Aetiology of Autism Spectrum Disorders



Autism spectrum disorders (ASD) are a very current problem in the modern age. There exist a wide range of theories regarding the aetiology of ASD: from social explanations to biological ones. This review paper is aimed at introducing the reader to some of the research directions in this field. It describes some of the studies on the following kinds of factors: genetic and prenatal factors, factors, related to the structure and functioning of the nervous and immune systems, as well as gastrointestinal factors.

General Information

Keywords: autism, autism spectrum disorders (ASD), aetiology of ASD, foreign literature, review of literature

Journal rubric: Medical Psychology

Article type: scientific article

For citation: Vinogradova K.N. Aetiology of Autism Spectrum Disorders [Elektronnyi resurs]. Sovremennaia zarubezhnaia psikhologiia = Journal of Modern Foreign Psychology, 2014. Vol. 3, no. 4, pp. 112–131. (In Russ., аbstr. in Engl.)


  1. A clinicopathological study of autism / Bailey A. [et al.]. Brain, 1998. Vol. 121, no. 5, pp. 889–905.
  2. A novel functional brain imaging endophenotype of autism: the neural response to facial expression of emotion / Spencer M.D. [et al.]. Transl Psychiatry, 2011. Vol. 1, e19, pp. 1–7. doi: 10.1038/tp.2011.18.
  3. A vaccine and diagnostic target for Clostridium bolteae, an autism-associated bacterium / Pequegnat B. [et al.]. Vaccine, 2013. Vol. 31, no. 26, pp. 2787–2790. doi: 10.1016/j.vaccine.2013.04.018.
  4. Abnormal intestinal permeability in children with autism / D'Eufemia P. [et al.]. Acta Paediatr, 1996. Vol. 85, no. 9, pp. 1076–1079.
  5. Abrahams B.S., Geschwind D.H. Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet, 2008. Vol. 9, no. 5, pp. 341–355.
  6. Accelerated maturation of white matter in young children with autism: a high b value DWI study / Ben Bashat D. [et al.]. Neuroimage, 2007. Vol. 37, no. 1, pp. 40–47.
  7. Advancing Maternal Age Is Associated With Increasing Risk for Autism: A Review and Meta-Analysis / Sandin S. [et al.]. Journal of the American Academy of Child & Adolescent Psychiatry, 2012. Vol. 51, no. 5, e471, pp. 477–486..
  8. Advancing paternal age and autism / A. Reichenberg [et al.]. Archives of Genetic Psychiatry, 2006. Vol. 63, no. 9, pp. 1026–1032. doi: 10.1001/archpsyc.63.9.1026.
  9. Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A / Vojdani A. [et al.]. J. Neuroimmunol, 2002. Vol. 129, no. 1–2, pp. 168–177.
  10. Anti-brain antibodies are associated with more severe cognitive and behavioral profiles in Italian children with Autism Spectrum Disorder / Piras I.S. [et al.]. Brain, behavior, and immunity, 2014. Vol. 38, pp. 91–99. doi: 10.1016/j.bbi.2013.12.020.
  11. Application of Novel PCR-Based Methods for Detection, Quantitation, and Phylogenetic Characterization of Sutterella Species in Intestinal Biopsy Samples from Children with Autism and Gastrointestinal Disturbances [Electronic resource] / Williams B.L. [et al.]. mBio, 2012. Vol. 3, no. 1, e00261–00211. doi: 10.1128/mBio.00261-11. URL: (дата обращения: 15.12.2014).
  12. Arousal and Childhood Autism / Hutt, C. [et al.]. Nature, 1964. Vol. 204, no. 4961, pp. 908–909.
  13. Asperger H. Die ‘Autistischen Psychopathen’ im Kindesalter. Archiv fur Psychiatrie und Nervenkrankheiten, 1944. Vol. 117, no. 1ю P. 76–136.
  14. Atypical reflexive gaze patterns on emotional faces in autism spectrum disorders / Kliemann D. [et al.]. J. Neurosci, 2010. Vol. 30, no. 37, pp. 12281–12287. doi: 10.1523/jneurosci.0688-10.2010.
