Exploratory Analysis of Sleep Deprivation Effects on Gene Expression and Regional Brain Metabolism

Sleep deprivation affects cognitive performance and immune function, yet its mechanisms and biomarkers remain unclear. This study explored the relationships among gene expression, brain metabolism, sleep deprivation, and sex differences.

Fluorodeoxyglucose-18 positron emission tomography measured brain metabolism in regions of interest, and RNA analysis of blood samples assessed gene expression pre- and post-sleep deprivation. Mixed model regression and principal component analysis identified significant genes and regional metabolic changes.

There were 23 and 28 differentially expressed probe sets for the main effects of sex and sleep deprivation, respectively, and 55 probe sets for their interaction (FDR-corrected p < 0.05). Functional analysis of genes affected by sleep deprivation revealed pathway enrichment in nucleoplasm- and UBL conjugation-related genes. Genes with significant sex effects mapped to chromosomes Y and 19 (Benjamini-Hochberg FDR p < 0.05), with 11 genes (4%) and 29 genes (10.5%) involved, respectively. Differential gene expression highlighted sex-based differences in innate and adaptive immunity. For brain metabolism, sleep deprivation resulted in significant decreases in the left insula, left medial prefrontal cortex (BA32), left somatosensory cortex (BA1/2), and left motor premotor cortex (BA6) and increases in the right inferior longitudinal fasciculus, right primary visual cortex (BA17), right amygdala, left cerebellum, and bilateral pons.

Sleep deprivation broadly impacts brain metabolism, gene expression, and immune function, revealing cellular stress responses and hemispheric vulnerability. These findings enhance our understanding of the molecular and functional effects of sleep deprivation.