Skip to main content
SpringerLink
Log in

Oxytocin and Autism

  • Chapter
The Neurochemical Basis of Autism

Abstract

Disturbed social interaction is a central feature of autism and the source of many of the everyday impairments of patients, their relatives and their caregivers. Therefore, it made and still makes sense to study the neurobiology of social function. In addition to helping us understand the disorder, this also holds promise for defining targets that could lead to new and more targeted treatments. An excellent candidate for this approach is oxytocin (OT), a hormone that is central to social processes throughout the animal kingdom, especially for attachment other so-called "prosocial behaviors". In this chapter, we first review the evidence for the neurobiological function of OT in humans, which is now coming together. Then, we review emerging evidence that OT and the neural and hormonal systems to which it is linked are abnormal in autism. Finally, we discuss attempts to use OT to treat autism.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adolphs R (2003) Investigating the cognitive neusroscience of social behavior. Neuropsychologia 41:119–126.

    Article  PubMed  Google Scholar 

  • Adolphs R, Sears L, Piven J (2001) Abnormal processing of social information from faces in autism. J Cogn Neurosci 13:232–240.

    Article  CAS  PubMed  Google Scholar 

  • Adolphs R, Gosselin F, Buchanan TW, Tranel D, Schyns P, Damasio AR (2005) A mechanism for impaired fear recognition after amygdala damage. Nature 433:68–72.

    Article  CAS  PubMed  Google Scholar 

  • Amaral DG, Schumann CM, Nordahl CW (2008) Neuroanatomy of autism. Trends Neurosci 31:137–145.

    Article  CAS  PubMed  Google Scholar 

  • Appenrodt E, Schnabel R, Schwarzberg H (1998) Vasopressin administration modulates anxiety-related behavior in rats. Physiol Behav 64:543–547.

    Article  CAS  PubMed  Google Scholar 

  • Aylward EH, Minshew NJ, Goldstein G, Honeycutt NA, Augustine AM, Yates KO, Barta PE, Pearlson GD (1999) MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults. Neurology 53:2145–2150.

    CAS  PubMed  Google Scholar 

  • Bakermans-Kranenburg MJ, van Ijzendoorn MH (2008) Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. Soc Cogn Affect Neurosci 3:128–134.

    Article  PubMed  Google Scholar 

  • Baron-Cohen S, Ring HA, Bullmore ET, Wheelwright S, Ashwin C, Williams SC (2000) The amygdala theory of autism. Neurosci Biobehav Rev 24:355–364.

    Article  CAS  PubMed  Google Scholar 

  • Baron-Cohen S, Ring HA, Wheelwright S, Bullmore ET, Brammer MJ, Simmons A, Williams SC (1999) Social intelligence in the normal and autistic brain: an fMRI study. Eur J Neurosci 11:1891–1898.

    Article  CAS  PubMed  Google Scholar 

  • Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E (2008) Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron 58:639–650.

    Article  CAS  PubMed  Google Scholar 

  • Bielsky IF, Hu SB, Szegda KL, Westphal H, Young LJ (2004) Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice. Neuropsychopharmacology 29:483–493.

    Article  CAS  PubMed  Google Scholar 

  • Bittel DC, Kibiryeva N, Dasouki M, Knoll JH, Butler MG (2006) A 9-year-old male with a duplication of chromosome 3p25.3p26.2: clinical report and gene expression analysis. Am J Med Genet A 140:573–579.

    PubMed  Google Scholar 

  • Blaicher W, Gruber D, Bieglmayer C, Blaicher AM, Knogler W, Huber JC (1999) The role of oxytocin in relation to female sexual arousal. Gynecologic and Obstetric Investigation 47:125–126.

    Article  CAS  PubMed  Google Scholar 

  • Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL (2002) Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci 5:514–516.

    Article  CAS  PubMed  Google Scholar 

  • Bosch OJ, Meddle SL, Beiderbeck DI, Douglas AJ, Neumann ID (2005) Brain oxytocin correlates with maternal aggression: link to anxiety. J Neurosci 25:6807–6815.

    Article  CAS  PubMed  Google Scholar 

  • Buijs RM, de Vries GJ, van Leeuwen FW (1985) The distribution and synaptic release of oxytocin in the central nervous system. In: Oxytocin. Clinical and laboratory studies (Amico JA, Robinson AG, eds), pp. 77–86. Amsterdam: Elsevier.

    Google Scholar 

  • Carmichael MS, Warburton VL, Dixen J, Davidson JM (1994) Relationships among cardiovascular, muscular, and oxytocin responses during human sexual activity. Archives of Sexual Behavior 23:59–79.

