The Influence of GBA and LRRK2 on Mood Disorders in Parkinson's Disease

Jake DeBroff, Nurit Omer, Batsheva Cohen, Nir Giladi, Meir Kestenbaum, Julia C. Shirvan, Jesse M. Cedarbaum, Mali Gana-Weisz, Orly Goldstein, Avi Orr-Urtreger, Anat Mirelman, Avner Thaler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Mood disorders have emerged as major non-motor comorbidities in Parkinson's disease (PD) even at the prodromal stage of the disease. Mutations in the LRRK2 and GBA genes are common among Ashkenazi Jews, with more severe phenotype reported for GBA-PD. Objective: To explore the association between genetic status and mood related disorders before and after diagnosis of PD and the association between mood-related medications, phenotype, and genetic status. Methods: Participants were genotyped for mutations in the LRRK2 and GBA genes. State of depression, anxiety and non-motor features were evaluated using validated questionnaires. History of mood disorders prior to diagnosis of PD and use of mood-related medications were assessed. Results: The study included 105 idiopathic PD (iPD), 55 LRRK2-PD and 94 GBA-PD. Scores on mood related questionnaires and frequency of depression and anxiety before diagnosis were similar between the groups (p>0.05). 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). LRRK2-PD and GBA-PD receiving mood-related medications at time of assessment had worse motor and non-motor phenotype compared to those that did not (p<0.05). LRRK2-PD receiving mood related-medications at time of assessment, scored higher on mood-related questionnaires compared to LRRK2-PD not receiving such medications (p<0.04). Conclusions: Prodromal GBA-PD are more frequently treated with mood related-medications despite equal rates of reported mood-related disorders, while LRRK2-PD with mood-related disorders experience high rates of anxiety and depression despite treatment, attesting to the need of more precise assessment and treatment of these genetic subgroups.

Original languageEnglish
Pages (from-to)606-616
Number of pages11
JournalMovement Disorders Clinical Practice
Issue number4
StatePublished - Apr 2023


  • GBA
  • LRRK2
  • Parkinson's disease
  • anxiety
  • depression


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