Category: Parkinson's Disease: Genetics
Objective: To study the interaction between GBA1 mutations, sex and other clinical factors in shaping depression outcomes in Parkinson’s Disease.
Background: Depression affects 35% of Parkinson’s disease (PD) patients and is closely linked to both motor and non-motor symptoms, making it one of the most significant predictors of reduced quality of life. Neuropsychiatric symptoms are common in PD carriers of GBA1 mutations (GBA-PD) although the impact of other clinical features and sex in predicting their severity remains unclear.
Method: This is a multicenter study involving 4 Italian centers. A cross-sectional analysis was conducted in 78 GBA-PD and 156 nonGBA-PD patients matched in a 1:2 ratio based on age, disease duration and cognitive profile (MoCA scores). Depressive features were explored using BDI-II scores and compared between PD groups and stratified by sex. A multivariate regression model was performed to identify predictors of depressive symptoms. Moreover, a longitudinal analysis on 57 GBA-PD and 83 nonGBA-PD patients with BDI-II scores available at 3-year follow-up was performed using a linear mixed-effects model.
Results: GBA-PD had worse BDI-II scores, with 3-times higher odds of clinically significant depression (BDI≥14) compared to nonGBA-PD. Assessing sex/genotype combined effect, depressive symptoms were significantly less prevalent in nonGBA-PD males compared to all other groups. In GBA-PD, only RBDSQ predicted depressive symptoms, whereas sex, UPDRS-IV, and MoCA emerged as predictors in nonGBA-PD. Longitudinally, GBA-PD patients showed faster progression of depressive symptoms than nonGBA-PD and these were more severe in those with clinically RBD at baseline, regardless of sex. Contrarily, sex had an impact on BDI-II scores overtime in nonGBA-PD, with females showing significantly higher scores than males.
Conclusion: GBA mutations are associated with a distinct pattern of depressive symptoms in PD, characterized by a stronger link with RBD and a faster progression of severity over time, regardless of sex differences.
To cite this abstract in AMA style:
M. Avenali, P. Mitrotti, CA. Artusi, R. de Micco, G. Giannini, S. Caminiti, C. Ledda, L. Gallo, C. Galandra, A. Mascia, M. Siciliano, F. Pagliuca, L. Sambati, V. Sant'Elia, G. Vornetti, G. Calandra-Buonaura, L. Lopiano, R. Lodi, A. Tessitore, M. Bozzali, EM. Valente. Interplay of GBA1 mutations and sex on determining depressive symptoms in Parkinson’s Disease [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/interplay-of-gba1-mutations-and-sex-on-determining-depressive-symptoms-in-parkinsons-disease/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/interplay-of-gba1-mutations-and-sex-on-determining-depressive-symptoms-in-parkinsons-disease/