Objective: To assess the influence of mutations in the LRRK2 and GBA genes on mood disorders among patients with Parkinson’s disease (PD)

Background: Mood disorders have emerged as major non-motor comorbidities in Parkinson’s disease (PD) both during the prodromal stage and throughout the disease course. Mutations in the LRRK2 and GBA genes are common among Ashkenazi Jews, with more severe phenotype reported for GBA-PD. We analyzed the relationship between genotype and mood disorders among patients with PD before and after diagnosis and explored the association between mood related medications, phenotype, and genetic status.

Method: This cross-sectional study collected information on depression, anxiety and non-motor features from validated questionnaires as well as anti-depressive and anti-anxiolytic medication history. PD severity was assessed using the MDS-UPDRS. The Montreal Cognitive Assessment was used to determine global cognitive functions; depression was assessed using the Beck Depression Inventory and the Geriatric Depression Scale-15. Anxiety was assessed using the State-Trait Anxiety Inventory.

Results: 254 patients with PD were included in this study: 105 idiopathic PD (iPD), 55 LRRK2-PD and 94 GBA-PD. Frequency of depression and anxiety before diagnosis was similar between the groups. However, more GBA-PD patients used mood related medications before PD diagnosis than LRRK2-PD and iPD (16.5% vs 7.1% and 8.2%, p=0.044).There was no difference in age of onset between those reporting depression and those without (p=0.126) nor was there a difference in age of onset between those receiving anti-depressive medication and those who did not (p=0.436) in any of the groups. Patients receiving mood related medications had worse disease phenotype (motor and non-motor) compared to those that did not. Mood related medications seemed to be effective for affective symptoms in GBA-PD and iPD groups but less so in LRRK2-PD as higher depression scores were observed in the LRRK2-PD group taking mood related medications compared to those that did not.

Conclusion: GBA-PD reported higher rates of treatment of mood related disorders prior to diagnosis of PD, despite similar frequencies of depression and anxiety. Patients with diagnosed mood disorders showed overall more severe PD symptoms suggesting a link between motor and non-motor symptoms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-influence-of-gba-and-lrrk2-on-mood-disorders-in-parkinsons-disease/