+1 (502) 904-2126   One Westbrook Corporate Center, Suite 300, Westchester, IL 60154, USA   Site Map
ISSN: 2574 -1241

Impact Factor : 0.548

  Submit Manuscript

Review ArticleOpen Access

Autism Spectrum Disorder (An Update) Volume 56- Issue 4

Michael Mikhail1*, Lara Kanber Agha1, Kristina Hobby2, Lourdes Illa-Sanchez2 and Ashraf Mikhail3

  • 1Royal College of Surgeons – Ireland, Ireland
  • 2Coastal Carolina Neuropsychiatric Center, Jacksonville, NC; Campbell University, United States
  • 3Campbell University School of Osteopathic Medicine, United States

Received: May 07, 2024; Published: May 15, 2024

*Corresponding author: Michael Mikhail, Royal College of Surgeons – Ireland, Dublin, Ireland

DOI: 10.26717/BJSTR.2024.56.008878

Abstract PDF


Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that typically manifests in early childhood as impaired social communication and restricted, repetitive behaviors which falls as a spectrum from mild to severe. In the past 5 decades, ASD has gone from a narrowly defined, rare disorder of childhood onset to a wellresearched, life-long condition which is relatively common and heterogeneous .The prevalence of ASD has been increasing in the United States over the last two decades, which is most likely related to change in diagnostic criteria, increased public awareness , and improved screening. The prognosis of ASD today is much brighter than it was in the past and more people with the condition are able to speak, read and live independently in the community. Early diagnosis is very important as early intensive behavioral interventions have shown to improve functional outcomes and quality of life. Comprehensive, multidisciplinary evaluation is needed for the diagnosis of ASD which should include the use of standardized measures as the Autism Diagnostic Interview- Revised and the Autism Diagnostic Observation Schedule-second edition. High rate of medical and psychiatric comorbidity have seen in individuals with ASD including epilepsy, depression, anxiety, and sleep difficulties. Early and intensive behavior interventions have shown to be beneficial in improving social communication, language and play. Pharmacological treatment is indicated for psychiatric comorbidity such as attention-deficit hyperactivity disorder, emotional dysregulation, irritability and aggression.


“Autism” derived from the Greek word “autos, or “self”, refers to someone who lives in a world of his own. Leo Kanner [1], first introduced the term autism as a diagnostic label to define a specific syndrome in young children characterized by early onset of impaired social and emotional relationship. Since then, autism is now recognized as Autism Spectrum Disorder (ASD) which is a neurodevelopmental disorder defined by social communication impairments and restricted, repetitive behaviors [2,3]. Early diagnosis is important because early diagnosis and early intensive behavioral intervention programs have been shown to improve functional outcomes and quality of life [4,5]. Unfortunately, early diagnosis of ASD can be challenging and despite much earlier concerns by caregivers for possible ASD, it is often diagnosed after the age of three [6,7]. The challenges in early diagnosis might be related to complexity and heterogeneity of ASD, leading to different presentations of individuals with ASD. ASD is also associated with significant psychiatric and medical comorbidity including language disorder, intellectual disability, sleep problems, anxiety, depression, obsessive compulsive disorder, attention deficit hyperactivity disorder and epilepsy [8-10]. The exact etiology of ASD is unknown but it is thought to have strong and complex genetic underpinnings with environmental factors modulating the phenotypic expression [11,12].


Among eight years old in the U.S., the prevalence is 2.3% in 2018 compared to 1.8% in 2008 with male to female ratio of 4:1 [13]. Black children with ASD tend to present at older ages than white children and often present with intellectual disability [14]. Several factors have likely contributed to the increased prevalence rate which includes change in the diagnostic criteria, increased awareness and increased access to services [15-19]. Children who often receive a late diagnosis include: females, ethnic minorities, low socioeconomic status, those from families who do not English, and those without language delay [20]. There is a concern that females are under-diagnosed and diagnosed at later age because of the belief that ASD occurs primarily in males [21]. There is also a possibility that the current diagnostic procedures are less sensitive to the presence of ASD among females or that females are more able to minimize ASD symptoms including social communication impairment (via camouflaging) [22,23]. Camouflaging can, for example, include suppression of repetitive movement, forcibly sustained eye contact or the use of learnt formulaic phrases [24].

