A randomized controlled trial of intranasal oxytocin in Phelan-McDermid syndrome

作者：Jarrett Fastman, Jennifer H. Foss‐Feig, Yitzchak Frank, Danielle Halpern, Hala Harony‐Nicolas, Christina Layton, Sven Sandin, Paige M. Siper, L. Tang, M. Pilar Trelles, Jessica Zweifach, Joseph D. Buxbaum, Alexander Kolevzon · 发表于：Molecular Autism · 年份：2021 · DOI：10.1186/s13229-021-00459-1 · 被引用次数：25 · 研究领域：Neuroendocrine regulation and behavior、Autism Spectrum Disorder Research、Human-Animal Interaction Studies

BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene and characterized by global developmental delays, deficits in speech and motor function, and autism spectrum disorder (ASD). Monogenic causes of ASD such as PMS are well suited to investigations with novel therapeutics, as interventions can be targeted based on established genetic etiology. While preclinical studies have demonstrated that the neuropeptide oxytocin can reverse electrophysiological, attentional, and social recognition memory deficits in Shank3-deficient rats, there have been no trials in individuals with PMS. The purpose of this study is to assess the efficacy and safety of intranasal oxytocin as a treatment for the core symptoms of ASD in a cohort of children with PMS. METHODS: Eighteen children aged 5-17 with PMS were enrolled. Participants were randomized to receive intranasal oxytocin or placebo (intranasal saline) and underwent treatment during a 12-week double-blind, parallel group phase, followed by a 12-week open-label extension phase during which all participants received oxytocin. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as a number of secondary outcome measures related to the core symptoms of ASD. Safety was monitored throughout the study period. RESULTS: There was no statistically significant improvement with oxytocin as compared to place...