IL-17C mediates the neuroticism-anxiety nexus: an inflammatory pathway linking personality trait to clinical symptomatology
BMC Psychology, 2026
Cheng S., Zhao J., Shen J., Li Y., Xu Z.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Background
While neuroticism is a core risk factor for anxiety disorders and inflammation contributes to their pathogenesis, specific biological mediators translating this personality vulnerability remain unidentified.
Objective
To identify anxiety-linked inflammation-associated proteins, characterize their associations with neuroticism and symptom severity, and evaluate their mediating role.
Methods
In a case–control study (49 anxiety patients, 19 controls), we profiled 92 serum inflammation-related proteins (Olink Target 96 Inflammation panel). Comprehensive phenotyping included neuroticism (CBF-PI-N), anxiety (GAD-7), and depression (PHQ-9). Group differences were assessed using non-parametric tests. Associations and mediation effects were evaluated across the entire cohort using partial correlations and pre-registered mediation models, rigorously controlling for sex and depressive symptoms.
Results
Anxiety patients showed elevated IL-17C, CCL25, and CX3CL1 versus controls. Only IL-17C correlated positively with both neuroticism (r = 0.386, p < 0.001) and anxiety severity (r = 0.472, p < 0.001), independent of their strong correlation (r = 0.692, p < 0.001). Following adjustment for sex and PHQ-9 scores, the associations remained remarkably robust: only IL-17C demonstrated significant positive correlations with anxiety severity (GAD-7: r = 0.457, p < 0.001) and Neuroticism (r = 0.364, p < 0.001). Mediation analysis confirmed IL-17C significantly mediated the neuroticism-anxiety relationship. It accounted for 27.14% of the total effect after adjusting for sex and depressive symptoms (indirect effect β = 0.0974, 95% CI: 0.0115–0.2329) and 11.91% adjusting for sex alone (β = 0.1282, 95% CI: 0.028–0.2698). The direct effect of neuroticism remained significant.ConclusionsIL-17C is a novel inflammatory mediator partially explaining the neuroticism-anxiety link, revealing a biological pathway. It represents a potential therapeutic target, warranting longitudinal validation.