Brain-based sex differences in autism spectrum disorder across the lifespan: A systematic review of structural MRI, fMRI, and DTI findings.
Brain-based sex differences in autism spectrum disorder across the lifespan: A systematic review of structural MRI, fMRI, and DTI findings.
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DOI：
10.1016/j.nicl.2021.102719
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Braden BB
中科院分区：
文献类型：
--
作者：
Walsh MJM;Wallace GL;Gallegos SM;Braden BB
有证据表明，ASD中基于神经成像的性别差异具有年龄依赖性。大多数研究在年龄上都失败了，可能掩盖了性别对诊断的影响。性别诊断的影响重叠的地区，表现出典型的性二型性。研究结果讨论的背景下，遗传和内分泌性别对大脑的影响。未来的研究将受益于大样本研究中的寿命方法。患有自闭症谱系障碍（ASD）的女性长期以来一直被神经科学研究所忽视，但新出现的证据表明，她们表现出不同的表型轨迹和与年龄相关的大脑差异。与性有关的生物因素（例如，激素、基因）可能在ASD病因学中起作用，并已显示影响神经发育轨迹。因此，有必要采用寿命方法来了解ASD中基于大脑的性别差异。对ASD中基于MRI的性别差异进行了系统性综述，以阐明整个寿命期间的变化，并为女性ASD的生物标志物发现提供信息。我们通过两次数据库检索确定了文章。50项研究符合标准，并进行了综合审查。我们发现，跨研究表达可复制的性别诊断差异的区域与神经型队列中显示性别差异的区域重叠。此外，调查年龄相关的大脑差异的研究表明，ASD女性有不同的神经发育模式。青年和成人研究的定性比较也支持这一假设。然而，许多研究在年龄上崩溃，这可能掩盖了差异。此外，越来越多的证据支持女性对ASD的保护作用，尽管只有一项研究检查了与"保护"有关的大脑回路。当与更广泛的文献综合时，ASD中基于大脑的性别差异可能来自各种来源，包括在早期发育，青春期和激素转换的其他寿命窗口中参与大脑“男性化”和“女性化”的遗传和内分泌过程。此外，与性相关的生物学可能与外周过程相互作用，特别是压力轴和大脑觉醒系统，在患有自闭症谱系障碍的男性和女性中产生不同的神经发育模式。未来对ASD中基于神经成像的性别差异的研究将受益于良好对照和多变量研究中的寿命方法。行为，性激素和ASD大脑发育之间的可能关系在很大程度上尚未得到研究。
Evidence suggests neuroimaging-based sex differences in ASD are age-dependent. Most studies collapse across age, possibly masking sex-by-diagnosis effects. Sex-by-diagnosis effects overlap with regions showing typical sexual dimorphism. Findings discussed in the context of genetic and endocrine sex effects on the brain. Future research would benefit from a lifespan approach in large-sample studies. Females with autism spectrum disorder (ASD) have been long overlooked in neuroscience research, but emerging evidence suggests they show distinct phenotypic trajectories and age-related brain differences. Sex-related biological factors (e.g., hormones, genes) may play a role in ASD etiology and have been shown to influence neurodevelopmental trajectories. Thus, a lifespan approach is warranted to understand brain-based sex differences in ASD. This systematic review on MRI-based sex differences in ASD was conducted to elucidate variations across the lifespan and inform biomarker discovery of ASD in females We identified articles through two database searches. Fifty studies met criteria and underwent integrative review. We found that regions expressing replicable sex-by-diagnosis differences across studies overlapped with regions showing sex differences in neurotypical cohorts. Furthermore, studies investigating age-related brain differences across a broad age-span suggest distinct neurodevelopmental patterns in females with ASD. Qualitative comparison across youth and adult studies also supported this hypothesis. However, many studies collapsed across age, which may mask differences. Furthermore, accumulating evidence supports the female protective effect in ASD, although only one study examined brain circuits implicated in “protection.” When synthesized with the broader literature, brain-based sex differences in ASD may come from various sources, including genetic and endocrine processes involved in brain “masculinization” and “feminization” across early development, puberty, and other lifespan windows of hormonal transition. Furthermore, sex-related biology may interact with peripheral processes, in particular the stress axis and brain arousal system, to produce distinct neurodevelopmental patterns in males and females with ASD. Future research on neuroimaging-based sex differences in ASD would benefit from a lifespan approach in well-controlled and multivariate studies. Possible relationships between behavior, sex hormones, and brain development in ASD remain largely unexamined.
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