    Article  CAS  PubMed  Google Scholar 

  • Carter CS (2007) Sex differences in oxytocin and vasopressin: implications for autism spectrum disorders? Behav Brain Res 176:170–186.

    Article  CAS  PubMed  Google Scholar 

  • Critchley HD, Daly EM, Bullmore ET, Williams SC, Van Amelsvoort T, Robertson DM, Rowe A, Phillips M, McAlonan G, Howlin P, Murphy DG (2000) The functional neuroanatomy of social behaviour: changes in cerebral blood flow when people with autistic disorder process facial expressions. Brain 123(Pt 11):2203–2212.

    Article  PubMed  Google Scholar 

  • Dalton KM, Nacewicz BM, Johnstone T, Schaefer HS, Gernsbacher MA, Goldsmith HH, Alexander AL, Davidson RJ (2005) Gaze fixation and the neural circuitry of face processing in autism. Nat Neurosci 8:519–526.

    CAS  PubMed  Google Scholar 

  • Davis M, Whalen PJ (2001) The amygdala: vigilance and emotion. Mol Psychiatry 6:13–34.

    Article  CAS  PubMed  Google Scholar 

  • Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC (2007a) Oxytocin improves "mind-reading" in humans. Biol Psychiatry 61:731–733.

    Article  CAS  PubMed  Google Scholar 

  • Domes G, Heinrichs M, Glascher J, Buchel C, Braus DF, Herpertz SC (2007b) Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol Psychiatry 62:1187–1190.

    Article  CAS  PubMed  Google Scholar 

  • Ferguson JN, Aldag JM, Insel TR, Young LJ (2001) Oxytocin in the medial amygdala is essential for social recognition in the mouse. J Neurosci 21:8278–8285.

    CAS  PubMed  Google Scholar 

  • Gimpl G, Fahrenholz F (2001) The oxytocin receptor system: structure, function, and regulation. Physiological Reviews 81:629–683.

    CAS  PubMed  Google Scholar 

  • Green L, Fein D, Modahl C, Feinstein C, Waterhouse L, Morris M (2001) Oxytocin and autistic disorder: alterations in peptide forms. Biol Psychiatry 50:609–613.

    Article  CAS  PubMed  Google Scholar 

  • Hammock EA, Young LJ (2005) Microsatellite instability generates diversity in brain and sociobehavioral traits. Science 308:1630–1634.

    Article  CAS  PubMed  Google Scholar 

  • Hammock EA, Young LJ (2006) Oxytocin, vasopressin and pair bonding: implications for autism. Philos Trans R Soc Lond B Biol Sci 361:2187–2198.

    Article  CAS  PubMed  Google Scholar 

  • Hariri AR, Tessitore A, Mattay VS, Fera F, Weinberger DR (2002) The amygdala response to emotional stimuli: a comparison of faces and scenes. Neuroimage 17:317–323.

    Article  PubMed  Google Scholar 

  • Hariri AR, Mattay VS, Tessitore A, Fera F, Weinberger DR (2003) Neocortical modulation of the amygdala response to fearful stimuli. Biol Psychiatry 53:494–501.

    Article  PubMed  Google Scholar 

  • Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U (2003) Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biological Psychiatry 54:1389–1398.

    Article  CAS  PubMed  Google Scholar 

  • Hollander E, Novotny S, Hanratty M, Yaffe R, DeCaria CM, Aronowitz BR, Mosovich S (2003) Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacol 28:193–198.

    Article  CAS  Google Scholar 

  • Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L, Anagnostou E, Wasserman S (2007) Oxytocin increases retention of social cognition in autism. Biol Psychiatry 61:498–503.

    Article  CAS  PubMed  Google Scholar 

  • Huber D, Veinante P, Stoop R (2005) Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala. Science 308:245–248.

    Article  CAS  PubMed  Google Scholar 

  • Ibragimov R (1990) Influence of neurohypophyseal peptides on the formation of active avoidance conditioned reflex behavior. Neurosci Behav Physiol 20:189–193.

    Article  PubMed  Google Scholar 

  • Insel TR, Young LJ (2001) The neurobiology of attachment. Nat Rev Neurosci 2:129–136.

    Article  CAS  PubMed  Google Scholar 

  • Insel TR, Fernald RD (2004) How the brain processes social information: searching for the social brain. Annu Rev Neurosci 27:697–722.

    Article  CAS  PubMed  Google Scholar 

  • Insel TR, O’Brien DJ, Leckman JF (1999) Oxytocin, vasopressin, and autism: is there a connection? Biol Psychiatry 45:145–157.

    Article  CAS  PubMed  Google Scholar 

  • Jacob S, Brune CW, Carter CS, Leventhal BL, Lord C, Cook EH, Jr. (2007) Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett 417:6–9.

