Autism spectrum disorder (ASD) is more common in males than females and has been linked to male-typical behavior. Accordingly, the “Extreme Male Brain” hypothesis suggests that ASD is associated with an exaggeratedly male-typical brain. To test this hypothesis, we derived a data-driven measure of individual differences along a male–female dimension based on sex differences in subcortical brain shape (i.e., brain maleness) by training our algorithm on two population samples (Queensland Twin IMaging study and Human Connectome Project; combined N = 2153). We then applied this algorithm to two clinical datasets (Autism Brain Imaging Data Exchange I and II; ASD N = 1060; neurotypical controls N = 1166) to obtain a brain maleness score for each individual, representing maleness of their brain on a male–female continuum. Consistent with the Extreme Male Brain hypothesis, we found a higher mean brain maleness score in the ASD group than in controls (d = 0.20 [0.12–0.29]), parallel to higher scores for control males than control females (d = 1.17 [1.05–1.29]). Further, brain maleness was positively associated with autistic symptoms. We tested the possibility this finding was driven by the ASD group's larger brains than controls (d = 0.17 [0.08–0.25]), given that males had larger brains than females (d = 0.96 [0.84–1.07]). Indeed, after adjusting for differences in brain size, the brain maleness difference between the ASD group and controls disappeared, and no association with autistic symptoms remained (after controlling for multiple comparisons), suggesting greater maleness of the autistic brain is driven by brain size. Brain maleness may be influenced by the same factors that influence brain size.

中文翻译：

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测试极端男性大脑假设：自闭症谱系障碍是否与更典型的男性大脑有关？

自闭症谱系障碍 (ASD) 在男性中比女性更常见，并且与男性典型行为有关。因此，“极端男性大脑”假设表明 ASD 与夸张的男性典型大脑有关。为了验证这一假设，我们通过在两个群体样本（昆士兰双胞胎成像研究和人类Connectome 项目；合并N  = 2153）。然后，我们将该算法应用于两个临床数据集（自闭症脑成像数据交换 I 和 II；ASD N  = 1060；神经典型控制N = 1166）以获得每个人的大脑男性性分数，代表他们大脑在男性 - 女性连续体上的男性性。与极端男性大脑假设一致，我们发现 ASD 组的平均大脑男性评分高于对照组（d  = 0.20 [0.12-0.29]），同时对照男性的得分高于对照女性（d  = 1.17 [1.05 –1.29]）。此外，大脑男性化与自闭症症状呈正相关。我们测试了这一发现是否由 ASD 组的大脑比对照组大 ( d  = 0.17 [0.08-0.25]) 驱动，因为男性的大脑比女性大 ( d = 0.96 [0.84–1.07]）。事实上，在调整大脑大小的差异后，ASD 组和对照组之间的大脑男性性差异消失了，并且与自闭症症状没有关联（在控制多重比较后），这表明自闭症大脑的更大男性性是由大脑大小驱动的。大脑男性化可能受到影响大脑大小的相同因素的影响。