Clinical Presentation

The key diagnostic features of ASD include deficit in social communication and restricted, repetitive pattern of behavior, interest, or activities. The presenting symptoms of ASD depend on age, language level, and cognitive functions. Some signs and symptoms of ASD may present between 6 and 12 months of age but reliable diagnosis, in many cases, can be made around 24 months of age [25,26]. Spoken language delay and social deficit are the most prominent features in children with ASD who are younger than three years old. Language delay without compensatory pointing or gesturing might help to differentiate ASD from expressive language delay [27,28]. The inability to coordinate one’s own attention between another person and distant object to share attention (joint attention) by 15 months of age should indicate the need for ASD evaluation [27,28]. Repetitive behavior and restricted range of interest may be less apparent in younger children. Many children with ASD have several coexisting conditions that impact the presentation and the level of impairment. The prevalence of ASD is higher in individuals with special health needs including people with visual impairment, hearing impairment, intellectual disability, and Fragile-X Syndrome [29-31]. Furthermore, psychiatric and medical comorbidity are very common in ASD population, particularly attention deficit hyperactivity disorder, anxiety, depression, aggression, self-injury, sleep difficulties, feeding problem and epilepsy [32-36]. Additionally, almost 30% of people with ASD present with special skills that exceed what seems humanly possible (savant skills) most commonly manifesting in mental arithmetic, art, and memory skills [37,38].


Many public health systems have attempted to identify very young children with ASD in the general population. However, screening tools have not been sensitive enough to effectively identify most of children with ASD in the general population in whom parents have not been already recognized a delay [39]. When parent have expressed concern, screening instruments become effective for predicting ASD in children as young as 18 months of age [40]. The American Academy of Pediatrics recommends that all children be screened for ASD at 18 and 24 months of age [41]. The modified-checklist for autism in toddlers, revised (M-CHAT-R), a 20 item screening questionnaire, is one of the frequently used ASD screening tools in primary care settings. It is designed to identify children 16 to 30 months who are at risk for ASD [42]. Children who have a positive screening test for ASD should undergo a comprehensive evaluation and referral for developmental services. Children who receive consistent pediatric care, are in frequent contact with grandmothers, and who have older siblings receive earlier diagnoses than those who do not [43,44].


For definitive diagnosis of ASD, a comprehensive assessment by a multidisciplinary team using standardized diagnostic tools to exclude other conditions, identifying any comorbid conditions and to assess the child’s overall level of function [45-47]. The most widely used diagnostic tools for ASD are the Autism Diagnostic Observation Schedule, second edition (ADOS-2) and the Autism Diagnostic Interview, Revised (ADI-R) [48]. The American Academy of Pediatrics and The American College of Medical Genetics and Genomics recommend genetic testing for individuals diagnosed with ASD [49]. In particular, chromosomal microarray is recommended to scan the genome for copy number variants. Adults seeking first diagnosis of ASD are typically have comorbid psychiatric disorders but are not intellectually disabled [50]. While brief self-reports do not have adequate specificity, versions of ADOS, and Social Responsiveness Scale (SRS) are appropriate for verbally fluent adults [51,52].

Risk Factors

74-93% of ASD risk is heritable [53]. Models for genetic risk in ASD propose that complex inheritance with additive contributions from common variants that individually make small contributions to risk as well as rare variants that have larger effect sizes [54]. Several environmental risk factors have also been identified including advanced maternal or paternal age, prenatal valproic acid exposure, preterm birth, low birth weight, small for gestational age status, and large for gestational age status [55-58].

Behavioral Treatment

Early behavioral intervention for at least 25 hours per week is recommended for young children with ASD [59]. Applied Behavioral Analysis is the cornerstone for early intensive behavioral interventions, which utilize applied behavior analytic principles of learning to teach children the appropriate skills in natural settings, have been shown to improve children’s language, play, and social communications [60,61]. Cognitive behavioral therapy can be very effective in reducing anxiety and depressive symptoms in individuals with ASD [62]. In school-age children without intellectual disabilities, social skills training can be useful in improving social skills and emotional dysfunctions [63]. Providing behavioral, speech, occupational and physical therapy in the school setting together with parent training resulted in improved language skills and decreased disruptive behavior in children with ASD [64].

