Mood disorders in Parkinson’s disease
https://doi.org/10.25587/2587-5590-2026-1-46-56
Abstract
Mood disorders in Parkinson’s Disease (PD) have traditionally been viewed as reactive conditions arising in response to motor deterioration and reduced quality of life. However, emerging evidence indicates that affective disturbances represent a distinct and integral component of the disease, reflecting profound dysregulation of neurotransmitter systems within the central nervous system. Of particular interest is the early manifestation of depression, anxiety, and apathy, which may precede the onset of motor symptoms and thus serve as prodromal markers of the disease. These early affective symptoms are frequently underrecognized by both patients and clinicians, leading to delayed diagnosis and postponement of targeted treatment interventions. The clinical and pathophysiological heterogeneity of affective symptoms in PD has led to the conceptualization of non-motor phenotypes analogous to the established motor subtypes. This article presents a comprehensive review of Russian and international studies published between 2009 and 2024, focusing on the neurochemical and clinical dimensions of depression, anxiety, and apathy in PD. Special attention is given to the roles of the noradrenergic, serotonergic, dopaminergic, and cholinergic systems in the development of mood disturbances. It is emphasized that imbalances among these neurotransmitter networks contribute to the persistence of affective disorders and diminished cognitive flexibility. Contemporary approaches to the phenotypic classification of emotional disturbances are discussed, incorporating data from neuroimaging and neurochemical profiling. Integrating these affective phenotypes into the broader typology of PD holds promise for enhancing diagnostic precision, risk stratification, and the development of personalized therapeutic strategies. The review also explores the interplay between affective and motor symptoms and their combined impact on the clinical trajectory and prognosis of PD. Identifying characteristic patterns of non-motor manifestations, including mood disorders, advances our understanding of the clinical heterogeneity of PD and informs the development of more effective diagnostic and therapeutic frameworks aimed at improving patient quality of life and reducing the risk of social maladaptation.
About the Authors
E. V. SmirnovaRussian Federation
Smirnova Elena Vladislavovna, Assistant Lecturer, Department of Neurology and Neurosurgery including Postgraduate Courses
644043, Omsk
N. G. Zhukova
Russian Federation
Zhukova Natalia Grigorievna, Dr. Sci. (Medicine), Professor, Department of Neurology and Neurosurgery
634050, Tomsk
References
1. Koszycki D., Taljaard M., Bradwejn J., Lee C., Tasca G. A., Grimes D.A. Interpersonal Psychotherapy for the Treatment of Depression in Parkinson’s Disease: Results of a Randomized Controlled Trial. Mov Disord. 2024 Nov 20. doi:10.1002/mds.30061
2. Jellinger K.A. The pathobiological basis of depression in Parkinson disease: challenges and outlooks. J Neural Transm (Vienna). 2022 Dec;129(12):1397–1418. doi:10.1007/s00702-022-02559-5.
3. Goncharova Z.A., Gelpey M.A., Mutalieva Kh.M. Non-motor symptoms in patients with Parkinson’s disease. Yuzhno-Rossiyskiy zhurnal terapevticheskoy praktiki. 2021;2(4):73–78 (in Russian). doi:10.21886/2712-8156-2021-2-4-73-78
4. Goncharova Z.A., Gelpey M.A., Rabadanova E.A. The impact of non-motor symptoms on the course of Parkinson’s disease and patients’ quality of life. Saratovskiy nauchno-meditsinskiy zhurnal. 2016;12(3):362–366. Elibrary ID: 28802368 (in Russian)
5. Pfeiffer R.F. Non-motor symptoms in Parkinson’s disease. Parkinsonism Relat Disord. 2016;22(Suppl S1):S119–S122. doi:10.1016/j.parkreldis.2015.09.004
6. Bukhurova E.R., Alipkhanova B.A., Shanibova D.Z., Sherieva A.Ch., Gitinavasova S.M., Temirov A.T. Depression and Parkinson’s disease. Vestnik nevrologii, psikhiatrii i neirokhirurgii. 2024;8:20–28 (in Russian). doi:10.33920/med-01-2408-03
7. Béreau M., Van Waes V., Servant M., et al. Apathy in Parkinson’s disease: clinical patterns and neurobiological basis. Cells. 2023 Jun 10;12(12):1599. doi:10.3390/cells12121599
8. Cong S., Xiang C., Zhang S., et al. Prevalence and clinical aspects of depression in Parkinson’s disease: a systematic review and meta-analysis of 129 studies. Neurosci Biobehav Rev. 2022 Oct;141:104749. doi:10.1016/j.neubiorev.2022.104749.
