Center for Developmental Psychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium.
Nat Commun. 2024 Jan 2;15(1):58. doi: 10.1038/s41467-023-44334-4.
Clinical efficacy of intranasal administration of oxytocin is increasingly explored in autism spectrum disorder, but to date, the biological effects of chronic administration regimes on endogenous oxytocinergic function are largely unknown. Here exploratory biological assessments from a completed randomized, placebo-controlled trial showed that children with autism (n = 79, 16 females) receiving intranasal oxytocin for four weeks (12 IU, twice daily) displayed significantly higher salivary oxytocin levels 24 hours after the last oxytocin nasal spray administration, but no longer at a four-week follow up session. Regarding salivary oxytocin receptor gene (OXTR) epigenetics (DNA-methylation), oxytocin-induced reductions in OXTR DNA-methylation were observed, suggesting a facilitation of oxytocin receptor expression in the oxytocin compared to the placebo group. Notably, heightened oxytocin levels post-treatment were significantly associated with reduced OXTR DNA-methylation and improved feelings of secure attachment. These findings indicate that four weeks of chronic oxytocin administration stimulated the endogenous oxytocinergic system in children with autism.
鼻内给予催产素在自闭症谱系障碍中的临床疗效越来越受到关注，但迄今为止，慢性给药方案对内源性催产素能功能的生物学影响在很大程度上尚不清楚。本研究从一项已完成的随机、安慰剂对照试验中进行了探索性生物学评估，结果显示，接受鼻内催产素治疗 4 周（12IU，每日两次）的自闭症儿童（n=79，16 名女性）在最后一次催产素鼻喷给药后 24 小时唾液催产素水平显著升高，但在 4 周随访时不再升高。关于唾液催产素受体基因（OXTR）表观遗传学（DNA 甲基化），观察到催产素诱导的 OXTR DNA 甲基化减少，提示与安慰剂组相比，催产素组的催产素受体表达得到促进。值得注意的是，治疗后催产素水平升高与 OXTR DNA 甲基化减少和安全感依恋感改善显著相关。这些发现表明，4 周的慢性催产素给药刺激了自闭症儿童的内源性催产素能系统。
