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LETTER TO THE EDITOR Table of Contents  
Ahead of print publication
Risk factors for Parkinson’s disease depression


1 Department of Medicine, Federal University of Santa Maria, Santa Maria, Brazil
2 Department of Medicine, Federal University of Fronteira Sul, Passo Fundo, Brazil

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Date of Submission18-Feb-2022
Date of Decision02-Mar-2022
Date of Acceptance04-Mar-2022
Date of Web Publication28-Jul-2022
 


How to cite this URL:
Rissardo JP, Caprara AL, Durante &. Risk factors for Parkinson’s disease depression. Ann Mov Disord [Epub ahead of print] [cited 2022 Aug 18]. Available from: https://www.aomd.in/preprintarticle.asp?id=352657




Dear Editor,

We have read the article entitled “Burden of nonmotor symptoms in Parkinson’s disease patients from eastern India” published in your esteemed journal “Annals of Movement Disorders” with great interest.[1] The authors Sahu et al. studied nonmotor symptoms in 150 patients with Parkinson’s disease (PD). The most common symptoms reported were unexplained pain, anxiety, constipation, insomnia, and memory impairment. In particular, depression was reported in 46.7% of the patients. They concluded that nonmotor symptoms significantly impact the quality of life and appear to be more prevalent in India than in other countries.

The rate of depression in patients with PD widely varies in the literature, with studies reporting it to be ranging from 5% to 80%. In addition, it is believed that in the next decade the burden and prevalence of this psychiatric manifestation will increase even further among patients with PD.[2] However, depression, anxiety, and fatigue are not well recognized as symptoms of PD in clinical practice and approximately half of the neurologists did not identify them during consultations.[3]

Here, we discuss the risk factors associated with Parkinson’s disease depression (PDD) ([Figure 1]).
Figure 1: Risk Factors for Parkinson’s Disease Depression

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We performed a literature search in Medline using a set of terms that included “Parkinson’s disease,” “depression,” and “risk factor” without language restriction ([Supplementary Material – Other 1]). We found the following risk factors: advanced/more severe disease, akinetic-rigid type of PD, alexithymia, country’s altitude, antiparkinsonian medication use when compared to drug-naïve patients, presence of any other psychiatric comorbidities besides depression, anxiety disorders, bradykinesia, balance and gait impairment, cancer history (any type), cognitive impairment, limitations in activities of daily living, depression severity, disabled individuals according to The National Health Interview Survey-Centers for Disease Control, presence of dyskinesia, presence of dysphagia, presence of dystonia, early/late stage of disease, ethnicity (nationality), family history of depression, female gender, financial status, genetic (Gly2019Ser mutation in the LRRK2 gene, CNR1 polymorphism), hallucinations, higher levodopa doses, history of any episode of depression, Hoehn and Yahr Scale severity, insomnia, lack of a sexual partner, levodopa-induced dyskinesia, long-term levodopa use, loneliness (living alone), longer duration of illness, nonmotor symptoms severity (Unified Parkinson’s Disease Rating Scale, UPDRS), motor disability severity, motor disability independent of the severity, motor fluctuations, non-smoking, more frequent off-periods, older age, psychosis, psychosocial factor/stigma, restless leg syndrome, salivation/drooling, self-isolation for fear of infection (COVID-19), skeletal muscle pain, sleep disorders, stress, clinical presentation suggesting atypical  Parkinsonism More Details, presence of tremor, UPDRS-III scores, years of formal education, and younger age at diagnosis.
Other 1: Risk Factors for Parkinson’s Disease Depression Reported in the Literature

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Of note, majority of the risk factors were found in only a small sample of studies. However, we encountered contradictory results in the literature. For example, for age at presentation, some studies showed that being younger is a risk factor, while other studies revealed that older age is a risk factor for the development of depression.

A recent study from Spain described that a decrease in neurotransmitters (dopamine, serotonin, and acetylcholine) may be a trigger for depression in PD.[2] In addition, impaired basal ganglia connections with the limbic system and orbitofrontal cortex are involved in the pathophysiology of PD-related depression. Furthermore, habenula impairment could contribute to depression in the early stages of premotor PD.

In 2013, while modeling depression in PD, Leentjens et al.[4] observed that nonspecific factors may be more prominent markers of depression than PD-specific factors. They described that sex, history of depression, familial history of depression, and history of anxiety are independent risk factors. On the other hand, cognitive impairment, limitations in activities of daily living, the UPDRS motor scale, and levodopa doses appear to be correlated and interlinked with the development of PDD.

Another study from China revealed that altitude could be a risk factor for PDD.[5] Cao et al. explained that hypoxic environments may have an influence on the disease. The finding that hypoxia is related to depression and PD can support the hypothesis that depression is a neurodegenerative clinical manifestation of PD, instead of only an independent illness. Some authors believe that the depressive symptoms may be better correlated with the severity of cognitive decline in PD.[6]

The systematic study of the risk factors for depression in PD is important since some of them can be modified or therapeutically managed, such as levodopa-induced dyskinesia and daily high levodopa doses. In conclusion, the risk factors associated with depression in PD remain poorly understood. Further studies that evaluate their occurrence and could contribute to the understanding of the pathophysiology of PD and the development of novel pharmacological treatments are needed.

Acknowledgements

None.

Author contribution

JPR and ALFC contributed equally to this work. JPR contributed to research project: conception, organization, execution; Statistical analysis: design, execution, review, and critique; Manuscript preparation: writing of the first draft, review, and critique. ALFC and ID contributed to research project: conception, organization, execution; Statistical analysis: design, execution, review, and critique; Manuscript preparation: writing of the first draft, review, and critique.

Ethical compliance statement

The authors confirm that neither informed patient consent nor the approval of an Institutional Review Board was necessary for this work. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sahu S, Mukherjee A, Biswas S, Leta V, Rukavina K, Das SK, Biswas A. Burden of nonmotor symptoms in Parkinson’s disease patients from eastern India. Ann Mov Disord 2021;4: 121-30.  Back to cited text no. 1
  [Full text]  
2.
Agüera-Ortiz L, García-Ramos R, Grandas Pérez FJ, López-Álvarez J, Montes Rodríguez JM, Olazarán Rodríguez FJ, et al. Focus on depression in parkinson’s disease: A delphi consensus of experts in psychiatry, neurology, and geriatrics. Parkinsons Dis 2021;2021:6621991.  Back to cited text no. 2
    
3.
Richard IH, Kurlan R. The under-recognition of depression in Parkinson’s disease. Neuropsychiatr Dis Treat 2006;2: 349-53.  Back to cited text no. 3
    
4.
Leentjens AF, Moonen AJ, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, et al. Modeling depression in Parkinson disease: Disease-specific and nonspecific risk factors. Neurology 2013;81:1036-43.  Back to cited text no. 4
    
5.
Cao Y, Li G, Xue J, Zhang G, Gao S, Huang Y, et al. Depression and related factors in patients with Parkinson’s disease at high altitude. Neuropsychiatr Dis Treat 2021;17:1353-62.  Back to cited text no. 5
    
6.
Petkus AJ, Filoteo JV, Schiehser DM, Gomez ME, Petzinger G. Worse cognitive performance predicts increased anxiety and depressive symptoms in patients with Parkinson’s disease: A bidirectional analysis. Neuropsychology 2019;33:35-46.  Back to cited text no. 6
    

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Correspondence Address:
Jamir Pitton Rissardo,
Av. Roraima, 1000 - Camobi, Santa Maria - RS - 97105-900
Brazil
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Source of Support: None, Conflict of Interest: None



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