Association Between the Probability of Autism Spectrum Disorder and Normative Sex-Related Phenotypic Diversity in Brain Structure (Retracted Article)
Association Between the Probability of Autism Spectrum Disorder and Normative Sex-Related Phenotypic Diversity in Brain Structure (Retracted Article)
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DOI：
10.1001/jamapsychiatry.2016.3990
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发表时间：
2017-04-01
期刊：
影响因子：
25.8
通讯作者：
Murphy, Declan G. M.
中科院分区：
文献类型：
--
作者：
Ecker, Christine;Andrews, Derek S.;Murphy, Declan G. M.
重要性
自闭症谱系障碍（ASD）在男性中的发病率是女性的2到5倍。虽然ASD在男性中患病率偏高可能部分由临床症状的性别差异所解释，但病因学模型表明，生物学上的男性表型比女性表型具有更高的ASD内在风险。据我们所知，这一假设从未被直接验证过，调节男性和女性ASD风险的神经生物学机制仍然难以捉摸。
目的
研究ASD的概率与大脑结构中正常的性别相关表型多样性的函数关系，并确定与ASD低概率或高概率相关的性别相关神经解剖学变异模式。
设计、环境和参与者
本研究对98名右利手、高功能的成年ASD患者和98名年龄在18到42岁的匹配的神经正常对照个体进行了横断面样本研究。采用多变量概率分类方法，基于通过磁共振成像在神经正常对照中评估的皮质厚度测量值，建立了一个生物学性别的预测模型。随后将该标准模型应用于ASD患者。研究时间为2005年6月至2009年10月，分析时间为2015年6月至2016年7月。
主要结果和测量指标
样本和人群中ASD概率估计值与大脑结构中正常的性别相关多样性的函数关系，以及男性和女性中与ASD低概率或高概率相关的神经解剖学模式。
结果
在98名ASD患者中，49名男性，49名女性，平均（标准差）年龄为26.88（7.18）岁。在98名对照中，51名男性，47名女性，平均（标准差）年龄为27.39（6.44）岁。ASD的样本概率随着男性神经解剖学大脑表型的预测概率显著增加。例如，具有更男性典型大脑解剖模式的生物学女性个体患ASD的可能性显著（即3倍）高于具有典型女性大脑表型的生物学女性个体（分别为P = 0.72对0.24；卡方(2)(1)=20.26；P < 0.001；P值差异为0.48；95%置信区间为0.29 - 0.68）。这一发现意味着人群患病率的估计变异分别从0.2%到1.3%。此外，携带ASD低概率或高概率的神经解剖学变异模式具有性别特异性（例如，在颞下回区域，ASD在男性和女性中有不同的神经生物学基础）。
结论和相关性
这些发现强调在确定个体患ASD的风险时需要考虑正常的性别相关表型多样性，并为介导ASD患病率性别差异的神经生物学机制提供了重要的新见解。
IMPORTANCE Autism spectrum disorder (ASD) is 2 to 5 times more common in male individuals than in female individuals. While the male preponderant prevalence of ASD might partially be explained by sex differences in clinical symptoms, etiological models suggest that the biological male phenotype carries a higher intrinsic risk for ASD than the female phenotype. To our knowledge, this hypothesis has never been tested directly, and the neurobiological mechanisms that modulate ASD risk in male individuals and female individuals remain elusive.OBJECTIVES To examine the probability of ASD as a function of normative sex-related phenotypic diversity in brain structure and to identify the patterns of sex-related neuroanatomical variability associated with low or high probability of ASD.DESIGN, SETTING, AND PARTICIPANTS This study examined a cross-sectional sample of 98 right-handed, high-functioning adults with ASD and 98 matched neurotypical control individuals aged 18 to 42 years. A multivariate probabilistic classification approach was used to develop a predictive model of biological sex based on cortical thickness measures assessed via magnetic resonance imaging in neurotypical controls. This normative model was subsequently applied to individuals with ASD. The study dates were June 2005 to October 2009, and this analysis was conducted between June 2015 and July 2016.MAIN OUTCOMES AND MEASURES Sample and population ASD probability estimates as a function of normative sex-related diversity in brain structure, as well as neuroanatomical patterns associated with low or high ASD probability in male individuals and female individuals.RESULTS Among the 98 individuals with ASD, 49 were male and 49 female, with a mean (SD) age of 26.88 (7.18) years. Among the 98 controls, 51 were male and 47 female, with a mean (SD) age of 27.39 (6.44) years. The sample probability of ASD increased significantly with predictive probabilities for the male neuroanatomical brain phenotype. For example, biological female individuals with a more male-typic pattern of brain anatomy were significantly (ie, 3 times) more likely to have ASD than biological female individuals with a characteristically female brain phenotype (P = .72 vs .24, respectively; chi(2)(1) = 20.26; P < .001; difference in P values, 0.48; 95% CI, 0.29-0.68). This finding translates to an estimated variability in population prevalence from 0.2% to 1.3%, respectively. Moreover, the patterns of neuroanatomical variability carrying low or high ASD probability were sex specific (eg, in inferior temporal regions, where ASD has different neurobiological underpinnings in male individuals and female individuals).CONCLUSIONS AND RELEVANCE These findings highlight the need for considering normative sex-related phenotypic diversity when determining an individual's risk for ASD and provide important novel insights into the neurobiological mechanisms mediating sex differences in ASD prevalence.