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Background <p>Major Depressive Disorder (MDD) is a common psychiatric condition with a multifactorial etiology that includes inflammatory mechanisms. Tumor Necrosis Factor-α (TNF-α), a pro-inflammatory cytokine, regulates several cellular functions in health and has been associated with reduced neuronal survival and increased inflammation in cortical areas related to reward processing, motivation, and decision-making in MDD. Although TNF-α has been studied in MDD, its precise role remains unclear, highlighting the need for further investigation. We therefore conducted a case-control study and a meta-analysis to better characterize peripheral blood TNF-α levels in first-episode, drug-naïve MDD patients compared with healthy controls.</p> Methods <p>In the case-control study, plasma TNF-α levels were measured in first-episode, drug-naïve patients with major depressive disorder (MDD) and healthy controls (HCs) matched on age, and sex, using high-sensitivity enzyme-linked immunosorbent assays (ELISAs). For the meta-analysis, we selected relevant case-control studies from systematic searches of PubMed, Embase, PsycINFO, and Web of Science. A random effects model was used to calculate combined standardized mean differences (SMD) and ratio of means (RoM) for result verification.</p> Results <p>A total of 63 MDD patients and 63 matched HCs were included in the case-control analysis. Plasma TNF-α levels were significantly higher in MDD patients than in HCs (<i>z</i> = -2.12, <i>p</i> &lt; 0.05). For the meta-analysis, 16 studies comprising 866 patients and 759 controls were included. Pooled results demonstrated significantly higher TNF-α levels in MDD patients compared with HCs (SMD: Hedges’ g = 0.65, 95% CI: 0.28 to 1.01, <i>p</i> &lt; 0.001). The RoM indicated a 30% higher mean concentration in patients (RoM = 1.30, 95% CI: 1.20 to 1.42, <i>p</i> &lt; 0.001). However, substantial cross-study heterogeneity was observed (SMD: <i>I²</i> = 91.2%, <i>p</i> &lt; 0.001; RoM: <i>I²</i> = 95.5%, <i>p</i> &lt; 0.001).</p> Conclusions <p>The results of both the case-control and meta-analysis portions of our study suggest that TNF-α levels are higher in first-episode, drug-naïve MDD patients than in healthy individuals. These findings imply that TNF-α plays an important role in the pathophysiology of MDD. Future work should examine sources of heterogeneity across studies on inflammatory factors in depression, and assess potential therapeutic targets associated with TNF-α.</p> Clinical trial number <p>Not applicable.</p>

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TNF-α levels in first-episode, drug-naïve patients with major depressive disorder: a case-control study and meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月26日

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  • Chunjing Li,
  • Ye Wang,
  • Jiarui Chen,
  • Sa Xiao,
  • Mingli Lou,
  • Mubing Ding,
  • Yurong Xing

摘要

Background

Major Depressive Disorder (MDD) is a common psychiatric condition with a multifactorial etiology that includes inflammatory mechanisms. Tumor Necrosis Factor-α (TNF-α), a pro-inflammatory cytokine, regulates several cellular functions in health and has been associated with reduced neuronal survival and increased inflammation in cortical areas related to reward processing, motivation, and decision-making in MDD. Although TNF-α has been studied in MDD, its precise role remains unclear, highlighting the need for further investigation. We therefore conducted a case-control study and a meta-analysis to better characterize peripheral blood TNF-α levels in first-episode, drug-naïve MDD patients compared with healthy controls.

Methods

In the case-control study, plasma TNF-α levels were measured in first-episode, drug-naïve patients with major depressive disorder (MDD) and healthy controls (HCs) matched on age, and sex, using high-sensitivity enzyme-linked immunosorbent assays (ELISAs). For the meta-analysis, we selected relevant case-control studies from systematic searches of PubMed, Embase, PsycINFO, and Web of Science. A random effects model was used to calculate combined standardized mean differences (SMD) and ratio of means (RoM) for result verification.

Results

A total of 63 MDD patients and 63 matched HCs were included in the case-control analysis. Plasma TNF-α levels were significantly higher in MDD patients than in HCs (z = -2.12, p < 0.05). For the meta-analysis, 16 studies comprising 866 patients and 759 controls were included. Pooled results demonstrated significantly higher TNF-α levels in MDD patients compared with HCs (SMD: Hedges’ g = 0.65, 95% CI: 0.28 to 1.01, p < 0.001). The RoM indicated a 30% higher mean concentration in patients (RoM = 1.30, 95% CI: 1.20 to 1.42, p < 0.001). However, substantial cross-study heterogeneity was observed (SMD: I² = 91.2%, p < 0.001; RoM: I² = 95.5%, p < 0.001).

Conclusions

The results of both the case-control and meta-analysis portions of our study suggest that TNF-α levels are higher in first-episode, drug-naïve MDD patients than in healthy individuals. These findings imply that TNF-α plays an important role in the pathophysiology of MDD. Future work should examine sources of heterogeneity across studies on inflammatory factors in depression, and assess potential therapeutic targets associated with TNF-α.

Clinical trial number

Not applicable.