Quantitative facial expression analysis revealed the efficacy and time course of oxytocin in autism
Quantitative facial expression analysis revealed the efficacy and time course of oxytocin in autism
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定量面部表情分析揭示了催产素治疗自闭症的功效和时间进程
DOI：
10.1093/brain/awz126
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发表时间：
2019
期刊：
影响因子：
14.5
通讯作者：
（他28名22番目）Yamamoto Maeri
中科院分区：
文献类型：
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作者：
Owada Keiho;（他28名22番目）Yamamoto Maeri
催产素治疗自闭症谱系障碍的单次给药和重复给药之间的疗效差异使研究人员假设，疗效的时程变化是由肽激素的重复给药引起的。然而，缺乏对自闭症谱系障碍核心症状的可重复，客观和定量测量，这使得难以检查疗效的潜在时间过程变化。我们通过对自闭症谱系障碍核心症状的可重复、客观和定量测量来验证这一假设。我们检查了在半结构化社交互动期间录制的视频，这些视频作为单点探索性（n =18，受试者内交叉设计）和多点验证性（n =106，平行组设计），双盲，安慰剂对照的6周试验的主要结局，这些试验在患有自闭症谱系障碍的成年男性中重复鼻内给予催产素（48 IU/天）。主要结果是自闭症诊断观察表中可重复部分的客观量化面部表情强度的统计代表值：中性面部表情概率密度函数的最大概率（即众数）和众数的自然对数以及快乐表情概率密度函数的众数的自然对数。我们最近的研究表明，这些指标的增加特征自闭症面部表情，与神经型个体相比。目前的结果显示，在探索性试验（效应量，-0.57; 95%CI，-1.27至0.13;P =0.023）和验证性试验（-0.41;-0.62至0.20;P <0.001）中，与安慰剂相比，催产素持续且显著地降低了中性面部表情概率密度函数的众数增加。时间进程与在验证性试验中发现，催产素对中性面部表情的概率密度函数的众数的自然对数的有效性经统计学处理，2周时疗效最佳（P <0.001，Cohen'sd =−0.78; 95% CI，−1.21至−0.35）和4周时疗效恶化（P =0.042，Cohen'sd =−0.46; 95% CI，−0.90至−0.01）和6周（P =0.10，Cohen'sd=-0.35; 95% CI，-0.77至0.08），而疗效在治疗后2周保持不变（即8周）（P <0.001，Cohen'sd =−1.24; 95%CI，−1.71至−0.78）。定量面部表情分析成功地验证了重复催产素对自闭症个体面部表情的积极影响，并证明了疗效的时间过程变化。目前的研究结果支持进一步开发催产素治疗的优化方案。
Discrepancies in efficacy between single-dose and repeated administration of oxytocin for autism spectrum disorder have led researchers to hypothesize that time-course changes in efficacy are induced by repeated administrations of the peptide hormone. However, repeatable, objective, and quantitative measurement of autism spectrum disorder’s core symptoms are lacking, making it difficult to examine potential time-course changes in efficacy. We tested this hypothesis using repeatable, objective, and quantitative measurement of the core symptoms of autism spectrum disorder. We examined videos recorded during semi-structured social interaction administered as the primary outcome in single-site exploratory (n =18, crossover within-subjects design) and multisite confirmatory (n =106, parallel-group design), double-blind, placebo-controlled 6-week trials of repeated intranasal administrations of oxytocin (48 IU/day) in adult males with autism spectrum disorder. The main outcomes were statistical representative values of objectively quantified facial expression intensity in a repeatable part of the Autism Diagnostic Observation Schedule: the maximum probability (i.e. mode) and the natural logarithm of mode on the probability density function of neutral facial expression and the natural logarithm of mode on the probability density function of happy expression. Our recent study revealed that increases in these indices characterize autistic facial expression, compared with neurotypical individuals. The current results revealed that oxytocin consistently and significantly decreased the increased natural logarithm of mode on the probability density function of neutral facial expression compared with placebo in exploratory (effect-size, −0.57; 95% CI, −1.27 to 0.13;P =0.023) and confirmatory trials (−0.41; −0.62 to −0.20;P <0.001). A significant interaction between time-course (at baseline, 2, 4, 6, and 8 weeks) and the efficacy of oxytocin on the natural logarithm of mode on the probability density function of neutral facial expression was found in confirmatory trial (P <0.001).Post hocanalyses revealed maximum efficacy at 2 weeks (P <0.001, Cohen’sd =−0.78; 95% CI, −1.21 to −0.35) and deterioration of efficacy at 4 weeks (P =0.042, Cohen’sd =−0.46; 95% CI, −0.90 to −0.01) and 6 weeks (P =0.10, Cohen’sd= −0.35; 95% CI, −0.77 to 0.08), while efficacy was preserved at 2 weeks post-treatment (i.e. 8 weeks) (P <0.001, Cohen’sd =−1.24; 95% CI, −1.71 to −0.78). Quantitative facial expression analyses successfully verified the positive effects of repeated oxytocin on autistic individuals’ facial expressions and demonstrated a time-course change in efficacy. The current findings support further development of an optimized regimen of oxytocin treatment.