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Molecular Autism
Published in: Molecular Autism 1/2012

Open Access 01-12-2012 | Research

Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial

Authors: Evdokia Anagnostou, Latha Soorya, William Chaplin, Jennifer Bartz, Danielle Halpern, Stacey Wasserman, A Ting Wang, Lauren Pepa, Nadia Tanel, Azadeh Kushki, Eric Hollander

Published in: Molecular Autism | Issue 1/2012

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Abstract

Background

There are no effective medications for the treatment of social cognition/function deficits in autism spectrum disorder (ASD), and adult intervention literature in this area is sparse. Emerging data from animal models and genetic association studies as well as early, single-dose intervention studies suggest that the oxytocin system may be a potential therapeutic target for social cognition/function deficits in ASD. The primary aim of this study was to examine the safety/therapeutic effects of intranasal oxytocin versus placebo in adults with ASD, with respect to the two core symptom domains of social cognition/functioning and repetitive behaviors.

Methods

This was a pilot, randomized, double-blind, placebo-controlled, parallel design trial of intranasal oxytocin versus placebo in 19 adults with ASD (16 males; 33.20 ± 13.29 years). Subjects were randomized to 24 IU intranasal oxytocin or placebo in the morning and afternoon for 6 weeks. Measures of social function/cognition (the Diagnostic Analysis of Nonverbal Accuracy) and repetitive behaviors (Repetitive Behavior Scale Revised) were administered. Secondary measures included the Social Responsiveness Scale, Reading-the-Mind-in-the-Eyes Test and the Yale Brown Obsessive Compulsive Scale – compulsion subscale and quality of life (World Health Organization Quality of Life Questionnaire – emotional/social subscales). Full-information maximum-likelihood parameter estimates were obtained and tested using mixed-effects regression analyses.

Results

Although no significant changes were detected in the primary outcome measures after correcting for baseline differences, results suggested improvements after 6 weeks in measures of social cognition (Reading-the-Mind-in-the-Eyes Test, p = 0.002, d = 1.2), and quality of life (World Health Organization Quality of Life Questionnaire – emotion, p = 0.031, d = 0.84), both secondary measures. Oxytocin was well tolerated and no serious adverse effects were reported.

Conclusions

This pilot study suggests that there is therapeutic potential to daily administration of intranasal oxytocin in adults with ASD and that larger and longer studies are warranted.