9. Ray S., Agarwal P. Depression and anxiety in Parkinson disease. Clin Geriatr Med. 2020 Feb;36(1):93–104. doi:10.1016/j.cger.2019.09.012
10. Pontone G.M., Mills K.A. Optimal treatment of depression and anxiety in Parkinson’s disease. Am J Geriatr Psychiatry. 2021 Jun;29(6):530–540. doi:10.1016/j.jagp.2021.02.037
11. De Waele S., Cras P., Crosiers D. Apathy in Parkinson’s disease: defining the Park apathy subtype. Brain Sci. 2022 Jul 14;12(7):923. doi:10.3390/brainsci12070923
12. Hinkle J.T., Perepezko K., Gonzalez L.L., et al. Apathy and anxiety in de novo Parkinson’s disease predict the severity of motor complications. Mov Disord Clin Pract. 2020 Dec 4;8(1):76–84. doi:10.1002/mdc3.13117
13. Ekimova I.V., Pazi M.B., Polonik S.G., et al. The chaperone inducer U133 eliminates anhedonia and prevents neurodegeneration in monoaminergic emotional structures of the brain in a preclinical model of Parkinson’s disease in aged rats. Zhurnal evolyutsionnoy biokhimii i fiziologii. 2021;107(10):1194–1208 (in Russian). doi:10.31857/S0869813921100046
14. Paredes-Rodriguez E., Vegas-Suarez S., Morera-Herreras T., et al. The noradrenergic system in Parkinson’s disease. Front Pharmacol. 2020 Apr 8;11:435. doi:10.3389/fphar.2020.00435
15. McMillan P.J., White S.S., Franklin A., et al. Differential response of the central noradrenergic nervous system to the loss of locus coeruleus neurons in Parkinson’s disease and Alzheimer’s disease. Brain Res. 2011;1373:240–252. doi:10.1016/j.brainres.2010.12.015
16. Castellanos G., Fernández-Seara M.A., Lorenzo-Betancor O., et al. Automated neuromelanin imaging as a diagnostic biomarker for Parkinson’s disease. Mov Disord. 2015 Jun;30(7):945–952. doi:10.1002/mds.26201
17. Schwarz S.T., Xing Y., Tomar P., et al. In vivo assessment of brainstem depigmentation in Parkinson disease: potential as a severity marker for multicenter studies. Radiology. 2017 Jun;283(3):789–798. doi:10.1148/radiol.2016160662
18. Wang Z., Becker K., Donadio V., et al. Skin α-synuclein aggregation seeding activity as a novel biomarker for Parkinson disease. JAMA Neurol. 2020 Sep 28;78(1):1–11. doi:10.1001/jamaneurol.2020.3311
19. Yao N., Pang S., Cheung C., et al. Resting activity in visual and corticostriatal pathways in Parkinson’s disease with hallucinations. Parkinsonism Relat Disord. 2015;21(2):131–137. doi:10.1016/j.parkreldis.2014.11.020
20. Pasquini J., Rizzo G., Ferrucci R., et al. Serotonergic system degeneration and depression in Parkinson disease: a systematic review and meta-analysis. JAMA Neurol. 2020;77(5):593–603. doi:10.1001/jamaneurol.2019.4745
21. Miquel-Rio L., Alarcón-Arís D., Torres-López M., et al. Human α-synuclein overexpression in mouse serotonin neurons triggers a depressive-like phenotype. Rescue by oligonucleotide therapy. Transl Psychiatry. 2022;12:79. doi:10.1038/s41398-022-01842-z
22. Qamhawi Z., Towey D., Shah B., et al. Clinical correlates of raphe serotonergic dysfunction in early Parkinson’s disease. Brain. 2015 Oct;138(Pt 10):2964–2973. doi:10.1093/brain/awv215
23. Politis M., Niccolini F. Serotonin in Parkinson’s disease. Behav Brain Res. 2015 Jan 15;277:136–145. doi:10.1016/j.bbr.2014.07.037. Epub 2014 Jul 31. PMID: 25086269
