Gray matter volume alterations in de novo Parkinson's disease: A mediational role in the interplay between sleep quality and anxiety

Abstract Objective Parkinson's disease (PD) is increasingly recognized for its non‐motor symptoms, among which emotional disturbances and sleep disorders frequently co‐occur. The commonality of neuroanatomical underpinnings for these symptoms is not fully understood. This study is intended to investigate the differences in gray matter volume (GMV) between PD patients with anxiety (A‐PD) and those without anxiety (NA‐PD). Additionally, it seeks to uncover the interplay between GMV variations and the manifestations of anxiety and sleep quality. Methods A total of 37 A‐PD patients, 43 NA‐PD patients, and 36 healthy controls (HCs) were recruited, all of whom underwent voxel‐based morphometry (VBM) analysis. Group differences in GMV were assessed using analysis of covariance (ANCOVA). Partial correlation between GMV, anxiety symptom, and sleep quality were analyzed. Mediation analysis explored the mediating role of the volume of GMV‐distinct brain regions on the relationship between sleep quality and anxiety within the PD patient cohort. Results A‐PD patients showed significantly lower GMV in the fusiform gyrus (FG) and right inferior temporal gyrus (ITG) compared to HCs and NA‐PD patients. GMV in these regions correlated negatively with Hamilton Anxiety Rating Scale (HAMA) scores (right ITG: r = −0.690, p < 0.001; left FG: r = −0.509, p < 0.001; right FG: r = −0.576, p < 0.001) and positively with sleep quality in PD patients (right ITG: r = 0.592, p < 0.001; left FG: r = 0.356, p = 0.001; right FG: r = 0.470, p < 0.001). Mediation analysis revealed that GMV in the FG and right ITG mediated the relationship between sleep quality and anxiety symptoms, with substantial effect sizes accounted for by the right ITG (25.74%) and FG (left: 11.90%, right: 15.59%). Conclusion This study has shed further light on the relationship between sleep disturbances and anxiety symptoms in PD patients. Given the pivotal roles of the FG and the ITG in facial recognition and the recognition of emotion‐related facial expressions, our findings indicate that compromised sleep quality, under the pathological conditions of PD, may exacerbate the reduction in GMV within these regions, impairing the recognition of emotional facial expressions and thereby intensifying anxiety symptoms.