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

Abstract

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.

Role of leukocytes, gender, and symptom domains in the influence of depression on hospitalization and mortality risk: Findings from the Moli-sani study

“…Similarly, the weight of somatic/neurovegetative (e.g., fatigue, psychomotor retardation, and altered appetite) and cognitive/psychological symptoms of depression (e.g., low mood, anhedonia, self-estimate, and suicidality) in this link is largely neglected, as well as the role of inflammation in these specific domains. Clarifying these aspects is of utter importance in light of two main findings: first, the association of somatic symptoms with circulating inflammation markers, consistently supported by independent studies ( 24 – 30 ), and second, a potential explanatory role of circulating inflammation in the relationship between the inflammatory potential of diet and the severity of depressive symptoms, which was prominent for somatic but not for cognitive symptoms, as supported by recent evidence ( 31 ). Here, we further explored the influence of depression severity on mortality and hospitalization risk for all and CVD causes by (i) analyzing potential effect modifications of gender, (ii) testing the independent influence of somatic and cognitive depressive symptoms on these clinical outcomes, and iii) examining in detail the potential mediation role of the single component biomarkers of INFLA score.…”

“…Here, we untangled the role of specific circulating inflammatory markers in the influence of depression severity on mortality and hospitalization risk, further elucidating differential associations within gender strata and with depressive symptom domains. Figure adapted from 31 .…”

“…To investigate specific domains of depressive symptoms, we derived latent variables tagging somatic (MR1) and cognitive symptoms (MR2), through a polychoric factor analysis, as described in ( 31 ). Briefly, using the psych package in R (see URLs), we first computed a polychoric correlation matrix of the available depression items and then derived two polychoric factors applying Oblimin (oblique) rotation.…”

“…Briefly, using the psych package in R (see URLs), we first computed a polychoric correlation matrix of the available depression items and then derived two polychoric factors applying Oblimin (oblique) rotation. The derived factors – with a Pearson’s r correlation of 0.72 – showed prominent loadings of neurovegetative/somatic and cognitive/affective symptoms, explaining 35.9 and 17.1% of their shared variance ( 31 ). Specifically, MR1 showed moderate to high loadings of impaired movements/speaking and concentration (0.8), altered appetite/eating, tiredness/low energy (0.7), and altered sleeping (0.6), while MR2 showed a high loading of anhedonia ( 1 ) and moderate loadings of low mood and suicidal ideation (0.4).…”

Brain-Derived Neurotrophic Factor and Extracellular Vesicle-Derived miRNAs in an Italian Cohort of Individuals With Obesity: A Key to Explain the Link Between Depression and Atherothrombosis

“…Recently, awareness has been raised regarding the relationship among obesity, depression and diet-related inflammation ( 46 , 47 ). Gialluisi et al ( 46 ) showed that the low-grade inflammation (INFLA)-score, based on four circulating inflammatory biomarkers (C-reactive protein, granulocyte-to-lymphocyte ratio, platelet and white blood cell counts), could explain the association between depressive symptoms and the dietary inflammatory index.…”