Gene expression is associated with brain function of insomnia disorder, rather than brain structure.

Previous research has found brain structural and functional abnormalities in patients with insomnia disorder (ID). However, the relationship between brain abnormalities in ID and brain gene expression is unclear. This study explored the relationship between gene expression and brain structural or functional abnormalities in ID, and we validated the reliability of the results with two independent datasets (discover dataset: healthy control (HC) = 129, ID = 264; validation dataset: HC = 160, ID = 115). Brain imaging results show that ID has abnormal resting-state spontaneous activity, regional homogeneity, and widespread gray matter volume reduction compared to HC. The association analysis results with gene expression further revealed that brain function abnormalities in ID were significantly associated with gene expression, but structural abnormalities were not. This study establishes a link between transcriptional changes and brain functional abnormalities in ID, revealing a genetic basis that may involve several biological pathways. Specifically, these pathways include hormonal regulation of the hypothalamic-pituitary-adrenal (HPA) axis, which plays a crucial role in stress response and sleep regulation; ion transport across membranes, vital for neuronal communication; and inhibitory neuronal regulation, essential for maintaining normal brain function. Furthermore, the ID-related genes are enriched for brain tissue and cortical cells, emphasizing their relevance in understanding the biological underpinnings of ID.