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Background <p>Tumor necrosis factor-alpha (TNF-α) is a key mediator in the inflammatory mechanisms of depression, yet its peripheral levels and contributors remain unclear in patients with depression without comorbid physical diseases. This study aimed to compare peripheral TNF-α levels between healthy controls and individuals with depression without physical diseases, and to investigate the associations of stressful life events and modifiable lifestyle factors with peripheral TNF-α levels.</p> Method <p>Participants were derived from the Depression Cohort in China study. Adults aged 18–65 years were included in the study. Participants included healthy controls and individuals with subthreshold depressive symptoms (SDS) or major depressive disorder (MDD), all of whom were free of physical diseases. Peripheral TNF-α was measured by ELISA. Stressful life events and lifestyle factors were assessed using questionnaires. General linear models were used to assess the associations of stressful life events and lifestyle factors with TNF-α. Dominance analysis was used to rank the relative importance of predictors, and Blinder–Oaxaca decomposition was used to quantify the extent to which these factors statistically explained the TNF-α difference between healthy controls and individuals with depression.</p> Results <p>A total of 414 physically healthy adults were recruited, including 154 healthy controls and 260 individuals with depression. Among those with depression, 185 had SDS and 75 had MDD. Compared with healthy controls, peripheral TNF-α was mildly but significantly elevated in SDS (<i>Cliff’s delta</i> = 0.293, <i>P</i> &lt; 0.001), and MDD (<i>Cliff’s delta</i> = 0.261, <i>P</i> &lt; 0.01). Multivariate general linear model found that smoking in the past month (<i>β</i> = 2.15, <i>P</i> = 0.003), sleep duration &lt; 6&#xa0;h per day (<i>β</i> = 1.95, <i>P</i> = 0.004), and experience ≥ 3 stressful life events (<i>β</i> = 3.14, <i>P</i> = 0.001) were significantly contributed to the total variance of peripheral TNF-α in all participants. Blinder–Oaxaca decomposition indicated that 44.7% of the difference in peripheral TNF-α between healthy controls and depression was attributable to lifestyle factors and stressful life events. Within this explained portion, smoking contributed 25.1%, sleep duration &lt; 6&#xa0;h contributed 32.5%, and experiencing ≥ 3 stressful life events contributed 29.8%. Stratified analyses suggested that stressful life events might moderate the effect of drinking alcohol on TNF-α.</p> Conclusion <p>Peripheral TNF-α was mildly elevated in physically healthy adults with depression, with comparable levels observed in SDS and MDD. Stressful life events and lifestyle factors were associated with peripheral TNF-α levels in this population.</p> Clinical trial number <p>Not applicable.</p>

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Stressful life events and lifestyle factors are associated with elevated peripheral TNF-α levels in adults with depression without physical diseases

  • 期刊论文

  • 发表日期：

    2026年7月30日

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  • Xiuwen Li,
  • Huimin Zhang,
  • Lan Guo,
  • Yuhua Liao,
  • Keying Wu,
  • Yifeng Liu,
  • Wanxin Wang,
  • Lingjiang Li,
  • Bo Yang,
  • Xiaojie Wang,
  • Xue Han,
  • Jiansong Zhou,
  • Ciyong Lu

摘要

Background

Tumor necrosis factor-alpha (TNF-α) is a key mediator in the inflammatory mechanisms of depression, yet its peripheral levels and contributors remain unclear in patients with depression without comorbid physical diseases. This study aimed to compare peripheral TNF-α levels between healthy controls and individuals with depression without physical diseases, and to investigate the associations of stressful life events and modifiable lifestyle factors with peripheral TNF-α levels.

Method

Participants were derived from the Depression Cohort in China study. Adults aged 18–65 years were included in the study. Participants included healthy controls and individuals with subthreshold depressive symptoms (SDS) or major depressive disorder (MDD), all of whom were free of physical diseases. Peripheral TNF-α was measured by ELISA. Stressful life events and lifestyle factors were assessed using questionnaires. General linear models were used to assess the associations of stressful life events and lifestyle factors with TNF-α. Dominance analysis was used to rank the relative importance of predictors, and Blinder–Oaxaca decomposition was used to quantify the extent to which these factors statistically explained the TNF-α difference between healthy controls and individuals with depression.

Results

A total of 414 physically healthy adults were recruited, including 154 healthy controls and 260 individuals with depression. Among those with depression, 185 had SDS and 75 had MDD. Compared with healthy controls, peripheral TNF-α was mildly but significantly elevated in SDS (Cliff’s delta = 0.293, P < 0.001), and MDD (Cliff’s delta = 0.261, P < 0.01). Multivariate general linear model found that smoking in the past month (β = 2.15, P = 0.003), sleep duration < 6 h per day (β = 1.95, P = 0.004), and experience ≥ 3 stressful life events (β = 3.14, P = 0.001) were significantly contributed to the total variance of peripheral TNF-α in all participants. Blinder–Oaxaca decomposition indicated that 44.7% of the difference in peripheral TNF-α between healthy controls and depression was attributable to lifestyle factors and stressful life events. Within this explained portion, smoking contributed 25.1%, sleep duration < 6 h contributed 32.5%, and experiencing ≥ 3 stressful life events contributed 29.8%. Stratified analyses suggested that stressful life events might moderate the effect of drinking alcohol on TNF-α.

Conclusion

Peripheral TNF-α was mildly elevated in physically healthy adults with depression, with comparable levels observed in SDS and MDD. Stressful life events and lifestyle factors were associated with peripheral TNF-α levels in this population.

Clinical trial number

Not applicable.