BACKGROUND: Neuroinflammation has been suggested as a contributor to the pathophysiology of depression; however, large case-control studies investigating cytokine levels in the cerebrospinal fluid (CSF) from patients with recent-onset depression by multiplex analyses are missing.

METHODS: An individually matched (sex and age) prospective case-control study comparing patients with recent-onset depression to healthy controls. CSF was analyzed with the Mesoscale V-PLEX Neuroinflammation Panel 1.

OUTCOMES: comparisons of analyte levels in the CSF between groups with interleukin (IL)-6 and IL-8 as primary outcomes and 23 other cytokines as secondary outcomes.

RESULTS: We included 106 patients (84.0% outpatients) with recent-onset depression and 106 healthy controls. There were no significant differences in the primary outcomes IL-6 (relative mean difference (MD): 1.10; 95% confidence interval (CI) 0.93-1.30; p = 0.276) or IL-8 levels (MD: 1.05; 95% CI 0.96-1.16; p = 0.249) relative to healthy controls. IL-4 was 40% higher (MD: 1.40; 95% CI 1.14-1.72; p = 0.001), monocyte chemoattractant protein (MCP)-1 was 25% higher (MD: 1.25; 95% CI 1.06-1.47; p = 0.009) and macrophage inflammatory protein (MIP)-1β was 16% higher (MD: 1.16; 95% CI 1.02-1.33; p = 0.025) in patients with depression relative to healthy controls. However, only IL-4 was significantly elevated after correction for multiple testing of secondary outcomes (p = 0.025).

CONCLUSION: We found no significant differences in CSF levels of the co-primary outcomes IL-6 and IL-8, however, the higher CSF levels of IL-4, MCP-1 and MIP-1β among patients with recent-onset depression compared to healthy controls indicate a potential role of these cytokines in the neuroinflammatory response to depression.