Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression

Joseph R. Scarpa, Peng Jiang, Vance D. Gao, Karrie Fitzpatrick, Joshua Millstein, Christopher Olker, Anthony Gotter, Christopher J. Winrow, John J. Renger, Andrew Kasarskis*, Fred W. Turek, Martha H. Vitaterna

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

To understand the transcriptomic organization underlying sleep and affective function, we studied a population of (C57BL/6J × 129S1/SvImJ) F2 mice by measuring 283 affective and sleep phenotypes and profiling gene expression across four brain regions. We identified converging molecular bases for sleep and affective phenotypes at both the single-gene and gene-network levels. Using publicly available transcriptomic datasets collected from sleep-deprived mice and patients with major depressive disorder (MDD), we identified three cortical gene networks altered by the sleep/wake state and depression. The network-level actions of sleep loss and depression were opposite to each other, providing a mechanistic basis for the sleep disruptions commonly observed in depression, as well as the reported acute antidepressant effects of sleep deprivation. We highlight one particular network composed of circadian rhythm regulators and neuronal activity–dependent immediate-early genes. The key upstream driver of this network, Arc, may act as a nexus linking sleep and depression. Our data provide mechanistic insights into the role of sleep in affective function and MDD.

Original languageEnglish (US)
Article numbereaat1294
JournalScience Advances
Volume4
Issue number7
DOIs
StatePublished - Jul 25 2018

ASJC Scopus subject areas

  • General

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    Scarpa, J. R., Jiang, P., Gao, V. D., Fitzpatrick, K., Millstein, J., Olker, C., Gotter, A., Winrow, C. J., Renger, J. J., Kasarskis, A., Turek, F. W., & Vitaterna, M. H. (2018). Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression. Science Advances, 4(7), [eaat1294]. https://doi.org/10.1126/sciadv.aat1294