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Reconsidering the reasons for heightened inflammation in major depressive disorder.

Authors
  • Palmos, Alish B1
  • Chung, Raymond1
  • Frissa, Souci2
  • Goodwin, Laura3
  • Hotopf, Matthew4
  • Hatch, Stephani L2
  • Breen, Gerome5
  • Powell, Timothy R6
  • 1 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
  • 2 Health Services & Population Research, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
  • 3 Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Department of Psychological Sciences, University of Liverpool, Liverpool, UK.
  • 4 Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; South London and Maudsley NHS Foundation Trust, London, UK; National Institute for Health Research Biomedical Research Centre, Institute of Psychiatry, Psychology and Neuroscience at the Maudsley Hospital and King's College London, UK.
  • 5 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre, Institute of Psychiatry, Psychology and Neuroscience at the Maudsley Hospital and King's College London, UK.
  • 6 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. Electronic address: [email protected]
Type
Published Article
Journal
Journal of affective disorders
Publication Date
Mar 01, 2021
Volume
282
Pages
434–441
Identifiers
DOI: 10.1016/j.jad.2020.12.109
PMID: 33422819
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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). 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. 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. The study utilized a cross-sectional design with a moderately sized sample. 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. Copyright © 2020. Published by Elsevier B.V.

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