Associations between systemic inflammation and somatic depressive symptoms: Findings from the Moli-sani study

The link between systemic inflammation and depression has been deeply investigated, but relatively few studies explored symptom-specific associations, mostly focusing on common inflammatory biomarkers like C-reactive protein (CRP) levels.

We investigated associations of low-grade inflammation with depressive symptoms assessed through a reduced version of Patient Health Questionnaire 9 (PHQ-9) in a large population-based cohort of adult Italians (N = 13 301). We built logistic regressions between each depressive symptom and composite index of systemic inflammation based on four circulating biomarkers, namely CRP, Plt, WBC, and GLR (INFLA)-score, a composite blood-based inflammation index, and with its component biomarkers, namely CRP, platelets count (Plt), white blood cells count (WBC), and granulocyte-to-lymphocyte ratio (GLR).

We observed a strong association of the altered appetite/eating symptom with standardized INFLA-score (OR [95% CI] = 1.19 [1.12-1.26]; corrected p = 3.0 × 10^-7 ), CRP (1.28 [1.20-1.36]; p = 1.9 × 10^-13 ), and WBC (1.13 [1.06-1.20]; p = 2.3 × 10^-3 ), and of tiredness/low energy with GLR (1.11 [1.05-1.17]; p = 9.4 × 10^-3 ). These associations remained stable within nondepressed participants (PHQ-9 < 10), and after adjustment for the use of antidepressants, main chronic conditions, and lifestyle factors; while they were notably attenuated within depressed participants (PHQ-9 ≥ 10) and-for altered appetite only-by adjustment for obesity.

This study provides a robust replication of the association previously reported between CRP and altered appetite in a large US population cohort, and supports a link between systemic inflammation, altered appetite, and tiredness. Moreover, it extends this evidence to inflammatory markers other than CRP and suggests new targets for the treatment of atypical depression.