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Pathogenesis, clinical features, and treatments of depression in Parkinson's disease

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Depression is the most common non-motor manifestation of Parkinson's disease (PD), which significantly affects the rate of disease progression and increases the risk of motor complications and dementia. The paper considers the etiology and pathogenesis, cause-and-effect factors of depression in PD, and features of its diagnosis and treatment. Attention is paid to the algorithm for a physician's actions in the detection of depressive disorder in a patient with PD, to the choice of an antidepressant, and to the promising areas of therapy.

About the Author

I. V. Milyukhina
Institute of Experimental Medicine; Acad. I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia
Russian Federation

Irina Valentinovna Milyutina

12, Academician Pavlov St., Saint Petersburg 197376, 6/8, Lev Tolstoy St., Saint Petersburg 197089


1. Epidemiology and etiology of Parkinson's disease: a review of the evidence. Eur J Epidemiol. 2011 Jun;26 Suppl 1:S1-58. doi: 10.1007/s10654-011-9581-6. Epub 2011 May 28.

2. Razdorskaya VV, Voskresenskaya ON, Yudina GK. arkinson's disease in Russia: prevalence and incidence. Saratovskii nauchno-meditsinskii zhurnal. 2016; 12(3):379-84. (In Russ.).

3. Dissanayaka NN, Sellbach A, Silburn PA et al. Factors associated with depression in Parkinson's disease. J Affect Disord. 2011 Jul; 132(1-2):82-8. doi: 10.1016/j.jad.2011.01.021. Epub 2011 Feb 26.

4. Nilsson FM, Kessing LV, Sorensen TM, et al. Major depressive disorder in Parkinson's disease: A register-based study. Acta Psychiatr Scand. 2002 Sep;106(3):202-11.

5. Becker C, Brobert GP, Johansson S, et al. Risk of incident depression in patients with Parkinson disease in the UK. Eur J Neurol. 2011 Mar;18(3):448-53. doi: 10.1111/j.1468-1331.2010.03176.x. Epub 2010 Aug 16.

6. Kua ZJ, Pachana NA, Byrne GJ, et al. How Well Do Caregivers Detect Depression and Anxiety in Patients With Parkinson Disease? J Geriatr Psychiatry Neurol. 2018 Sep;31(5): 227-236. doi: 10.1177/0891988718788641. Epub 2018 Aug 2.

7. Lopez FV, Split M, Filoteo JV, et al. Does the Geriatric Depression Scale measure depression in Parkinson's disease? Int J Geriatr Psychiatry. 2018 Dec;33(12):1662-1670. doi: 10.1002/gps.4970. Epub 2018 Sep 25.

8. Schrag A, Barone P, Brown RG, et al. Depression rating scales in Parkinson's disease: critique and recommendations. Mov Disord. 2007 Jun 15;22(8):1077-92.

9. Burn DJ, Tiangyou W, Allcock LM, et al. Allelic variation of a functional polymorphism in the serotonin transporter gene and depression in Parkinson's disease.2006. Parkinsonism Relat Disord. 2006 Apr;12(3):139-41. Epub 2006 Feb 3.

10. Hua P, Liu W, Kuo SH, et al. Association of Tef polymorphism with depression in Parkinson disease. Mov Disord. 2012 Nov;27(13):1694-7. doi: 10.1002/mds.25195. Epub 2012 Nov 8.

11. Senkevich KA, Milyukhina IV, Beletskaya MV, et al. Clinical features of Parkinson's disease in patients with mutations and polymorphic variants of the GBA gene. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2017;117(10): 81-6. (In Russ.).

12. Gaig C, Vilas D, Infante J, et al. Nonmotor symptoms in LRRK2 G20195 associated Parkinson's disease. PLoS One. 2014 Oct 17; 9(10):e108982. doi: 10.1371/journal.pone.0108982. eCollection 2014.

