Longitudinal transcriptome-wide gene expression analysis of sleep deprivation treatment shows involvement of circadian genes and immune pathways
Jerome C. Foo,
Stephanie H. Witt,
Carolina De La Torre,
Steffen Conrad von Heydendorff,
Christian C Witt,
Posted 10 May 2019
bioRxiv DOI: 10.1101/628172 (published DOI: 10.1038/s41398-019-0671-7)
Posted 10 May 2019
Background Therapeutic sleep deprivation (SD) rapidly induces robust, transient antidepressant effects in a large proportion of major mood disorder patients suffering from a depressive episode, but underlying biological factors remain poorly understood. Research suggests that these patients may have altered circadian molecular genetic ‘clocks’ and that SD functions through ‘resetting’ dysregulated genes; additional factors may be involved, warranting further investigation. Leveraging advances in microarray technology enabling the transcriptome-wide assessment of gene expression, this study aimed to examine gene expression changes accompanying SD and recovery sleep in patients suffering from an episode of depression. Methods Patients (N=78) and controls (N=15) underwent SD, with blood taken at the same time of day before, after one night of SD and after recovery sleep. A transcriptome-wide gene-by-gene approach was used, with a targeted look also taken at circadian genes. Furthermore, gene set enrichment, and longitudinal gene set analyses including the time point after recovery sleep, were conducted. Results Circadian genes were significantly affected by SD, with patterns suggesting that molecular clocks of responders and non-responders, as well as patients and controls respond differently to chronobiologic stimuli. Notably, gene set analyses revealed a strong widespread effect of SD on pathways involved in immune function and inflammatory response, such as those involved in cytokine and especially in interleukin signalling. Longitudinal gene set analyses showed that in responders these pathways were upregulated after SD; in non-responders, little response was observed. Conclusions Our findings emphasize the close relationship between circadian, immune and sleep systems and their link to etiology of depression at the transcriptomic level.
- Downloaded 353 times
- Download rankings, all-time:
- Site-wide: 43,210 out of 84,359
- In epidemiology: 689 out of 1,556
- Year to date:
- Site-wide: 41,409 out of 84,359
- Since beginning of last month:
- Site-wide: 55,271 out of 84,359
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!