Does the moderator matter? Identification of multiple moderators of the association between peripheral inflammatory markers and depression severity in a large racially diverse community cohort

Neuropsychopharmacology. 2022 Aug;47(9):1693-1701. doi: 10.1038/s41386-022-01341-1. Epub 2022 May 20.


Depressive symptomology has been linked to low-grade peripheral inflammatory markers (PIMs), specifically C-reactive protein (CRP) and white blood cell count (WBC). However, such associations may be affected by multiple moderators (including race/ethnicity), though few well-powered and racially diverse studies have examined this. We examined 31 moderators of PIM-depression relationships in a large racially diverse cohort (n = 21,570). We also examined if associations between PIM and depression severity were dependent on clinical cutpoints for moderate depressive symptoms and elevated CRP. We found several positive moderators of PIM-depression relationships for both WBC and CRP: ongoing medication use (antidepressant, statin, or any prescription drug), presence of sleep concerns, and poor health status (β's = 0.06-0.21, p's < 0.05). For both WBC and CRP, individuals of non-Hispanic White race/ethnicity were found to have stronger PIM-depression associations overall relative to minoritized groups (B's = 0.14 to 1.01, p's < 0.05). For CRP, stronger PIM-depression relationships existed for individuals with moderate (or greater) depression severity or elevated CRP (B's = 0.27 to 0.49, p's < 0.05). Thus, a wide range of moderators appears to affect PIM-depression associations. These results could help identify participants with strong coupling of PIM-depression severity, to guide future research and personalized treatments for depression and to indicate gaps in the applicability of widely referenced theoretical models among racial/ethnic minoritized groups.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antidepressive Agents* / therapeutic use
  • Biomarkers
  • C-Reactive Protein / metabolism
  • Depression* / drug therapy
  • Humans
  • White People


  • Antidepressive Agents
  • Biomarkers
  • C-Reactive Protein