Department of Radiology, The Second Affiliated Hospital of Shandong First Medical University, No. 706 Taishan Street, Tai'an 271000, China.
Department of Radiology, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 619 Changcheng Road, Tai'an 271016, China.
Cereb Cortex. 2023 Jun 8;33(12):7540-7552. doi: 10.1093/cercor/bhad059.
Bipolar disorder (BD) is a heritable psychiatric disorder with a complex etiology that is often associated with cortical alterations. Morphometric studies in adults with BD are well established; however, few have examined cortical changes in pediatric BD (PBD). Additionally, the correlation between cortical thickness (CT) changes in PBD and gene expression remains elusive. Here, we performed an integrative analysis using neuroimaging data from 58 PBD individuals and the Allen human brain transcriptomic dataset. We applied partial least squares (PLS) regression analysis on structural MRI data and cortical gene expression, enrichment and specific cell type analysis to investigate the genetic correlates of CT alterations in PBD. We found the expression levels of PBD-related genes showed significant spatial correlations with CT differences. Further enrichment and specific cell type analysis revealed that transcriptome signatures associated with cortical thinning were enriched in synaptic signaling, ion channels, astrocytes, and excitatory neurons. Neurodevelopmental patterns of these genes showed significantly increased expression in the cerebellum, cortex, and subcortical regions during the adolescence period. These results highlight neurodevelopmental transcriptional changes could account for most of the observed correlations with CT differences in PBD, which offers a novel perspective to understand biological conceptualization mechanisms for the genetic correlates of CT alterations.
双相情感障碍（BD）是一种遗传性精神疾病，其病因复杂，常与皮质改变有关。成人 BD 的形态计量学研究已经很成熟；然而，很少有研究检查儿科 BD（PBD）中的皮质变化。此外，PBD 中 CT 变化与基因表达之间的相关性仍不清楚。在这里，我们使用来自 58 名 PBD 个体的神经影像学数据和 Allen 人类大脑转录组数据集进行了综合分析。我们对结构 MRI 数据和皮质基因表达应用偏最小二乘（PLS）回归分析、富集分析和特定细胞类型分析，以研究 PBD 中 CT 改变的遗传相关性。我们发现 PBD 相关基因的表达水平与 CT 差异具有显著的空间相关性。进一步的富集和特定细胞类型分析表明，与皮质变薄相关的转录组特征在突触信号、离子通道、星形胶质细胞和兴奋性神经元中富集。这些基因的神经发育模式在青春期期间在小脑、皮质和皮质下区域表现出明显增加的表达。这些结果强调了神经发育转录变化可能解释了 PBD 中与 CT 差异相关的大多数观察到的相关性，为理解 CT 改变的遗传相关性的生物学概念化机制提供了新的视角。
