Integrating Treatment for Autism: Etiology and Life Cycle



Autism Spectrum Disorder (ASD) is linked to a multitude of genes, epigenetics, and environmental factors, which contribute to the complexities of treating ASD. A large body of literature suggests benefits from perinatal, early, and later intervention. It is common for physicians to struggle with making a diagnosis of ASD, but once it is made, parents who have been taught effective strategies can be impactful in their child’s positive development. Neuroimaging studies of children, adolescents and young adults with ASD suggest that their brain structures change over time and are also capable of being shaped through appropriate interventions. Interventions are also being adapted for adults with ASD to better address their needs, such as employment training programs. We review the wide array of risk factors and interventions to mitigate the challenges individuals with ASD face in their daily lives.

General Information

Keywords: autism, risk factors, endophenotypes, intervention, adaptive functioning, primary care

Journal rubric: Education & Intervention Methods

Article type: scientific article


For citation: Tsipan R.M., Parenteau C.I., Hendren R.L. Integrating Treatment for Autism: Etiology and Life Cycle. Autizm i narusheniya razvitiya = Autism and Developmental Disorders, 2020. Vol. 18, no. 3, pp. 28–37. DOI: 10.17759/autdd.2020180304.


  1. Allis C.D., Jenuwein T. The molecular hallmarks of epigenetic control. Nature Reviews Genetics, 2016, vol. 17, no. 8,  pp. 487—500. DOI: 10.1038/nrg.2016.59
  2. Bölte S., Girdler S., Marschik P.B. The contribution of environmental exposure to the etiology of autism spectrum disorder. Cellular and Molecular Life Sciences, 2018, vol. 76, no. 7, pp. 1275—1297. DOI: s00018-018-2988-4
  3. Calleja S., Islam F., Kingsley  J.,  McDonald  R.  The  disparities  of  healthcare  access  for  adults  with  autism  spectrum disorder: Protocol for a systematic review. Medicine, 2019, vol. 98, no. 7, p. e14480. DOI: 10.1097/ MD.0000000000014480
  4. Cannell J.J. Vitamin D and Autism, What’s New? Reviews in Endocrine and Metabolic Disorders, 2017, vol. 18, no. 2,    pp. 183—193. DOI: 10.1007/s11154-017-9409-0
  5. Carbone P.S., Murphy N.A., Norlin C., Azor V., Sheng X., Young P.C. Parent and pediatrician perspectives regarding the primary care of children with autism spectrum disorders. Journal of Autism and Developmental Disorders, 2013, vol. 43, no. 4, pp. 964—972. DOI:  10.1007/s10803-012-1640-7
  6. Cashin A., Buckley T., Trollor J.N., Lennox N. A scoping review of what is known  of  the  physical  health  of  adults with autism spectrum disorder. Journal of Intellectual Disabilities, 2018, vol. 22, no. 1, pp. 96—108. DOI: 10.1177/1744629516665242
  7. Data & Statistics on Autism Spectrum Disorder / Centers for Disease Control and Prevention [Web resource]. URL:  (Accessed  20.08.2020).
  8. De la Torre-Ubieta L., Won H., Stein J., Geschwind D.H. Advancing the understanding of autism disease mechanisms through genetics. Nature Medicine, 2016, vol. 22, no. 4, pp. 345—361. DOI: 10.1038/nm.4071
  9. Ecker C., Bookheimer S.Y., Murphy D.G.M. Neuroimaging in autism spectrum disorder: brain structure and function across the lifespan. The Lancet Neurology, 2015, vol. 14, no. 11, pp. 1121—1134. DOI:10.1016/s1474-4422(15)00050-2
  10. Fu Z., Tu Y., Di X., Du Y., Sui J., Biswal B., Zhang Z., Lacy N., Calhoun V. Transient increased thalamic-sensory connectivity and decreased whole-brain dynamism in autism. NeuroImage, 2018, vol. 190, no. 16, pp. 191—204. https://doi. org/10.1016/j.neuroimage.2018.06.003
