Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.
Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.
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DOI：
10.1038/tp.2016.152
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发表时间：
2016-08-23
影响因子：
6.8
通讯作者：
Wada Y
中科院分区：
文献类型：
--
作者：
Kosaka H;Okamoto Y;Munesue T;Yamasue H;Inohara K;Fujioka T;Anme T;Orisaka M;Ishitobi M;Jung M;Fujisawa TX;Tanaka S;Arai S;Asano M;Saito DN;Sadato N;Tomoda A;Omori M;Sato M;Okazawa H;Higashida H;Wada Y
最近的研究表明，长期服用催产素可以缓解自闭症谱系障碍（ASD）的症状；然而，影响其功效的因素仍不清楚。我们对患有高功能 ASD 的年轻人进行了一项单中心 2 期、试点、随机、双盲、安慰剂对照、平行组临床试验，以确定催产素剂量和催产素受体的遗传背景是否影响催产素疗效。该试验包括双盲（12 周）、开放标签（12 周）和随访阶段（8 周）。为了检查剂量依赖性，在双盲阶段，60 名参与者被随机分配到高剂量（每天 32IU）或低剂量鼻内催产素（每天 16IU）或安慰剂组。接下来，我们测量了催产素受体基因 (OXTR) 中的单核苷酸多态性 (SNP)。在意向治疗人群中，施用催产素后结果没有改善。然而，在男性参与者中，高剂量组（而非低剂量组）的临床总体印象改善（CGI-I）评分显着高于安慰剂组。此外，我们还检查了 CGI-I 评分中反映的催产素功效是否受到男性参与者的估计每日剂量和 OXTR 多态性的影响。我们发现每天 >21 IU 的催产素比每天 ⩽21 IU 的催产素更有效，并且 OXTR (rs6791619) 中的 SNP 预测每天 ⩽21 IU 催产素治疗的 CGI-I 评分。没有发生严重不良事件。这些结果表明，长期服用催产素对患有高功能自闭症谱系障碍的年轻男性的疗效取决于催产素剂量和催产素受体的遗传背景，这有助于催产素治疗自闭症谱系障碍的有效性。
Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.
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影响因子：
6.2
作者：
Anagnostou E;Soorya L;Chaplin W;Bartz J;Halpern D;Wasserman S;Wang AT;Pepa L;Tanel N;Kushki A;Hollander E
通讯作者：
Hollander E
影响因子：
11.3
作者：
Hofmann SG;Fang A;Brager DN
通讯作者：
Brager DN
影响因子：
3.9
作者：
Dadds, Mark R.;MacDonald, Elayne;Brennan, John
通讯作者：
Brennan, John
影响因子：
7.6
作者：
Guastella, Adam J.;Gray, Kylie M.;Einfeld, Stewart L.
通讯作者：
Einfeld, Stewart L.
影响因子：
10.6
作者：
Feifel, David;Macdonald, Kai;Hadley, Allison
通讯作者：
Hadley, Allison