What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Obesity and depressive symptoms (n=96). Intervention: Obesity vs. Normal weight. Primary outcome: Depressive symptoms (BDI scores), plasma CRP, and LPS-stimulated monocytic TNF production.

What does this research mean for the field?

Obesity is associated with significantly higher depressive symptoms and basal inflammation (plasma CRP), but lower LPS-stimulated monocytic TNF production compared to normal weight. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to explore the relationship between depressive symptoms, obesity, and inflammatory responses.

May 8, 2026Open Access

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

Key Result

Obesity was associated with significantly higher depressive symptoms (P<0.05) and plasma CRP (P<0.01), but lower LPS-stimulated monocytic TNF production (P<0.01) compared to normal weight.

Key Points

This research aims to explore the relationship between depressive symptoms, obesity, and inflammatory responses.
Assess immune activities and depressive symptoms using the Beck Depression Inventory (BDI) in 96 participants.
Measure percent adiposity via dual-energy X-ray absorptiometry and plasma inflammatory markers by immunoassay.
Evaluate LPS-stimulated intracellular TNF in peripheral blood monocytes by flow cytometry after rTNF incubation.
Obese participants exhibited significantly higher BDI scores and CRP levels, but lower LPS-stimulated monocytic TNF production.
Depressive symptoms showed associations with BMI and body fat percentages, but associations lessened after adjusting for covariates.
Prolonged exposure to rTNF suppressed LPS-stimulated TNF production in monocytes, indicating complex immune responses.

Study Design

Type

Cross-Sectional (n=96)

Structured PICO

Population

96 participants of a weight range (normal weight, overweight, or obesity)

Comparator

Normal-weight subjects

Outcome

Depressive symptoms (Beck Depression Inventory), plasma inflammatory markers (CRP, TNF, IL-1β, IL-6), and LPS-stimulated intracellular TNF in peripheral blood monocytessurrogate

Greater adiposity is associated with elevated depressive symptoms and basal inflammation, but lower monocyte reactivity to immune challenge.

Limitations

Inconclusive whether immunologic dysregulation underlies the depressive mood-adiposity association

Abstract

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 (LPS)-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 (r’s .22 - .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 (std = -0.33), %total fat (std = -0.54) and %trunk fat (std = -0.57) remained significant predictors for monocyte TNF production even after controlling for demographic and plasma inflammatory marker levels (All P’s < 0.01). Prolonged (24-hour) 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.