El complicado proceso neurobiológico de la depresión en la enfermedad de Parkinson
Keywords:
depresión, neurotrsansmisores, enfermedad de Párkinson, muerte neuronal.Abstract
Introducción: En la enfermedad de Parkinson, la depresión, es un síntoma no motor de esta enfermedad que aparece en estos sujetos y que compromete sustancialmente la calidad de vida.
Objetivo: Describir el proceso neurobiológico de la depresión en la EP
Desarrollo: La depresión se presenta con una media aproximada del 55% en la EP, mientras que en un 25% aparece antes de los síntomas motores.
En esta enfermedad hay afectación progresiva de la dopamina, originada por la muerte de las neuronas que producen este neurotransmisor, que conduce a un desequilibrio de los neurotransmisores serotoninérgicos y noradrenérgicos, e intensifican el proceso degenerativo y empeoran los síntomas motores y no motores de la enfermedad
La EP, como todo proceso degenerativo se acompaña de una inflamación sistémica crónica y un proceso inmunitario, asociado al estrés oxidativo, mediante un mecanismo complicado de retroalimentación, que intensifica la muerte de las neuronas dopaminérgica, y la afectación de las vías serotoninérgica y noradrenérgicas que empeora los síntomas de la enfermedad.
Existe un proceso neuroinmune, una afectación disfunción del eje hipotálamo-hipófisis-adrenal con aumento del cortisol, que incrementan la enfermedad..
Además, la influencia de determinados factores genéticos puede aumentar los síntomas motores y no motores de forma individual o ambos de forma similar
Conclusiones: El complicado proceso neurobiológico de la EP, conlleva a lesiones atróficas corticales en determinadas áreas del cerebro, como los núcleos basales, y alcanza zonas de la corteza cerebral, en áreas fronto – temporales.
Downloads
References
1. González-Pal S, Tudurí-García R, Cabrera-Muñoz A, Durán-Mpra. Inestabilidad de la personalidad o neuroticismo en una muestra de pacientes adultos con epilepsia.. Rev Hosp Psiq Hab Internet [Internet]. agosto de 2019;16(2). Disponible en: https://revhph.sld.cu/index.php/hph/article/view/141
2. González-Pal S. La depresión como comorbilidad más frecuent en el enfermo con epilepsia. Rev Hosp Psiquiátrico Habana [Internet]. 2024;21(3). Disponible en: https://revhph.sld.cu/index.php/hph/article/view/646
3. Marras C, Beck J, Bower J, Roberts E, Ritz B, Ross G, et al. Prevalence of Parkinson’s disease across North America. NPJ Parkinsons Dis. NPJ Park Dis. julio de 2018;4(21):1-15.
4. Huang Y, Gan Y, Yang L, Cheng W, Yu J. Depression in Alzheimer’s disease: epidemiology, mechanisms, and treatment. Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2023.10.008. 1 de junio de 2023;95(11):992-1005.
5. Balasubramanian S, Mehmood K, Al-Baldawi S, Zuñiga D. Behind the Mask: Parkinson’s Disease and Depression. Cureus. 21 de enero de 2024;16(1):e 52663.
6. Bukhurova E, Alipkhanova B, Shanibova D, Sherieva AC, Gitinavasova S, Temirov A. Depression and Parkinson’s disease. Вестник Неврологии Психиатрии И Нейрохирургии. 2024;8:982-9.
7. Leung D, Chan W, Spector A, Wong G. Prevalence of depression, anxiety, and apathy symptoms across dementia stages: A systematic review and meta-analysis. Int J Geriatr Psychiatry. Int J Geriatr Psychiatry. septiembre de 2021;36(9):1330-13-134.
8. Cong S, Xian C, Zhang S, Zhang T, Wang H, Cong S. Prevalence and clinical aspects of depression in Parkinson’s disease: A systematic review and meta‑analysis of 129 studies. Neurosci Biobehav Rev. octubre de 2022;141(104749).
9. Schmauss M. Depression and Parkinson’s Disease. Fortschritte Neurol. 1 de abril de 2022;90(04):145-6.
10. Sujith P, Arjunan P, Iype T, Natarajan V. Correlation Between Depression and Quality of Life Among Patients With Parkinson’s Disease: An Analytical Cross-Sectional Study. Cureus. febrero de 2024;16(2):e54736.
11. Orji O, Ijioma C, Odarah J, Okeji I, Areh J, Anele D, et al. Influence of Depression on the Quality of Life in Patients With Parkinson’s Disease in Southwest Nigeria. Cureus. 22 de julio de 2024;16(7):e65077.
12. Li Y, Huang P, Guo T, Guan X, Gao T, Sheng W, et al. Brain structural correlates of depressive symptoms in Parkinson’s disease patients at different disease stage. Psychiatry Res Neuroimaging. febrero de 2020;29(296):11029.
