Depressive Symptoms in Obese Individuals Accompanied by Greater Basal Inflammation but Lower Monocyte Inflammatory Responses to LPS: A Quest to Uncover Immunologic Links between Depression and Obesity.

INTRODUCTION

Despite the high prevalence of co-occurring conditions between obesity and depression, the knowledge of the underlying mechanisms remains limited. Given the existing evidence of obesity being an inflammatory condition and the association between elevated inflammation and treatment-resistant depression, investigations to uncover immune pathways underlying the obesity-depression link will shed light on the mechanisms and therapeutic options. We investigated whether depressive symptoms and adiposity are associated with greater inflammation and with suppressed innate immune responses to an immune challenge.

METHODS

Immune activities and depressive symptoms using the Beck Depression Inventory (BDI) were assessed in 96 participants of a weight range (normal weight, overweight, or obesity). Percent adiposity was measured by dual-energy X-ray absorptiometry. Plasma C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin (IL)-1β, and IL-6 levels were determined by immunoassay. Lipopolysaccharides (LPSs)-stimulated intracellular TNF in peripheral blood monocytes was assessed by flow cytometry, which was also examined after incubation with recombinant TNF (rTNF) in 10 healthy participants of normal body mass index (BMI).

RESULTS

Obese, but not overweight, participants showed significantly higher BDI scores (T93 = 2.70, p < 0.05) and plasma levels of CRP (T95 = 3.71, p < 0.01), but lower LPS-stimulated monocytic TNF production (T93 = 3.23, p < 0.01), than normal-weight subjects. Depressive symptoms were associated with BMI, % total and trunk fat, and plasma CRP levels (rs 0.22-0.35) but not with monocytic TNF production in univariate model. The association between BDI and inflammatory markers largely diminished after adjusting for demographic variables and blood pressure, and the association with obesity/adiposity disappeared in the final multivariate model. Plasma TNF levels and monocytic TNF production were negatively associated (r = -0.37, p < 0.05) in univariate but not in multivariate models after controlling for covariates. BMI (βstd = -0.33), %total fat (βstd = -0.54), and %trunk fat (βstd = -0.57) remained significant predictors for monocyte TNF production even after controlling for demographic and plasma inflammatory marker levels (all ps < 0.01). Prolonged (24-h) exposure of blood monocytes to rTNF in vitro suppressed LPS-stimulated monocytic TNF production in a dose-dependent manner, whereas acute rTNF pre-treatment potentiated TNF production.

CONCLUSION

Our findings provide the evidence that greater adiposity is associated with depressive symptoms and that obese individuals even without clinical depression experience elevated depressive symptoms. Whether immunologic dysregulation underlies this depressive mood-adiposity association is inconclusive despite greater CRP and lower monocyte reactivity among the obese, but low-grade inflammation in obesity may contribute to impaired innate immune responses to immunological challenge. Additional mechanistic investigations of obesity-related immune dysregulation underlying mood disorders would inform effective therapeutics.