Deciphering the Heterogeneity of Schizophrenia: A Multimodal and Multivariate Neuroimaging Framework for Unveiling Brain-Symptom Relationships and Underlying Subtypes

作者：Luli Wei, Wei Liu, Xin Li, Yu Zhang, Yun Luo, Yingying Xie, Liyuan Lin, Zhongyu Chang, Xiaotong Du, Xiaotong Wei, Yi Ji, Zhen Zhao, Meng Liang, Hao Ding, Liping Liu, Xijin Wang, Lina Wang, Hongjun Tian, Gang Wang, Bin Zhang, Juanjuan Ren, Chen Zhang, Chunshui Yu, Wen Qin · 发表于：Schizophrenia Bulletin · 年份：2025 · DOI：10.1093/schbul/sbaf037 · 被引用次数：3 · 研究领域：Functional Brain Connectivity Studies、Schizophrenia research and treatment、Advanced Neuroimaging Techniques and Applications

BACKGROUND AND HYPOTHESIS: Schizophrenia manifests large heterogeneities in either symptoms or brain abnormalities. However, the neurobiological basis of symptomatic diversity remains poorly understood. We hypothesized that schizophrenia's diverse symptoms arise from the interplay of structural and functional alterations across multiple brain regions, rather than isolated abnormalities in a single area. STUDY DESIGN: A total of 495 schizophrenia patients and 507 healthy controls from 8 sites were recruited. Five symptomatic dimensions of schizophrenia patients were derived from the Positive and Negative Syndrome Scale. Multivariate canonical correlation analysis was introduced to identify symptom-related multimodal magnetic resonance imaging composite indicators (MRICIs) derived from gray matter volume, functional connectivity strength, and white matter fractional anisotropy. The intergroup differences in MRICIs were compared, and the paired-wise correlations between symptom dimensions and MRICIs were resolved. Finally, K-means clustering was used to identify the underlying biological subtypes of schizophrenia based on MRICIs. STUDY RESULTS: Canonical correlation analysis identified 15 MRICIs in schizophrenia that were specifically contributed by the neuroimaging measures of multiple regions, respectively. These MRICIs can effectively characterize the complexity of symptoms, showing correlations within and across symptom dimensions, and were consistent across both first-episo...