  15. Autism as a strongly genetic disorder: evidence from a British twin study / Bailey A. [et al.]. Psychol. Med., 1995. Vol. 25, no. 1, pp. 63–77.
  16. Autism in thalidomide embriopathy: a population study / Strömland, K. [et al.]. Developmental Medicine & Child Neurology, 1994. Vol. 36, no. 4, pp. 351–356. doi: 10.1111/j.1469-8749.1994.tb11856.x.
  17. Autism prevalence following prenatal exposure to hurricanes and tropical storms in Louisiana / Kinney D.K. [et al.]. J. Autism Dev Disord, 2008. Vol. 38, no. 3, pp. 481–488. doi: 10.1007/s10803-007-0414-0.
  18. Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes / Castelli F. [et al.]. Brain, 2002. Vol. 125, no. 8, pp. 1839–1849.
  19. Behavioral Correlates of Maternal Antibody Status Among Children with Autism / Braunschweig D. [et al.]. Journal of Autism and Developmental Disorders, 2012. Vol. 42, no. 7, pp. 1435–1445. doi: 10.1007/s10803-011-1378-7.
  20. Bleuler E. Dementia Praecox oder Gruppe der Schizophrenien. Handbuch der Psychiatrie. G. Aschaffenburg, ed. 1911, Leipzig: Deuticke, pp. 1–420.
  21. Brain-Specific Autoantibodies in the Plasma of Subjects with Autistic Spectrum Disorder / Cabanlit M. [et al.]. Annals of the New York Academy of Sciences, 2007. Vol. 1107, no. 1, pp. 92–103. doi: 10.1196/annals.1381.010.
  22. Cannell J.J. Autism and vitamin D. Med Hypotheses, 2008. Vol. 70, no. 4, pp. 750–759. doi: 10.1016/j.mehy.2007.08.016.
  23. Cerebral Lobes in Autism: Early Hyperplasia and Abnormal Age Effects / Carper R.A. [et al.]. NeuroImage, 2002. Vol. 16, no. 4, pp. 1038–1051. doi:
  24. Circulating autoantibodies to neuronal and glial filament proteins in autism / Singh V.K. [et al.]. Pediatr. Neurol., 1997. Vol. 17, no. 1, pp. 88–90.
  25. Corpus Callosum Morphometrics in Young Children with Autism Spectrum Disorder / Boger-Megiddo I. [et al.]. Journal of Autism and Developmental Disorders, 2006. Vol. 36, no. 6, pp. 733–739. doi: 10.1007/s10803-006-0121-2.
  26. Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity / Just M.A. [et al.]. Brain, 2004. Vol. 127, no. Pt 8, pp. 1811–1821. doi: 10.1093/brain/awh199.
  27. Cortical underconnectivity coupled with preserved visuospatial cognition in autism: Evidence from an fMRI study of an embedded figures task / Damarla S.R. [et al.]. Autism Research, 2010. Vol. 3, no. 5, pp. 273–279.
  28. Courchesne E., Pierce K. Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection. Current Opinion in Neurobiology, 2005. Vol. 15, no. 2, pp. 225–230. doi:
  29. Crespi B., Badcock C. Psychosis and autism as diametrical disorders of the social brain. Behav. Brain. Sci., 2008. Vol. 31, no. 3, pp. 241–261; discussion 261–320. doi: 10.1017/s0140525x08004214.
  30. Croen L.A., Grether J.K., Selvin S. Descriptive epidemiology of autism in a California population: who is at risk? J. Autism Dev. Disord., 2002. Vol. 32, no. 3, pp. 217–224.
  31. Decreased transforming growth factor beta1 in autism: A potential link between immune dysregulation and impairment in clinical behavioral outcomes / Ashwood P. [et al.]. Journal of Neuroimmunology, 2008. Vol. 204, no. 1, pp. 149–153. . doi: 10.1016/j.jneuroim.2008.07.006.
  32. Denney D.R., Frei B.W., Gaffney G.R. Lymphocyte subsets and interleukin-2 receptors in autistic children. J. Autism Dev. Disord., 1996. Vol. 26, no. 1, pp. 87–97.
  33. Differential activation of the amygdala and the 'social brain' during fearful face-processing in Asperger Syndrome / Ashwin C. [et al.]. Neuropsychologia, 2007. Vol. 45, no. 1, pp. 2–14. doi: 10.1016/j.neuropsychologia.2006.04.014.