Pharmacological Treatment

No medication is available to target core symptoms of ASD, but medications can be useful to target specific maladaptive behaviors which did not respond to intensive behavioral therapy. In addition medications can be useful to target comorbid psychiatric conditions [27]. Risperidone and aripiprazole have shown to improve symptoms of irritability and agitation in children and adolescents with ASD and are the only medications approved by the U.S. Food and Drug Administration for the treatment of ASD-Associated Irritability [65,66]. Psychostimulants (methylphenidate) and non-stimulants (atomoxetine and guanfacine) have shown to be effective in the management of ADHD symptoms in individuals with ASD [67]. Melatonin may also be useful for sleep disturbances [68]. The current evidence does not support the use of any supplement for the treatment of core ASD symptoms but N-acetylcysteine and sulforaphane have demonstrated some efficacy for behavioral and emotional symptoms associated with ASD [69].


Current studies show that there has been a significant improvement in outcomes of individuals with ASD in the current studies compared to the old data [70]. However, adults with ASD continue to be less likely to live independently or be employed and more likely to use mental health services compared to individuals without ASD diagnosis [71]. Better outcomes are reported in individuals with ASD with higher cognitive abilities, had earlier referrals, more intensive early behavioral interventions and fewer pharmacological interventions [72,73]. Mortality rates are approximately 2-fold higher for individuals with ASD compared to general populations and suicide rates are much higher in this population compared to the general population [74,75].


Life for many children and adults with ASD have improved compared to when autism was first described by Leo Kanner. More individuals with ASD can talk, read, graduate from school and live independently. ASD affect over 2% of children and adults in the U.S. The evidence continues to support early intensive behavioral interventions delivered by a multidisciplinary team as a first-line therapy, while comorbid mental health conditions such as ADHD, anxiety and aggression may be treated by specific behavioral therapy or medicine.


