Increased circulating IL-18 levels in severe mental disorders indicate systemic inflammasome activation
By
Attila Szabo,
Kevin S O`Connell,
Thor Ueland,
Mashhood A Sheikh,
Ingrid Agartz,
Dimitrios Andreou,
Pal Aukrust,
Birgitte Boye,
Erlend Boen,
Ole Kristian Drange,
Torbjorn Elvsashagen,
John Abel Engh,
Sigrun Hope,
Margrethe Collier Hoegh,
Inge Joa,
Erik Johnsen,
Rune Andreas Kroken,
Trine Vik Lagerberg,
Tove Lekva,
Ulrik Fredrik Malt,
Ingrid Melle,
Gunnar Morken,
Terje Naerland,
Vidar Martin Steen,
Kjetil Sorensen,
Kirsten Wedervang-Resell,
Melissa Auten Weibell,
Lars T. Westlye,
Nils Eiel Steen,
Ole A. Andreassen,
Srdjan Djurovic
Posted 31 May 2021
medRxiv DOI: 10.1101/2021.05.28.21258013
Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) that are part of a psychosis continuum, and dysregulated innate immune responses have been suggested to be involved in their pathophysiology. However, disease-specific immune mechanisms in SMI are not known yet. Recently, dyslipidemia has been linked to systemic inflammasome activation, and elevated atherogenic lipid ratios have been shown to correlate with circulating levels of inflammatory biomarkers in SMI. It is, however, not yet known if increased systemic cholesterol load leads to inflammasome activation in these patients. Methods: We tested the hypothesis that patients with SCZ and BD display higher circulating levels compared to healthy individuals of key members of the IL-18 system using a large patient cohort (n=1632; including 737 SCZ and 895 BD), and healthy controls (CTRL; n=1070). In addition, we assessed associations with coronary artery disease risk factors in SMI, focusing on relevant inflammasome-related, neuroendocrine, and lipid markers. Results: We report higher baseline levels of circulating IL-18 system components (IL-18, IL-18BPA) as well as increased expression of inflammasome-related genes (NLRP3 and NLRC4) in the blood of patients relative to CTRL. We demonstrate a cholesterol dyslipidemia pattern in psychotic disorders, and report correlations between levels of blood cholesterol species and the expression of inflammasome system elements in SMI. Conclusions: Based on these results, we suggest a link between systemic inflammasome activation/dysregulation and cholesterol load in SMI. Our findings further the understanding of possible underlying inflammatory and metabolic mechanisms and may expose important therapeutic targets in SMI.
Download data
- Downloaded 264 times
- Download rankings, all-time:
- Site-wide: 149,103
- In psychiatry and clinical psychology: 814
- Year to date:
- Site-wide: 100,015
- Since beginning of last month:
- Site-wide: 84,061
Altmetric data
Downloads over time
Distribution of downloads per paper, site-wide
PanLingua
News
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 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!