Intranasal administration of oxytocin is increasingly explored as a new approach to facilitate social development and reduce disability associated with a diagnosis of autism spectrum disorder (ASD). The efficacy of multiple-dose oxytocin administration in children with ASD is, however, not well established. A double-blind, randomized, placebo-controlled trial with parallel design explored the effects of a 4-week intranasal oxytocin administration (12 IU, twice daily) on parent-rated social responsiveness (Social Responsiveness Scale: SRS-2) in pre-pubertal school-aged children (aged 8–12 years, 61 boys, 16 girls). Secondary outcomes included a questionnaire-based assessment of repetitive behaviors, anxiety, and attachment. Effects of oxytocin were assessed immediately after the administration period and at a follow-up, 4 weeks after the last administration. The double-blind phase was followed by a 4-week single-blind phase during which all participants received intranasal oxytocin. In the double-blind phase, both the oxytocin and placebo group displayed significant pre-to-post-improvements in social responsiveness and secondary questionnaires, but improvements were not specific to the intranasal oxytocin. Notably, in the single-blind phase, participants who were first allocated to intranasal placebo and later changed to intranasal oxytocin displayed a significant improvement in social responsiveness, over and above the placebo-induced improvements noted in the first phase. Participants receiving oxytocin in the first phase also showed a significant further improvement upon receiving a second course of oxytocin, but only at the 4-week follow-up. Further, exploratory moderator analyses indicated that children who received psychosocial trainings (3 or more sessions per month) along with oxytocin administration displayed a more pronounced improvement in social responsiveness. Future studies using larger cohorts and more explicitly controlled concurrent psychosocial trainings are warranted to further explore the preliminary moderator effects, also including understudied populations within the autism spectrum, such as children with co-occurring intellectual disabilities. Four weeks of oxytocin administration did not induce treatment-specific improvements in social responsiveness in school-aged children with ASD. Future studies are warranted to further explore the clinical efficacy of oxytocin administration paired with targeted psychosocial trainings that stimulate socio-communicative behaviors. Trial registration The trial was registered with the European Clinical Trial Registry (EudraCT 2018-000769-35) on June 7th, 2018 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-000769-35/BE ).

中文翻译：

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多剂量鼻内催产素对自闭症儿童社会反应的影响：一项随机、安慰剂对照试验

作为促进社会发展和减少与自闭症谱系障碍 (ASD) 诊断相关的残疾的新方法，越来越多地探索鼻内施用催产素。然而，多剂量催产素对 ASD 儿童的疗效尚未确定。一项采用平行设计的双盲、随机、安慰剂对照试验探讨了为期 4 周的鼻内催产素给药（12 IU，每天两次）对 pre-pre- 父母评估的社会反应能力（社会反应能力量表：SRS-2）的影响青春期学龄儿童（8-12 岁，男孩 61 名，女孩 16 名）。次要结果包括基于问卷的重复行为、焦虑和依恋评估。催产素的作用在给药期后和随访时立即进行评估，最后一次给药后 4 周。双盲阶段之后是为期 4 周的单盲阶段，在此期间所有参与者都接受了鼻内催产素。在双盲阶段，催产素组和安慰剂组在社会反应和二次问卷调查方面均显示出显着的前后改善，但改善并非鼻内催产素所特有。值得注意的是，在单盲阶段，首先分配给鼻内安慰剂然后改为鼻内催产素的参与者在社交反应方面表现出显着改善，超过了第一阶段注意到的安慰剂引起的改善。在第一阶段接受催产素的参与者在接受第二个疗程的催产素后也表现出显着的进一步改善，但仅限于 4 周的随访。更远，探索性调节分析表明，接受心理社会培训（每月 3 次或更多次）以及催产素给药的儿童在社会反应能力方面表现出更明显的改善。未来的研究需要使用更大的队列和更明确控制的同步社会心理训练，以进一步探索初步的调节效应，还包括自闭症谱系中未被充分研究的人群，例如同时患有智力障碍的儿童。服用催产素 4 周后，学龄 ASD 儿童的社会反应能力并没有因治疗而得到改善。未来的研究有必要进一步探索催产素给药与刺激社会交流行为的有针对性的社会心理培训相结合的临床疗效。