Association between iron deposition and emotional disorder in Parkinson’s patients: a systematic review and meta-analysis

OBJECTIVE: Depression, anxiety and apathy are the most common emotional symptoms in patients with Parkinson’s disease (PD). However, the association between these symptoms and brain iron deposition remains unclear. This study aimed to systematically evaluate the strength of association between brain iron deposition and anxiety, depression, and apathy in PD patients. METHODS: A systematic search was conducted in PubMed, Embase, and Web of Science databases from their inception to September 2025 to include eligible observational studies investigating the association between brain iron deposition and anxiety, depression, or apathy in PD patients. Heterogeneity among studies was assessed via Cochran’s Q test and I2 statistic, and a fixed-effects or random-effects model was selected to pool effect sizes based on the heterogeneity level. Subgroup analyses (stratified by outcome measures and brain regions), sensitivity analysis, and publication bias assessment (Egger’s test and Begg’s test) were conducted to verify the robustness of the results. RESULTS: A total of 8 cross-sectional studies were finally included, with a total sample size of 855. The overall risk of bias of the included studies was manageable. Meta-analysis results showed a significant association between brain iron deposition and the occurrence of anxiety and depression in PD patients, with a pooled standardized mean difference (SMD) of 0.95 (95% confidence interval [95%CI]: 0.73–1.17). The results of the subgroup analysis showed that the results of the depression subgroup were highly stable (I2 = 25%). In brain region stratification, iron deposition in the substantia nigra (SMD = 1.01, 95%CI: 0.82–1.19) and general subcortical nuclei (SMD = 0.53, 95%CI: 0.23–0.84) were significantly associated with emotional symptoms, and the heterogeneity among the subgroups was low. Only 1 study was included in the apathy subgroup or the cortical subgroup. CONCLUSION: Brain iron deposition in PD patients is significantly associated with the occurrence of anxiety and depression, with the substantia nigra and general subcortical nuclei as the core associated brain regions. These findings can provide potential biomarkers for the early prediction and targeted intervention of emotional symptoms in PD.