Trial registration

NCT00490802

Literature
  1. Striepens N, Kendrick KM, Maier W, Hurlemann R: Prosocial effects of oxytocin strand clinical evidence for its therapeutic potential. Front Neuroendocrinol. 2011, 32: 426-450. 10.1016/j.yfrne.2011.07.001.View ArticlePubMed
  2. Bittel DC, Kibiryeva N, Dasouki M, Knoll JH, Butler MG: A 9-year-old male with a duplication of chromosome 3p25.3p26.2: clinical report and gene expression analysis. Am J Med Genet. 2006, 140: 573-579.PubMed CentralView ArticlePubMed
  3. Gregory S, Connelly JJ, Towers AJ, Johnson J, Biscocho D, Markunas CA, Lintas C, Abramson KA, Wright HH, Ellis P, Langford CF, Worley G, Delong GR, Murphy SK, Cuccaro ML, Persico A, Pericak-Vance M: Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med. 2009, 7: 62-10.1186/1741-7015-7-62.PubMed CentralView ArticlePubMed
  4. Jacob S, Brune CW, Carter CS, Leventhal BL, Lord C, Cook EH: Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett. 2007, 417: 6-9. 10.1016/j.neulet.2007.02.001.PubMed CentralView ArticlePubMed
  5. Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Kicks J, Spence SJ, Lee AT, Puura K, Lehtimäki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M: Strong association of de novo copy number mutations with autism. Science. 2007, 316: 445-449. 10.1126/science.1138659.PubMed CentralView ArticlePubMed
  6. Andari E, Duhamel J, Zalla T, Herbrecht E, Leboyer M, Sirigu A: Promoting social behavior with oxytocin in high functioning autism spectrum disorders. Proc Natl Acad Sci U S A. 2010, 107: 4389-4394. 10.1073/pnas.0910249107.PubMed CentralView ArticlePubMed
  7. Green LA, Fein D, Modahl C, Feinstein C, Waterhouse L, Morris M: Oxytocin and autistic disorder: alteration in peptide forms. Biol Psychiatry. 2001, 50: 609-613. 10.1016/S0006-3223(01)01139-8.View ArticlePubMed
  8. Modahl C, Green LA, Fein D, Morris M, Waterhouse L, Feinstein C, Levin H: Plasma oxytocin levels in autistic children. Biol Psychiatry. 1998, 43: 270-277. 10.1016/S0006-3223(97)00439-3.View ArticlePubMed
  9. Carter CS: Neuroendocrine perspectives on social attachment and love. Psychoneuroendocrinology. 1998, 23: 779-818. 10.1016/S0306-4530(98)00055-9.View ArticlePubMed
  10. Insel TR, Obrien DJ, Leckman JF: Oxytocin, vasopressin, and autism: is there a connection. Biol Psychiatry. 1999, 45: 145-157. 10.1016/S0006-3223(98)00142-5.View ArticlePubMed
  11. Ferguson JN, Young LJ, Hearn EF, Matzuk MM, Insel TR, Winslow JT: Social amnesia in mice lacking the oxytocin gene. Nat Genet. 2000, 25: 284-288. 10.1038/77040.View ArticlePubMed
  12. Takayanagi Y, Yoshida M, Bielsky IF, Ross H, Kawamata M, Onaka T, Yanagisawa T, Kimura T, Matzuk M, Young LJ, Nishimori K, Pfaff DW: Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proc Natl Acad Sci U S A. 2005, 102: 16096-16101. 10.1073/pnas.0505312102.PubMed CentralView ArticlePubMed
  13. Sala M, Braida D, Lentini D, Busnelli M, Bulgheroni E, Capurro V, Finardi A, Donzelli A, Pattini L, Rubino T, Parolaro D, Nishimori K, Parenti M, Chini B: Pharmacological rescue of impaired cognitive flexibility, social deficits, increased aggression, and seizure susceptibility in oxytocin receptor null mice: a neurobehavioral model of autism. Biol Psychiatry. 2011, 69: 875-882. 10.1016/j.biopsych.2010.12.022.View ArticlePubMed
  14. Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E: Oxytocin increases trust in humans. Nature. 2005, 435: 673-676. 10.1038/nature03701.View ArticlePubMed
  15. Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A: Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci. 2005, 25: 11489-11493. 10.1523/JNEUROSCI.3984-05.2005.View ArticlePubMed
  16. Domes G, Heinrichs M, Gläscher J, Büchel C, Braus DF, Herpertz SC: Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol Psychiatry. 2007, 62: 1187-1190. 10.1016/j.biopsych.2007.03.025.View ArticlePubMed
  17. Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC: Oxytocin improves ‘mind-reading’ in humans. Biol Psychiatry. 2006, 61: 731-733.View ArticlePubMed
  18. Guastella AJ, Mitchell PB, Dadds MR: Oxytocin increases gaze to the eye region of human faces. Biol Psychiatry. 2007, 63: 3-5.View ArticlePubMed
  19. Savaskan E, Ehrhardt R, Schulz A, Walter M, Schachinger H: Post-learning intranasal oxytocin modulates human memory for facial identity. Psychoneuroendocrinology. 2008, 33: 368-374. 10.1016/j.psyneuen.2007.12.004.View ArticlePubMed
