Abstract：
Early-onset Schizophrenia (EOS) is a profoundly progressive psychiatric disorder characterized by both positive and negative symptoms, whose pathogenesis is influenced by genes, environment and brain structure development. In this study, the MIND (Morphometric Inverse Divergence) network was employed to explore the relationship between morphological similarity and specific transcriptional expression patterns in EOS patients. This study involved a cohort of 187 participants aged between 7 and 17 years, consisting of 97 EOS patients and 90 healthy controls (HC). Multiple morphological features were used to construct the MIND network for all participants. Furthermore, we explored the associations between MIND network and brain-wide gene expression in EOS patients through partial least squares (PLS) regression, shared genetic predispositions with other psychiatric disorders, functional enrichment of PLS weighted genes, as well as transcriptional signature assessment of cell types, cortical layers, and developmental stages. The MIND showed similarity differences in the orbitofrontal cortex, pericalcarine cortex, lingual gyrus, and multiple networks in EOS patients compared to HC. Moreover, our exploration revealed a significant overlap of PLS2 weighted genes linking to EOS-related MIND differences and the dysregulated genes reported in other psychiatric diseases. Interestingly, genes correlated with MIND changes (PLS2-) exhibited a significant enrichment not only in metabolism-related pathways, but also in specific astrocytes, cortical layers (specifically layer I and III), and posterior developmental stages (late infancy to young adulthood stages). However, PLS2+ genes were primarily enriched in synapses signaling-related pathways and early developmental stages (from early-mid fetal to neonatal early infancy) but not in special cell types or layers. These findings provide a novel perspective on the intricate relationship between macroscopic morphometric structural abnormalities and microscopic transcriptional patterns during the onset and progression of EOS.
摘要：
早发性精神分裂症（EOS）是一种严重的进行性精神疾病，其特征是阳性和阴性症状。其发病机制受基因影响，环境和大脑结构发育。在这项研究中,MIND（形态计量逆发散）网络用于探索EOS患者的形态相似性与特定转录表达模式之间的关系。这项研究涉及187名年龄在7至17岁之间的参与者，由97名EOS患者和90名健康对照（HC）组成。使用多种形态特征来构建所有参与者的MIND网络。此外，我们通过偏最小二乘(PLS)回归研究了EOS患者的MIND网络与全脑基因表达之间的关联，与其他精神疾病有共同的遗传倾向，PLS加权基因的功能富集，以及细胞类型的转录特征评估，皮质层，和发展阶段。MIND显示眶额皮质的相似性差异，果皮皮质，舌回,与HC相比，EOS患者的多个网络。此外，我们的研究发现,与EOS相关的MIND差异相关的PLS2加权基因和其他精神疾病中报道的失调基因存在显著重叠.有趣的是,与MIND变化相关的基因（PLS2-）不仅在代谢相关途径中表现出显著的富集，而且在特定的星形胶质细胞中，皮质层（特别是I层和III层），和后发育阶段（婴儿期晚期到成年期）。然而,PLS2+基因主要富集在突触信号传导相关途径和早期发育阶段(从胎儿早期中期到新生儿早期婴儿期),但不富集在特殊细胞类型或层中。这些发现为EOS的发生和发展过程中宏观形态结构异常与微观转录模式之间的复杂关系提供了新的视角。