  11. Gerber J.S., Offit P.A. Vaccines and Autism: A Tale of Shifting Hypotheses. Clinical Infectious Diseases, 2009, vol. 48, no. 4, pp. 456—461. DOI:10.1086/596476
  12. Goldin R.L, Matson J.S. Premature birth as a risk factor for autism spectrum disorder. Developmental Neurorehabilitation, 2016, vol. 19, no. 3, pp. 203—206. DOI: 10.3109/17518423.2015.1044132
  13. Gore A.C., Martien K.M., Gagnidze K., Pfaff D. Implications of Prenatal Steroid Perturbations for Neurodevelopment, Behavior, and Autism. Endocrine Reviews, vol. 35, no. 6, pp. 961—991. DOI:10.1210/er.2013-1122
  14. Halladay A.K., Bishop S., Constantino J.N., Daniels A.M., Koenig K., Palmer K., Messinger D., Pelphrey K., Sanders S.J., Tepper Singer A., Lounds Taylor J., Szatmari P. Sex and gender differences in autism spectrum disorder: summarizing evidence gaps and identifying emerging areas of priority. Molecular Autism, 2015, vol. 6, article no. 36. DOI:10.1186/ s13229-015-0019-y
  15. Hallmayer J., Cleveland S., Torres A., Phillips J., Cohen B., Torigoe T., Miller J., Fedele A., Collins J., Smith K., Lotspeich L., Croen L.A., Ozonoff S., Lajonchere C., Grether J.K., Risch N. Genetic heritability and shared environmental factors among twin pairs with autism. Archives of General Psychiatry, 2011, vol. 68, no. 11, pp. 1095—1102. DOI:10.1001/ archgenpsychiatry.2011.76
  16. Hazlett H.C., Poe M., Gerig G., Styner M., Chappell C., Gimpel Smith R. Vachet C., Piven J. Early Brain Overgrowth in Autism Associated with an Increase in Cortical Surface Area Before Age 2. Archives of General Psychiatry, 2011, vol. 68, no. 5, pp. 467—476. DOI:10.1001/archgenpsychiatry.2011.39
  17. Hendren R. L. Autism: biomedical complementary treatment approaches. Child and Adolescent Psychiatric Clinics of North America, 2013, vol. 22, no. 3, pp. 443—456. DOI:10.1016/j.chc.2013.03.002
  18. Herbert M.R. Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Current Opinion in Neurology, 2010, vol. 23, no. 2, pp. 103—110. DOI: 10.1097/WCO.0b013e328336a01f
  19. Krakowiak P., Walker C.K., Bremer A.A., Baker A.S., Ozonoff S., Hansen R.L., Hertz-Picciotto I. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics, 2012, vol. 129, no. 5, pp. e1121—e1128. DOI:10.1542/peds.2011-2583
  20. Krumm N., Turner T., Baker C., Vives L., Mohajeri K., Witherspoon K., Raja A., Coe B.P., Stessman H.A., He Z.X., Leal S.M., Bernier R., Eichler E.E. Excess of rare, inherited truncating mutations in autism. Nature Genetics, 2015, vol. 47, no. 6, pp. 582—588. DOI: 10.1038/ng.3303
  21. Blusztajn J.K., Slack B.E., Mellott T.J. Neuroprotective Actions of Dietary Choline. Nutrients, 2017, vol. 9, no. 8, p. 815. DOI:10.3390/nu9080815
  22. Keen D., Couzens D., Muspratt S., Rodger S. The effects of a parent-focused intervention for children with a recent diagnosis of autism spectrum disorder on parenting stress and competence. Research in Autism Spectrum Disorders, 2010, vol. 4, no. 2, pp. 229—241. DOI:10.1016/j.rasd.2009.09.009
  23. Lane M., Robker R.L., Robertson S.A. Parenting from before conception, Science, 2014, vol. 345, no. 6198, pp. 756—760. DOI:10.1126/science.1254400
  24. Levine S.Z., Kodesh A., Viktorin A., Smith L., Uher R., Reichenberg A., Sandin S. Association of Maternal Use of Folic Acid and Multivitamin Supplements in the Periods Before and During Pregnancy With the Risk of Autism Spectrum Disorder in Offspring. The Journal of the American Medical Association: Psychiatry, 2018, vol. 75, no. 2, pp. 176—184. DOI:10.1001/ jamapsychiatry.2017.4050