13. Jellinger K. The pathobiological basis of depression in Parkinson disease: challenges and outlooks. J Neural Trans (Vienna). diciembre de 2022;129(12):1397-418.
14. Cong S, Klinger H, Laurecin C, Danaila T, Thobois S. Depression in Patients with Parkinson’s Disease: Current Understanding of its Neurobiology and Implications for Treatment. Drugs Aging. Drugs Aging. junio de 2022;39(6):417-439.
15. Rotaru L, Gavriliuc O, Grosu O. Depression in patients with Parkinson’s disease. Preliminary results of the cohort study. Med Sience [Internet]. 2022;74(3). Disponible en: DOI: https://doi.org/10.52692/1857-0011.2022.3-74.16
16. Badenoch J, París A, Jacobs B, Noyce A, Marshall C, Waters S. Neuroanatomical and prognostic associations of depression in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 17 de septiembre de 2024;95(10):966-73.
17. Bloem B, Okun M, Kein C. Parkinson’s disease. Lancet. 12 de junio de 2021;397(10291):2284-303.
18. Postuma R, Berg D, Sterm M, Poewe W, Olanow C, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Movement Disorders. Mov Disord. 2015;30:1591-601.
19. Watanabe H, Hara K, Ito M, Katsuno M, Sobue G. Criteria for Parkinson’s Disease: MDS-PD. Brain Nerve. 2018;70:139-46.
20. Prime M, McKay J, Bay A, Hart A, Kim C, Abraham A, et al. Differentiating Parkinson Disease Subtypes Using Clinical Balance Measures. J Neurol Phys Ther. . enero de 2020;44(1).
21. Sheikh, J, Yesavage J. Geriatric Depression Scale (GDS): Recent evidence and development of a shorter version. Clin Gerontol J Aging Ment Health. 1986;5:165-73.
22. Soto-Insuga V, González-Aguacil E, García-Peñas J. Estado epiléptico pediátrico. Rev Neurol. 2022;16(75 (8)):225-.
23. Schrag A, Barone P, Brown R, Leentjens A, McDonald W, Starkstein S, et al. Depression rating scales in Parkinson’s disease: critique and recommendations. Mov Disord. 15 de junio de 2007;22(8):1077-92.
24. Camerucci E, Lyons K, Pahwa R. Predicting Depression in Parkinson’s Disease Using Commonly Available PD Questionnaires. J Clin Med. 3 de abril de 2024;13(7).
25. Lotharius J, Brundin P. Pathogenesis of Parkinson’s disease: dopamine, vesicles and alpha-synuclein. Nat Rev Neurosci. diciembre de 2002;3(12):932-42.
26. Muñoz A, López-López A, Labandeira C, Labandeira-García J. Interacciones entre los sistemas serotoninérgicos y otros neurotransmisores en los ganglios basales: papel en la enfermedad de Parkinson y efectos adversos de la L-DOPA. Neuroanat Front. junio de 2020;4(14):26.
27. Lian T, Guo P, Zuo L, Hu Y, Yu S, Liu L, et al. An Investigation on the Clinical Features and Neurochemical Changes in Parkinson’s Disease With Depression. Front Psychiatry. enero de 2019;18(9):723.
28. Fontoura J, Baptista C, Pedroso F, Pochapski J, Miyoshi E, Ferro M. Depression in Parkinson’s Disease: The Contribution from Animal Studies. Parkinson’DiseaseDis [Internet]. octubre de 2017;2017(9124160). Disponible en: https/doi.org/10.1155/2017/9124160.
29. Jeong E, Lee J, Song Y. Longitudinal Serotonergic and Dopaminergic Binding: Impact on Parkinson’s Disease Progression and Levodopa Dyskinesia. J Neuroimaging. 2025 Jan-Feb;35(1):e70014. PMID: 39800858. J Neuroimaging. febrero de 2025;35(1).
30. Miguelez C, Benazzouz A, Ugedo L, Deurwaerdère, P. Impairment of Serotonergic Transmission by the Antiparkinsonian Drug L-DOPA: Mechanisms and Clinical Implications. Front Cell Neurosci. septiembre de 2017;11:274.
31. González- Delgado E, Hector-Martínez M. Psicosis en la enfermedad de Parkinson. Rev Hosp Psiq Hab Internet [Internet]. 12 de diciembre de 2023;20(3). Disponible en: https://revhph.sld.cu/index.php/hph/article/view/429
32. Lipari N, Galfano A, Venkatesh F, Grezenko H, Sandoval I, Manfredsson F, et al. The effects of chemogenetic targeting of serotonin-projecting pathways on L-DOPA-induced dyskinesia and psychosis in a bilateral rat model of Parkinson’s disease. Front Neural Circuits. noviembre de 2024;18.