    Article  CAS  PubMed  Google Scholar 

  • Juranek J, Filipek PA, Berenji GR, Modahl C, Osann K, Spence MA (2006) Association between amygdala volume and anxiety level: magnetic resonance imaging (MRI) study in autistic children. J Child Neurol 21:1051–1058.

    Article  PubMed  Google Scholar 

  • Kim SJ, Young LJ, Gonen D, Veenstra-VanderWeele J, Courchesne R, Courchesne E, Lord C, Leventhal BL, Cook EH, Jr., Insel TR (2002) Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism. Mol Psychiatry 7:503–507.

    Article  CAS  PubMed  Google Scholar 

  • Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A (2005) Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci 25:11489–11493.

    Article  CAS  PubMed  Google Scholar 

  • Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E (2005) Oxytocin increases trust in humans. Nature 435:673–676.

    Article  CAS  PubMed  Google Scholar 

  • Lang PJ, Bradley MM, Cuthbert BN (1997) International Affective Picture System (IAPS): Technical Manual and Affective Ratings Gainesville, FL: National Institute of Mental Health Center for the Study of Emotion and Attention.

    Google Scholar 

  • Lerer E, Levi S, Salomon S, Darvasi A, Yirmiya N, Ebstein RP (2007) Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition. Mol Psychiatry.

    Google Scholar 

  • Liebsch G, Wotjak CT, Landgraf R, Engelmann M (1996) Septal vasopressin modulates anxiety-related behaviour in rats. Neurosci Lett 217:101–104.

    Article  CAS  PubMed  Google Scholar 

  • Loup F, Tribollet E, Dubois-Dauphin M, Dreifuss JJ (1991) Localization of high-affinity binding sites for oxytocin and vasopressin in the human brain. An autoradiographic study. Brain Res 555:220–232.

    Article  CAS  PubMed  Google Scholar 

  • McCarthy MM, McDonald CH, Brooks PJ, Goldman D (1996) An anxiolytic action of oxytocin is enhanced by estrogen in the mouse. Physiol Behav 60:1209–1215.

    Article  CAS  PubMed  Google Scholar 

  • McCauley JL, Li C, Jiang L, Olson LM, Crockett G, Gainer K, Folstein SE, Haines JL, Sutcliffe JS (2005) Genome-wide and Ordered-Subset linkage analyses provide support for autism loci on 17q and 19p with evidence of phenotypic and interlocus genetic correlates. BMC Med Genet 6:1.

    Article  PubMed  Google Scholar 

  • McNeilly AS, Robinson IC, Houston MJ, Howie PW (1983) Release of oxytocin and prolactin in response to suckling. Br Med J (Clin Res Ed) 286:257–259.

    Article  CAS  Google Scholar 

  • Meyer-Lindenberg A, Hariri AR, Munoz KE, Mervis CB, Mattay VS, Morris CA, Berman KF (2005) Neural correlates of genetically abnormal social cognition in Williams syndrome. Nat Neurosci 8:991–993.

    Article  CAS  PubMed  Google Scholar 

  • Meyer-Lindenberg A, Kolachana B, Gold B, Olsh A, Nicodemus KK, Mattay V, Dean M, Weinberger DR (2008) Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans. Mol Psychiatry.

    Google Scholar 

  • Modahl C, Green L, Fein D, Morris M, Waterhouse L, Feinstein C, Levin H (1998) Plasma oxytocin levels in autistic children. Biol Psychiatry 43:270–277.

    Article  CAS  PubMed  Google Scholar 

  • Munson J, Dawson G, Abbott R, Faja S, Webb SJ, Friedman SD, Shaw D, Artru A, Dager SR (2006) Amygdalar volume and behavioral development in autism. Arch Gen Psychiatry 63:686–693.

    Article  PubMed  Google Scholar 

  • Nacewicz BM, Dalton KM, Johnstone T, Long MT, McAuliff EM, Oakes TR, Alexander AL, Davidson RJ (2006) Amygdala volume and nonverbal social impairment in adolescent and adult males with autism. Arch Gen Psychiatry 63:1417–1428.

    Article  PubMed  Google Scholar 

  • Panksepp J (1993) Commentary on the possible role of oxytocin in autism. J Autism Dev Disord 23:567–569.

    Article  CAS  PubMed  Google Scholar 

  • Pedersen CA, Prange AJ, Jr. (1979) Induction of maternal behavior in virgin rats after intracerebroventricular administration of oxytocin. Proc Natl Acad Sc USA 76:6661–6665.

    Article  CAS  Google Scholar 

  • Petrovic P, Kalisch R, Singer T, Dolan RJ (2008) Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity. J Neurosci 28:6607–6615.

