Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose core symptoms include deficits in social interaction and communication besides restricted and repetitive behaviors. Although ASD is highly prevalent, affecting 1/100 in the general population, no medication for the core symptoms has been established. Therefore, the disorder is considered a huge unmet medical need and a heavy burden on individuals with ASD, their families, and entire society. Oxytocin is expected to be a potential therapeutic resource for the social core symptoms of ASD, since this neuropeptide can modulate human social behavior and cognition. This review article provides an overview of both experimental and clinical studies on effects of oxytocin administration on behavior, neural underpinnings, and symptomatology of ASD. Although the number of studies is increasing, several issues remain for further development of clinical application of the neuropeptide. The issues include optimization of administration route, doses, treatment duration, interval of administrations, and timing of starting treatment. Additional issues involve investigating neurobiological mechanisms of treatment and developing a reliable tool to accurately and objectively assess longitudinal changes in the core symptoms of ASD. Some of these issues are discussed in this review.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Althaus M, Groen Y, Wijers AA, Noltes H, Tucha O, Hoekstra PJ (2015) Oxytocin enhances orienting to social information in a selective group of high-functioning male adults with autism spectrum disorder. Neuropsychologia 79:53–69
Anagnostou E, Soorya L, Chaplin W, Bartz J, Halpern D, Wasserman S et al (2012) Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol Autism 3(1):16
Andari E, Andari E, Duhamel J-R, Duhamel J-R, Zalla T, Herbrecht E et al (2010) Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci U S A 107(9):4389–4394
Andari E, Richard N, Leboyer M, Sirigu A (2016) Adaptive coding of the value of social cues with oxytocin, an fMRI study in autism spectrum disorder. Cortex 76:79–88
Aoki Y, Yahata N, Watanabe T, Takano Y, Kawakubo Y, Kuwabara H et al (2014) Oxytocin improves behavioural and neural deficits in inferring others’ social emotions in autism. Brain 137(11):3073–3086
Aoki Y, Watanabe T, Abe O, Kuwabara H, Yahata N, Takano Y et al (2015) Oxytocin’s neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial. Mol Psychiatry 20(4):447–453
Auyeung B, Lombardo MV, Heinrichs M, Chakrabarti B, Sule A, Deakin JB et al (2015) Oxytocin increases eye contact during a real-time, naturalistic social interaction in males with and without autism. Transl Psychiatry 5:e507
Bales KL, Perkeybile AM, Conley OG, Lee MH, Guoynes CD, Downing GM et al (2013) Chronic intranasal oxytocin causes long-term impairments in partner preference formation in male prairie voles. Biol Psychiatry 74(3):180–188
Baron-Cohen S, Wheelwright S, Hill J, Raste Y, Plumb I (2001) The “reading the mind in the eyes” test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism. J Child Psychol Psychiatry 42(2):241–251
Bartz JA, Zaki J, Ochsner KN, Bolger N, Kolevzon A, Ludwig N et al (2010) Effects of oxytocin on recollections of maternal care and closeness. Proc Natl Acad Sci U S A 107(50):21371–21375
Bartz JA, Zaki J, Bolger N, Ochsner KN (2011) Social effects of oxytocin in humans: context and person matter. Trends Cogn Sci 15(7):301–309
Baum KM, Nowicki S (1989) Perception of emotion: measuring decoding accuracy of adult prosodic cues varying in intensity. J Nonverbal Behav 22:89–107
Bodfish JW, Symons FJ, Parker DE, Lewis MH (2000) Varieties of repetitive behavior in autism: comparisons to mental retardation. J Autism Dev Disord 30:237–243
Carter C (2007) Sex differences in oxytocin and vasopressin: implications for autism spectrum disorders? Behav Brain Res 176(1):170–186
Chakrabarti S, Fombonne E (2005) Pervasive developmental disorders in preschool children: confirmation of high prevalence. Am J Psychiatry 162(6):1133–1141
