Reconsidering the reasons for heightened inflammation in major depressive disorder

Palmos, AB and Chung, R and Frissa, S and Goodwin, L and Hotopf, M and Hatch, SL and Breen, G and Powell, TR (2021) Reconsidering the reasons for heightened inflammation in major depressive disorder. Journal of Affective Disorders, 282. pp. 434-441. ISSN 0165-0327

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Background Increased circulating pro-inflammatory markers have repeatedly been associated with major depressive disorder (MDD). However, it remains unclear whether inflammation represents a causal mechanism for MDD, or whether the association is influenced by confounding factors such as body mass index (BMI). Methods To better understand this complex relationship, we generated polygenic risk scores (PRS) for MDD and BMI in a population cohort and attempted to isolate the impact these potential risk factors have on adulthood inflammation. Peripheral blood samples were collected as part of the South East London Community Health study, where we generated individualized PRS for MDD and BMI and quantified inflammatory markers using multiplex ELISA-based technology. We performed linear regressions to investigate the effects of PRS for MDD and BMI on inflammatory marker levels. Results Out of 35 inflammatory markers, we found a nominal effect of PRS for MDD on interleukin-10. We also found a significant positive effect of BMI on nine inflammatory markers, of which the two most strongly affected markers, interleukin-6 (IL-6) and C-reactive protein (CRP), were also nominally predicted by BMI PRS. Limitations The study utilized a cross-sectional design with a moderately sized sample. Conclusions Our findings suggest there may not be a shared genetic mechanism contributing to MDD and higher inflammatory marker levels. However, there may be shared genetic etiology between BMI and adulthood levels of CRP and IL-6. Therefore, polygenic risk scores for BMI may represent a useful indicator for heightened levels of inflammation in adulthood.

Item Type:
Journal Article
Journal or Publication Title:
Journal of Affective Disorders
Additional Information:
This is the author’s version of a work that was accepted for publication in journal of Affective Disorders. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Affective Disorders, 282, 2021 DOI: 10.1016/j.jad.2020.12.109
Uncontrolled Keywords:
?? clinical psychologypsychiatry and mental health ??
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Deposited On:
22 Feb 2022 11:25
Last Modified:
28 Nov 2023 11:38