Possible association between the <i>lrrk2</i> gene and anxiety behavior: a systematic literature review

Júnior, Renato Elias Moreira; Souza, RM; Carvalho, JG de; Bergamini, JP; Godard, Ana Lúcia Brunialti

doi:10.1080/01677063.2022.2144293

Journal of Neurogenetics

2022

DOI: 10.1080/01677063.2022.2144293

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Possible association between the lrrk2 gene and anxiety behavior: a systematic literature review

Renato Elias Moreira Júnior

RM Souza

JG de Carvalho

et al.

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Cited by 2 publications

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“…Depression frequency estimations in LRRK2 ‐PD vary between 30%‐65% 17,18 . With elevated rates of anxiety observed in this group 19 . Recent studies postulate that LRRK2's ability to regulate the downstream pathway of glucocerebrosidase, may play a role in its altered motor and non‐motor outcomes among PD patients 20 .…”

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“…17,18 With elevated rates of anxiety observed in this group. 19 Recent studies postulate that LRRK2's ability to regulate the downstream pathway of glucocerebrosidase, may play a role in its altered motor and non-motor outcomes among PD patients. 20 Moreover, increased serotonin receptor binding was observed in LRRK2 carriers, underscoring another potential connection between PD associated mutations and mood disorders.…”

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

DeBroff

Omer

Cohen³

et al. 2023

Movement Disord Clin Pract

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BackgroundBackground: 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 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 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. ResultsResults: 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 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.Mood disorders such as depression and anxiety are common conditions in Parkinson's disease (PD) impacting patient outcomes. Recent studies estimate that 35% of PD patients will have clinically significant depression, a percentage which likely underestimates the underreported and underdiagnosed condition in PD. 1,2 Dopaminergic, serotonergic and adrenergic system changes have all been implicated in the development of concurrent mood disorders in PD 1,2 even at the prodromal stage of the disease, likely due to involvement of their respective nuclei (substantia nigra, raphe nuclei and locus coeruleus). 3 In addition to PD related medications (MAO B inhibitors, amantadine, dopamine agonists and L-DOPA), treatment options for depression and anxiety in PD are similar to those provided to patients without neurodegenerative conditions. 4 Standard pharmacologic treatment with antidepressants such as Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs), and Tricyclic Antidepressants (TCAs) has shown some success in PD. 5 In addition, PD related medication such as dopamine agonists and amantadine have antidepressive properties.

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confidence: 99%

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

DeBroff

Omer

Cohen³

et al. 2023

Movement Disord Clin Pract

View full text Add to dashboard Cite

show abstract

Current genetic data on depression and anxiety in Parkinson's disease patients

Kalinderi,

Papaliagkas,

Fidani

2024

Parkinsonism & Related Disorders

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Possible association between the lrrk2 gene and anxiety behavior: a systematic literature review

Cited by 2 publications

References 118 publications

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

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

Current genetic data on depression and anxiety in Parkinson's disease patients

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