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.
Subscribe to Journal
Get full journal access for 1 year
only $59.00 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
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.
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).
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).
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.
Brugha, T., Bankart, J., McManus, S. & Gullon-Scott, F. CDC autism rate: misplaced reliance on passive sampling? Lancet 392, 732–733 (2018).
Baxter, A. J. et al. The epidemiology and global burden of autism spectrum disorders. Psychol. Med. 45, 601–613 (2015).
Elsabbagh, M. et al. Global prevalence of autism and other pervasive developmental disorders. Autism Res. 5, 160–179 (2012).
Magnusson, C. et al. Migration and autism spectrum disorder: population-based study. Br. J. Psychiatry 201, 109–115 (2012).
Goodman, R. & Richards, H. Child and adolescent psychiatric presentations of second-generation Afro-Caribbeans in Britain. Br. J. Psychiatry 167, 362–369 (1995).
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).
Keen, D. V., Reid, F. D. & Arnone, D. Autism, ethnicity and maternal immigration. Br. J. Psychiatry 196, 274–281 (2010).
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).
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).
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).
Brugha, T. C. et al. Autism Spectrum Disorder, Adult Psychiatric Morbidity Survey 2014. (2014).
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).
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).
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).
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).
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).
Lai, M.-C., Lombardo, M. V. & Baron-Cohen, S. Autism. Lancet 383, 896–910 (2014).
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).
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).
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).
Ozonoff, S. et al. Recurrence risk for autism spectrum disorders: a baby siblings research consortium study. Pediatrics 128, e488–e495 (2011).
Jones, R. M. & Lord, C. Diagnosing autism in neurobiological research studies. Behav. Brain Res. 251, 113–124 (2013).
Johnson, M. H. Autism: demise of the innate social orienting hypothesis. Curr. Biol. 24, R30–R31 (2014).
Johnson, M. H., Jones, E. J. H. & Gliga, T. Brain adaptation and alternative developmental trajectories. Dev. Psychopathol. 27, 425–442 (2015).
The Lancet Psychiatry. Of mice and mental health. Lancet Psychiatry 6, 877 (2019).
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).
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).
Gaugler, T. et al. Most genetic risk for autism resides with common variation. Nat. Genet. 46, 881–885 (2014).
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).
Sanders, S. J. et al. Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron 87, 1215–1233 (2015).
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).
Sanders, S. J. et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485, 237–241 (2012).
Neale, B. M. et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 485, 242–245 (2012).
O’Roak, B. J. et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 485, 246–250 (2012).
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).
Levy, D. et al. Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron 70, 886–897 (2011).
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.
Grove, J. et al. Identification of common genetic risk variants for autism spectrum disorder. Nat. Genet. 51, 431–444 (2019).
Willsey, J. et al. De novo coding variants are strongly associated with Tourette syndrome. Eur. Neuropsychopharmacol. 29, S737 (2019).
Epi4K Consortium. Epi4K: gene discovery in 4,000 genomes. Epilepsia 53, 1457–1467 (2012).
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.
Iossifov, I. et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature 515, 216–221 (2014).
De Rubeis, S. et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 515, 209–215 (2014).
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).
State, M. W. & Sestan, N. The emerging biology of autism spectrum disorders. Science 337, 1301–1303 (2012).
Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427 (2014).
Devlin, B. & Scherer, S. W. Genetic architecture in autism spectrum disorder. Curr. Opin. Genet. Dev. 22, 229–237 (2012).
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).
SFARI Gene Website. https://gene.sfari.org/ (2019).
Parikshak, N. N. et al. Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism. Cell 155, 1008–1021 (2013).
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).
Willsey, A. J. et al. Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell 155, 997–1007 (2013).
Pinto, D. et al. Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466, 368–372 (2010).
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).
Fuccillo, M. V. Striatal circuits as a common node for autism pathophysiology. Front. Neurosci. 10, 27 (2016).
Velmeshev, D. et al. Single-cell genomics identifies cell type-specific molecular changes in autism. Science 364, 685–689 (2019).
Mendell, J. R. et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N. Engl. J. Med. 377, 1713–1722 (2017).
Mercuri, E. et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N. Engl. J. Med. 378, 625–635 (2018).