33. Prange S, Metereauinger E, Klinger H, Huddlestone M, De Oliveira M, Duperrier S, et al. Serotonergic dysfunction in patients with impulse control disorders in Parkinson’s disease. Brain. junio de 2025;148(6):2108-21.
34. Cilia R, Valtteri K. Overcoming the dopamine-centric model of impulse control disorders in Parkinson’s disease: the role of 5-HT. Brain. junio de 2025;148(Issue 6):1853-6.
35. Maillet A, Météreau E, Tremblay, L, Favre E, Klinger H, Lhommée E, et al. Serotonergic and Dopaminergic Lesions Underlying Parkinsonian Neuropsychiatric Signs. ;36(12):Epub 2021 Sep 8. PMID: 34494685. Mov Disord. diciembre de 2021;36(12):2888-2900.
36. Politis M, Loane C. Serotonergic dysfunction in Parkinson’s disease and its relevance to disability. ScientificWorldJournal. 2011;11(1726-34).
37. Zhou W, Chu H. Progressive noradrenergic degeneration and motor cortical dysfunction in Parkinson’s disease. Acta Pharmacol Sin. 2025;46:829-35.
38. Pifl C, Kish S, Hornykiewicz O. Thalamic noradrenaline in Parkinson’s disease: deficits suggest role in motor and non-motor symptoms. 2012;27:1618-24.
39. Sheng S, Qingshan W, Lulu J, Oyarzabal N, Esteban A, Riddick B, et al. Noradrenergic dysfunction accelerates LPS-elicited inflammation-related ascending sequential neurodegeneration and deficits in non-motor/motor functions. Brain Behav Immun. 23 jun2019;81:384-9.
40. Laurencin C, Lancelot S, Thobois S, Boulinguez P, Ballanger B. Altérations du système noradrénergique dans la maladie de Parkinson : une étude combinée en IRM-TEP à la 11C-yohimbine Centre national de la recherche scientifique, University of Lyon 31 Mar 2024 - Revue Neurologique. Rev Neurol (Paris). abril de 2024;180(Supplement):S14-5.
41. Song S, Wang Q, Jiang L, Riddick N, Oyarzabal E, Wilson B, et al. Noradrenergic dysfunction accelerates LPS-elicited inflammation-related ascending sequential neurodegeneration and deficits in non-motor/motor functions. Brain Behav Immun. 23 de junio de 2019;81:374-87.
42. Jovanovic P, Wang Y, Vit JP, Novinbakht E, Morones N, Hogg E, et al. Sustained chemogenetic activation of locus coeruleus norepinephrine neurons promotes dopaminergic neuron survival in synucleinopathy. PLOS ONE. 2022;17:e0263074.
43. Belujon P, Bezard E, Taupignon A, Bioulac B, Benazzouz A. Noradrenergic modulation of subthalamic nucleus activity : Behavioral and electrophysiological evidence in intact and 6-hydroxydopamine-lesioned rats. J Neurosci. 2007;27:9595-606.
44. Thome A, Wang J, Atassi F, Thonhoff J, Faridar A, Zhao W, et al. Peripheral monocyte transcriptional signatures of inflammation and oxidative stress in Parkinson’s disease. Front Immunol. 23 de julio de 2025;16:1571074.
45. Farroqui T, Farroqui A. Lipid-mediated oxidative stress and inflammation in the pathogenesis of Parkinson’s disease. 2011;2011:247467. Park Dis. 15 de febrero de 2011;2011:247-67.
46. de Farías C, Maes M, Bonifácio K, Matsumoto A, Bortolasci C, Nogueira A de S, et al. Parkinson’s Disease is Accompanied by Intertwined Alterations in Iron Metabolism and Activated Immune-inflammatory and Oxidative Stress Pathways. Cns Neurol Disord-Drug Targets. 2017;16:484-91.
47. He J, Wang G, Zhang F. Oxidative Stress and Neuroinflammation Potentiate Each Other to Promote Progression of Dopamine Neurodegeneration. Célula Oxid Med Longev [Internet]. 3 de julio de 2020;2020:2020:6137521. Disponible en: https://doi.org/10.1155/2020/6137521.
48. Mani A, Sevanan M, Krishnamoorthy A, Sekar S. A systematic review of molecular approaches that link mitochondrial dysfunction and neuroinflammation in Parkinson’s disease. Neurol Sci. noviembre de 2021;42(11):4459-69.
