Hostname: page-component-586b7cd67f-dlnhk Total loading time: 0 Render date: 2024-11-22T22:02:51.442Z Has data issue: false hasContentIssue false
  • English
  • Français

Visual systemizing preference in children with autism: A randomized controlled trial of intranasal oxytocin

Published online by Cambridge University Press:  17 July 2017

Lane Strathearn ,
Sohye Kim ,
D. Anthony Bastian ,
Jennifer Jung ,
Udita Iyengar ,
Sheila Martinez ,
Robin P. Goin-Kochel  and
Peter Fonagy
Lane Strathearn*
Affiliation:
University of Iowa Baylor College of Medicine Texas Children's Hospital
Sohye Kim
Affiliation:
Baylor College of Medicine Texas Children's Hospital
D. Anthony Bastian
Affiliation:
Baylor College of Medicine Texas Tech Paul L. Foster School of Medicine
Jennifer Jung
Affiliation:
Baylor College of Medicine
Udita Iyengar
Affiliation:
Baylor College of Medicine University College London
Sheila Martinez
Affiliation:
Baylor College of Medicine
Robin P. Goin-Kochel
Affiliation:
Baylor College of Medicine Texas Children's Hospital
Peter Fonagy
Affiliation:
Baylor College of Medicine University College London
*
Address correspondence and reprint requests to: Lane Strathearn, Center for Disabilities and Development, University of Iowa Children's Hospital, 100 Hawkins Drive, 213F CDD, Iowa City, IA 52246-1011; E-mail: [email protected].
Get access Rights & Permissions [Opens in a new window]

Abstract

Several studies have suggested that the neuropeptide oxytocin may enhance aspects of social communication in autism. Little is known, however, about its effects on nonsocial manifestations, such as restricted interests and repetitive behaviors. In the empathizing–systemizing theory of autism, social deficits are described along the continuum of empathizing ability, whereas nonsocial aspects are characterized in terms of an increased preference for patterned or rule-based systems, called systemizing. We therefore developed an automated eye-tracking task to test whether children and adolescents with autism spectrum disorder (ASD) compared to matched controls display a visual preference for more highly organized and structured (systemized) real-life images. Then, as part of a randomized, double-blind, placebo-controlled crossover study, we examined the effect of intranasal oxytocin on systemizing preferences in 16 male children with ASD, compared with 16 matched controls. Participants viewed 14 slides, each containing four related pictures (e.g., of people, animals, scenes, or objects) that differed primarily on the degree of systemizing. Visual systemizing preference was defined in terms of the fixation time and count for each image. Unlike control subjects who showed no gaze preference, individuals with ASD preferred to fixate on more highly systemized pictures. Intranasal oxytocin eliminated this preference in ASD participants, who now showed a similar response to control subjects on placebo. In contrast, control participants increased their visual preference for more systemized images after receiving oxytocin versus placebo. These results suggest that, in addition to its effects on social communication, oxytocin may play a role in some of the nonsocial manifestations of autism.

Type
Regular Articles
Information
Development and Psychopathology , Volume 30 , Issue 2 , May 2018 , pp. 511 - 521
Copyright
Copyright © Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

This work was funded by the Baylor College of Medicine Junior Faculty Seed Funding Program, 2009–2010 (Grant 2531915102), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD065819). Peter Fonagy was partially supported by the NIHR [National Institute for Health Research] Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North Thames at Barts Health NHS [National Health Service] Trust and by an NIHR Senior Investigator Award (NF-SI-0514-10157). The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health, the NHS, the NIHR, or the UK Department of Health.