  25. Lordo D.N., Bertolin M., Sudikoff E.L., Keith C., Braddock B., Kaufman D.A. Parents Perceive Improvements in Socio- emotional Functioning in Adolescents with ASD Following Social Skills Treatment. Journal of Autism and Developmental Disorders, 2017, vol. 47, no. 1, pp. 203—214. DOI:10.1007/s10803-016-2969-0
  26. Lyall K., Schmidt R.J., Hertz-Picciotto I. Maternal lifestyle and environmental risk factors for autism spectrum disorders. International Journal of Epidemiology, 2014, vol. 43, no. 2, pp. 443—464. DOI:10.1093/ije/dyt282
  27. Matthews N.L., Smith C.J., Pollard E., Ober-Reynolds S., Kirwan J., Malligo A. Adaptive Functioning in Autism Spectrum Disorder During the Transition to Adulthood.  Journal of Autism and Developmental Disorders, 2015,  vol.  45,  no.  8, pp. 2349—2360. DOI: 10.1007/s10803-015-2400-2
  28. Mazina V., Gerdts J., Trinh S., Ankenman K., Ward T., Dennis M.Y., Girirajan S., Eichler E.E., Bernier R. Epigenetics of autism-related impairment: copy number variation and maternal infection. Journal of Developmental and Behavioral Pediatrics, 2015, vol. 36, no. 2, pp. 61—67. DOI: 10.1097/DBP.0000000000000126
  29. McLaughlin K., Travers B.G., Dadalko O., Dean D.C., Tromp D., Adluru N., Destiche D., Freeman A., Prigge M.D., Froehlich A., Duffield T.C., Zielinski B.A., Bigler E.D., Lange N., Anderson J.S., Alexander A.L., Lainhart J.E. Longitudinal development of thalamic and internal capsule microstructure in autism spectrum disorder. Autism Research, 2018, vol. 11, no. 3, pp. 450— 462.  DOI: 10.1002/aur.1909
  30. Modabbernia A., Velthorst E., Reichenberg A. Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Molecular Autism, 2017, vol. 8, article no. 13. DOI: 10.1186/s13229-017-0121-4
  31. Moss P., Mandy W., Howlin P. Child and Adult Factors Related to Quality of Life in Adults with Autism. Journal of Autism and Developmental Disorders, 2017, vol. 47, no. 6, pp. 2830—1837. DOI: 10.1007/s10803-017-3105-5
  32. Miles J.H. Autism spectrum disorders — A genetics review. Genetics in Medicine, 2011, vol. 13, no. 4, pp. 278—294. DOI:10.1097/GIM.0b013e3181ff67ba
  33. Mumper E. Can Awareness of Medical Pathophysiology in Autism Lead to Primary Care Autism Prevention Strategies? North American Journal of Medicine and Science, 2013, vol. 6, no. 3, pp. 134—144. DOI:10.7156/najms.2013.0603134]
  34. Neale B.M., Kou Y., Liu L., Ma’ayan A., Samocha K.E., Sabo A., Lin C.F., Stevens C., Wang L.S., Makarov V., Polak P.,   Yoon S., Maguire J., Crawford E.L., Campbell N.G., Geller E.T., Valladares O., Schafer C., Liu H., Daly M.J. et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature, 2012, vol. 485, no. 7397, pp. 242—345. DOI:10.1038/nature11011
  35. Nicolaidis C., Kripke C.C., Raymaker D. Primary care for adults on the autism spectrum. Medical Clinics of North America, 2014, vol. 98, no. 5, pp. 1169—1191. DOI: 10.1016/j.mcna.2014.06.011
  36. Ornoy A., Weinstein-Fudim L., Ergaz Z. Prenatal factors associated with autism spectrum disorder (ASD). Reproductive Toxicology, 2015, vol. 56, pp. 155—169. DOI: 10.1016/j.reprotox.2015.05.007
  37. Peñagarikano O., Geschwind D.H. What does CNTNAP2 reveal about Autism Spectrum Disorder? Trends in Molecular Medicine, 2012, vol. 18, no. 3, pp. 156—163. DOI: 10.1016/j.molmed.2012.01.003
  38. Robison J.E. Autism prevalence and outcomes in older adults. Autism Research, 2019, vol. 12, no. 3, pp. 370—374. DOI:10.1002/aur.2080
