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. 2025 Mar 24;11(1):50-71.
doi: 10.1159/000545461. eCollection 2025 Jan-Dec.

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

Lily Bai  1 , Ramanuj Sarkar  2 , Faith Lee  3 , Joseph Chong-Sang Wu  4 , Marquis P Vawter  5
Affiliations

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

Lily Bai et al. Complex Psychiatry. .

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Affymetrix microarray; Fluorodeoxyglucose-18 positron emission tomography; Psychomotor Vigilance; Stanford Sleepiness Scale.

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Conflict of interest statement

Marquis P. Vawter was a member of the journal’s Editorial Board at the time of submission.

Figures

Fig. 1.
Fig. 1.
a Gene expression PCA plots. b Brain region PCA plots.
Fig. 2.
Fig. 2.
PC2 versus PC3 scatter plot for ROI showing moderate grouping by sex.
Fig. 3.
Fig. 3.
Labeling of segmentation ROI (region of interest) with significant SD effect on plane 28. a Left somatosensory BA1/BA2. b Left medial prefrontal superior BA32. c Left primary motor premotor BA6/BA4. Red fill indicates increased metabolism following SD.
Fig. 4.
Fig. 4.
Labeling of segmentation ROI (region of interest) with significant SD effect on plane 40. a Left insula. b Right occipital cortex primary visual BA17. Red fill indicates increased metabolism following SD. Green fill indicates increased metabolism following SD. BA, Brodmann area.
Fig. 5.
Fig. 5.
Labeling of segmentation ROI (region of interest) with significant SD effect on plane 55. a Left cerebellum. b Right cerebellum. c Left pons. d Right pons. e Right amygdala. f Right inferior longitudinal. Green fill indicates increased metabolism following SD.
Fig. 6.
Fig. 6.
PC2 versus PC3 scatter plot for gene expression suggesting moderate grouping by sex.
See this image and copyright information in PMC

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