13. Dan X, Wang C, Zhang J, et al. Association between common genetic risk variants and depression in Parkinson's disease: A dPD study in Chinese. Parkinsonism Relat Disord. 2016 Dec;33:122-126. doi: 10.1016/j.parkreldis.2016.09.029. Epub 2016 Sep 29.

14. Abbas MM, Govindappa ST, Sudhaman S, et al. Early onset Parkinson's disease due to DJ1 mutations: An Indian study. Parkinsonism Relat Disord. 2016 Nov;32:20-24. doi: 10.1016/j.parkreldis.2016.04.024. Epub 2016 Apr 24.

15. Hanagasi HA, Giri A, Kartal E, et al. A novel homozygous DJ1 mutation causes parkinsonism and ALS in a Turkish family. Parkinsonism Relat Disord. 2016 Aug;29:117-20. doi: 10.1016/j.parkreldis.2016.03.001. Epub 2016 Mar 3.

16. Georgiev D, Hamberg K, Hariz M, et al. Gender differences in Parkinson's disease: A clinical perspective. Acta Neurol Scand. 2017 Dec;136(6):570-584. doi: 10.1111/ane.12796. Epub 2017 Jul 2.

17. Palhagen SE, Carlsson M, Curman E, et al. Depressive illness in Parkinson's disease indication of a more advanced and widespread neurodegenerative process? Acta Neurol Scand. 2008 May;117(5):295-304. doi: 10.1111/j.16000404.2007.00986.x. Epub 2008 Feb 13.

18. Goodarzi Z, Mrklas KJ, Roberts DJ, et al. Detecting depression in Parkinson disease: a systematic review and meta-analysis. Neurology. 2016 Jul 26;87(4):426-37. doi: 10.1212/WNL.0000000000002898. Epub 2016 Jun 29.

19. Dogan B, Akyol A, Memis CO, et al. The relationship between temperament and depression in Parkinson's disease patients under dopaminergic treatment. Psychogeriatrics. 2019 Jan;19(1):73-79. doi: 10.1111/psyg.12366. Epub 2018 Aug 23.

20. Richard IH, Justus AW, Kurlan R. Relationship between mood and motor fluctuations in Parkinson's disease. J Neuropsychiatry Clin Neurosci. 2001 Winter;13(1):35-41.

21. Ehrt U, Brњnnick K, Leentjens AF, et al. Depressive symptom profile in Parkinson's disease: a comparison with depression in elderly patients without Parkinson's disease. Int J Geriatr Psychiatry. 2006 Mar;21(3):252-8.

22. Myslobodsky M, Lalonde FM, Hicks L. Are patients with Parkinson's disease suicidal? J Geriatr Psychiatry Neurol. 2001 Fall;14(3):120-4.

23. Ishihara L, Brayne C. What is the evidence for a premorbid parkinsonian personality: a systematic review. Mov Disord. 2006 Aug;21(8): 1066-72.

24. Milyukhina IV, Gracheva EV. Modern ideas about walking disorders in Parkinson's disease and methods of their correction. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2018;118(6):96-101. (In Russ.).

25. Herman T, Shema-Shiratzky S, Arie L, et al. Depressive symptoms may increase the risk of the future development of freezing of gait in patients with Parkinson's disease: Findings from a 5-year prospective study. Parkinsonism Relat Disord. 2018 Sep 11. pii: S1353-8020 (18)30398-5. [Epub ahead of print]

26. Ng A, Chander RJ, Tan LC, Kandiah N. Influence of depression in mild Parkinson's disease on longitudinal motor and cognitive function. Parkinsonism Relat Disord. 2015 Sep; 21(9):1056-60. doi: 10.1016/j.parkreldis.2015.06.014. Epub 2015 Jun 18.

27. Lee Y, Oh JS, Chung SJ, et al. The presence of depression in de novo Parkinson's disease reflects poor motor compensation. PLoS One. 2018 Sep 19;13(9):e0203303. doi: 10.1371/journal.pone.0203303. eCollection 2018.