    Article  CAS  PubMed  Google Scholar 

  • Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, Kolachana BS, Egan MF, Mattay VS, Hariri AR, Weinberger DR (2005) 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci 8:828–834.

    Article  CAS  PubMed  Google Scholar 

  • Prather MD, Lavenex P, Mauldin-Jourdain ML, Mason WA, Capitanio JP, Mendoza SP, Amaral DG (2001) Increased social fear and decreased fear of objects in monkeys with neonatal amygdala lesions. Neuroscience 106:653–658.

    Article  CAS  PubMed  Google Scholar 

  • Prichard ZM, Mackinnon AJ, Jorm AF, Easteal S (2007) AVPR1A and OXTR polymorphisms are associated with sexual and reproductive behavioral phenotypes in humans. Mutation in brief no. 981. Online. Hum Mutat 28:1150.

    Article  PubMed  Google Scholar 

  • Rapin I, Katzman R (1998) Neurobiology of autism. Ann Neurol 43:7–14.

    Article  CAS  PubMed  Google Scholar 

  • Schumann CM, Hamstra J, Goodlin-Jones BL, Lotspeich LJ, Kwon H, Buonocore MH, Lammers CR, Reiss AL, Amaral DG (2004) The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. J Neurosci 24:6392–6401.

    Article  CAS  PubMed  Google Scholar 

  • Sparks BF, Friedman SD, Shaw DW, Aylward EH, Echelard D, Artru AA, Maravilla KR, Giedd JN, Munson J, Dawson G, Dager SR (2002) Brain structural abnormalities in young children with autism spectrum disorder. Neurology 59:184–192.

    CAS  PubMed  Google Scholar 

  • Stoehr JD, Cramer CP, North WG (1992) Oxytocin and vasopressin hexapeptide fragments have opposing influences on conditioned freezing behavior. Psychoneuroendocrinology 17:267–271.

    Article  CAS  PubMed  Google Scholar 

  • Stone VE, Baron-Cohen S, Calder A, Keane J, Young A (2003) Acquired theory of mind impairments in individuals with bilateral amygdala lesions. Neuropsychologia 41:209–220.

    Article  PubMed  Google Scholar 

  • Wang AT, Dapretto M, Hariri AR, Sigman M, Bookheimer SY (2004) Neural correlates of facial affect processing in children and adolescents with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry 43:481–490.

    Article  PubMed  Google Scholar 

  • Wassink TH, Piven J, Vieland VJ, Pietila J, Goedken RJ, Folstein SE, Sheffield VC (2004) Examination of AVPR1a as an autism susceptibility gene. Mol Psychiatry 9:968–972.

    Article  CAS  PubMed  Google Scholar 

  • Windle RJ, Shanks N, Lightman SL, Ingram CD (1997) Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats. Endocrinology 138: 2829–2834.

    Article  CAS  PubMed  Google Scholar 

  • Winslow JT, Insel TR (2004) Neuroendocrine basis of social recognition. Curr Opin Neurobiol 14:248–253.

    Article  CAS  PubMed  Google Scholar 

  • Winston JS, Strange BA, O‘Doherty J, Dolan RJ (2002) Automatic and intentional brain responses during evaluation of trustworthiness of faces. Nat Neurosci 5:277–283.

    Article  CAS  PubMed  Google Scholar 

  • Wu S, Jia M, Ruan Y, Liu J, Guo Y, Shuang M, Gong X, Zhang Y, Yang X, Zhang D (2005) Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biol Psychiatry 58:74–77.

    Article  CAS  PubMed  Google Scholar 

  • Yirmiya N, Rosenberg C, Levi S, Salomon S, Shulman C, Nemanov L, Dina C, Ebstein RP (2006) Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills. Mol Psychiatry 11:488–494.

    Article  CAS  PubMed  Google Scholar 

  • Yrigollen CM, Han SS, Kochetkova A, Babitz T, Chang JT, Volkmar FR, Leckman JF, Grigorenko EL (2008) Genes controlling affiliative behavior as candidate genes for autism. Biol Psychiatry 63:911–916.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Central Institute of Mental Health, J5, 68159, Mannheim, Germany

    Peter Kirsch M.D., Ph.D & Andreas Meyer-Lindenberg

Authors
  1. Peter Kirsch M.D., Ph.D
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andreas Meyer-Lindenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andreas Meyer-Lindenberg .

Editor information

Editors and Affiliations

  1. Laboratory for Autism Neuroscience Research, Department of Anatomy and Neurobiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118-2526, USA

    Gene J. Blatt

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Kirsch, P., Meyer-Lindenberg, A. (2010). Oxytocin and Autism. In: Blatt, G.J. (eds) The Neurochemical Basis of Autism. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-1272-5_10

Download citation

Publish with us

Policies and ethics

Search

Navigation