Dadds MR, MacDonald E, Cauchi A, Williams K, Levy F, Brennan J (2014) Nasal oxytocin for social deficits in childhood autism: a randomized controlled trial. J Autism Dev Disord 44(3):521–531
Domes G, Heinrichs M, Michel A, Berger C, Herpertz S (2007) Oxytocin improves “mind-reading” in humans. Biol Psychiatry 61(6):731–733
Domes G, Heinrichs M, Kumbier E, Grossmann A, Hauenstein K, Herpertz SC (2013) Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder. Biol Psychiatry 74(3):164–171
Domes G, Kumbier E, Heinrichs M, Herpertz SC (2014) Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with Asperger syndrome. Neuropsychopharmacology 39(3):698–706
Donaldson ZR, Young LJ (2008) Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322(5903):900–904
Furman DJ, Chen MC, Gotlib IH (2011) Variant in oxytocin receptor gene is associated with amygdala volume. Psychoneuroendocrinology 36(6):891–897
Gordon I, Zagoory-Sharon O, Leckman JF, Feldman R (2010) Oxytocin and the development of parenting in humans. Biol Psychiatry 68(4):377–382
Gordon I, Vander Wyk BC, Bennett RH, Cordeaux C, Lucas MV, Eilbott JA et al (2013) Oxytocin enhances brain function in children with autism. Proc Natl Acad Sci U S A 110(52):20953–20958
Guastella AJ, Hickie IB (2015) Oxytocin treatment, circuitry and autism: a critical review of the literature placing oxytocin into the autism context. Biol Psychiatry 79(3):234–242
Guastella A, Einfeld S, Gray K, Rinehart N, Tonge B, Lambert T et al (2010) Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry 67(7):692–694
Guastella AJ, Gray KM, Rinehart NJ, Alvares GA, Tonge BJ, Hickie IB et al (2015) 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(4):444–452
Hollander E, Novotny S, Hanratty M, Yaffe R, DeCaria C, Aronowitz B et al (2003) Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology 28(1):193–198
Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L et al (2007) Oxytocin increases retention of social cognition in autism. Biol Psychiatry 61(4):498–503
Inoue H, Yamasue H, Tochigi M, Abe O, Liu X, Kawamura Y et al (2010) Association between the oxytocin receptor gene and amygdalar volume in healthy adults. Biol Psychiatry 68(11):1066–1072
Insel TR (2010) The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior. Neuron 65(6):768–779
Kanat M, Heinrichs M, Domes G (2014) Oxytocin and the social brain: neural mechanisms and perspectives in human research. Brain Res 1580:160–171
Kanat M, Spenthof I, Riedel A, van Elst LT, Heinrichs M, Domes G (2017) Restoring effects of oxytocin on the attentional preference for faces in autism. Transl Psychiatry 7:e1097. doi:10.1038/tp.2017.67
Kosaka H, Munesue T, Ishitobi M, Asano M, Omori M, Sato M et al (2012) Long-term oxytocin administration improves social behaviors in a girl with autistic disorder. BMC Psychiatry 12:110
LoParo D, Waldman ID (2015) The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis. Mol Psychiatry 20(5):640–646
Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M (2011) Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat Rev Neurosci 12(9):524–538
Munesue T, Yokoyama S, Nakamura K, Anitha A, Yamada K, Hayashi K et al (2010) Two genetic variants of CD38 in subjects with autism spectrum disorder and controls. Neurosci Res 67(2):181–191
Munesue T, Nakamura H, Kikuchi M, Miura Y, Takeuchi N, Anme T et al (2016) Oxytocin for male subjects with autism spectrum disorder and comorbid intellectual disabilities: a randomized pilot study. Front Psychiatry 7:2
Nagasawa M, Okabe S, Mogi K, Kikusui T (2012) Oxytocin and mutual communication in mother-infant bonding. Front Hum Neurosci 6:31
Philip RC, Dauvermann MR, Whalley HC, Baynham K, Lawrie SM, Stanfield AC (2012) A systematic review and meta-analysis of the fMRI investigation of autism spectrum disorders. Neurosci Biobehav Rev 36(2):901–942