  1. Kanner L (1943) Autism disturbances of affective contact . Nervous Child 32: 217-253.
  2. (2013) Diagnostic and Statistical Manual of Mental Disorders (5th)., American Psychiatric Association.
  3. Autism spectrum disorder (ASD) Centers for Disease Control and Prevention.
  4. Zwaigenbaum L, Bauman ML, Choueiri R, Wendy L Stone, Nurit Yirmiya, et al. (2015) Early intervention for children with Autism Spectrum disorder under 3 years of age: recommendation for practice and research. Pediatrics 136 Suppl 1: S 60-81
  5. Warren Z, McPheeters ML, Sathe N, Jennifer H Foss-Feig, Allison Glasser, et al. (2011) A systematic review of early intensive intervention for autism spectrum disorders. Pediatrics 127: e1303-11.
  6. Johnson CP, Myers SM (2007) American Academy of Pediatrics Council on children with disabilities. Identification and evaluation of children with autism spectrum disorders. Pediatrics 120: 1183-215.
  7. Zuckerman KE, Lindly OL, Sinchene BK (2015) Parental concerns, provider response,and timeliness of autism spectrum disorder diagnosis . J Pediatr 166: 1431-1439
  8. Lai MC, Kassee C, Besney R, Bonato S, Hull L, et al. (2019) Prevalence of co-occurring mental health diagnoses in the autism population: a systematic review and meta-analysis. Lancet Psychiatry 6(10): 819-829.
  9. Rydzewska E, Dunn K, Cooper SA (2021) Umbrella systematic review of systematic reviews and meta-analyses on comorbid physical conditions in people with autism spectrum disorder. Br J Psychiatry 218(1): 10-19.
  10. Mannion A, Leader G (2013) Comorbidity in Autism Spectrum Disorder: A literature review. Res Autism Spectr Disord 7: 1595-616.
  11. Bailey A, Phillips W, Rutter M (1996) Autism: towards an integration of clinical, genetic, neuropsychological, and neurolobiological perspectives. J Child Psychol Psychiatry 37: 89-126.
  12. Hofer J, Hoffmann F, Kemp-Becker L, Poustka L, Roessner V, et al. (2019) Pathways to diagnosis of Autism Spectrum Disorder in Germany: A survey of parents. Child Adolesc. Psychiatry Ment Health 13: 16.
  13. Maenner MJ, Shaw KA, Bakian AV, Zachary Warren, Mary E cogswell, et al. (2021) Prevalence and characteristics of autism spectrum disorder among children aged 8 years: Autism and Developmental Disabilities Monitoring Network, 11sites, United States, 2018. MMWR Surveill Summ 70(11): 1-16.
  14. Constantino JN, Abbacchi AM, Saulneir C, Cheryl Klaiman, Daniel H Geschwind, et al. (2020) Timing of the Diagnosis of Autism in African American Children. Pediatrics 146(3): e20193629.
  15. Blenner S, Augustyn M (2014) Is the prevalence of autism increasing in the United States? BMJ 348: g3088
  16. Zylstra RG, Prater CD, Walthour AE, Aponte AF (2014) Autism: why the rise in rates? J Fam Pract 63(6): 316-320.
  17. Blumberg SJ, Bramlett MD, Kogan MD, Schieve LA, Jones JR, et al. (2013) Changes in prevalence of parent-reported autism spectrum disorder in school-aged U.S. children: 2007 to 2011-2012. Natl Health Stat Report (65): 1-11.
  18. Hansen SN, Schendel DE, Parner ET (2015) Explaining the increase in the prevalence of autism spectrum disorders: the proportion attributable to changes in reporting practices. JAMA Pediatr 169(1): 56-62.
  19. Zeidan J, Fombonne E, Scorah J, Alaa Ibrahim, Maureen S Durkin, et al. (2022) Global prevalence of autism: a systematic review update. Autism Res 15(5): 778-790.
  20. (2014) Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators; Centers for Disease Control and Prevention. Prevalence of autism spectrum disorder among children aged 8 years—Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2010. MMWR Surveill Summ 63: 1-21.
  21. Halladay AK, Bishop S, Constantino JN, Peter Szatmari, Kevin Pelphrey, et al. (2015) Sex and gender differences in autism spectrum disorder: summarizing evidence gaps and identifying emerging areas of priority. Mol Autism 6: 36.
  22. Fombonne E (2020) Camouflage and autism. J Child Psychol Psychiatry 61(7): 735-738.
  23. Lai MC, Lombardo MV, Ruigrok AN, Peter Szatmari, Simon Baron-Cohen, et al. (2017) MRC AIMS Consortium. Quantifying and exploring camouflaging in men and women with autism. Autism 21(6): 690-702.
  24. Cook J, Hull L, Crane L, Mandy W (2021) Camouflaging in Autism: a systemic review. Clin Psychol Rev 89: 102080.
  25. Lord C, Risi S, DiLavore PS, Shulman C, Thurm A, et al. (2006) Autism from 2 to 9 years of age. Arch Gen Psychiatry 63 (6): 694-701.
  26. Guthrie W, Swineford LB, Nottke C, Wetherby AM (2013) Early diagnosis of autism spectrum disorder: stability and change in clinical diagnosis and symptom presentation. J Child Psychol Psychiatry 54(5): 582-590.
  27. Carbone PS, Farley M, Davis T (2010) Primary care for children with autism. Am Fam Physician 81(4): 453-460.
  28. Johnson CP (2008) Recognition of autism before age 2 years. Pediatr Rev 29(3): 86-96.