References

Anagnostou, E., Soorya, L., Chaplin, W., Bartz, J., Halpern, D., Wasserman, S., … Hollander, E. (2012). Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: A randomized controlled trial. Molecular Autism, 3, 16. doi:10.1186/2040-2392-3-16Google Scholar
Andari, E., Duhamel, J. R., Zalla, T., Herbrecht, E., Leboyer, M., & Sirigu, A. (2010). Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proceedings of the National Academy of Sciences, 107, 4389–4394. doi:10.1073/pnas.0910249107Google Scholar
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (DSM-5) (5th ed.). Washington, DC: Author.Google Scholar
Auyeung, B., Wheelwright, S., Allison, C., Atkinson, M., Samarawickrema, N., & Baron-Cohen, S. (2009). The children's empathy quotient and systemizing quotient: Sex differences in typical development and in autism spectrum conditions. Journal of Autism and Developmental Disorders, 39, 1509–1521. doi:10.1007/s10803-009-0772-xGoogle Scholar
Baker, J. P. (2013). Autism at 70—Redrawing the boundaries. New England Journal of Medicine, 369, 1089–1091. doi:10.1056/NEJMp1306380Google Scholar
Bales, K. L., & Perkeybile, A. M. (2012). Developmental experiences and the oxytocin receptor system. Hormones and Behavior, 61, 313–319. doi:10.1016/j.yhbeh.2011.12.013Google Scholar
Bales, K. L., Perkeybile, A. M., Conley, O. G., Lee, M. H., Guoynes, C. D., Downing, G. M., … Mendoza, S. P. (2013). Chronic intranasal oxytocin causes long-term impairments in partner preference formation in male prairie voles. Biological Psychiatry, 74, 180–188. doi:10.1016/j.biopsych.2012.08.025Google Scholar
Bales, K. L., van Westerhuyzen, J. A., Lewis-Reese, A. D., Grotte, N. D., Lanter, J. A., & Carter, C. S. (2007). Oxytocin has dose-dependent developmental effects on pair-bonding and alloparental care in female prairie voles. Hormones and Behavior, 52, 274–279. doi:10.1016/j.yhbeh.2007.05.004Google Scholar
Baron-Cohen, S. (2009). Autism: The empathizing-systemizing (E-S) theory. Annals of the New York Academy of Sciences, 1156, 68–80. doi:10.1111/j.1749-6632.2009.04467.xGoogle Scholar
Baron-Cohen, S., Knickmeyer, R. C., & Belmonte, M. K. (2005). Sex differences in the brain: Implications for explaining autism. Science, 310, 819–823. doi:10.1126/science.1115455Google Scholar
Baron-Cohen, S., Leslie, A. M., & Frith, U. (1985). Does the autistic child have a “theory of mind”? Cognition, 21, 37–46.Google Scholar
Baron-Cohen, S., Richler, J., Bisarya, D., Gurunathan, N., & Wheelwright, S. (2003). The systemizing quotient: An investigation of adults with Asperger syndrome or high-functioning autism, and normal sex differences. Philosophical Transactions of the Royal Society B: Biological Sciences, 358, 361–374. doi:10.1098/rstb.2002.1206Google Scholar
Baron-Cohen, S., & Wheelwright, S. (2004). The empathy quotient: An investigation of adults with Asperger syndrome or high functioning autism, and normal sex differences. Journal of Autism and Developmental Disorders, 34, 163–175.Google Scholar
Baron-Cohen, S., Wheelwright, S., Skinner, R., Martin, J., & Clubley, E. (2001). The autism-spectrum quotient (AQ): Evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians. Journal of Autism and Developmental Disorders, 31, 5–17.Google Scholar
Bartz, J. A., & Hollander, E. (2008). Oxytocin and experimental therapeutics in autism spectrum disorders. In Neumann, I. D. & Landgraf, R. (Eds.), Progress in brain research. Advances in vasopressin and oxytocin—From genes to behaviour to disease (Vol. 170, pp. 451–462). New York: Elsevier.Google Scholar
Bartz, J. A., Simeon, D., Hamilton, H., Kim, S., Crystal, S., Braun, A., … Hollander, E. (2011). Oxytocin can hinder trust and cooperation in borderline personality disorder. Social Cognitive and Affective Neuroscience, 6, 556–563. doi:10.1093/scan/nsq085Google Scholar
Bartz, J. A., Zaki, J., Bolger, N., Hollander, E., Ludwig, N. N., Kolevzon, A., & Ochsner, K. N. (2010). Oxytocin selectively improves empathic accuracy. Psychological Science, 21, 1426–1428. doi:10.1177/0956797610383439Google Scholar