24. Frisina P.G., Haroutunian V., Libow L.S. The neuropathological basis for depression in Parkinson’s disease. Parkinsonism Relat Disord. 2009 Jun;15(5):144–148. doi:10.1016/j.parkreldis.2008.03.004
25. Paulus W., Jellinger K. The neuropathologic basis of different clinical subgroups of Parkinson’s disease. J Neuropathol Exp Neurol. 1991;50(6):743–755
26. Pasquini J., Ceravolo R., Brooks D.J., et al. Progressive loss of raphe nuclei serotonin transporter in early Parkinson’s disease: a longitudinal 123I-FP-CIT SPECT study. Parkinsonism Relat Disord. 2020 Aug;77:170 175. doi:10.1016/j.parkreldis.2019.03.025
27. Kotagal V., Müller M.L., Koeppe R.A., et al. Neuroimaging evidence of cholinergic and dopaminergic deficits in Parkinson’s disease with REM sleep behavior disorder. Neurology. 2012 Apr 17;78(16):1120–1126. doi:10.1212/WNL.0b013e31824f804f. PMID: 22491867
28. Müller M.L.T.M., Bohnen N.I. Cholinergic dysfunction in Parkinson's disease. Curr Neurol Neurosci Rep. 2013;13(12):377. doi:10.1007/s11910-013-0377-1
29. Perez-Lloret S., Barrantes F.J. Deficits in cholinergic neurotransmission and their clinical correlates in Parkinson’s disease. NPJ Parkinsons Dis. 2016;2:16001. doi:10.1038/npjparkd.2016.1
30. Brown R.G., Landau S., Hindle J.V., et al.; PROMS-PD Study Group. Depression and anxiety related subtypes in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2011 Jul;82(7):803–809. doi:10.1136/jnnp.2010.213652
31. Khan A.F., Adewale Q., Lin S.J., Baumeister T.R., Zeighami Y., Carbonell F., Palomero-Gallagher N., Iturria-Medina Y. Patient-specific models link neurotransmitter receptor mechanisms with motor and visuospatial axes of Parkinson’s disease. Nat Commun. 2023 Sep 26;14(1):6009. doi:10.1038/s41467-023-41677-w
32. Fereshtehnejad S.M., Zeighami Y., Dagher A., Postuma R.B. Clinical criteria for subtyping Parkinson’s disease: biomarkers and longitudinal progression. Brain. 2017 Jul 1;140(7):1959–1976. doi:10.1093/brain/ awx118
33. Kazmi H., Walker Z., Booij J., et al. Late onset depression: dopaminergic deficit and clinical features of prodromal Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2021;92(2):158–164. doi:10.1136/jnnp-2020-323332
34. Nodel M.R., Makhmudova G.Zh., Niynoya I.V., Romanov D.V. Characteristics of patients with depression in the early stages of Parkinson’s disease: a cross-sectional observational study. Consilium Medicum. 2022;24(2):118–122 (in Russian). doi:10.26442/20751753.2022.2.201507
35. Kopylova L.I., Tappakhov A.A., Nikolaeva T.Ya., et al. Clinical and genetic predictors of anxiety in patients with Parkinson’s disease. Vestnik of North-Eastern Federal University. 2025;2(39):23–31(in Russian). doi:10.25587/2587-5590-2025-2-23-31
36. Hodgson P., Jordan A., Sinani C., et al. The relationship between physical function and psychological symptoms in Parkinson’s disease: a systematic review and meta-regression analysis. CNS Neurosci Ther. 2024 Feb;30(2):e14562. doi:10.1111/cns.14562
Review
For citations:
Smirnova E.V., Zhukova N.G. Mood disorders in Parkinson’s disease. Vestnik of North-Eastern Federal University. Medical Sciences. 2026;42(1):46-56. (In Russ.) https://doi.org/10.25587/2587-5590-2026-1-46-56
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