1. Quantitative facial expression analysis revealed the efficacy and time course of oxytocin in autism
- Author
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Seico Benner, Walid Yassin, Yota Uno, Haruhiro Higashida, Takashi Okada, Nanayo Ogawa, Kaori Matsumoto, Toshio Munesue, Yuko Yoshimura, Toru Fujioka, Teruko Yuhi, Naoko Kawano, Yuko Okamoto, Hirotaka Kosaka, Yosuke Eriguchi, Yuko Arioka, Masaki Kojima, Miho Kuroda, Yuki Kawakubo, Maeri Yamamoto, Yukiko Kano, Keiho Owada, Yukari Uemura, Norio Ozaki, Itaru Kushima, Daisuke Mori, Kiyoto Kasai, Hidenori Yamasue, and Hitoshi Kuwabara
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Time Factors ,Adolescent ,Autism Spectrum Disorder ,Oxytocin ,Confirmatory trial ,Autism Diagnostic Observation Schedule ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,medicine ,Pervasive developmental disorder ,Humans ,Interpersonal Relations ,Administration, Intranasal ,Facial expression ,Cross-Over Studies ,business.industry ,Middle Aged ,medicine.disease ,Facial Expression ,030104 developmental biology ,Autism spectrum disorder ,Asperger syndrome ,Autism ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Neurotypical - Abstract
Discrepancies in efficacy between single-dose and repeated administration of oxytocin for autism spectrum disorder have led researchers to hypothesize that time-course changes in efficacy are induced by repeated administrations of the peptide hormone. However, repeatable, objective, and quantitative measurement of autism spectrum disorder’s core symptoms are lacking, making it difficult to examine potential time-course changes in efficacy. We tested this hypothesis using repeatable, objective, and quantitative measurement of the core symptoms of autism spectrum disorder. We examined videos recorded during semi-structured social interaction administered as the primary outcome in single-site exploratory (n = 18, crossover within-subjects design) and multisite confirmatory (n = 106, parallel-group design), double-blind, placebo-controlled 6-week trials of repeated intranasal administrations of oxytocin (48 IU/day) in adult males with autism spectrum disorder. The main outcomes were statistical representative values of objectively quantified facial expression intensity in a repeatable part of the Autism Diagnostic Observation Schedule: the maximum probability (i.e. mode) and the natural logarithm of mode on the probability density function of neutral facial expression and the natural logarithm of mode on the probability density function of happy expression. Our recent study revealed that increases in these indices characterize autistic facial expression, compared with neurotypical individuals. The current results revealed that oxytocin consistently and significantly decreased the increased natural logarithm of mode on the probability density function of neutral facial expression compared with placebo in exploratory (effect-size, −0.57; 95% CI, −1.27 to 0.13; P = 0.023) and confirmatory trials (−0.41; −0.62 to −0.20; P < 0.001). A significant interaction between time-course (at baseline, 2, 4, 6, and 8 weeks) and the efficacy of oxytocin on the natural logarithm of mode on the probability density function of neutral facial expression was found in confirmatory trial (P < 0.001). Post hoc analyses revealed maximum efficacy at 2 weeks (P < 0.001, Cohen’s d = −0.78; 95% CI, −1.21 to −0.35) and deterioration of efficacy at 4 weeks (P = 0.042, Cohen’s d = −0.46; 95% CI, −0.90 to −0.01) and 6 weeks (P = 0.10, Cohen’s d = −0.35; 95% CI, −0.77 to 0.08), while efficacy was preserved at 2 weeks post-treatment (i.e. 8 weeks) (P < 0.001, Cohen’s d = −1.24; 95% CI, −1.71 to −0.78). Quantitative facial expression analyses successfully verified the positive effects of repeated oxytocin on autistic individuals’ facial expressions and demonstrated a time-course change in efficacy. The current findings support further development of an optimized regimen of oxytocin treatment.
- Published
- 2019