Bartz, J. A., Zaki, J., Bolger, N., & Ochsner, K. N. (2011). Social effects of oxytocin in humans: Context and person matter. Trends in Cognitive Sciences, 15, 301–309. doi:10.1016/j.tics.2011.05.002Google 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. doi:10.1016/j.neuron.2008.04.009Google Scholar
Boraston, Z., & Blakemore, S. J. (2007). The application of eye-tracking technology in the study of autism. Journal of Physiology, 581, 893–898. doi:10.1113/jphysiol.2007.133587Google Scholar
Cardoso, C., Ellenbogen, M. A., & Linnen, A. M. (2014). The effect of intranasal oxytocin on perceiving and understanding emotion on the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Emotion, 14, 43–50. doi:10.1037/a0034314Google Scholar
Centers for Disease Control and Prevention. (2016). Prevalence and characteristics of autism spectrum disorders among children aged 8 years—Autism and developmental disabilities monitoring network, 11 sites, United States, 2012. Morbidity and Mortality Weekly Report, 65, 1–23.Google Scholar
Champagne, F. A. (2008). Epigenetic mechanisms and the transgenerational effects of maternal care. Frontiers in Neuroendocrinology, 29, 386–397. doi:10.1016/j.yfrne.2008.03.003Google Scholar
Champagne, F. A., Diorio, J., Sharma, S., & Meaney, M. J. (2001). Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. Proceedings of the National Academy of Sciences, 98, 12736–12741.Google Scholar
Chevallier, C., Kohls, G., Troiani, V., Brodkin, E. S., & Schultz, R. T. (2012). The social motivation theory of autism. Trends in Cognitive Sciences, 16, 231–239. doi:10.1016/j.tics.2012.02.007Google Scholar
Crespi, B. J. (2016). Oxytocin, testosterone, and human social cognition. Biological Reviews of the Cambridge Philosophical Society, 91, 390–408. doi:10.1111/brv.12175Google Scholar
Dadds, M. R., MacDonald, E., Cauchi, A., Williams, K., Levy, F., & Brennan, J. (2014). Nasal oxytocin for social deficits in childhood autism: A randomized controlled trial. Journal of Autism and Developmental Disorders, 44, 521–531. doi:10.1007/s10803-013-1899-3Google Scholar
Declerck, C. H., Boone, C., & Kiyonari, T. (2010). Oxytocin and cooperation under conditions of uncertainty: The modulating role of incentives and social information. Hormones and Behavior, 57, 368–374. doi:10.1016/j.yhbeh.2010.01.006Google Scholar
De Dreu, C. K., Greer, L. L., Handgraaf, M. J., Shalvi, S., Van Kleef, G. A., Baas, M., … Feith, S. W. (2010). The neuropeptide oxytocin regulates parochial altruism in intergroup conflict among humans. Science, 328, 1408–1411. doi:10.1126/science.1189047Google Scholar
Domes, G., Heinrichs, M., Kumbier, E., Grossmann, A., Hauenstein, K., & Herpertz, S. C. (2013). Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder. Biological Psychiatry, 74, 164–171. doi:10.1016/j.biopsych.2013.02.007Google Scholar
Domes, G., Heinrichs, M., Michel, A., Berger, C., & Herpertz, S. C. (2007). Oxytocin improves “mind-reading” in humans. Biological Psychiatry, 61, 731–733.Google Scholar
Domes, G., Kumbier, E., Heinrichs, M., & Herpertz, S. C. (2014). Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with Asperger syndrome. Neuropsychopharmacology, 39, 698–706. doi:10.1038/npp.2013.254Google Scholar
Domes, G., Lischke, A., Berger, C., Grossmann, A., Hauenstein, K., Heinrichs, M., & Herpertz, S. C. (2010). Effects of intranasal oxytocin on emotional face processing in women. Psychoneuroendocrinology, 35, 83–93. doi:10.1016/j.psyneuen.2009.06.016Google Scholar
Feldman, R. (2012). Oxytocin and social affiliation in humans. Hormones and Behavior, 61, 380–391. doi:10.1016/j.yhbeh.2012.01.008Google Scholar
Feldman, R., Golan, O., Hirschler-Guttenberg, Y., Ostfeld-Etzion, S., & Zagoory-Sharon, O. (2014). Parent-child interaction and oxytocin production in pre-schoolers with autism spectrum disorder. British Journal of Psychiatry, 205, 107–112. doi:10.1192/bjp.bp.113.137513Google Scholar
Goodman, R. (1997). The Strengths and Difficulties Questionnaire: A research note. Journal of Child Psychology and Psychiatry, 38, 581–586.Google Scholar