Matharu, N. et al. CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency. Science 363, eaau0629 (2019).
Abudayyeh, O. O. et al. RNA targeting with CRISPR–cas13. Nature 550, 280–284 (2017).
Power, J. D. et al. Customized head molds reduce motion during resting state fMRI scans. NeuroImage 189, 141–149 (2019).
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).
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).
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).
Langen, M. et al. Changes in the development of striatum are involved in repetitive behavior in autism. Biol. Psychiatry 76, 405–411 (2014).
Elsabbagh, M. & Johnson, M. H. Autism and the social brain: the first-year puzzle. Biol. Psychiatry 80, 94–99 (2016).
Courchesne, E. et al. Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology 57, 245–254 (2001).
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).
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).
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.
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).
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).
Smith, E. et al. Cortical thickness change in autism during early childhood: CT in early childhood ASD. Hum. Brain Mapp. 37, 2616–2629 (2016).
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).
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).
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).
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).
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).
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).
Doyle-Thomas, K. A. R. et al. Atypical functional brain connectivity during rest in autism spectrum disorders. Ann. Neurol. 77, 866–876 (2015).
Supekar, K. et al. Brain hyperconnectivity in children with autism and its links to social deficits. Cell Rep. 5, 738–747 (2013).
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).
Hull, J. V. et al. Resting-state functional connectivity in autism spectrum disorders: a review. Front. Psychiatry 7, 205 (2017).
Lombardo, M. V. et al. Different functional neural substrates for good and poor language outcome in autism. Neuron 86, 567–577 (2015).
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).
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).
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).
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).
Levisohn, P. M. The autism-epilepsy connection. Epilepsia 48, 33–35 (2007).
Cantor, D. S., Thatcher, R. W., Hrybyk, M. & Kaye, H. Computerized EEG analyses of autistic children. J. Autism Dev. Disord. 16, 169–187 (1986).
Lefebvre, A. et al. Alpha waves as a neuromarker of autism spectrum disorder: the challenge of reproducibility and heterogeneity. Front. Neurosci. 12, 662 (2018).
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).
Oberman, L. M. et al. EEG evidence for mirror neuron dysfunction in autism spectrum disorders. Cogn. Brain Res. 24, 190–198 (2005).
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).
Southgate, V. & Hamilton, A. F. Unbroken mirrors: challenging a theory of autism. Trends Cogn. Sci. 12, 225–229 (2008).
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).
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).
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.
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).
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).
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).
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).
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.
Barraza, P. et al. Implementing EEG hyperscanning setups. MethodsX 6, 428–436 (2019).
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).
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).
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).
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).
Kolesnik, A. et al. Increased cortical reactivity to repeated tones at 8 months in infants with later ASD. Transl. Psychiatry 9, 46 (2019).
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).
Rosenberg, A., Patterson, J. S. & Angelaki, D. E. A computational perspective on autism. Proc. Natl Acad. Sci. USA 112, 9158–9165 (2015).
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).
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).
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).
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).
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).
Engemann, D. A. et al. Robust EEG-based cross-site and cross-protocol classification of states of consciousness. Brain 141, 3179–3192 (2018).
Open Science Collaboration. Psychology. Estimating the reproducibility of psychological science. Science 349, aac4716 (2015).
Lord, C. et al. Autism diagnostic observation schedule: ADOS-2 (Western Psychological Services, 2012).
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).
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th Edn (American Psychiatric Association, 2013).
World Health Organization. International classification of diseases for mortality and morbidity statistics (11th Revision). https://icd.who.int/browse11/l-m/en (WHO, 2018).
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).
Lord, C. A multisite study of the clinical diagnosis of different autism spectrum disorders. Arch. Gen. Psychiatry 69, 306–313 (2012).
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).
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edn (American Psychiatric Association, 1994).
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).
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).
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).
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).
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).
Rutter, M., LeCouteur, A. & Lord, C. Autism Diagnostic Interview-Revised (ADI-R). (Western Psychological Services, 2003).
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.
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).
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).
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).
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).
Fountain, C., Winter, A. S. & Bearman, P. S. Six developmental trajectories characterize children with autism. Pediatrics 129, e1112–e1120 (2012).
