Prodromal Depression and Subsequent Risk of Developing Parkinson’s Disease: A Systematic Review With meta-analysis

Bareeqa, Syeda Beenish; Samar, Syeda Sana; Kamal, Sufiyan; Masood, Yasir; Allahyar,; Ahmed, Syed Ijlal; Hayat, Ghazala

doi:10.2217/nmt-2022-0001

Cited by 10 publications

(8 citation statements)

References 33 publications

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“…Nonetheless, studies have suggested an increased risk of developing PD for patients with a previous diagnosis of depression [ 50, 60 ]. This observation is supported by further reports of a higher incidence rate of depressive symptoms among PD patients, particularly during the prodromal phase [ 60 ]. In addition, the onset of depressive symptoms among individuals with PD is observed between 2–10 [ 61 ] and up to 17 years [ 62 ] before PD diagnosis or the manifestation of predominant motor symptoms.…”

Section: Discussionsupporting

confidence: 85%

Investigating the Shared Genetic Etiology Between Parkinson’s Disease and Depression

Reyes-Pérez,

García-Marín,

Aman

et al. 2024

JPD

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Background: Depression is a common symptom in Parkinson’s disease (PD), resulting from underlying neuropathological processes and psychological factors. However, the extent to which shared genetic risk factors contribute to the relationship between depression and PD is poorly understood. Objective: To examine the effects of common genetic variants influencing the etiology of PD and depression risk at the genome-wide and local genomic regional level. Methods: We comprehensively investigated the genetic relationship between PD and depression using genome-wide association studies data. First, we estimated the genetic correlation at the genome-wide level using linkage-disequilibrium score regression, followed by local genetic correlation analysis using the GWAS-pairwise method and functional annotation to identify genes that may jointly influence the risk for both traits. Also, we performed Latent Causal Variable, Latent Heritable Confounder Mendelian Randomization, and traditional Mendelian Randomization analyses to investigate the potential causal relationship. Results: Although the genetic correlation between PD and depression was not statistically significant at the genome-wide level, GWAS-pairwise analyses identified 16 genomic segments associated with PD and depression, implicating nine genes. Further analyses revealed distinct patterns within individual genes, suggesting an intricate pattern. These genes involve various biological processes, including neurotransmitter regulation, senescence, and nucleo-cytoplasmic transport mechanisms. We did not observe genetic evidence of causality between PD and depression. Conclusions: Our findings did not support a genome-wide genetic correlation or a causal association between both conditions. However, we identified genomic segments but identified genomic segments linked to distinct biological pathways influencing their etiology.Further research is needed to understand their functional consequences.

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Section: Discussionsupporting

confidence: 85%

Investigating the Shared Genetic Etiology Between Parkinson’s Disease and Depression

Reyes-Pérez,

García-Marín,

Aman

et al. 2024

JPD

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“…Depression in early PD is regarded a risk factor for worse motor and global prognosis (Bega et al 2015 ; Marras et al 2008 ; Post et al 2011 ), and higher depression scores were found in patients with dyskinesias and/or motor fluctuations (Dissanayaka et al 2011 ; Wichowicz et al 2006 ), also correlating with bradykinesia (Papapetropoulos et al 2006 ; Rojo et al 2003 ). On the other hand, a history of depression is a risk factor for developing PD (Aarsland et al 2011 ; Bareeqa et al 2022 ; Gustafsson et al 2015 ; Inoue et al 2010 ; Jeong et al 2021 ; Leentjens et al 2003 ; Nagayama and Kimura 2015 ; Schuurman et al 2002 ; Shen et al 2013 ), and neurological symptoms may worsen depression severity in PD (Assogna et al 2013 ; Dissanayaka et al 2011 ), but depression may also occur after PD onset (DeMarco et al 2022 ). DPD is also associated with cognitive impairment (CI) (Fujishiro et al 2015 ; Wertman et al 1993 ), and has important impact on autonomic symptoms in early and middle stages of PD (Sklerov et al 2022 ), with greater depression being associated with severe autonomic dysfunction (Matsubara et al 2018 ).…”

Section: Pd-depression and Other Symptomsmentioning

confidence: 99%

The pathobiological basis of depression in Parkinson disease: challenges and outlooks

Ka¹

2022

J Neural Transm

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Depression, with an estimated prevalence of about 40% is a most common neuropsychiatric disorder in Parkinson disease (PD), with a negative impact on quality of life, cognitive impairment and functional disability, yet the underlying neurobiology is poorly understood. Depression in PD (DPD), one of its most common non-motor symptoms, can precede the onset of motor symptoms but can occur at any stage of the disease. Although its diagnosis is based on standard criteria, due to overlap with other symptoms related to PD or to side effects of treatment, depression is frequently underdiagnosed and undertreated. DPD has been related to a variety of pathogenic mechanisms associated with the underlying neurodegenerative process, in particular dysfunction of neurotransmitter systems (dopaminergic, serotonergic and noradrenergic), as well as to disturbances of cortico-limbic, striato-thalamic-prefrontal, mediotemporal-limbic networks, with disruption in the topological organization of functional mood-related, motor and other essential brain network connections due to alterations in the blood–oxygen-level-dependent (BOLD) fluctuations in multiple brain areas. Other hypothetic mechanisms involve neuroinflammation, neuroimmune dysregulation, stress hormones, neurotrophic, toxic or metabolic factors. The pathophysiology and pathogenesis of DPD are multifactorial and complex, and its interactions with genetic factors, age-related changes, cognitive disposition and other co-morbidities awaits further elucidation.

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“…The non-motor symptoms such as depression, anxiety, or psychosis are based on the dysregulation of dopaminergic processes of mainly mesocortical and mesolimbic pathways, non-dopaminergic processes, and their interactions [ 33 , 34 ]. The subsequent risk of PD is significantly higher in patients with depression as compared with healthy individuals [ 35 , 36 ]. These connections may run deeper, as PD may directly precipitate mood disorders.…”

Section: Introductionmentioning

confidence: 99%

Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression

Brazdis,

von Zimmermann,

Lenz

et al. 2024

IJMS

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Due to the high comorbidity of Parkinson’s disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we investigated the peripheral expression levels of three primarily PD-associated genes: α-synuclein (SNCA), lysosomal enzyme β-glucocerebrosidase (GBA1), and UDP-glucose ceramide glucosyltransferase (UGCG) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated n = 63, medicated n = 66) and controls (remitted MDD n = 39, healthy subjects n = 61). We observed that expression levels of SNCA (p = 0.036), GBA1 (p = 0.014), and UGCG (p = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of GBA1 and UGCG decreased in medicated patients during three weeks of therapy. Additionally, in subgroups, expression was positively correlated with the severity of depression and anxiety. Furthermore, we identified correlations between the gene expression levels and PD-related laboratory parameters. Our findings suggest that SNCA, GBA1, and UGCG analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.

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Prodromal Depression and Subsequent Risk of Developing Parkinson’s Disease: A Systematic Review With meta-analysis

Cited by 10 publications

References 33 publications

Investigating the Shared Genetic Etiology Between Parkinson’s Disease and Depression

Investigating the Shared Genetic Etiology Between Parkinson’s Disease and Depression

The pathobiological basis of depression in Parkinson disease: challenges and outlooks

Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression

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