Gordon, I., Jack, A., Pretzsch, C. M., Vander Wyk, B., Leckman, J. F., Feldman, R., & Pelphrey, K. A. (2016). Intranasal oxytocin enhances connectivity in the neural circuitry supporting social motivation and social perception in children with autism. Scientific Reports, 6, 35054. doi:10.1038/srep35054Google Scholar
Gordon, I., Vander Wyk, B. C., Bennett, R. H., Cordeaux, C., Lucas, M. V., Eilbott, J. A., … Pelphrey, K. A. (2013). Oxytocin enhances brain function in children with autism. Proceedings of the National Academy of Sciences, 110, 20953–20958. doi:10.1073/pnas.1312857110Google Scholar
Green, L., Fein, D., Modahl, C., Feinstein, C., Waterhouse, L., & Morris, M. (2001). Oxytocin and autistic disorder: Alterations in peptide forms. Biological Psychiatry, 50, 609–613.Google Scholar
Groppe, S. E., Gossen, A., Rademacher, L., Hahn, A., Westphal, L., Grunder, G., & Spreckelmeyer, K. N. (2013). Oxytocin influences processing of socially relevant cues in the ventral tegmental area of the human brain. Biological Psychiatry, 74, 172–179. doi:10.1016/j.biopsych.2012.12.023Google Scholar
Grove, R., Baillie, A., Allison, C., Baron-Cohen, S., & Hoekstra, R. A. (2013). Empathizing, systemizing, and autistic traits: Latent structure in individuals with autism, their parents, and general population controls. Journal of Abnormal Psychology, 122, 600–609. doi:10.1037/a0031919Google Scholar
Guastella, A. J., Einfeld, S. L., Gray, K. M., Rinehart, N. J., Tonge, B. J., Lambert, T. J., & Hickie, I. B. (2010). Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biological Psychiatry, 67, 692–694. doi:10.1016/j.biopsych.2009.09.020Google Scholar
Guastella, A. J., Gray, K. M., Rinehart, N. J., Alvares, G. A., Tonge, B. J., Hickie, I. B., … Einfeld, S. L. (2015). The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: A randomized controlled trial. Journal of Child Psychology and Psychiatry, 56, 444–452. doi:10.1111/jcpp.12305Google Scholar
Guastella, A. J., Mitchell, P. B., & Dadds, M. R. (2008). Oxytocin increases gaze to the eye region of human faces. Biological Psychiatry, 63, 3–5. doi:10.1016/j.biopsych.2007.06.026Google Scholar
Hirosawa, T., Kikuchi, M., Higashida, H., Okumura, E., Ueno, S., Shitamichi, K., … Minabe, Y. (2012). Oxytocin attenuates feelings of hostility depending on emotional context and individuals’ characteristics. Scientific Reports, 2, 384. doi:10.1038/srep00384Google Scholar
Hollander, E., Novotny, S., Hanratty, M., Yaffe, R., DeCaria, C. M., Aronowitz, B. R., & Mosovich, S. (2003). Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger's disorders. Neuropsychopharmacology, 28, 193–198.Google Scholar
Hurlemann, R., Patin, A., Onur, O. A., Cohen, M. X., Baumgartner, T., Metzler, S., … Kendrick, K. M. (2010). Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans. Journal of Neuroscience, 30, 4999–5007. doi:10.1523/jneurosci.5538-09.2010Google Scholar
Insel, T. R. (2010). The challenge of translation in social neuroscience: A review of oxytocin, vasopressin, and affiliative behavior. Neuron, 65, 768–779. doi:10.1016/j.neuron.2010.03.005Google Scholar
Kanner, L. (1943). Autistic disturbances of affective contact. Nervous Child, 2, 217–250.Google Scholar
Kim, S., Fonagy, P., Koos, O., Dorsett, K., & Strathearn, L. (2014). Maternal oxytocin response predicts mother-to-infant gaze. Brain Research, 1580, 133–142. doi:10.1016/j.brainres.2013.10.050Google Scholar
Kosfeld, M., Heinrichs, M., Zak, P. J., Fischbacher, U., & Fehr, E. (2005). Oxytocin increases trust in humans. Nature, 435, 673–676.Google Scholar
Kumsta, R., Hummel, E., Chen, F. S., & Heinrichs, M. (2013). Epigenetic regulation of the oxytocin receptor gene: Implications for behavioral neuroscience. Frontiers in Neuroscience, 7, 83. doi:10.3389/fnins.2013.00083Google Scholar
Leckman, J. F., Goodman, W. K., North, W. G., Chappell, P. B., Price, L. H., Pauls, D. L., … McDougle, C. J. (1994). Elevated cerebrospinal fluid levels of oxytocin in obsessive-compulsive disorder. Comparison with Tourette's syndrome and healthy controls. Archives of General Psychiatry, 51, 782–792.Google Scholar