  20. Rimelle U, Hediger K, Heinrichs M, Klaver P: Oxytocin makes a face memory familiar. J Neurosci. 2009, 29: 38-42. 10.1523/JNEUROSCI.4260-08.2009.View Article
  21. Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L, Anagnostou E, Wasserman S: Oxytocin increases retention of social cognition in autism. Biol Psychiatry. 2007, 61: 498-503. 10.1016/j.biopsych.2006.05.030.View ArticlePubMed
  22. Hollander E, Novotny S, Hanratty M, Yaffe R, DeCaria CM, Aronowitz BR, Mosovich S: Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology. 2003, 28: 193-198. 10.1038/sj.npp.1300021.View ArticlePubMed
  23. Guastella A, Einfeld S, Gray K, Rinehart N, Tonge B, Lambert TJ, Hickie IB: Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry. 2009, 67: 692-694.View ArticlePubMed
  24. Lord C, Risi S, Lambrecht L, Cook EH, Leventhal BL, DiLavore PC, Pickles A, Rutter M: The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord. 2000, 30: 205-223. 10.1023/A:1005592401947.View ArticlePubMed
  25. Lord C, Rutter M, Le Couteur A: Autism diagnostic interview – revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord. 1994, 24: 659-685. 10.1007/BF02172145.View ArticlePubMed
  26. Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, Heninger GR, Charney DS: The Yale-brown obsessive compulsive scale. I. Development, use, and reliability. Arch Gen Psychiat. 1989, 46: 1006-1011. 10.1001/archpsyc.1989.01810110048007.View ArticlePubMed
  27. Bodfish JW, Symons FJ, Parker DE, Lewis MH: Varieties of repetitive behavior in autism: comparisons to mental retardation. J Autism Dev Disord. 2000, 30: 237-243. 10.1023/A:1005596502855.View ArticlePubMed
  28. Constantino JN: The Social Responsiveness Scale. 2002, Los Angeles, CA: Western Psychological Services
  29. Baron-Cohen S, Wheelwright S, Hill J, Raste Y, Plumb I: 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. 2001, 42: 241-251. 10.1111/1469-7610.00715.View ArticlePubMed
  30. Baum KM, Nowicki S: Perception of emotion: measuring decoding accuracy of adult prosodic cues varying in intensity. J Nonverbal Behav. 1989, 22: 89-107.View Article
  31. Skevington SM, Lotfy M, O'Connell KA: The World Health Organization's WHOQOL-BREF quality of life assessment: psychometric properties and results of the international field trial. A report from the WHOQOL group. Qual Life Res. 2004, 13: 299-310.View ArticlePubMed
  32. Georgiades S, Papageorgiou V, Anagnostou E: Brief report: repetitive behaviors in Greek individuals with autism spectrum disorder. J Autism Dev Disord. 2010, 40: 903-906. 10.1007/s10803-009-0927-9.View ArticlePubMed
  33. Anagnostou E, Chaplin W, Watner D, Silverman JM, Smith CJ, Zagursky K, Kryzak LA, Corwin TE, Feirsen N, Tanel N, Hollander E: Factor analysis of repetitive behaviors in autism as measured by the Y-BOCS. J Neuropsychiatry Clin Neurosci. 2011, 23: 332-339. 10.1176/appi.neuropsych.23.3.332.View ArticlePubMed
  34. Feifel D, Macdonald K, Nguyen A, Cobb P, Warlan H, Galangue B, Minassian A, Becker O, Cooper J, Perry W, Lefebvre M, Gonzales J, Hadley A: Adjunctive intranasal oxytocin reduces symptoms in schizophrenia patients. Biol Psychiatry. 2010, 68: 678-680. 10.1016/j.biopsych.2010.04.039.View ArticlePubMed
  35. Guastella AJ, Howard AL, Dadds MR, Mitchell P, Carson DS: A randomized controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety disorder. Psychoneuroendocrinology. 2009, 34: 917-923. 10.1016/j.psyneuen.2009.01.005.View ArticlePubMed
  36. Churchland PS, Winkielman P: Modulating social behavior with oxytocin: how does it work? What does it mean?. Horm Behav. 2012, 61: 392-399. 10.1016/j.yhbeh.2011.12.003.PubMed CentralView ArticlePubMed
  37. Derntl B, Kryspin-Exner I, Fernbach E, Moser E, Habel U: Emotion recognition accuracy in healthy young females is associated with cycle phase. Horm Behav. 2008, 53: 90-95. 10.1016/j.yhbeh.2007.09.006.View ArticlePubMed
  38. Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL: Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci. 2002, 5: 514-516. 10.1038/nn0602-849.View ArticlePubMed
Metadata
Title
Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial
Authors
Evdokia Anagnostou
Latha Soorya
William Chaplin
Jennifer Bartz
Danielle Halpern
Stacey Wasserman
A Ting Wang
Lauren Pepa
Nadia Tanel
Azadeh Kushki
Eric Hollander
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2012
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/2040-2392-3-16

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