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Circulating Inflammation Markers Partly Explain the Link Between the Dietary Inflammatory Index and Depressive Symptoms

  • Gialluisi, Alessandro1
  • Santonastaso, Federica2
  • Bonaccio, Marialaura1
  • Bracone, Francesca1
  • Shivappa, Nitin3, 4
  • Hebert, James R3, 4
  • Cerletti, Chiara1
  • Donati, Maria Benedetta1
  • de Gaetano, Giovanni1
  • Iacoviello, Licia1, 2
  • 1 Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli , (Italy)
  • 2 Department of Medicine and Surgery, University of Insubria, Varese , (Italy)
  • 3 Cancer Prevention and Control Program and Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC
  • 4 Department of Nutrition, Connecting Health Innovations LLC, Columbia, SC
Published Article
Journal of Inflammation Research
Publication Date
Sep 28, 2021
DOI: 10.2147/JIR.S312925
PMID: 34611421
PMCID: PMC8487281
PubMed Central
  • Original Research


Background Depression is a mood disorder characterized by a high rate of resistance to pharmacological treatments, which has often been linked to chronic inflammation. This can be influenced by different environmental factors, in particular pro-inflammatory diets. However, a mediating role of circulating inflammation has never been observed. Aim To test the association between a dietary inflammatory index (DII®) and continuous depressive symptoms (adapted version of PHQ9) in an Italian population cohort (N=13,301), along with potential explanatory effect of a composite index (INFLA-score) based on four circulating inflammatory biomarkers: C-reactive protein, granulocyte-to-lymphocyte ratio, platelet and white blood cell counts. Results Significant positive associations were observed between DII and total depressive symptoms (standardized β (SE) = 0.038 (0.005), p < 0.001), and with two factors tagging somatic (0.012 (0.003), p < 0.001) and cognitive symptoms (0.012 (0.003), p < 0.001), after adjustment for different potential confounders (socioeconomic status, chronic health conditions and lifestyles). These associations were about twice as strong in women than in men. INFLA-score explained a small but significant proportion of the association with total depressive symptoms (0.90–2.30%, p < 0.05), which was mainly driven by granulocyte-to-lymphocyte ratio (1.18–1.65%). This effect was even stronger for the somatic (2.66–4.66%) but not for the cognitive factor (0%). Conclusion These findings support a strong link between inflammatory diet and depression, especially with somatic symptoms and within women. Moreover, they provide novel evidence for a potential explanatory role of circulating inflammation in this association, suggesting new paths for prevention and treatment of major and atypical depression.

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