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).
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).
Zerbi, V. et al. Dysfunctional autism risk genes cause circuit-specific connectivity deficits with distinct developmental trajectories. Cereb. Cortex 28, 2495–2506 (2018).
Fein, D. et al. Optimal outcome in individuals with a history of autism. J. Child Psychol. Psychiatry 54, 195–205 (2013).
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).
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).
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).
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).
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).
Øien, R. A. et al. Clinical features of children with autism who passed 18-month screening. Pediatrics 141, e20173596 (2018).
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).
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).
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).
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).
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).
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).
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).
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).
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.
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).
Brugha, T. S. The Psychiatry of Adult Autism and Asperger Syndrome: a Practical Guide (Oxford Univ. Press, 2018).
Epstein, J., Johnson, D. E. & Conners, C. K. Conners Adult ADHD Diagnostic Interview for DSM-IV (CAADID) (MHS, 2001).
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).
Havdahl, A. & Bishop, S. Heterogeneity in prevalence of co-occurring psychiatric conditions in autism. Lancet Psychiatry 6, 794–795 (2019).
Croen, L. A. et al. The health status of adults on the autism spectrum. Autism 19, 814–823 (2015).
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).
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).
Chandler, S. et al. Emotional and behavioural problems in young children with autism spectrum disorder. Dev. Med. Child Neurol. 58, 202–208 (2016).
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).
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).
Hirvikoski, T. et al. Premature mortality in autism spectrum disorder. Br. J. Psychiatry 208, 232–238 (2016).
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).
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).
Schreibman, L. et al. Naturalistic developmental behavioral interventions: empirically validated treatments for autism spectrum disorder. J. Autism Dev. Disord. 45, 2411–2428 (2015).
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).
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).
Lovaas, O. I. Behavioral treatment and normal educational and intellectual functioning in young autistic children. J. Consult. Clin. Psychol. 55, 3–9 (1987).
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).
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).
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).
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).
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).
Green, J. et al. Parent-mediated communication-focused treatment in children with autism (PACT): a randomised controlled trial. Lancet 375, 2152–2160 (2010).
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).
Dawson, G. et al. Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics 125, e17–e23 (2010).
Charman, T. Editorial: trials and tribulations in early autism intervention research. J. Am. Acad. Child Adolesc. Psychiatry 58, 846–848 (2019).
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).
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).
Myers, S. M., Johnson, C. P. & The Council on Children With Disabilities. Management of children with autism spectrum disorders. Pediatrics 120, 1162–1182 (2007).
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).
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).
Brignell, A. et al. Communication interventions for autism spectrum disorder in minimally verbal children. Cochrane Database Syst. Rev. 11, CD012324 (2018).
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).
Keefer, A. et al. Exploring relationships between negative cognitions and anxiety symptoms in youth with autism spectrum disorder. Behav. Ther. 49, 730–740 (2018).
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).
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).
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).
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).
Taylor, J. L. et al. A systematic review of vocational interventions for young adults with autism spectrum disorders. Pediatrics 130, 531–538 (2012).
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).
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).
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).
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).
McCracken, J. T. et al. Risperidone in children with autism and serious behavioral problems. N. Engl. J. Med. 347, 314–321 (2002).
Owen, R. et al. Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics 124, 1533–1540 (2009).
McPheeters, M. L. et al. A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics 127, e1312–e1321 (2011).
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).
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).
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).
Scahill, L. et al. Extended-release guanfacine for hyperactivity in children with autism spectrum disorder. Am. J. Psychiatry 172, 1197–1206 (2015).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Krueger, D. A. et al. Everolimus for treatment of tuberous sclerosis complex-associated neuropsychiatric disorders. Ann. Clin. Transl. Neurol. 4, 877–887 (2017).
Georgiades, S. & Kasari, C. Reframing optimal outcomes in autism. JAMA Pediatr. 172, 716–717 (2018).
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).
The WHOQOL Group. Development of the World Health Organization WHOQOL-BREF quality of life assessment. Psychol. Med. 28, 551–558 (1998).
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).
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).
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).
Henninger, N. A. & Taylor, J. L. Outcomes in adults with autism spectrum disorders: a historical perspective. Autism 17, 103–116 (2013).
