4.7 Article

Low-grade inflammation and endothelial dysfunction predict four-year risk and course of depressive symptoms: The Maastricht study

Journal

BRAIN BEHAVIOR AND IMMUNITY
Volume 97, Issue -, Pages 61-67

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2021.06.013

Keywords

Low-grade inflammation; Endothelial dysfunction; Depressive disorder; Prospective; PHQ-9; Etiology

Funding

  1. European Regional Development Fund via OP-Zuid
  2. Province of Limburg
  3. Dutch Ministry of Economic Affairs [31O.041]
  4. Stichting De Weijerhorst (Maastricht, The Netherlands)
  5. Pearl String Initiative Diabetes (Amsterdam, the Netherlands)
  6. CARIM School for Cardiovascular Diseases (Maastricht, the Netherlands)
  7. CAPHRI Care and Public Health Research Institute (Maastricht, the Netherlands)
  8. NUTRIM School for Nutrition and Translational Research in Metabolism (Maastricht, the Netherlands)
  9. Health Foundation Limburg (Maastricht, the Netherlands)
  10. Perimed (Jadrfalla, Sweden)
  11. Janssen-Cilag B.V. (Tilburg, the Netherlands)
  12. Novo Nordisk Farma B.V. (Alphen aan den Rijn, the Netherlands)
  13. Sanofi-Aventis Netherlands B.V. (Gouda, the Netherlands)
  14. Cardiovascular Center (CVC, Maastricht, the Netherlands)
  15. Stichting Annadal (Maastricht, the Netherlands)

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In this study, low-grade inflammation (LGI) and endothelial dysfunction (ED) were found to be associated with incident depressive symptoms, with the latter association being substantially mediated by LGI. ED was further associated with a persistent course of depressive symptoms, while LGI was associated with remission of depression symptoms. These results suggest a temporal, vascular contribution of both LGI and ED to the etiology and chronicity of depressive symptoms.
Background: Low-grade inflammation (LGI) and endothelial dysfunction (ED) might play a key role in the development of depression. We investigated the associations and mediation of LGI and ED with four-year incidence and course of depressive symptoms (remitted, recurrent or persistent). Design, setting, participants, measurements: In this prospective cohort study (mean age 59.6 +/- 8.2 years, 48.9% women, 26.6% diabetes by design), Cox and multinomial regression analyses, adjusted for age, sex, educational level and diabetes status were used to investigate the associations of LGI and ED with onset and course of depressive symptoms as assessed by the PHQ-9 questionnaire. Results: During 10,847 person-years of follow-up, 264 participants developed incident depression. Higher levels of LGI (OR [95%CI] per SD 1.32[1.16-1.49], p < 0.001) and ED (1.26[1.11-1.43], p < 0.001) were associated with incident depressive symptoms. In mediation analysis, 60% of the total effect of ED with incident depressive symptoms could be attributed to LGI. 76 out of 2637 participants had a persistent course of depressive symptoms. Higher levels of LGI (1.75[1.40-2.19], p < 0.001) and ED (1.33[1.04-1.71], p = 0.021) were associated with a persistent course of depressive symptoms. Higher ED was more strongly associated with persistent depressive symptoms (1.33[1.04-1.71], p = 0.021), while LGI was associated with remission of depression symptoms. Conclusions: LGI and ED were both associated with incident depressive symptoms, where the latter association was substantially mediated by LGI. ED was further associated with a persistent course of depressive symptoms, while LGI was not. These results suggest a temporal, vascular contribution of both LGI and ED to the etiology and chronicity of depressive symptoms.

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