Preti A, Melis M, Siddi S, Vellante M, Doneddu G, Fadda R (2014) Oxytocin and autism: a systematic review of randomized controlled trials. J Child Adolesc Psychopharmacol 24(2):54–68
Quintana DS, Alvares GA, Hickie IB, Guastella AJ (2015) Do delivery routes of intranasally administered oxytocin account for observed effects on social cognition and behavior? A two-level model. Neurosci Biobehav Rev 49:182–192
Saito Y, Suga M, Tochigi M, Abe O, Yahata N, Kawakubo Y et al (2014) Neural correlate of autistic-like traits and a common allele in the oxytocin receptor gene. Soc Cogn Affect Neurosci 9(10):1443–1450
Shahrestani S, Kemp AH, Guastella AJ (2013) The impact of a single administration of intranasal oxytocin on the recognition of basic emotions in humans: a meta-analysis. Neuropsychopharmacology 38(10):1929–1936
Tachibana M, Shamay-Tsoory SG, Fischer M, Taniike M, Dvash J, Harari H et al (2012) Long-term administration of intranasal oxytocin is a safe and promising therapy for early adolescent boys with autism spectrum disorders. J Child Adolesc Psychopharmacol:1–33
Tost H, Kolachana B, Hakimi S, Lemaitre H, Verchinski BA, Mattay VS et al (2010) A common allele in the oxytocin receptor gene (OXTR) impacts prosocial temperament and human hypothalamic-limbic structure and function. Proc Natl Acad Sci U S A 107(31):13936–13941
Tyzio R, Cossart R, Khalilov I, Minlebaev M, Hübner CA, Represa A et al (2006) Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery. Science 314(5806):1788–1792
van IJzendoorn MH, Bakermans-Kranenburg MJ (2012) A sniff of trust: meta-analysis of the effects of intranasal oxytocin administration on face recognition, trust to in-group, and trust to out-group. Psychoneuroendocrinology 37(3):438–443
Watanabe T, Abe O, Kuwabara H, Yahata N, Takano Y, Iwashiro N et al (2014) Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity: a randomized trial. JAMA Psychiat 71(2):166–175
Watanabe T, Kuroda M, Kuwabara H, Aoki Y, Iwashiro N, Tatsunobu N et al (2015) Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain 138(Pt 11):3400–3412
Yamasue H (2013) Function and structure in social brain regions can link oxytocin-receptor genes with autistic social behavior. Brain Dev 35(2):111–118
Yamasue H (2015) Using endophenotypes to examine molecules related to candidate genes as novel therapeutics: the endophenotype-associated surrogate endpoint (EASE) concept. Neurosci Res 99:1–7
Yamasue H (2016) Promising evidence and remaining issues regarding the clinical application of oxytocin in autism spectrum disorders. Psychiatry Clin Neurosci 70(2):89–99
Yamasue H, Kuwabara H, Kawakubo Y, Kasai K (2009) Oxytocin, sexually dimorphic features of the social brain, and autism. Psychiatry Clin Neurosci 63(2):129–140
Yamasue H, Yee JR, Hurlemann R, Rilling JK, Chen FS, Meyer-Lindenberg A et al (2012) Integrative approaches utilizing oxytocin to enhance prosocial behavior: from animal and human social behavior to autistic social dysfunction. J Neurosci 32(41):14109–14117
Yatawara CJ, Einfeld SL, Hickie IB, Davenport TA, Guastella AJ (2016) The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial. Mol Psychiatry 21(9):1225–1231
Young LJ, Wang Z (2004) The neurobiology of pair bonding. Nat Neurosci 7(10):1048–1054
Acknowledgments
The writing of this paper was in part supported by a grant from the German Research Foundation awarded to G.D. (DFG Do1312/2-3) and the Japanese grant KAKENHI (26250024 to H.Y.).
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this chapter
Cite this chapter
Yamasue, H., Domes, G. (2017). Oxytocin and Autism Spectrum Disorders. In: Hurlemann, R., Grinevich, V. (eds) Behavioral Pharmacology of Neuropeptides: Oxytocin. Current Topics in Behavioral Neurosciences, vol 35. Springer, Cham. https://doi.org/10.1007/7854_2017_24
Download citation
DOI: https://doi.org/10.1007/7854_2017_24
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-63738-9
Online ISBN: 978-3-319-63739-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)