The neurodevelopmental model of schizophrenia is supported by multi-level impairments shared among schizophrenia and neurodevelopmental disorders. Despite schizophrenia and typical neurodevelopmental disorders, i.e., autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), as disorders of brain dysconnectivity, no study has ever elucidated whether whole-brain white matter (WM) tracts integrity alterations overlap or diverge between these three disorders. Moreover, whether the linked dimensions of cognition and brain metrics per the Research Domain Criteria framework cut across diagnostic boundaries remains unknown. We aimed to map deviations from normative ranges of whole-brain major WM tracts for individual patients to investigate the similarity and differences among schizophrenia (281 patients subgrouped into the first-episode, subchronic and chronic phases), ASD (175 patients), and ADHD (279 patients). Sex-specific WM tract normative development was modeled from diffusion spectrum imaging of 626 typically developing controls (5–40 years). There were three significant findings. First, the patterns of deviation and idiosyncrasy of WM tracts were similar between schizophrenia and ADHD alongside ASD, particularly at the earlier stages of schizophrenia relative to chronic stages. Second, using the WM deviation patterns as features, schizophrenia cannot be separated from neurodevelopmental disorders in the unsupervised machine learning algorithm. Lastly, the canonical correlation analysis showed schizophrenia, ADHD, and ASD shared linked cognitive dimensions driven by WM deviations. Together, our results provide new insights into the neurodevelopmental facet of schizophrenia and its brain basis. Individual’s WM deviations may contribute to diverse arrays of cognitive function along a continuum with phenotypic expressions from typical neurodevelopmental disorders to schizophrenia.

精神分裂症的神经发育模型得到精神分裂症和神经发育障碍共有的多层次损伤的支持。尽管精神分裂症和典型的神经发育障碍，即自闭症谱系障碍 (ASD) 和注意力缺陷/多动障碍 (ADHD)，作为大脑连接障碍的障碍，但没有研究阐明全脑白质 (WM) 束完整性改变是否重叠或在这三种疾病之间发生分歧。此外，根据研究领域标准框架，认知和大脑指标的相关维度是否跨越诊断边界仍然未知。我们旨在绘制个体患者全脑主要 WM 束正常范围的偏差，以研究精神分裂症（281 名患者分为首发期、亚慢性期和慢性期）、ASD（175 名患者）和 ADHD 之间的相似性和差异性（279 名患者）。根据 626 个典型发育对照（5-40 岁）的扩散光谱成像模拟了性别特异性 WM 束规范发育。有三个重要发现。首先，WM 束的偏差和特质模式在精神分裂症和 ADHD 以及 ASD 之间相似，特别是在精神分裂症相对于慢性阶段的早期阶段。其次，使用 WM 偏差模式作为特征，在无监督机器学习算法中不能将精神分裂症与神经发育障碍分开。最后，典型相关分析显示精神分裂症、ADHD 和 ASD 共享由 WM 偏差驱动的相关认知维度。总之，我们的结果为精神分裂症的神经发育方面及其大脑基础提供了新的见解。从典型的神经发育障碍到精神分裂症，个体的 WM 偏差可能会导致一系列不同的认知功能以及表型表达的连续体。