Serum VIP and IL‐1β Levels Are Associated With Anxiety and Depression in Patients With Parkinson's Disease: A Cross‐Sectional Study

BACKGROUND: Anxiety and depressive symptoms frequently accompany Parkinson's disease (PD), yet the biological processes underlying these affective complications and their potential peripheral indicators remain incompletely understood. This study evaluated whether circulating concentrations of vasoactive intestinal peptide (VIP), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) differed according to the presence of anxiety and depressive symptoms among individuals with PD. METHODS: This exploratory study included 56 individuals with PD and 40 neurologically healthy participants matched for age and sex who were enrolled at the same institution. Clinical characterization included Hoehn-Yahr staging, assessment of daily living function (ADL), cognitive evaluation using MMSE, and measurement of anxiety and depressive symptoms with HAMA-14 and HAMD-17. PD-AD status was determined when participants simultaneously met the predefined cutoff values for both anxiety and depression assessment scales. Circulating concentrations of VIP, TNF-α, and IL-1β were measured using enzyme-linked immunosorbent assays. Relationships between biomarkers and clinical variables were examined through Spearman correlation testing, binary logistic regression modeling, and receiver operating characteristic (ROC) analysis. RESULTS: Relative to healthy participants, the PD group showed lower circulating VIP concentrations and higher IL-1β and TNF-α concentrations, with all comparisons reaching statistical significance (p < 0.01). Among participants with PD, those meeting criteria for anxiety and depression showed an additional reduction in VIP accompanied by increased IL-1β concentrations. Lower VIP concentrations were associated with higher HAMA-14 and HAMD-17 scores (r = -0.559 and r = -0.853, respectively), whereas IL-1β concentrations demonstrated positive relationships with both symptom scales. ROC analysis identified VIP as the biomarker with the strongest ability to distinguish PD-AD from PD patients without affective symptoms (AUC = 0.892, 95% CI: 0.799 to 0.986; sensitivity: 0.842; specificity: 0.814). IL-1β demonstrated a moderate capacity for classification, with an AUC of 0.796 (95% CI: 0.666 to 0.926). CONCLUSION: These results suggest that alterations in VIP and IL-1β are associated with affective symptoms in PD and may contribute to biomarker-based recognition of PD-AD in clinical practice. Nevertheless, interpretation of these findings is limited by the observational cross-sectional design and relatively small cohort size; future studies involving larger longitudinal populations are required for validation.