Circulating miR-425 can be a biomarker for depression in patients with Parkinson's disease

Introduction: Depression, a common comorbidity in patients with Parkinson's disease (PD), is often under-diagnosed and undertreated. Circulating microRNAs (miRNAs) have been proved to be promising biomarker candidates for PD. However, no miRNAs are currently available as biochemical markers of depression in PD. Method: Serum samples from 52 healthy controls, 69 non-depressed PD patients (PD-ND), and 62 depressed PD patients (PD-D) were analyzed using qPCR to measure miR-425 levels. All the participants were assessed using detailed clinical scales. Results: miRNA-425 (miR-425) expression in PD-D patients was downregulated compared with that in PD-ND patients, with an area under the curve of 0.867 in receiver operating characteristic curve analysis. miR-425 levels were negatively correlated with the severity of depression (HAMD, r =-0.423, p < 0.001) and anxiety (HAMA, r =-0.469, p < 0.001). Additionally, PD-D patients scored higher in H-Y, MDS-UPDRS (I, II, and III), NMSS (1, 3, 5, and 9), HAMD, HAMA, RBDSQ, ESS, and ADL and lower in NMSS7, MMSE, SS-16, and PDQ-39 than PD-ND patients. Binary logistic regression analysis identified that cognitive impairment (MMSE, p = 0.001) and anxiety (HAMA, p < 0.001) were significantly associated with depression in PD. Conclusion: Circulating miR-425 shows significant potential as a biomarker for depression in PD, with distinct downregulation in PD-D patients and a strong correlation with depression severity. Our findings suggest a unique potential for improving PD-D diagnosis and understanding its pathophysiology.