  34. Diffusion tensor imaging of the corpus callosum in Autism / Alexander A.L. [et al.]. NeuroImage, 2007. Vol. 34, no. 1, pp. 61–73. doi:
  35. Electrodermal reactivity to emotion processing in adults with autistic spectrum disorders / Hubert B.E. [et al.]. Autism, 2009. Vol. 13, no. 1, pp. 9–19.
  36. Elevated immune response in the brain of autistic patients / Li X. [et al.]. J Neuroimmunol, 2009. Vol. 207, no. 1–2, pp. 111–116.
  37. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome / Ashwood P. [et al.]. Brain. Behav. Immun., 2011. Vol. 25, no. 1, pp. 40–45. doi: 10.1016/j.bbi.2010.08.003.
  38. FMRI Investigation of Working Memory for Faces in Autism: Visual Coding and Underconnectivity with Frontal Areas / Koshino, H. [et al.]. Cerebral Cortex, 2008. Vol. 18, no. 2, pp. 289–300.
  39. Functional and Anatomical Cortical Underconnectivity in Autism: Evidence from an fMRI Study of an Executive Function Task and Corpus Callosum Morphometry / Just M.A. [et al.]. Cerebral Cortex, 2007. Vol. 17, no. 4, pp. 951–961.
  40. Functional Connectivity of the Inferior Frontal Cortex Changes with Age in Children with Autism Spectrum Disorders: A fcMRI Study of Response Inhibition / Lee P.S. [et al.]. Cerebral Cortex, 2009. Vol. 19, no. 8, pp. 1787–1794.
  41. Gastrointestinal flora and gastrointestinal status in children with autism – comparisons to typical children and correlation with autism severity [Electronic resource] / Adams J.B. [et al.]. BMC Gastroenterol, 2011. Vol. 11. doi: 10.1186/1471-230x-11-22. URL: (дата обращения: 15.12.2014).
  42. Gastrointestinal Symptoms in a Sample of Children with Pervasive Developmental Disorders / Nikolov R. [et al.]. Journal of Autism and Developmental, Disorders 2009. Vol. 39, no. 3, pp. 405–413. doi: 10.1007/s10803-008-0637-8.
  43. Gaze fixation and the neural circuitry of face processing in autism / Dalton K.M. [et al.]. Nat Neurosci, 2005. Vol. 8, no. 4, pp. 519–526. doi: 10.1038/nn1421.
  44. Genetics and child psychiatry: II Empirical research findings / Rutter M. [et al.]. J. Child Psychol. Psychiatry, 1999. Vol. 40, no. 1, pp. 19–55.
  45. Gillberg C., Schaumann H., Gillberg I.C. Autism in immigrants: children born in Sweden to mothers born in Uganda. Journal of Intellectual Disability Research, 1995. Vol. 39, no. 2, pp. 141–144. doi: 10.1111/j.1365-2788.1995.tb00482.x.
  46. Gray and white matter imbalance--typical structural abnormality underlying classic autism? / Bonilha L. [et al.]. Brain Dev 2008. Vol. 30, no. 6, pp. 396–401. doi: 10.1016/j.braindev.2007.11.006.
  47. Hirstein W., Iversen P., Ramachandran V.S. Autonomic responses of autistic children to people and objects. Proceedings of the Royal Society of London B: Biological Sciences, 2001. Vol. 268, no. 1479, pp. 1883–1888.
  48. Horvath K., Perman J.A. Autism and gastrointestinal symptoms. Curr. Gastroenterol. Rep., 2002. Vol. 4, no. 3, pp. 251–258.
  49. Hsiao E.Y. Gastrointestinal issues in autism spectrum disorder. Harv Rev Psychiatr,y 2014. Vol. 22, no. 2, pp. 104–111. doi: 10.1097/hrp.0000000000000029.
  50. Hultman C.M., Sparén P., Cnattingius S. Perinatal risk factors for infantile autism [Electronic resource]. Epidemiology, 2002. Vol. 13, no. 4, P. 417–423. URL: (дата обращения: 15.12.2014).
  51. Hypothesis: dysregulation of methylation of brain-expressed genes on the X chromosome and autism spectrum disorders / Jones J.R. [et al.]. Am. J. Med. Genet. A, 2008. Vol. 146A, no. 17, pp. 2213–2220.
  52. Identification of MeCP2 mutations in a series of females with autistic disorder / Carney R.M. [et al.]. Pediatr Neurol 2003. Vol. 28, no. 3, pp. 205–211.