Howlin, P. & Moss, P. Adults with autism spectrum disorders. Can. J. Psychiatry 57, 275–283 (2012).
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).
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).
Lai, M.-C. et al. Quantifying and exploring camouflaging in men and women with autism. Autism 21, 690–702 (2016).
van Heijst, B. F. & Geurts, H. M. Quality of life in autism across the lifespan: a meta-analysis. Autism 19, 158–167 (2015).
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).
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).
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).
Mason, D. et al. Predictors of quality of life for autistic adults. Autism Res. 11, 1138–1147 (2018).
Autistica. Your questions shaping future autism research. https://www.autistica.org.uk/downloads/files/Autism-Top-10-Your-Priorities-for-Autism-Research.pdf (2016).
Ontario Brain Institute. Community priorities for research on neurodevelopmental disorders. http://braininstitute.ca/img/JLA-NDD-Final-Report.pdf (2018).
den Houting, J. Neurodiversity: an insider’s perspective. Autism 23, 271–273 (2018).
Szatmari, P. Risk and resilience in autism spectrum disorder: a missed translational opportunity? Dev. Med. Child Neurol. 60, 225–229 (2018).
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).
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).
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).
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).
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).
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).
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).
Lord, C., Bishop, S. & Anderson, D. Developmental trajectories as autism phenotypes. Am. J. Med. Genet. C Semin. Med. Genet. 169, 198–208 (2015).
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).
Kahn, R. S. et al. Schizophrenia. Nat. Rev. Dis. Primers 1, 15067 (2015).
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).
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).
World Health Organization. Training parents to transform children’s lives. https://www.who.int/mental_health/maternal-child/PST/en/ (WHO, 2019).
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).
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.
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).
Hermelin, B. & O’Connor, N. Psychological Experiments with Autistic Children (Pergamon Press, 1970).
Rimland, B. Infantile Autism: the Syndrome and its Implications for a Neural Theory of Behaviour (Meredith Publishing Company, 1964).
Frith, U. Studies in pattern detection in normal and autistic children: I. Immediate recall of auditory sequences. J. Abnorm. Psychol. 76, 413–420 (1970).
Folstein, S. & Rutter, M. in Autism (eds. Rutter M. & Schopler E.) 219–241 (Springer, 1978).
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).
Schopler, E. & Reichler, R. J. Parents as cotherapists in the treatment of psychotic children. J. Autism Child. Schizophr. 1, 87–102 (1971).
Sinclair, J. Don’t mourn for us. Autism Network International http://www.autreat.com/dont_mourn.html (1993).
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).
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).
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).
Christensen, J. et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA 309, 1696–1703 (2013).
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).
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).
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).
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).
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).
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).
Lyall, K. et al. The changing epidemiology of autism spectrum disorders. Annu. Rev. Public Health 38, 81–102 (2017).
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).
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).
Lehti, V. et al. Autism spectrum disorders in IVF children: a national case-control study in Finland. Hum. Reprod. 28, 812–818 (2013).
Rossignol, D. A., Genuis, S. J. & Frye, R. E. Environmental toxicants and autism spectrum disorders: a systematic review. Transl. Psychiatry 4, e360 (2014).
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).
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).
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).
Sparrow, S. S., Cicchetti, D. & Balla, D. A. Vineland Adaptive Behavior Scales, 2nd Edn. https://doi.org/10.1037/t15164-000 (AGS, 2005).
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).
Lord, C., Elsabbagh, M., Baird, G. & Veenstra-Vanderweele, J. Autism spectrum disorder. Lancet 392, 508–520 (2018).
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).
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.
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.
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.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
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
A Preliminary Exploration of Virtual Reality-Based Visual and Touch Sensory Processing Assessment for Adolescents With Autism Spectrum Disorder
IEEE Transactions on Neural Systems and Rehabilitation Engineering (2021)
Potential effects of mesenchymal stem cell derived extracellular vesicles and exosomal miRNAs in neurological disorders
Neural Regeneration Research (2021)
Brain Sciences (2021)
International Journal of Eating Disorders (2021)
Frontiers in Cellular Neuroscience (2021)