Mood disorders represent a major cause of morbidity and mortality worldwide but the brain-related molecular pathophysiology in mood disorders remains largely undefined. Because the anterior insula is reduced in volume in patients with mood disorders, RNA was extracted from the anterior insula postmortem anterior insula of mood disorder samples and compared with unaffected controls for RNA-sequencing identification of differentially expressed genes (DEGs) in (a) bipolar disorder (BD; n = 37) versus (vs.) controls (n = 33), and (b) major depressive disorder (MDD n = 30) vs. controls, and (c) low vs. high axis I comorbidity (a measure of cumulative psychiatric disease burden). Given the regulatory role of transcription factors (TFs) in gene expression via specific-DNA-binding domains (motifs), we used JASPAR TF binding database to identify TF-motifs. We found that DEGs in BD vs. controls, MDD vs. controls, and high vs. low axis I comorbidity were associated with TF-motifs that are known to regulate expression of toll-like receptor genes, cellular homeostatic-control genes, and genes involved in embryonic, cellular/organ, and brain development. Robust imaging-guided transcriptomics by using meta-analytic imaging results to guide independent postmortem dissection for RNA-sequencing was applied by targeting the gray matter volume reduction in the anterior insula in mood disorders, to guide independent postmortem identification of TF motifs regulating DEG. Our findings of TF-motifs that regulate the expression of immune, cellular homeostatic-control, and developmental genes provide novel information about the hierarchical relationship between gene regulatory networks, the TFs that control them, and proximate underlying neuroanatomical phenotypes in mood disorders.

情绪障碍是全世界发病和死亡的主要原因，但情绪障碍中与大脑相关的分子病理生理学在很大程度上仍不清楚。由于情绪障碍患者的前岛叶体积减小，因此从情绪障碍样本死后的前岛叶中提取 RNA，并与未受影响的对照进行比较，以进行 RNA 测序鉴定（a）双相情感障碍中的差异表达基因（DEG）障碍（BD； n = 37）与对照（ n = 33）相比，（b）重度抑郁症（MDD n = 30）与对照相比，（c）低与高轴 I 合并症（a累积精神疾病负担的衡量标准）。鉴于转录因子 (TF) 通过特定 DNA 结合域（基序）在基因表达中的调节作用，我们使用 JASPAR TF 结合数据库来识别 TF 基序。我们发现 BD 与对照、MDD 与对照以及高轴 I 合并症与低轴 I 合并症中的 DEG 与已知调节 Toll 样受体基因、细胞稳态控制基因和基因表达的 TF 基序相关。参与胚胎、细胞/器官和大脑发育。通过使用荟萃分析成像结果指导独立的死后解剖进行 RNA 测序，应用稳健的成像引导转录组学，以情绪障碍中前岛叶灰质体积减少为目标，指导独立的死后鉴定调节 DEG 的 TF 基序。 我们对调节免疫、细胞稳态控制和发育基因表达的 TF 基序的发现提供了有关基因调控网络、控制它们的 TF 以及情绪障碍中的邻近潜在神经解剖表型之间的层次关系的新信息。