OBJECTIVE Sex differences in the brain are traditionally treated as binary. We present new evidence that a continuous measure of sex differentiation of the brain can explain sex differences in psychopathology. The degree of sex-differentiated brain features (ie, features that are more common in one sex) may predispose individuals toward sex-biased psychopathology and may also be influenced by the genome. We hypothesized that individuals with a female-biased differentiation score would have greater female-biased psychopathology (internalizing symptoms, such as anxiety and depression), whereas individuals with a male-biased differentiation score would have greater male-biased psychopathology (externalizing symptoms, such as disruptive behaviors). METHOD Using the Philadelphia Neurodevelopmental Cohort database acquired from database of Genotypes and Phenotypes, we calculated the sex differentiation measure, a continuous data-driven calculation of each individual's degree of sex-differentiating features extracted from multimodal brain imaging data (magnetic resonance imaging [MRI] /diffusion MRI) from the imaged participants (n = 866, 407 female and 459 male). RESULTS In male individuals, higher differentiation scores were correlated with higher levels of externalizing symptoms (r = 0.119, p = .016). The differentiation measure reached genome-wide association study significance (p < 5∗10-8) in male individuals with single nucleotide polymorphisms Chromsome5:rs111161632:RASGEF1C and Chromosome19:rs75918199:GEMIN7, and in female individuals with Chromosome2:rs78372132:PARD3B and Chromosome15:rs73442006:HCN4. CONCLUSION The sex differentiation measure provides an initial topography of quantifying male and female brain features. This demonstration that the sex of the human brain can be conceptualized on a continuum has implications for both the presentation of psychopathology and the relation of the brain with genetic variants that may be associated with brain differentiation.

中文翻译：

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超越性别的二进制分类：脑性别差异，精神病理学和基因型的检查。

目的大脑中的性别差异传统上被视为二进制。我们提供了新的证据，即连续测量大脑的性别分化可以解释心理病理学中的性别差异。性别差异性脑部特征的程度（即一种性别中更常见的特征）可能使个体倾向于性别偏向的心理病理学，并且也可能受到基因组的影响。我们假设具有女性偏见得分的个体会有更大的女性偏向心理病理学（内在症状，例如焦虑和抑郁），而具有男性偏见得分的个体会有更大的男性偏向心理病理学（外部症状，例如作为破坏性行为）。方法使用从基因型和表型数据库中获得的费城神经发育队列数据库，我们计算了性别差异测度，这是从多模态脑成像数据（磁共振成像[MRI]）中提取的每个人的性别差异特征程度的连续数据驱动计算/扩散MRI）（n = 866、407女和459男）。结果在男性个体中，较高的分化评分与较高水平的外在症状相关（r = 0.119，p = .016）。在具有单核苷酸多态性Chromsome5：rs111161632：RASGEF1C和Chromosome19：rs75918199：GEMIN7的男性个体以及具有Chromosome2：rs78372132的女性个体中，该分化测定达到了全基因组关联研究的意义（p <5 * 10-8）。PARD3B和染色体15：rs73442006：HCN4。结论性别差异测量提供了量化男性和女性大脑特征的初步地形。可以在一个连续统上概念化人脑性别的论证对心理病理学的表现以及脑与可能与脑分化相关的遗传变异的关系都有影响。