  53. Immune abnormalities in patients with autism / Warren, R.P., et al.. J Autism Dev. Disord., 1986. Vol. 16, no. 2, pp. 189–197.
  54. Immune transcriptome alterations in the temporal cortex of subjects with autism / Garbett K. [et al.]. Neurobiol. Dis., 2008. Vol. 30, no. 3, pp. 303–311. doi: 10.1016/j.nbd.2008.01.012.
  55. Increased trinucleotide repeat instability with advanced maternal age / Kaytor M.D. [et al.]. Hum. Mol. Genet., 1997. Vol. 6, no. 12, pp. 2135–2139.
  56. Jyonouchi H., Sun S., Itokazu N. Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder. Neuropsychobiology, 2002. Vol. 46, no. 2, pp. 76–84.
  57. Kanner L. Autistic disturbances of affective contact. Nervous Child, 1943. Vol. 2, pp. 217–250.
  58. Maternal antibrain antibodies in autism / Zimmerman A.W. [et al.]. Brain. Behav. Immun., 2007. Vol. 21, no. 3, pp. 351–357. doi: 10.1016/j.bbi.2006.08.005.
  59. Maternal autoantibodies are associated with abnormal brain enlargement in a subgroup of children with autism spectrum disorder / Nordahl C.W. [et al.]. Brain. Behav. Immun., 2013. Vol. 30, P. 61–65. doi: 10.1016/j.bbi.2013.01.084.
  60. Mathersul D., McDonald S., Rushby J.A. Automatic facial responses to briefly presented emotional stimuli in autism spectrum disorder. Biological Psychology, 2013. Vol. 94, no. 2, pp. 397–407. doi:
  61. Mayer E.A. Gut feelings: the emerging biology of gut-brain communication. Nature reviews Neuroscience, 2011. Vol. 12, no. 8, pp. 453–466. doi:
  62. Mehta S.Q., Nurmi E.L. Genetic pathways to autism spectrum disorders. Neuropsychiatry 2013. Vol. 3, no. 2, pp. 193–207. doi: 10.2217/npy.13.16.
  63. Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism / Sanders S. J. [et al.]. Neuron, 2011. Vol. 70, no. 5, pp. 863–885. doi: 10.1016/j.neuron.2011.05.002.
  64. Neul, J.L. The relationship of Rett syndrome and MECP2 disorders to autism. Dialogues in Clinical Neuroscience, 2012. Vol. 14, no. 3, pp. 253–262.
  65. Neural activation to emotional faces in adolescents with autism spectrum disorders / Weng S.J. [et al.]. J. Child Psychol Psychiatry, 2011. Vol. 52, no. 3, pp. 296–305. doi: 10.1111/j.1469-7610.2010.02317.x.
  66. Neural correlates of facial affect processing in children and adolescents with autism spectrum disorder / Wang A.T. [et al.]. J. Am. Acad. Child. Adolesc. Psychiatry, 2004. Vol. 43, no. 4, pp. 481–490. doi: 10.1097/00004583-200404000-00015.
  67. Neuron number and size in prefrontal cortex of children with autism / Courchesne E. [et al.]. JAMA, 2011. Vol. 306, no. 18, pp. 2001–2010. doi: 10.1001/jama.2011.1638.
  68. Penrose L.S. Parental Age and Mutation. The Lancet, 1955. Vol. 266, no. 6885, pp. 312–313. doi: 10.1016/S0140-6736(55)92305-9.
  69. Perinatal factors and the development of autism: A population study / Glasson E.J. [et al.]. Archives of General Psychiatry, 2004. Vol. 61, no. 6, pp. 618–627. doi: 10.1001/archpsyc.61.6.618.
  70. Physiologic arousal to social stress in children with Autism Spectrum Disorders: A pilot study / Levine T.P. [et al.]. Research in Autism Spectrum Disorders, 2012. Vol. 6, no. 1, pp. 177–183. doi:
  71. Prevalence of autism in Missouri: changing trends and the effect of a comprehensive state autism project / Hillman R.E. [et al.]. Mo Med, 2000. Vol. 97, no. 5, pp. 159–163.
  72. Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses / Gilman S.R. [et al.]. Neuron, 2011. Vol. 70, no. 5, pp. 898–907. doi: 10.1016/j.neuron.2011.05.021.
