Stanford University, CA.
Stanford University, CA.
J Am Acad Child Adolesc Psychiatry. 2019 Aug;58(8):787-798. doi: 10.1016/j.jaac.2018.09.425. Epub 2018 Oct 9.
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).
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).
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) 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.
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.
传统上，大脑的性别差异被视为二元的。我们提出了新的证据，表明大脑性别分化的连续测量可以解释精神病理学中的性别差异。大脑性别特征的分化程度（即更常见于一种性别的特征）可能使个体更容易出现性别偏向的精神病理学，并且也可能受到基因组的影响。我们假设，具有女性偏向分化评分的个体将具有更大的女性偏向的精神病理学（例如，焦虑和抑郁等内化症状），而具有男性偏向分化评分的个体将具有更大的男性偏向的精神病理学（例如，破坏性行为等外化症状）。
我们使用从基因型和表型数据库中获取的费城神经发育队列数据库，计算了性别分化指标，这是一种从成像参与者的多模态脑成像数据（磁共振成像[MRI]/扩散 MRI）中提取的个体性别分化特征的连续数据驱动计算（n=866，407 名女性和 459 名男性）。
在男性个体中，更高的分化评分与更高水平的外化症状相关（r=0.119，p=0.016）。分化指标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:PARD3B 和 Chromosome15:rs73442006:HCN4 的女性个体中达到了全基因组关联研究的显著水平（p<5∗10）。
性别分化指标提供了量化男性和女性大脑特征的初始拓扑结构。这种证明人类大脑的性别可以连续概念化的方法，既对精神病理学的表现有影响，也对大脑与可能与大脑分化相关的遗传变异体的关系有影响。
