Department of Radiology, The Fourth Affiliated Hospital of Anhui Medical University, Hefei 230012, China.
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Cereb Cortex. 2023 Feb 20;33(5):2328-2341. doi: 10.1093/cercor/bhac211.
Brain structural damage is a typical feature of schizophrenia. Investigating such disease phenotype in patients with drug-naive first-episode schizophrenia (DFSZ) may exclude the confounds of antipsychotics and illness chronicity. However, small sample sizes and marked clinical heterogeneity have precluded definitive identification of gray matter volume (GMV) changes in DFSZ as well as their underlying genetic mechanisms. Here, GMV changes in DFSZ were assessed using a neuroimaging meta-analysis of 19 original studies, including 605 patients and 637 controls. Gene expression data were derived from the Allen Human Brain Atlas and processed with a newly proposed standardized pipeline. Then, we used transcriptome-neuroimaging spatial correlations to identify genes associated with GMV changes in DFSZ, followed by a set of gene functional feature analyses. Meta-analysis revealed consistent GMV reduction in the right superior temporal gyrus, right insula and left inferior temporal gyrus in DFSZ. Moreover, we found that these GMV changes were spatially correlated with expression levels of 1,201 genes, which exhibited a wide range of functional features. Our findings may provide important insights into the genetic mechanisms underlying brain morphological abnormality in schizophrenia.
脑结构损伤是精神分裂症的典型特征。在未经药物治疗的首发精神分裂症（DFSZ）患者中研究这种疾病表型可以排除抗精神病药物和疾病慢性的混杂因素。然而，样本量小和显著的临床异质性使得 DFSZ 中的灰质体积（GMV）变化及其潜在的遗传机制无法得到明确的确定。在这里，我们通过对 19 项原始研究的神经影像学荟萃分析，评估了 DFSZ 中的 GMV 变化，这些研究包括 605 名患者和 637 名对照。基因表达数据来源于 Allen 人类大脑图谱，并使用新提出的标准化管道进行处理。然后，我们使用转录组-神经影像学空间相关性来识别与 DFSZ 中 GMV 变化相关的基因，随后进行了一系列基因功能特征分析。荟萃分析显示 DFSZ 中右侧颞上回、右侧岛叶和左侧颞下回的 GMV 减少一致。此外，我们发现这些 GMV 变化与 1201 个基因的表达水平具有空间相关性，这些基因表现出广泛的功能特征。我们的研究结果可能为精神分裂症大脑形态异常的遗传机制提供重要的见解。
