Effect of intranasal oxytocin on the core social symptoms of autism spectrum disorder: a randomized clinical trial
Effect of intranasal oxytocin on the core social symptoms of autism spectrum disorder: a randomized clinical trial
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DOI：
10.1038/s41380-018-0097-2
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发表时间：
2020-08-01
影响因子：
11
通讯作者：
Kosaka, Hirotaka
中科院分区：
文献类型：
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作者：
Yamasue, Hidenori;Okada, Takashi;Kosaka, Hirotaka
虽然小规模的研究已经描述了催产素对自闭症谱系障碍（ASD）社交缺陷的影响，但还没有进行大规模的研究。在这项在日本进行的随机、平行组、多中心、安慰剂对照、双盲试验中，106名ASD个体（18-48岁）在2015年1月至2016年3月期间入组。参与者被随机分配到6周鼻内催产素（48 IU/天，n = 53）或安慰剂（n = 53）组。对103名参与者进行了分析。由于催产素降低了主要终点，自闭症诊断观察计划（ADOS）的互惠性，（从8.5到7.7;P < .001），但安慰剂也降低了评分（8.3至7.2;P < .001），未发现组间差异（效应量-0.08; 95%CI，-0.46至0.31;P = 0.69）;然而，与安慰剂组相比，催产素组的血浆催产素仅从基线至终点升高（效应量-1.12; -1.53至-0.70;P < .0001）。在次要终点中，与安慰剂（2.0至1.8;P = .43）相比，催产素减少了ADOS重复行为（2.0至1.5;P < .0001）（效应量0.44; 0.05至0.83;P = .026）。此外，与安慰剂组（45.7 - 40.4;P = 0.25）相比，催产素组（41.2 - 52.3;P = 0.03）增加了另一个次要终点，即注视社会相关区域的持续时间（效应量0.55; 0.10 - 1.0;P = 0.018）。未观察到其他次要终点的显著影响。两组之间不良事件的发生率没有显著差异，尽管一名参与者在催产素给药期间经历了暂时性男性乳房发育。根据目前的研究结果，我们不能推荐以当前剂量和持续时间单独持续鼻内催产素治疗成年男性高功能ASD的核心社会症状，尽管这项大规模试验表明催产素治疗ASD重复行为的可能性。
Although small-scale studies have described the effects of oxytocin on social deficits in autism spectrum disorder (ASD), no large-scale study has been conducted. In this randomized, parallel-group, multicenter, placebo-controlled, double-blind trial in Japan, 106 ASD individuals (18-48 y.o.) were enrolled between Jan 2015 and March 2016. Participants were randomly assigned to a 6-week intranasal oxytocin (48IU/day,n = 53) or placebo (n = 53) group. One-hundred-three participants were analyzed. Since oxytocin reduced the primary endpoint, Autism Diagnostic Observation Schedule (ADOS) reciprocity, (from 8.5 to 7.7;P < .001) but placebo also reduced the score (8.3 to 7.2;P < .001), no between-group difference was found (effect size -0.08; 95% CI, -0.46 to 0.31;P = .69); however, plasma oxytocin was only elevated from baseline to endpoint in the oxytocin-group compared with the placebo-group (effect size -1.12; -1.53 to -0.70;P < .0001). Among the secondary endpoints, oxytocin reduced ADOS repetitive behavior (2.0 to 1.5;P < .0001) compared with placebo (2.0 to 1.8;P = .43) (effect size 0.44; 0.05 to 0.83;P = .026). In addition, the duration of gaze fixation on socially relevant regions, another secondary endpoint, was increased by oxytocin (41.2 to 52.3;P = .03) compared with placebo (45.7 to 40.4;P = .25) (effect size 0.55; 0.10 to 1.0;P = .018). No significant effects were observed for the other secondary endpoints. No significant difference in the prevalence of adverse events was observed between groups, although one participant experienced temporary gynecomastia during oxytocin administration. Based on the present findings, we cannot recommend continuous intranasal oxytocin treatment alone at the current dose and duration for treatment of the core social symptoms of high-functioning ASD in adult men, although this large-scale trial suggests oxytocin's possibility to treat ASD repetitive behavior.