autism Project (SNAP). Psychol. Med. 41, 619–627 (2011).

    Article  CAS  PubMed  Google Scholar 

  284. Sparrow, S. S., Cicchetti, D. & Balla, D. A. Vineland Adaptive Behavior Scales, 2nd Edn. https://doi.org/10.1037/t15164-000 (AGS, 2005).

  285. Jones, R. M., Pickles, A. & Lord, C. Evaluating the quality of peer interactions in children and adolescents with autism with the Penn Interactive Peer Play Scale (PIPPS). Mol. Autism 8, 28 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  286. Lord, C., Elsabbagh, M., Baird, G. & Veenstra-Vanderweele, J. Autism spectrum disorder. Lancet 392, 508–520 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  287. Duncan, A. W. & Bishop, S. L. Understanding the gap between cognitive abilities and daily living skills in adolescents with autism spectrum disorders with average intelligence. Autism 19, 64–72 (2015).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank J. McCauley, S. Gaspar, K. Byrne and A. Holbrook from UCLA for help with manuscript preparation. S. Tromans is thanked for his updated review of the epidemiology literature. We recognize the many investigators who contributed research that we cannot cite due to space limitations. C.L. is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHHD; R01 HD081199), the National Institute of Mental Health (NIMH; R01MH081873-01A1) and the Simons Foundation. T.S.B. is supported by grants from the Health and Social Care Information Centre, Leeds, and the National Institute for Health Research (NIHR HTA; grant ref. NIHR127337). T.C. is supported by grants from Innovative Medicines Initiative 2 (no. 777394), the Medical Research Council (MRC; grants MR/K021389/1) and the NIHR (grant 13/119/18). J.C. is funded by Autistica. G.D. is supported by the Institut Pasteur. T.F. is supported by the Autism Speaks Foundation. E.J.H.J. is supported by grants from the Economic and Social Research Council (ESRC; ES/R009368/1), the Innovative Medicines Initiative 2 (no. 777394), the MRC (MR/K021389/1) and the Simons Foundation (609081). R.M.J. acknowledges the Mortimer D. Sackler Family and the NIMH (R01MH114999). J.L.T. is supported by grants from the FAR fund and the NIMH (R34 MH104428, R03 MH 112783 and R01 MH116058). A.P. is partially supported by the Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR (NF-SI-0617-10120). M.W.S. is supported by the National Institutes of Health (NIH; MH106934, MH109901, MH110928, MH116487 MH102342, MH111662, MH105575 and MH115747), the Overlook International Foundation and the Simons Foundation. J.V.-V. is supported by the NIH (MH016434 and MH094604), the Simons Foundation and the New York State Psychiatric Institute. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.

Author information

Authors and Affiliations

  1. Departments of Psychiatry and School of Education, University of California, Los Angeles, Los Angeles, CA, USA

    Catherine Lord

  2. Department of Health Sciences, University of Leicester, Leicester, UK

    Traolach S. Brugha

  3. Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK

    Tony Charman & Andrew Pickles

  4. Autistica, London, UK

    James Cusack

  5. Institut Pasteur, UMR3571 CNRS, Université de Paris, Paris, France

    Guillaume Dumas

  6. Autism Speaks, New York, NY, USA

    Thomas Frazier

  7. Centre for Brain & Cognitive Development, University of London, London, UK

    Emily J. H. Jones

  8. The Sackler Institute for Developmental Psychobiology, New York, NY, USA

    Rebecca M. Jones

  9. The Center for Autism and the Developing Brain, White Plains, NY, USA

    Rebecca M. Jones

  10. Department of Psychiatry, Langley Porter Psychiatric Institute and Weill Institute for Neurosciences, University of California, San Francisco, CA, USA

    Matthew W. State

  11. Department of Pediatrics and Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, TN, USA

    Julie Lounds Taylor

  12. Department of Psychiatry, Columbia University, New York, NY, USA

    Jeremy Veenstra-VanderWeele

Authors
  1. Catherine Lord
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Traolach S. Brugha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tony Charman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James Cusack
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guillaume Dumas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Thomas Frazier
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Emily J. H. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rebecca M. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andrew Pickles
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Matthew W. State
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Julie Lounds Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jeremy Veenstra-VanderWeele
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors read and edited the full document. Introduction (C.L.), Epidemiology (T.S.B.), Mechanisms/pathophysiology (M.W.S., G.D., R.M.J., T.C. and E.J.H.J.), Diagnosis, screening and prevention (T.C., E.J.H.J. and T.S.B.), Management (T.S.B., T.C., E.J.H.J., J.L.T. and J.V.-V.), Quality of life (J.L.T., J.C. and T.F.), Outlook (C.L. and A.P.), Overview of Primer (C.L.).

Corresponding author

Correspondence to Catherine Lord.

Ethics declarations

Competing Interests

C.L. acknowledges the receipt of royalties from Western Psychological Services for the sale of the Autism Diagnostic Interview-Revised (ADIR), the Autism Diagnostic Observation Schedule (ADOS) and the Social Communication Questionnaire (SCQ). T.S.B. has received royalties from Cambridge University Press and Oxford University Press. T.C. has served as a consultant to F. Hoffmann-La Roche. and has received royalties from Guilford Publications and Sage Publications. T.F. has received federal funding research support from, acted as a consultant to, received travel support from, and/or received a speaker’s honorarium from the Brain and Behaviour Research Foundation, Bristol-Myers Squibb, the Cole Family Research Fund, EcoEos, Forest Laboratories, Ingalls Foundation, IntegraGen, Kugona LLC, the National Institutes of Health, Roche Pharma, Shire Development and the Simons Foundation. J.L.T. receives compensation from Sage Publishers for editorial work. A.P. receives royalties from Imperial College Press, Oxford University Press and Western Psychological Services. M.W.S. serves on the scientific advisory boards and has stock or stock options for Arett Pharmaceuticals and BlackThorn Therapeutics. J.V.-V. has consulted or served on an advisory board for Novartis, Roche Pharmaceuticals and SynapDx, has received research funding from Forest, Novartis, Roche Pharmaceuticals, Seaside Therapeutics, SynapDx, and has received an editorial stipend from Springer and Wiley. All other authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Disease Primers thanks S. Spence, P. Szatmari and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lord, C., Brugha, T.S., Charman, T. et al. Autism spectrum disorder. Nat Rev Dis Primers 6, 5 (2020). https://doi.org/10.1038/s41572-019-0138-4

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41572-019-0138-4

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing