Association of Heritable Cognitive Ability and Psychopathology With White Matter Properties in Children and Adolescents
Association of Heritable Cognitive Ability and Psychopathology With White Matter Properties in Children and Adolescents
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DOI：
10.1001/jamapsychiatry.2017.4277
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发表时间：
2018-03-01
期刊：
影响因子：
25.8
通讯作者：
Westlye, Lars T.
中科院分区：
文献类型：
--
作者：
Alnaes, Dag;Kaufmann, Tobias;Westlye, Lars T.
许多精神障碍出现在青春期，这可能反映了在这一时期提供的大脑可塑性潜力的成本。脑连接障碍已被认为是跨诊断类别的共同因素。目的探讨脑连接障碍是一种青春期易患性和精神疾病症状增加的跨诊断表型。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中调查了6487名年龄在8至21岁的个体的临床症状和认知功能，并分析了748名参与者的弥散磁共振成像脑部扫描。主要结果和测量方法采用独立成分分析得出维度精神病理评分，并采用全基因组复杂性状分析估计其遗传力。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、平均扩散系数、径向扩散系数、L1（主要扩散张量成像特征值）、各向异性模式、主要和次要纤维取向、结构连接密度的贡献，以及它们与一般精神病理和认知的关系。结果对729例个体（年龄8 ~ 22岁，平均[SD]年龄15.1[3.3]岁，女性343例[46%]）进行10倍交叉验证和排列检验，结果显示机器学习与一般精神病理水平（r = 0.24, P < .001）和认知水平（r = 0.39, P < .001）有显著相关性。反映额颞叶连通性和钩状束交叉纤维的脑白质模式是这两种特征最相关的特征。跨一系列临床领域和认知测试分数的单变量分析证实了其跨诊断的重要性。一般精神病理因素（16%，SE, 0.095, P = 0.05）和认知因素（18%，SE, 0.09, P = 0.01）均为遗传因子，呈负相关。维度和遗传的一般认知和精神病理因素与白质特性的特定模式相关，表明连接障碍是精神障碍易感性和症状增加的个体的一种跨诊断的基于大脑的表型。
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.