Intranasal administration of the neuropeptide oxytocin (IN-OT) is increasingly explored as a potential treatment for targeting the core symptoms of autism spectrum disorder (ASD). To date, however, the impact of multiple-dose IN-OT treatment on human neural circuitry is largely unknown, and also the possibility that long-term IN-OT use may induce long-lasting neural adaptations remains unexplored. Using a double-blind, randomized, placebo-controlled, between-subject design (including 38 adult men with ASD), this treatment-mechanism study showed that 4 weeks of daily oxytocin administration (24 IU/day) significantly altered intrinsic (resting-state fMRI) functional connectivity of the amygdala to core regions of the "social brain" (particularly orbitofrontal cortex and superior temporal sulcus) up to 4 weeks and 1 year post treatment. The neural adaptations in functional coupling of the amygdala to the orbitofrontal cortex were associated with reduced feelings of avoidance toward others and-at the trend level-reduced repetitive behaviors. These observations contribute to a deeper mechanistic understanding of the neural substrates that underlie behavioral effects of multiple-dose IN-OT treatment, and provide initial insights into the long-lasting neural consequences of chronic IN-OT use on amygdala circuitry. Future studies are however warranted to further elucidate the long-term impact of IN-OT treatment on human neural circuitry and its behavioral consequences.

中文翻译：

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催产素诱导自闭症杏仁核回路内的长期适应：一项随机安慰剂对照设计的治疗机制研究。

神经肽催产素 (IN-OT) 的鼻内给药越来越多地被探索为针对自闭症谱系障碍 (ASD) 核心症状的潜在治疗方法。然而，迄今为止，多剂量 IN-OT 治疗对人类神经回路的影响在很大程度上是未知的，而且长期使用 IN-OT 可能诱导长期神经适应的可能性仍有待探索。使用双盲、随机、安慰剂对照、受试者间设计（包括 38 名患有 ASD 的成年男性），这项治疗机制研究表明，每天给予 4 周催产素（24 IU/天）显着改变内在（静息-状态功能磁共振成像）杏仁核与“社交大脑”核心区域（特别是眶额皮质和颞上沟）的功能连接，最长可达治疗后 4 周和 1 年。杏仁核与眶额皮质功能耦合的神经适应与减少对他人的回避感有关，并且在趋势水平上减少重复行为。这些观察有助于更深入地了解构成多剂量 IN-OT 治疗的行为影响的神经基质，并初步了解长期使用 IN-OT 对杏仁核电路的长期神经后果。然而，未来的研究有必要进一步阐明 IN-OT 治疗对人类神经回路及其行为后果的长期影响。这些观察有助于更深入地了解构成多剂量 IN-OT 治疗的行为影响的神经基质，并初步了解长期使用 IN-OT 对杏仁核电路的长期神经后果。然而，未来的研究有必要进一步阐明 IN-OT 治疗对人类神经回路及其行为后果的长期影响。这些观察有助于更深入地了解构成多剂量 IN-OT 治疗的行为影响的神经基质，并初步了解长期使用 IN-OT 对杏仁核电路的长期神经后果。然而，未来的研究有必要进一步阐明 IN-OT 治疗对人类神经回路及其行为后果的长期影响。