  39. Rosenberg R.E., Law J.K., Yenokyan G., McGready J., Kaufmann W.E., Law P.A. Characteristics and concordance of autism spectrum disorders among 277 twin pairs. Archives of Pediatric and Adolescent Medicine, 2009, vol. 163, no. 10, pp. 907— 914.  DOI:10.1001/archpediatrics.2009.98
  40. Rossignol D.A., Genuis S.J., Frye R.E. Environmental toxicants and autism spectrum disorders: a systematic review. Translational Psychiatry, 2014, vol. 4, no. 2, article no. e360. DOI:10.1038/tp.2014.4
  41. Roux A.M., Shattuck P.T., Cooper B.P., Anderson K.A., Wagner M., Narendorf S.C. Postsecondary employment experiences among young adults with an autism spectrum disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 2013, vol. 52, no. 9, pp. 931—939. DOI: 10.1016/j.jaac.2013.05.019
  42. Rubenstein E., Wiggins L.D., Lee L. AReviewofthe Differencesin Developmental, Psychiatric, and Medical Endophenotypes Between Males and Females with Autism Spectrum Disorder. Journal of Developmental and Physical Disabilites, 2015, vol. 27, no. 1, pp. 119—139. DOI: 10.1007/s10882-014-9397-x
  43. Rutten B.P.F., Mill J. Epigenetic Mediation of Environmental Influences in Major Psychotic Disorders. Schizophrenia Bulletin, 2009, vol. 35, no. 6, pp. 1045—1056. DOI: 10.1093/schbul/sbp104
  44. Sanders S., Murtha M., Gupta A., Murdoch J.D., Raubeson M.J., Willsey J.A.A., Ercan-Sencicek  G.,  DiLullo  N.N.,  Neelroop N.,Parikshak J.L., Stein M.F., Walker G.T., Ober N.A., Teran Y.S., El-Fishawy P., Murtha R.C., Choi M., Overton J.D., Bjornson R.D., State M.W. et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature, 2012, vol. 484, no. 13, pp. 237—241. DOI:10.1038/nature10945
  45. Sandin S., Lichtenstein P., Kuja-Halkola R., Larsson H., Hultman C.M.,  Reichenberg  A.  The  familial  risk  of  autism. The Journal of the American Medical Association, 2014, vol. 311, no. 17, pp. 1770—1777. DOI:10.1001/ jama.2014.4144
  46. Sandin S., Schendel D., Magnusson P., Hultman C., Surén P., Susser E., Grønborg T., Gissler M., Gunnes N., Gross R., Henning M., Bresnahan M., Sourander A., Hornig M., Carter K., Francis R., Parner E., Leonard H., Rosanoff M., Stoltenberg C., Reichenberg A. Autism risk associated with parental age and with increasing difference in age between the parents. Molecular Psychiatry, 2016, vol. 21, no. 5, pp. 693—700. DOI:10.1038/mp.2015.70
  47. Saqr Y., Braun E., Porter  K.,  Barnette  D.,  Hanks  C.  Addressing  medical  needs  of  adolescents  and  adults  with autism spectrum disorders in a primary care setting. Autism, 2018, vol. 22, no. 1, pp. 51—61. DOI:10.1177/1362361317709970
  48. Schmidt R.J., Tancredi D.J., Krakowiak P., Hansen R.L., Ozonoff S. Maternal Intake of Supplemental Iron and Risk of Autism Spectrum Disorder. American Journal of Epidemiology, 2014, vol. 180, no. 9, pp. 890—900. DOI:10.1093/aje/ kwu208
  49. Solek C.M., Farooqi N., Verly M., Lim T.K., Ruthazer E.S. Maternal immune activation in neurodevelopmental disorders. Developmental Dynamics, 2018, vol. 247, no. 4, pp. 588—619. DOI:10.1002/dvdy.24612
  50. Starkstein S., Gellar S., Parlier M., Payne L., Piven J. High rates of parkinsonism in adults with autism. Journal of Neurodevelopmental Disorders, 2015, vol. 7, article no. 29. DOI:10.1186/s11689-015-9125-6
  51. Stotland N.E., Sutton P.M., Trowbridge J., Atchley D.S., Conry J.A., Trasande L., Gerbert B., Charlesworth A., Woodruff T.J. Counseling Patients on Preventing Prenatal Environmental Exposures — A Mixed-Methods Study of Obstetricians. PLoS ONE, 2014, vol. 9, no. 6, article no. e0098771. DOI:10.1371/journal.pone.0098771
