Importance Many mental disorders emerge during adolescence, which may reflect a cost of the potential for brain plasticity offered during this period. Brain dysconnectivity has been proposed as a common factor across diagnostic categories.

Objective To investigate the hypothesis that brain dysconnectivity is a transdiagnostic phenotype in adolescence with increased susceptibility and symptoms of psychiatric disease.

Design, Setting, and Participants We investigated clinical symptoms as well as cognitive function in 6487 individuals aged 8 to 21 years from November 1, 2009, to November 30, 2011, in the Philadelphia Neurodevelopmental Cohort and analyzed diffusion magnetic resonance imaging brain scans for 748 of the participants.

Main Outcomes and Measures Independent component analysis was used to derive dimensional psychopathology scores, and genome-wide complex trait analysis was used to estimate its heritability. Multimodal fusion simultaneously modeled contributions of the diffusion magnetic resonance imaging metrics fractional anisotropy, mean diffusivity, radial diffusivity, L1 (the principal diffusion tensor imaging eigen value), mode of anisotropy, as well as dominant and secondary fiber orientations, and structural connectivity density, and their association with general psychopathology and cognition.

Results Machine learning with 10-fold cross-validation and permutation testing in 729 individuals (aged 8 to 22 years; mean [SD] age, 15.1 [3.3] years; 343 females [46%]) revealed significant association with general psychopathology levels (r = 0.24, P < .001) and cognition (r = 0.39, P < .001). A brain white matter pattern reflecting frontotemporal connectivity and crossing fibers in the uncinate fasciculus was the most associated feature for both traits. Univariate analysis across a range of clinical domains and cognitive test scores confirmed its transdiagnostic importance. Both the general psychopathology (16%; SE, 0.095; P = .05) and cognitive (18%; SE, 0.09; P = .01) factor were heritable and showed a negative genetic correlation.

Conclusion and relevance Dimensional and heritable general cognitive and psychopathology factors are associated with specific patterns of white matter properties, suggesting that dysconnectivity is a transdiagnostic brain-based phenotype in individuals with increased susceptibility and symptoms of psychiatric disorders.

重要性 青春期期间会出现许多精神障碍，这可能反映出在此期间可能提供的大脑可塑性的成本。已经提出脑部不连通性是诊断类别中的共同因素。

目的 探讨假说：大脑不连通性是青春期的一种可转诊的表型，其易感性和精神疾病症状增加。

设计，环境和参与者 从2009年11月1日至2011年11月30日，我们在费城神经发育队列研究了6487名8至21岁的个体的临床症状和认知功能，并分析了748例弥散磁共振成像的脑部扫描的参与者。

主要结果和措施使用 独立成分分析得出维度心理病理学评分，并使用全基因组复杂性状分析评估其遗传力。多模态融合同时模拟了扩散磁共振成像指标分数各向异性，平均扩散率，径向扩散率，L1（主扩散张量成像本征值），各向异性的模式以及主要和次要纤维方向以及结构连接密度的贡献，以及它们与一般心理病理学和认知的关系。

结果 729名个体（年龄为8至22岁；平均[SD]年龄为15.1 [3.3]岁； 343名女性[46％]）中的机器学习以及10倍交叉验证和排列测试表明，其与一般的心理病理学水平密切相关（r  = 0.24，P  <.001）和认知（r  = 0.39，P  <.001）。这两种性状最相关的特征是反映白额束中额颞连接和交叉纤维的脑白质模式。对一系列临床领域和认知测验分数的单变量分析证实了其转诊的重要性。一般的精神病理学（16％; SE，0.095; P  = 0.05）和认知（18％; SE，0.09; P = .01）因子是可遗传的，并且显示出负的遗传相关性。

结论与相关性 维度和可遗传的一般认知和心理病理因素与白质特性的特定模式相关，这表明，在患有精神疾病的易感性和症状增加的个体中，失联是一种基于脑的经诊断性表型。