The study investigates the effects of chronic intranasal oxytocin administration on the oxytocinergic system in children with autism. A randomized, placebo-controlled trial was conducted, where 79 children with autism (16 females) received either oxytocin (12 IU twice daily) or a placebo for four weeks. The results showed that children who received oxytocin had significantly higher salivary oxytocin levels 24 hours after the last administration but not at the four-week follow-up. Additionally, oxytocin-induced reductions in DNA methylation of the oxytocin receptor gene (OXTR) were observed, suggesting increased oxytocin receptor expression. Notably, higher oxytocin levels post-treatment were significantly associated with reduced OXTR DNA methylation and improved feelings of secure attachment. These findings indicate that chronic oxytocin administration stimulated the endogenous oxytocinergic system in children with autism, potentially through epigenetic mechanisms. The study highlights the importance of combining oxytocin administration with social stimulation for optimal therapeutic outcomes.The study investigates the effects of chronic intranasal oxytocin administration on the oxytocinergic system in children with autism. A randomized, placebo-controlled trial was conducted, where 79 children with autism (16 females) received either oxytocin (12 IU twice daily) or a placebo for four weeks. The results showed that children who received oxytocin had significantly higher salivary oxytocin levels 24 hours after the last administration but not at the four-week follow-up. Additionally, oxytocin-induced reductions in DNA methylation of the oxytocin receptor gene (OXTR) were observed, suggesting increased oxytocin receptor expression. Notably, higher oxytocin levels post-treatment were significantly associated with reduced OXTR DNA methylation and improved feelings of secure attachment. These findings indicate that chronic oxytocin administration stimulated the endogenous oxytocinergic system in children with autism, potentially through epigenetic mechanisms. The study highlights the importance of combining oxytocin administration with social stimulation for optimal therapeutic outcomes.