28. Shoval G, Stubbs B, Balicer RD, et al. Low adherence to antidepressants is associated with increased mortality in Parkinson disease patients. Parkinsonism Relat Disord. 2017 Oct;43: 92-96. doi: 10.1016/j.parkreldis.2017.07.032. Epub 2017 Aug 1.

29. Rod NH, Bordelon Y, Thompson A, et al. Major life events and development of major depression in Parkinson's disease patients. Eur J Neurol. 2013 Apr;20(4):663-70. doi: 10.1111/ene.12019. Epub 2012 Oct 30.

30. Chagas MHN, Tumas V, Pena-Pereira MA, et al. Neuroimaging of major depression in Parkinson's disease: cortical thickness, cortical and subcortical volume, and spectroscopy findings. J Psychiatr Res. 2017 Jul;90:40-45. doi: 10.1016/j.jpsychires.2017.02.010. Epub 2017 Feb 13.

31. Hu X, Song X, Li E, et al. Altered restingstate brain activity and connectivity in depressed Parkinson's disease. PLoS One. 2015 Jul 6;10(7):e0131133. doi: 10.1371/journal.pone.0131133. eCollection 2015.

32. Nodel' MR. Depression in Parkinson's disease as a leading factor in the deterioration of quality of life. Meditsinskii Sovet. 2013;(4):36-41. (In Russ.)

33. Thobois S, Prange S, Sgambato-Faure V, et al. Imaging the Etiology of Apathy, Anxiety, and Depression in Parkinson's Disease: Implication for Treatment. Curr Neurol Neurosci Rep. 2017 Aug 18;17(10):76. doi: 10.1007/s11910-017-0788-0.

34. Milyukhina IV, Karpenko MN, Timofeeva AA, et al. The role of inflammation in the pathogenesis ofParkinson's disease. Nevrologicheskii zhurnal. 2013;(3):51-5. (In Russ.).

35. Wang Q, Liu Y, Zhou J. Neuroinflammation in Parkinson's disease and its potential as therapeutic target. Transl Neurodegener. 2015 Oct 12; 4:19. doi: 10.1186/s40035-015-0042-0. eCollection 2015.

36. Lindqvist D, Hall S, Surova Y, et al. Cerebrospinal fluid inflammatory markers in Parkinson's disease-associations with depression, fatigue, and cognitive impairment. Brain Behav Immun. 2013 Oct;33:183-9. doi: 10.1016/j.bbi.2013.07.007. Epub 2013 Jul 31.

37. Milyukhina IV, Karpenko MN, Klimenko VM. Comparison of clinical parameters and levels of some cytokines in blood and cerebrospinal fluid in patients with Parkinson's disease. Klinicheskaya meditsina. 2015;(1):51-6. (In Russ.)

38. Smith RS. The macrophage theory of depression. Med Hypotheses. 1991 Aug;35(4): 298-306.

39. Panagiotakos DB, Pitsavos C, Chrysohoou C, et al. Inflammation, coagulation, and depressive symptomatology in cardiovascular disease-free people; the ATTICA study. Eur Heart J. 2004 Mar;25(6):492-9.

40. Shao HC, Chen CT, Lin WC, et al. Clinical Factors Associated with the Risks of Depression in Patients with Parkinson's Disease. Neuropsychiatry (London). 2017;7(4):416-23.

41. Wu YH, Chen YH, Chang MH, Lin CH. Depression in Parkinson's disease: A case-control study. PLoS One. 2018 Feb 1;13(2): e0192050. doi: 10.1371/journal.pone.0192050. eCollection 2018.

42. Nodel' MR. Depression in Parkinson's disease. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2010;2(4):11-7. (In Russ.). doi: 10.14412/2074-2711-2010-110

43. Devos D, Dujardin K, Poirot I, et al. Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: A double-blind, randomized, placebocontrolled study. Mov Disord. 2008 Apr 30;23(6):850-7. doi: 10.1002/mds.21966.