  29. Do B, Lynch P, Macris EM, B Smyth, S stavrinakis, et al. (2017) Systematic review and meta-analysis of the association of autism spectrum disorder in visually or hearing impaired children. Ophthalmic Physiol Opt 37(2): 212-224.
  30. Tonnsen BL, Boan AD, Bradley CC, Charles J, Cohen A, et al. (2016) revalence of autism spectrum disorders among children with intellectual disability. Am J Intellect Dev Disabil 121(6): 487-500.
  31. Richards C, Jones C, Groves L, Moss J, Oliver C, et al. (2015) Prevalence of autism spectrum disorder phenomenology in genetic disorders: a systematic review and meta-analysis. Lancet Psychiatry 2(10): 909-916.
  32. Mutluer T, Aslan Genç H, Özcan Morey A, Yapici Eser H, Ertinmaz B, et al. (2022) Population-based psychiatric comorbidity in children and adolescents with autism spectrum disorder: ameta-analysis. Front Psychiatry.
  33. O’Halloran L, Coey P, Wilson C (2022) Suicidality in autistic youth: a systematic review and meta-analysis. Clin Psychol Rev 93: 102144.
  34. Hawks ZW, Constantino JN (2020) Neuropsychiatric “Comorbidity “ as Causal Influence in Autism. J Am Acad Child Adolesc Psychiatry 59(2): 229-235.
  35. Amiet C, Gourfinkel-An I, Bouzamondo A, Torjman S, Baulac M, et al. (2008) Epilepsy in autism is associated with intellectual disability and gender: evidence from a meta-analysis. Biol Psychiatry 64(7): 577-582.
  36. Mayes SD, Zickgraf H (2019) Atypical eating behaviors in children and adolescents with autism, ADHD, other disorders, and typical development. Res Autism Spectr Disord 64: 76-83.
  37. Happé F (2018) Why are savant skills and special talents associated with autism? World Psychiatry 17(3): 280-281.
  38. Howlin P, Goode S, Hutton J, Rutter M (2009) Savant skills in autism: psychometric approaches and parental reports. Philos Trans R Soc Lond B Biol Sci 364(1522): 1359-1367.
  39. Mandell D, Mandy W (2015) Should all young children be screened for autism spectrum disorder? Autism19: 895-896.
  40. Havdahl KA, Bishop SL, Surén P, Camilla Stoltenberg, Mady Hornig, et al. (2017) The influence of parental concern on the utility of autism diagnostic instruments. Autism Res 10: 1672-1686.
  41. Hyman SL, Levy SE, Myers SM (2020) COUNCIL ON CHILDREN WITH DISABILITIES, SECTION ON DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS. Identification, evaluation, and management of children with autism spectrum disorder. Pediatrics 145 (1): e20193447.
  42. Robins DL, Casagrande K, Barton M, Chen CM, Dumont-Mathieu T, et al. (2014) Validation of the modified checklist for autism in toddlers, revised with follow-up (M-CHAT-R/F). Pediatrics 133(1): 37-45.
  43. Emerson ND, Morrell HER, Neece C (2016) Predictors of age of diagnosis for children with autism spectrum disorder: The role of a consistent source of medical care, race, and condition severity. J Autism Dev Disord 46: 127-138.
  44. Sicherman N, Loewenstein G, Tavassoli T, Buxbaum JD (2018) Grandma knows best: Family structure and age of diagnosis of autism spectrum disorder. Autism 22: 368-376.
  45. (2006) Council on children with disabilities; Section on Developmental Behavioral Pediatrics; Bright future Steering Committee ;Medical home initiatives for Children With Special Needs Project Advisory Committee. Identifying infants and young children with developmental disorders in the medical home; an algorithm for developmental surveillance and screening. Pediatrics 118(1): 405-420
  46. Volkmar F, Siegel M, Woodbury-Smith M, King B, McCracken J, et al. (2014) American Academy of Child and Adolescent Psychiatry Committee on Quality Issues. Practice parameter forbthe assessment and treatment of children and adolescents with autism spectrum disorder J Am Acad Child Adolesc Psychiatry 53(2): 237-257
  47. Zwaigenbaum L, Bauman ML, Fein D, Robin L Hansen, Wendy L Stone, et al. (2015) Early screening of autism spectrum disorder: recommendations for practice and research. Pediatrics 136(suppl 1): S41-S59.
  48. Lebersfeld JB, Swanson M, Celso CD, O’Kelly SE (2021) Systematic review and meta-analysis of the clinical utility of the ADOS-2 and ADI-R in diagnosis of autism spectrum disorders in children. J Autism Dev Disord 51(11): 4101-4114.
  49. Schaefer GB, Mendelsohn NJ (2013) Professional Practice and Guidelines Committee . Clinical genetics evaluation in identifying the etiology of autism spectrum disorders:2013 guideline revisions. Genet Med 15(5): 399-407.
  50. Happé FG, Mansour H, Barrett P, Brown T, Abbott P, et al. (2016) Demographic and cognitive profile of individuals seeking a diagnosis of autism spectrum disorder in adulthood. J Autism Dev Disord 6(11): 3469-3480.
  51. Chan W, Smith LE, Hong J, Greenberg JS, Mailick MR, et al. (2017) Validating the social responsiveness scale for adults with autism. Autism Res 10(10): 166371.