  52. Stubbs G., Henley K., Green J. Autism: Will vitamin D supplementation during pregnancy and early childhood reduce the recurrence rate of autism in newborn siblings? Medical Hypotheses, 2016, vol. 88, no. 17, pp. 74—78. DOI:10.1016/j. mehy.2016.01.015
  53. Wallace G.L., Kenworthy L., Pugliese C.E., Popal H.S., White E., Brodsky E., Martin A. Real-World Executive Functions  in Adults with Autism Spectrum Disorder: Profiles of Impairment and Associations with Adaptive Functioning and Co- morbid Anxiety and Depression. Journal of Autism and Developmental Disorders, 2016, vol. 46, no. 3, pp. 1071—1083. DOI:10.1007/s10803-015-2655-7
  54. Wang C., Geng H., Liu W., Zhang G. Prenatal, perinatal, and postnatal factors associated with autism: A meta-analysis. Medicine (Baltimore), 2017, vol. 96, no. 18, p. e6696. DOI: 10.1097/MD.0000000000006696
  55. Warfield M.E., Crossman M.K., Delahaye J., Der Weerd E., Kuhlthau K.A. Physician Perspectives on Providing Primary Medical Care to Adults with Autism Spectrum Disorders (ASD). Journal of Autism and Developmental Disorders, 2015, vol. 45, no. 7, pp. 2209—2217. DOI:10.1007/s10803-015-2386-9
  56. Wehman P.H, Schall C.M., McDonough J., Kregel J., Brooke V., Molinelli A., Ham W., Graham C.W., Erin Riehle J.,      Collins H.T., Thiss W. Competitive employment for youth with autism spectrum disorders: early results from a randomized clinical trial. Journal of Autism and Developmental Disorders, 2014, vol. 44, no. 3, pp. 487—500. DOI:10.1007/s10803- 013-1892-x
  57. Weiss J.A., Burnham Riosa P. Thriving in Youth with Autism Spectrum Disorder and Intellectual Disability. Journal of Autism and Developmental Disorders, 2015, vol. 45, no. 8, pp. 2474—2486. DOI:10.1007/s10803-015-2412-y
  58. Yassa H.A. Autism: A form of lead and mercury toxicity. Environmental Toxicology and Pharmacology, 2014, vol. 38, no. 3, pp.  1016—1024.  DOI:10.1016/j.etap.2014.10.005
  59. Yip B.H.K., Leonard H., Stock S., Stoltenberg C., Francis R.W., Gissler M., Gross R., Schendel D., Sandin S. Caesarean section and risk of autism across gestational age: a multi-national cohort study of 5 million births, International Journal of Epidemiology, 2017, vol. 46, no. 2, pp. 429—439. DOI:10.1093/ije/dyw336
  60. Zerbo O., Iosif A.M., Walker C., Ozonoff S., Hansen R.L., Hertz-Picciotto I. Is maternal influenza or fever during pregnancy associated with autism or developmental delays? Results from the CHARGE (Childhood Autism Risks from Genetics and Environment) study. Journal of Autism and Developmental Disorders, 2013, vol. 43, no. 1, pp. 25—33. DOI:10.1007/ s10803-012-1540-x
  61. Zerbo O., Massolo M.L., Qian Y., Croen L.A. A Study of Physician Knowledge and Experience with Autism in Adults in a Large Integrated Healthcare System. Journal of Autism and Developmental Disorders, 2015, vol. 45, no. 12, pp. 4002— 4014.  DOI:10.1007/s10803-015-2579-2

Information About the Authors

Rachel M. Tsipan, Research Assistant of the Department of Psychiatry, University of California Berkeley, San Francisco, USA, ORCID:, e-mail:

China I. Parenteau, Clinical Research Coordinator of the Department of Psychiatry, University of California San Francisco, San Francisco, USA, ORCID:, e-mail:

Robert L. Hendren, DO, Professor of Psychiatry, Director of Program for Research on Neurodevelopmental and Translational Outcomes (PRONTO), University of California San Francisco, San Francisco, USA, ORCID:, e-mail:



Total: 848
Previous month: 8
Current month: 2


Total: 397
Previous month: 2
Current month: 0