49. Chang K, Chen C. The Role of Oxidative Stress in Parkinson’s Disease. Antioxid Basel. 8 de julio de 2020;9(7):597.
50. Fedorova T, Logvinenko A, Poleshchuk V, Muzychuk O, Shabalina A, Illarioshkin S. Lipid Peroxidation Products in the Blood Plasma of Patients with Parkinson’s Disease as Possible Biomarkers of Different Stages of the Disease. Neurochem J. 2019;13:391-5.
51. d’Ischia M, Costantini C, Prota G. Reaction of Dopamine with Malondialdehyde: A Possible Underlying Event in Parkinson′s Disease. ChemInform [Internet]. 1993;3(24). Disponible en: https://doi.org/10.100. 2/CHIN.199345308.
52. van Wamelen D, Wan Y, Ray Chaudhuri K, Jenner P. Stress and cortisol in Parkinson’s disease. Int Rev Neurobiol. 19 de febrero de 2020;152:131-56.
53. Soares N, Pereira G, Altmann V, Almeida R, de, Reider C. Cortisol levels, motor, cognitive and behavioral symptoms in Parkinson’s disease: a systematic review.. Neural Transm Vienna. 2019;126(3):219-32.
54. Ibrahimagić O, Jakubovic A, Smajlovic D, Dostović Z, Kunić S, Iljazović A. Psychological Stress and Changes of Hypothalamic-Pituitary-Adrenal Axis in Patients with “De Novo” Parkinson’s Disease. Med Arch Sarajevo Bosnia Herzeg. 2016;70:445-8.
55. Goltz F, van der Heide A, HHelmich R. Alleviating Stress in Parkinson’s Disease: Symptomatic Treatment, Disease Modification, or Both? J Park Dis [Internet]. 2024; Disponible en: https://doi.org/10.3233/jpd-230211.
56. Cherian A, K P D, Vijayaraghavan A. Parkinson’s disease - genetic cause. Curr Opin Neurol. 1 de agosto de 2023;36(4):292-301.
57. Panicker N, Ge p, Dawson V, Dawson T. The cell biology of Parkinson’s disease. J Cell Biol. 5 de abril de 2021;220(4).
58. Halliday M, Radford H, Mallucci G. Prions: generation and spread versus neurotoxicity. J Biol Chem. julio de 2024;18(289(29)):19862-8.
59. Gokuladhas S, Fadason T, Farrow S, Cooper A, O’Sullivan J. Discovering genetic mechanisms underlying the co-occurrence of Parkinson’s disease and non-motor traits. NPJ Park Dis. 23 de enero de 2024;10(1):27.
60. Carrasco J, Antón R, Valbuena A, Pantoja-Uceda D, Mukhi M, Hervás R, et al. Metamorphism in TDP-43 prion-like domain determines chaperone recognition. Nat Commun. 28 de enero de 2023;14(1):46.
61. Gasser T. The global dimension of Parkinson’s disease genetics. Lancet Neurol. Lancet Neurol. diciembre de 2024;23(12):1178-1179.
62. Hosseini S, Sohrabi-Ashlaghi A, Kolahi S, Azizi N, Borooghani H, Gharaylou Z, et al. Structural and diffusion imaging in olfactory-related brain regions in Parkinson’s disease: predictors of clinical progression. Sci Rep. 13 de octubre de 2025;15(1):35636.
63. Yang W, Bai X, Guan X, Zhou C, Guo T, Wu J, et al. The longitudinal volumetric and shape changes of subcortical nuclei in Parkinson’s disease. Sci Rep. 29 de marzo de 2024;14(1):7494.
64. Yang Y, Wang JZ. From Structure to Behavior in Basolateral Amygdala-Hippocampus Circuits. Front Neural Circuits [Internet]. 2017;1186.
65. Filippi M, Sarasso E, Piramide N, Stojkovic T, Stankovic I, Basaia S, et al. Progressive brain atrophy and clinical evolution in Parkinson’s disease. Neuroimage Clin. 2020;28:102374.
66. Benninger D, von Meyenburg J, Dukart, J, Bassetti C, Kollias S, Iseki K, et al. Clinical Phenotype Imprints on Brain Atrophy Progression in Parkinson’s Disease. Clin Transl Neurosci [Internet]. 2023;7(8). Disponible en: https://doi.org/10.3390/ctn7010008
67. Jia X, Liang P, Li Y, Shi L, Wang D, Li K. Longitudinal Study of Gray Matter Changes in Parkinson Disease. AJNR Am J Neuroradiol. 2015ic;36(12):2219-26.
68. Eid A, Grossen S, Tanenbaum A, Hwang H, Cash T, Franklin E, et al. Longitudinal brain morphometry in Parkinson’s disease clinical subtypes: Distinct signatures forecast behavioral change within subtypes. Relat Disord Park. enero de 2026;142:108141.
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Salvador González-Pal
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