44. Menza M, Dobkin RD, Marin H, et al. A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology. 2009 Mar 10;72(10):886-92. doi: 10.1212/01.wnl.0000336340.89821.b3. Epub 2008 Dec 17.

45. Bomasang-Layno E, Fadlon I, Murray AN et al. Antidepressive treatments for Parkinson's disease: A systematic review and meta-analysis. Parkinsonism Relat Disord. 2015 Aug;21(8): 833-42; discussion 833. doi: 10.1016/j.parkreldis.2015.04.018. Epub 2015 May 16.

46. Cooney JW, Stacy M. Neuropsychiatric issues in Parkinson's disease. Curr Neurol Neurosci Rep. 2016 May;16(5):49. doi: 10.1007/s11910-016-0647-4.

47. Zahodne LB, Bernal-Pacheco O, Bowers D, et al. Are selective serotonin reuptake inhibitors associated with greater apathy in Parkinson's disease? J Neuropsychiatry Clin Neurosci. 2012 Summer;24(3):326-30. doi: 10.1176/appi.neuropsych.11090210.

48. Mills KA, Greene MC, Dezube R, et al. Efficacy and tolerability of antidepressants in Parkinson's disease: A systematic review and network meta-analysis. Int J Geriatr Psychiatry. 2018 Apr;33(4):642-651. doi: 10.1002/gps.4834. Epub 2017 Dec 13.

49. Zhuo C, Xue R, Luo L, et al. Efficacy of antidepressive medication for depression in Parkinson disease. Medicine (Baltimore). 2017 Jun;96(22):e6698. doi: 10.1097/MD.0000000000006698.

50. Stahl SM. Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): enhancing serotonin release by combining serotonin (5HT) transporter inhibition with actions at 5HT receptors (5HT1A, 5HT1B, 5HT1D, 5HT7 receptors). CNS Spectr. 2015 Apr;20(2):93-7. doi: 10.1017/S1092852915000139.

51. Christensen MC, Loft H, McIntyre RS. Vortioxetine improves symptomatic and functional outcomes in major depressive disorder: A novel dual outcome measure in depressive disorders. J Affect Disord. 2018 Feb;227:787-794. doi: 10.1016/j.jad.2017.11.081. Epub 2017 Nov 16.

52. Koesters M, Ostuzzi G, Guaiana G, et al. Vortioxetine for depression in adults. Cochrane Database Syst Rev. 2017 Jul 5;7:CD011520. doi: 10.1002/14651858.CD011520.pub2.

53. Timmer MHM, van Beek MHCT, Bloem BR, Esselink RAJ. What a neurologist should know about depression in Parkinson's disease. Pract Neurol. 2017 Oct;17(5):359-368. doi: 10.1136/practneurol-2017-001650. Epub 2017 Jul 24.

54. Rosenquist PB, Youssef NA, Surya S, et al. When All Else Fails. Psychiatr Clin North Am. 2018 Sep;41(3):355-371. doi: 10.1016/j.psc.2018.04.002. Epub 2018 Jun 15.

55. Koychev I, Okai D. Cognitive-behavioural therapy for non-motor symptoms of Parkinson's disease: a clinical review. Evid Based Ment Health. 2017 Feb;20(1):15-20. doi: 10.1136/eb-2016-102574. Epub 2017 Jan 10.

56. Wu PL, Lee M, Huang TT. Effectiveness of physical activity on patients with depression and Parkinson's disease: A systematic review. PLoS One. 2017 Jul 27;12(7):e0181515. doi: 10.1371/journal.pone.0181515. eCollection 2017.


For citation:

Milyukhina I.V. Pathogenesis, clinical features, and treatments of depression in Parkinson's disease. Neurology, Neuropsychiatry, Psychosomatics. 2019;11(2):93-99. (In Russ.)

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ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)