Department of Applied Psychology, Guangdong University of Finance and Economics, Guangzhou, China.
Key Laboratory of Brain, Cognition and Education Sciences (South China Normal University), Ministry of Education, Guangzhou, China.
Autism Res. 2021 Jun;14(6):1115-1126. doi: 10.1002/aur.2506. Epub 2021 Mar 26.
Autism spectrum disorder (ASD) is diagnosed much more often in males than females. This male predominance has prompted a number of studies to examine how sex differences are related to the neural expression of ASD. Different theories, such as the "extreme male brain" theory, the "female protective effect" (FPE) theory, and the gender incoherence (GI) theory, provide different explanations for the mixed findings of sex-related neural expression of ASD. This study sought to clarify whether either theory applies to the brain structure in individuals with ASD by analyzing a selective high-quality data subset from an open data resource (Autism Brain Imaging Data Exchange I and II) including 35 males/35 females with ASD and 86 male/86 female typical-controls (TCs). We examined the sex-related changes in ASD in gray matter asymmetry measures (i.e., asymmetry index, AI) derived from voxel-based morphometry using a 2 (diagnosis: ASD vs. TC) × 2 (sex: female vs. male) factorial design. A diagnosis-by-sex interaction effect was identified in the planum temporale/Heschl's gyrus: (i) compared to females, males exhibited decreased AI (indicating more leftward brain asymmetry) in the TC group, whereas AI was greater (indicating less leftward brain asymmetry) for males than for females in the ASD group; and (ii) females with ASD showed reduced AI (indicating more leftward brain asymmetry) compared to female TCs, whereas there were no differences between ASDs and TCs in the male group. This interaction pattern supports the FPE theory in showing greater brain structure changes (masculinization) in females with ASD. LAY SUMMARY: To understand the neural mechanisms underlying male predominance in autism spectrum disorder (ASD), we investigated the sex differences in ASD-related alterations in brain asymmetry. We found greater changes in females with ASD compared with males with ASD, revealing a female protective effect. These findings provide novel insights into the neurobiology of sex differences in ASD.
自闭症谱系障碍（ASD）在男性中比女性中更为常见。这种男性优势促使许多研究检查性别差异与 ASD 的神经表达有何关系。不同的理论，如“极端男性大脑”理论、“女性保护效应”（FPE）理论和性别不一致（GI）理论，为 ASD 的性别相关神经表达的混合发现提供了不同的解释。本研究通过分析来自开放数据资源（自闭症脑成像数据交换 I 和 II）的选择性高质量数据集，试图阐明这些理论中的任何一个是否适用于 ASD 个体的大脑结构，该数据集包括 35 名 ASD 男性/女性和 86 名 ASD 男性/女性典型对照组（TCs）。我们使用基于体素的形态计量学，通过 2（诊断：ASD 与 TC）×2（性别：女性与男性）因子设计，检查了 ASD 中与性别相关的灰质不对称性测量（即，不对称指数，AI）的变化。在颞叶平面/ Heschl 回中发现了诊断-性别相互作用效应：（i）与女性相比，TC 组中男性表现出 AI 降低（表明大脑左侧更为不对称），而 ASD 组中男性的 AI 大于女性；（ii）与女性 TCs 相比，ASD 女性的 AI 降低（表明大脑左侧更为不对称），而男性组中 ASDs 和 TCs 之间没有差异。这种相互作用模式支持 FPE 理论，表明 ASD 女性的大脑结构变化（男性化）更大。
自闭症谱系障碍（ASD）在男性中比女性中更为常见。为了了解 ASD 中男性优势的神经机制，我们研究了 ASD 相关大脑不对称性改变中的性别差异。我们发现，与 ASD 男性相比，ASD 女性的变化更大，这揭示了一种女性保护效应。这些发现为 ASD 中的性别差异的神经生物学提供了新的见解。
