Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial

H. Kosaka, Y. Okamoto, T. Munesue, H. Yamasue, K. Inohara, T. Fujioka, T. Anme, M. Orisaka, M. Ishitobi, M. Jung, T. X. Fujisawa, S. Tanaka, S. Arai, M. Asano, D. N. Saito, N. Sadato, A. Tomoda, M. Omori, M. Sato, H. OkazawaH. Higashida, Y. Wada

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44 Citations (Scopus)

Abstract

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

Original languageEnglish
Pages (from-to)e872
JournalTranslational Psychiatry
Volume6
Issue number8
DOIs
Publication statusPublished - 2016 Aug 23
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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    Kosaka, H., Okamoto, Y., Munesue, T., Yamasue, H., Inohara, K., Fujioka, T., Anme, T., Orisaka, M., Ishitobi, M., Jung, M., Fujisawa, T. X., Tanaka, S., Arai, S., Asano, M., Saito, D. N., Sadato, N., Tomoda, A., Omori, M., Sato, M., ... Wada, Y. (2016). Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial. Translational Psychiatry, 6(8), e872. https://doi.org/10.1038/tp.2016.152