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RESEARCH PAPER ANALYSIS

Perspective: Depression in Persons with Parkinson's Disease.

This perspective summarizes prevalence, diagnostic challenges, putative neurobiology (dopaminergic, serotonergic, noradrenergic systems and HPA axis), validated assessment tools, standard pharmacologic and psychotherapeutic treatments, and emerging methods (DBS, neuroimaging, ecological momentary…

PMID41916878
JournalMovement disorders : official journal of the Movement Disorder Society
Publication Date2026-03-31
Ingested2026-04-28 08:58 PM
EXECUTIVE SUMMARY

What the AI sees

This perspective summarizes prevalence, diagnostic challenges, putative neurobiology (dopaminergic, serotonergic, noradrenergic systems and HPA axis), validated assessment tools, standard pharmacologic and psychotherapeutic treatments, and emerging methods (DBS, neuroimaging, ecological momentary…

WHY IT MATTERS

Research significance

Clinically useful for improving identification and symptomatic management of depression in PD and for informing research on affective circuitry and neuromodulation, but offers limited direct insight into molecular disease-modifying targets for Parkinson's therapeutic discovery.

ABSTRACT

Source abstract

Depression is a prevalent and disabling syndrome characterized by sustained sadness and/or anhedonia, as well as cognitive and physical symptoms. In Parkinson's disease (PD), depression is both common and clinically challenging due to overlapping symptoms and complex etiologic interactions. Major depressive disorder occurs in approximately 17% of PD patients, while clinically significant depressive symptoms affect over one-third. Both PD-specific and general risk factors contribute to this burden, with the latter playing a greater role. Diagnosis is complicated by symptom overlap, prompting recommendations for an inclusive diagnostic approach and use of rating scales specifically validated in PD. Differentiation from related syndromes such as apathy, demoralization and anxiety disorders is essential for appropriate management. Treatment follows general population algorithms, incorporating pharmacotherapy-particularly selective serotonergic reuptake inhibitors, serotonin and noradrenalin reuptake inhibitors, and tricyclic antidepressants-and psychotherapy such as cognitive behavioral or interpersonal therapy, though adjustments are needed to account for PD-related vulnerabilities. Access to adequate care is often hampered by the lack of mental health specialists with specific expertise in PD. From a research standpoint, PD provides a unique model for studying the neurobiology of mood regulation, implicating dopaminergic, serotonergic, and noradrenergic systems, as well as hypothalamic-pituitary-adrenal axis dysfunction. Emerging methods, including deep brain stimulation, ecological momentary assessment, neuroimaging, and machine learning, are expanding insights into emotional processing and its neurophysiological underpinnings. Clinically, routine screening and evidence-based treatment have improved care. Future research promises to refine diagnostic criteria, optimize therapies, and deepen understanding of affective dysregulation in Parkinson's disease. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

