Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305;
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305.
Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):8119-8124. doi: 10.1073/pnas.1705521114. Epub 2017 Jul 10.
Autism spectrum disorder (ASD) is characterized by core social deficits. Prognosis is poor, in part, because existing medications target only associated ASD features. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may be a blood-based biomarker of social functioning and a possible treatment for ASD. However, prior OXT treatment trials have produced equivocal results, perhaps because of variability in patients' underlying neuropeptide biology, but this hypothesis has not been tested. Using a double-blind, randomized, placebo-controlled, parallel design, we tested the efficacy and tolerability of 4-wk intranasal OXT treatment (24 International Units, twice daily) in 32 children with ASD, aged 6-12 y. When pretreatment neuropeptide measures were included in the statistical model, OXT compared with placebo treatment significantly enhanced social abilities in children with ASD [as measured by the trial's primary outcome measure, the Social Responsiveness Scale (SRS)]. Importantly, pretreatment blood OXT concentrations also predicted treatment response, such that individuals with the lowest pretreatment OXT concentrations showed the greatest social improvement. OXT was well tolerated, and its effects were specific to social functioning, with no observed decrease in repetitive behaviors or anxiety. Finally, as with many trials, some placebo-treated participants showed improvement on the SRS. This enhanced social functioning was mirrored by a posttreatment increase in their blood OXT concentrations, suggesting that increased endogenous OXT secretion may underlie this improvement. These findings indicate that OXT treatment enhances social abilities in children with ASD and that individuals with pretreatment OXT signaling deficits may stand to benefit the most from OXT treatment.
自闭症谱系障碍（ASD）的特征是核心社交缺陷。预后较差，部分原因是现有药物仅针对相关的 ASD 特征。新出现的证据表明，神经肽催产素（OXT）可能是社交功能的基于血液的生物标志物，也是 ASD 的潜在治疗方法。然而，先前的 OXT 治疗试验产生了模棱两可的结果，这可能是由于患者潜在的神经肽生物学的变异性，但这一假设尚未得到检验。使用双盲、随机、安慰剂对照、平行设计，我们测试了 32 名 6-12 岁 ASD 儿童接受 4 周鼻内 OXT 治疗（24 国际单位，每日两次）的疗效和耐受性。当将预处理神经肽测量值纳入统计模型时，与安慰剂治疗相比，OXT 显著增强了 ASD 儿童的社交能力[如试验的主要结局测量，社交反应量表（SRS）]。重要的是，预处理血液 OXT 浓度也预测了治疗反应，即预处理 OXT 浓度最低的个体表现出最大的社交改善。OXT 耐受性良好，其作用特异性于社交功能，没有观察到重复行为或焦虑的减少。最后，与许多试验一样，一些接受安慰剂治疗的参与者在 SRS 上的表现有所改善。这种增强的社交功能反映在治疗后他们的血液 OXT 浓度增加，表明增加内源性 OXT 分泌可能是这种改善的基础。这些发现表明 OXT 治疗增强了 ASD 儿童的社交能力，并且预处理 OXT 信号缺陷的个体可能最受益于 OXT 治疗。