  52. Hus V, Lord C (2014) The autism diagnostic observation schedule, module 4: revised algorithm and standardized severity scores. J Autism Dev Disord 44(8): 1996-2012.
  53. Tick B, Bolton P, Happé F, Rutter M, Rijsdijk F, et al. (2016) Heritability of autism spectrum disorders: a meta-analysis of twin studies. J Child Psychol Psychiatry 57(5): 585-595.
  54. Gaugler T, Klei L, Sanders SJ, Dina Manaa, Yudi Pawitan, et al. (2014) Most genetic risk for autism resides with common variation. Nat Genet 46(8): 881-885.
  55. Idring S, Magnusson C, Lundberg M, Brian K Lee, Christina Dalman, et al. (2014) Parental age and the risk of autism spectrum disorders: findings from a Swedish population-based cohort. Int J Epidemiol 43(1): 107-15.
  56. Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, et al. (2013) Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA 309(16): 1696-1703.
  57. Lampi KM, Lehtonen L, Tran PL, Suominen A, Lehti V, et al. (2012) Risk of autism spectrum disorders in low birth weight and small for gestational age infants. J Pediatr 161(5): 830-836.
  58. Moore GS, Kneitel AW, Walker CK, Gilbert WM, Xing G, et al. (2012) Autism risk in small- and large-for-gestational-age infants. Am J Obstet Gynecol 206(4): 314.e1-9.
  59. Maglione MA, Gans D, Das L, Timbie J, Kasari C, et al. (2012) Technical Expert Panel; HRSA Autism Intervention Research–Behavioral Network. Nonmedical interventions for children with ASD: recommended guidelines and further research needs. Pediatrics 130( suppl 2): S169-S178
  60. Schreibman L, Dawson G, Stahmer AC, Landa R, Rogers SJ, et al. (2015) Naturalistic developmental behavioral interventions: empirically validated treatments for autism spectrum disorder. J Autism Dev Disord 45(8): 2411-2428.
  61. Sandbank M, Bottema-Beutel K, Crowley S, Cassidy M, Dunham K, et al. (2020) Project AIM: autism intervention meta-analysis for studies of young children. Psychol Bull 146(1): 1-29.
  62. White SW, Simmons GL, Gotham KO, Conner CM, Smith IC, et al. (2018) 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(10): 82.
  63. Weitlauf AS, McPheeters ML, Peters B, Nila Sathe, Rachel Aiello, et al. (2014) Therapies for children with autism spectrum disorder: behavioral interventions update (internet). Rockville (MD): AHRQ (US) Report no.14-EHC036-EF. PMID: 25210724
  64. Bearss K, Johnson C, Smith T, Yanhong Deng, Lawrence Scahill, et al. (2015) Effect of parent training vs parent education on behavioral problems in children with autism spectrum disorder: a randomized clinical trial JAMA 313(15): 1524-1533.
  65. Kent JM, Kushner S, Ning X, Archer K, Ness S, et al. (2013) Risperidone dosing in children and adolescents with autistic disorder: a double-blind, placebo-controlled study. J Autism Dev Disord 43: 1773–1783.
  66. Owen R, Sikich L, Marcus RN, Corey-Lisle P, Manos G, et al. (2009) Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics 124: 1533-1540.
  67. Rodrigues R, Lai MC, Beswick A, Gorman DA, Anangnostou E, et al. (2021) Practitioner review: pharmacological treatment of attention-deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta-analysis. J Child Psychol Psychiatry 62(6): 680-700.
  68. Rossignol DA, Frye RE (2011) Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev Med Child Neurol 53(9): 783-792.
  69. Zimmerman AW, Singh K, Connors SL, Liu H, Panjwani AA, et al. (2021) Randomized controlled trial of sulforaphane and metabolite discovery in children with autism spectrum disorder. Mol Autism 12(1): 38.
  70. Farley MA, McMahon WM, Fombonne E, Hilary Coon, Edward R Rirvo, et al. (2009) Twenty-year outcome for individuals with autism and average or near-average cognitive abilities. Autism Res 2(2): 109-118.
  71. Mason D, Capp SJ, Stewart GR, Kempton MJ, Glazer K, et al. (2021) Howlin P, Happe F. Ameta-analysis of outcome studies of autistic adults: quantifying effect size, quality, and meta-regression. J Autism Dev Disord 51(9): 3165-3179.
  72. Pickles A, McCauley JB, Pepa LA, Huerta M, Lord C, et al. (2020) The adult outcome of children referred for autism: typology and prediction from childhood. J Child Psychol Psychiatry 61(7): 760-767.
  73. Orinstein AJ, Helt M, Troyb E, Tyson KE, Barton ML, et al. (2014) Intervention for optimal outcome in children and adolescents with a history of autism. J Dev Behav Pediatr 35(4): 247-256.
  74. Catalá-López F, Hutton B, Page MJ, Driver JA Ridao M, Alonso-Arroyo A Valencia A, et al. (2011) Mortality in persons with autism spectrum disorder or attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. JAMA Pediatr 176(4): e216401.
  75. Kõlves K, Fitzgerald C, Nordentoft M, Wood SJ, Erlangsen A, et al. (2021) Assessment of suicidal behaviors among individuals with autism spectrum disorder in Denmark. JAMA Netw Open 4(1): e2033565.