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

Abstract

Background 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. Methods 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). Results 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. Conclusions 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.

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

“…In light of the known link between atypical depression and resistance to pharmacological antidepressant treatments, [5][6][7] if future analyses will confirm our findings in a longitudinal setting, these may suggest an alternative way to treat this depression subtype, through promoting healthy lifestyles and in particular healthy nutritional habits. In the future, this approach may be used not only for the prevention of depression onset, but also for coadjuvant treatment.…”

“… 42 This evidence was supported by a multi-sample network analysis in depressed and general population cohorts, and is also consistent with previous observational studies on circulating inflammation markers in population cohorts. 7 , 43 Moreover, Mendelian randomization analyses suggested a causal effect of increased CRP on somatic symptoms (appetite alterations, tiredness/fatigue and psychomotor changes), and of IL-6 on cognitive symptoms (suicidality). 41 …”

“…To assess depressive symptoms, the Patient Health Questionnaire 9 (PHQ9) was administered to a subset of the Moli-sani participants, as in. 7,11,24 The PHQ9 scale assesses the severity of depression by scoring the frequency of nine specific domains, typically affecting depressed subjects, in the two weeks before the interview. These include anhedonia, low mood, alteration of sleeping patterns or eating behaviors, feeling of failure/low self-estimate, fatigue, troubles in mental concentration, hypo-/hyperactivity behaviors, and suicidal ideation.…”

“… 23 Finally, we repeated the same analysis with two factors tagging cognitive and somatic depressive symptoms, so to possibly detect domain-specific associations. This study represents an advance compared to our previous analysis of symptoms-specific associations with circulating inflammation in the Moli-sani study, 7 since here we add a further piece to the puzzle, namely the relation between dietary inflammation and DII, and then investigate the role of circulating inflammation in this link, using both an overall scale of depressive symptoms and a factor-based approach. Moreover, we investigate associations stratified by gender and chronic health conditions.…”

“…4 This applies especially to "atypical" depression, which is characterized by somatic/neurovegetative symptoms like fatigue, psychomotor retardation, altered sleep and appetite. [5][6][7] This subtype of depression has often and robustly been linked to systemic inflammation by independent lines of evidence, [7][8][9][10] underlining the importance of healthy lifestyles to reduce the risk of this disease and to possibly treat it. 11 In particular, dietary habits and nutritional patterns have shown a prominent influence on the risk of depression, 12,13 as well as on circulating inflammation.…”