Sex-specific gray matter underpinnings of anxiety and their mediating mechanisms in de novo Parkinson’s disease

Objective: PD patients. Methods: PD patients were enrolled. Anxiety and depressive symptoms were assessed using the Hamilton Anxiety Rating Scale (HAMA) and the 24-item Hamilton Depression Rating Scale (HAMD-24), respectively. Whole-brain GMV was analyzed using voxel-based morphometry (VBM) on T1-weighted MRI data. A 2 × 2 analysis of variance (sex × anxiety status) was conducted to examine main and interaction effects, controlling for age, education, HAMD-24 total score, and total intracranial volume. Sex-stratified, cross-sectional mediation analyses were subsequently performed. Results: = 0.004). Mediation analyses suggested that right precuneus GMV partially mediated the association between HAMD-24 and HAMA scores in males (mediation proportion: 17.1%). Similarly, left insular GMV partially mediated this association in females (mediation proportion: 15.4%). Conclusion: PD, primarily involving the precuneus in males and the insula in females. These structural differences may partially underlie the co-occurrence of depressive and anxiety symptoms, highlighting sexually dimorphic neuroanatomical substrates for affective disturbances in PD.