  73. Reading affect in the face and voice: Neural correlates of interpreting communicative intent in children and adolescents with autism spectrum disorders / Wang A. [et al.]. Archives of General Psychiatry, 2007. Vol. 64, no. 6, pp. 698–708. doi: 10.1001/archpsyc.64.6.698.
  74. Reduced functional connectivity between V1 and inferior frontal cortex associated with visuomotor performance in autism / Villalobos M.E. [et al.]. NeuroImage 2005. Vol. 25, no. 3, pp. 916–925. doi:
  75. Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots / Wan M. [et al.]. Am. J. Hum. Genet., 1999. Vol. 65, no. 6, pp. 1520–1529. doi: 10.1086/302690.
  76. Riby D.M., Whittle L., Doherty-Sneddon G. Physiological reactivity to faces via live and video-mediated communication in typical and atypical development. Journal of Clinical and Experimental Neuropsychology, 2012. Vol. 34, no. 4, pp. 385–395. doi: 10.1080/13803395.2011.645019.
  77. Risk Factors for Autism: Perinatal Factors, Parental Psychiatric History, and Socioeconomic Status / Larsson H.J. [et al.]. American Journal of Epidemiology, 2005. Vol. 161, no. 10, pp. 916–925. doi: 10.1093/aje/kwi123.
  78. Roman G.C. Autism: transient in utero hypothyroxinemia related to maternal flavonoid ingestion during pregnancy and to other environmental antithyroid agents. J. Neurol. Sci., 2007. Vol. 262, no. 1–2, pp. 15–26. doi: 10.1016/j.jns.2007.06.023.
  79. Samsam M., Ahangari R., Naser S.A. Pathophysiology of autism spectrum disorders: Revisiting gastrointestinal involvement and immune imbalance. World Journal of Gastroenterology : WJG, 2014. Vol. 20, no. 29, pp. 9942–9951. doi: 10.3748/wjg.v20.i29.9942.
  80. Sentence comprehension in autism: thinking in pictures with decreased functional connectivity / Kana R.K. [et al.]. Brain, 2006. Vol. 129, no. 9, pp. 2484–2493.
  81. Short-term benefit from oral vancomycin treatment of regressive-onset autism / Sandler R.H. [et al.]. J. Child. Neurol., 2000. Vol. 15, no. 7, pp. 429–435.
  82. Singh V.K., Singh E.A., Warren R.P. Hyperserotoninemia and serotonin receptor antibodies in children with autism but not mental retardation. Biol. Psychiatry,1997. Vol. 41, no. 6, pp. 753–755. : 10.1016/s0006–3223(96)00522–7.
  83. Social-cognitive, physiological, and neural mechanisms underlying emotion regulation impairments: understanding anxiety in autism spectrum disorder / White S.W. [et al. ]. International Journal of Developmental Neuroscience, 2014. Vol. 39, no. 0, pp. 22–36. doi:
  84. Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome / Neul J.L. [et al.]. Neurology, 2008. Vol. 70, no. 16, pp. 1313–1321. doi: 10.1212/01.wnl.0000291011.54508.aa.
  85. Structural Variation of Chromosomes in Autism Spectrum Disorder / Marshall C.R. [et al.]. The American Journal of Human Genetics, 2008. Vol. 82, no. 2, pp. 477–488. doi:
  86. Stubbs E.G., Crawford M.L. Depressed lymphocyte responsiveness in autistic children. J. Autism Child. Schizophr., 1977. Vol. 7, no. 1, pp. 49–55.
  87. The functional neuroanatomy of social behaviour: changes in cerebral blood flow when people with autistic disorder process facial expressions / Critchley H.D. [et al.]. Brain ,2000. Vol. 123 ( Pt 11), no, pp. 2203–2212.
  88. Warren R.P., Foster A.N.N., Margaretten N.C. Reduced Natural Killer Cell Activity in Autism. Journal of the American Academy of Child & Adolescent Psychiatry, 1987. Vol. 26, no. 3, pp. 333–335. doi:

Information About the Authors

K. N. Vinogradova, Student, University College London, e-mail:



Total: 3213
Previous month: 20
Current month: 3


Total: 5028
Previous month: 36
Current month: 4