Lord, C., Rutter, M., DiLavore, P. C., & Risi, S. (1999). Autism Diagnostic Observation Schedule manual. Los Angeles: Western Psychological Services.Google Scholar
McGregor, I. S., Callaghan, P. D., & Hunt, G. E. (2008). From ultrasocial to antisocial: A role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use? British Journal of Pharmacology, 154, 358–368.Google Scholar
Miller, G. (2013). The promise and perils of oxytocin. Science, 339, 267–269. doi:10.1126/science.339.6117.267Google Scholar
Modahl, C., Green, L., Fein, D., Morris, M., Waterhouse, L., Feinstein, C., & Levin, H. (1998). Plasma oxytocin levels in autistic children. Biological Psychiatry, 43, 270–277.Google Scholar
Modi, M. E., & Young, L. J. (2012). The oxytocin system in drug discovery for autism: Animal models and novel therapeutic strategies. Hormones and Behavior, 61, 340–350. doi:10.1016/j.yhbeh.2011.12.010Google Scholar
Pierce, K., Conant, D., Hazin, R., Stoner, R., & Desmond, J. (2011). Preference for geometric patterns early in life as a risk factor for autism. Archives of General Psychiatry, 68, 101–109. doi:10.1001/archgenpsychiatry.2010.113Google Scholar
Ring, R. H. (2011). A complicated picture of oxytocin action in the central nervous system revealed. Biological Psychiatry, 69, 818–819. doi:10.1016/j.biopsych.2011.03.020Google Scholar
Rutter, M., Bailey, A., & Lord, C. (2003). SCQ: Social Communication Questionnaire. Los Angeles: Western Psychological Services.Google Scholar
Sala, M., Braida, D., Lentini, D., Busnelli, M., Bulgheroni, E., Capurro, V., … Chini, B. (2011). Pharmacologic rescue of impaired cognitive flexibility, social deficits, increased aggression, and seizure susceptibility in oxytocin receptor null mice: A neurobehavioral model of autism. Biological Psychiatry, 69, 875–882. doi:10.1016/j.biopsych.2010.12.022Google Scholar
Sparrow, S. S. C., Cicchetti, D. V., & Balla, D. A. (2005). Vineland Adaptive Behavior Scales (2nd ed.). New York: Pearson.Google Scholar
Stavropoulos, K. K., & Carver, L. J. (2013). Research Review: Social motivation and oxytocin in autism—Implications for joint attention development and intervention. Journal of Child Psychology and Psychiatry, 54, 603–618. doi:10.1111/jcpp.12061Google Scholar
Strathearn, L. (2009). The elusive etiology of autism: Nature and nurture? Frontiers in Behavioral Neuroscience, 3, 11. doi:10.3389/neuro.08.011.2009Google Scholar
Strathearn, L., Fonagy, P., Amico, J. A., & Montague, P. R. (2009). Adult attachment predicts mother's brain and oxytocin response to infant cues. Neuropsychopharmacology, 34, 2655–2666. doi:10.1038/npp.2009.103Google Scholar
Strathearn, L., Iyengar, U., Fonagy, P., & Kim, S. (2012). Maternal oxytocin response during mother-infant interaction: Associations with adult temperament. Hormones and Behavior, 61, 429–435. doi:10.1016/j.yhbeh.2012.01.014Google Scholar
Tobii Technology. (2011). Accuracy and precision test report: Tobii T60 Eye tracker. Stockholm: Author.Google Scholar
Valstad, M., Alvares, G. A., Egknud, M., Matziorinis, A. M., Andreassen, O. A., Westlye, L. T., & Quintana, D. S. (2017). The correlation between central and peripheral oxytocin concentrations: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews, 78, 117–124. doi:10.1016/j.neubiorev.2017.04.017Google Scholar
Watanabe, T., Kuroda, M., Kuwabara, H., Aoki, Y., Iwashiro, N., Tatsunobu, N., … Yamasue, H. (2015). Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain, 138, 3400–3412. doi:10.1093/brain/awv249Google Scholar
Yatawara, C. J., Einfeld, S. L., Hickie, I. B., Davenport, T. A., & Guastella, A. J. (2016). The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: A randomized clinical crossover trial. Molecular Psychiatry, 21, 1225–1231. doi:10.1038/mp.2015.162Google Scholar
Zoghbi, H. Y., & Bear, M. F. (2012). Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities. Cold Spring Harbor Perspectives in Biology, 4. doi:10.1101/cshperspect.a009886Google Scholar