SUPPORTING PAPER SET

32 more papers to review

Ranked by current scoring engine
1 The cGAS-STING-Glymphatic-gut Axis in Parkinson's disease: A proposed self-amplifying triad of Neuroinflammation and therapeutic opportunity. International immunopharmacology 91.0 2 Immunosenescence and Inflammaging as Drivers of Neurodegeneration: Cellular Mechanisms, Neuroimmune Crosstalk, and Therapeutic Implications. Cells 91.0 3 Flavonoids improve neurotransmitters for Parkinson's treatment: mechanism and therapeutic potential. Frontiers in pharmacology 88.0 4 Alpha-Lipoic Acid and Biotin in Neurodegenerative Diseases: Convergent Mechanistic Insights from Preclinical Models to Clinical Perspectives. Neurology international 78.0 5 The Gut Microbiota in Parkinson's Disease: Mechanistic Insights into Microbial-Host Interactions. Microorganisms 85.0 6 Linking inflammation, metabolic dysfunction, and neurodegeneration: a comprehensive review of TLR2 pathways in type 2 diabetes. Frontiers in clinical diabetes and healthcare 80.0 7 Neuroprotective effects of GLP-2 and a GLP-2/GIP dual receptor agonist in an MPTP-induced mouse model of Parkinson's disease. Peptides 86.0 8 TNF alpha unmasks enteric malate aspartate shuttle dysfunction bridging Parkinson disease and intestinal inflammation. Nature communications 91.5 9 Lipid Metabolism and Neurodegeneration: Mechanistic Insights and Therapeutic Targets. Ageing research reviews 82.0 10 Shared functional microbiome signatures in Parkinson's disease and constipation predominate irritable bowel syndrome despite taxonomic divergence. Brain, behavior, & immunity - health 80.0 11 Benzimidazole as a Versatile Scaffold for Developing Neurotherapeutics Against Neurodegenerative Diseases. ChemMedChem 74.0 12 Biomimicking neuromelanin reverses the gait deficits and dopaminergic neuronal loss in the Parkinson's disease. Colloids and surfaces. B, Biointerfaces 86.0 13 Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases. Experimental physiology 84.0 14 Flavonoid Rutin Reduces Intestinal Inflammation in an Experimental Model of Parkinson's Disease. Neurotoxicity research 70.0 15 Nanostructured Lipid Carriers Enhance Brain Delivery and Antioxidant Efficacy of a Small-Molecule MAO B Inhibitor for Neurodegenerative Disease Therapy. Molecular pharmaceutics 78.0 16 Pathophysiological Role of the Gut Brain Axis in Parkinson's Disease: From Microbial Metabolites and Intestinal Permeability to Central Neuroinflammation. Current neurovascular research 86.0 17 Parkinson's Disease: From Metabolism to Genetics-A Comprehensive Review. Current issues in molecular biology 86.0 18 Navigating the cholesterol maze: Key insights on use of statins in neurodegenerative disorders. Neuroprotection (Chichester, England) 76.0 19 Integrative network pharmacology delineates dual GPCR and non-GPCR mechanisms of blended and individual Taikong Blue lavender and Pingyin rose essential oils in neurodegenerative and psychiatric disorders. Computers in biology and medicine 65.0 20 Models of neuroprotection in Parkinson's disease: Exploring cellular, molecular, and microenvironmental targets. Experimental neurology 78.0 21 Hyaluronic acid: emerging roles and biomaterial innovations in Alzheimer's and Parkinson's disease therapy. Frontiers in pharmacology 75.2 22 Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy. Frontiers in pharmacology 75.0 23 Lipid droplets in neurodegenerative diseases: pathological drivers and therapeutic vulnerabilities. Cell death discovery 82.0 24 Brain-gut-microbiota axis: a review on the bidirectional regulatory mechanisms between gut microbiota and brain and their disease interactions. Frontiers in microbiology 74.0 25 Long non-coding RNAs in neurodegenerative diseases - Molecular mechanisms, liquid biopsy biomarkers, and therapeutic targets: A review. Biomolecules & biomedicine 84.0 26 Neurosyphilis and Parkinsonism: Overlapping Pathophysiology and Emerging Therapeutic Insights. Current neurovascular research 76.0 27 Molecular biochemistry of soluble epoxide hydrolase in lipid mediator pathways and neuroinflammatory responses. The Journal of steroid biochemistry and molecular biology 82.0 28 Multifaceted role of CNPY2 beyond ER stress: Disease implications and therapeutic potential. Cell stress 83.3 29 Neuroprotective Role of Exercise-based Physiotherapy Combined with Pharmacological Agents in Parkinson's Disease. Central nervous system agents in medicinal chemistry 64.0 30 Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder. Signal transduction and targeted therapy 84.0 31 HMGB1-mediated neuroinflammation: molecular mechanisms and emerging therapeutic approaches. Inflammopharmacology 78.0 32 Beyond acid-base dyshomeostasis: Dynamic instability of neuronal lysosomal pH as a pathogenic mechanism and therapeutic target in neurological diseases. Biochemical pharmacology 88.0
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