On the heterogeneity of depression in Parkinson’s disease

Depression in Parkinson’s disease (PD) is one of the leading manifestations of the disease, which reduces quality of life in patients.

Objective: to compare the clinical features of depression at different stages of PD.

Patients and methods. Examinations were made in 162 PD patients aged 62.14±1.99 years without dementia (PD duration, 5.78±0.58 years; Stage, 2.5±0.6). The Unified PD Rating Scale (UPDRS), the Beck Depression Inventory (BDI), and the Spielberger Inventory, the 16-Item PD Fatigue Scale (PFS-16), and the Starkstein Apathy Scale were examined. Dopaminergic agents (DAAs) were prescribed when movement disorders were insufficiently corrected. Antidepressants were not used during the investigation. The follow-up period was 18 months.

Results and discussion. Depression was detected in 136 (84%) patients. Depression symptoms appeared in 16 (12%) patients within 1–8 years before the onset of motor symptoms (MS), in 37 (27%) in the first 2 years after the onset of MS, in 44 (32%) at Hoehn–Yahr stages 2–3 without motor fluctuations (MFs), and in 39 (29%) at the onset of MF. The most severity of depression was noted in cases of its development at the premotor stage and in the period of MF occurrence. During the follow-up, the manifestations of depression disappeared in 16% of the patients taking a DAA; these were relapsing-remitting in 9%, progressive in 11%, or remained stable in 64%. The patients with depression occurring at the premotor stage had a progressive course of depression and a low DAA efficacy: an increase in severity in 30% of cases despite therapy and a reversal in only 10% of cases (versus 25–45% of those at depression onset in the presence of MS). In cases of depression occurring in the first 2 years after MS onset, its reversal was observed in 45%; the group of patients with depression onset in the presence of MF showed a stable course with slight severity fluctuations in 77.8%.

Conclusion. Depression in PD is a heterogeneous affective disorder. There is a relatively favorable course of depression when the latter occurs in the first two years of MS onset. Along with DAA inefficacy, the more severity of depression is noted when the latter occurs in the premotor phase of PD and at the stage of MF.

1. Aarsland D, Pahlhagen S, Ballard CG, et al. Depression in Parkinson disease – epidemiology, mechanisms and management. Nat Rev Neurol. 2011 Dec 26;8(1):35-47. doi: 10.1038/nrneurol.2011.189

2. Reijnders J, Ehrt U, Weber W, et al. A systematic review of prevalence studies of depression in Parkinson's disease. Mov Disord. 2008 Jan 30;23(2):183-9; quiz 313. doi: 10.1002/mds.21803

3. Shrag A, Jahanshahi M, Quinn NP. What contributes to quality life in patients with Parkinsons disease? J Neurol Neurosurg Neuropsych. 2000 Sep;69(3):308-12. doi: 10.1136/jnnp.69.3.308

4. Mc Kinlay A, Grace RC, Dalrymple-Alford JC, et.al. A profile of neuropsychiatric problems and their relationship to quality of life for Parkinsons disease. Park Relat Disord. 2008;14(1):37-42. doi: 10.1016/j.parkreldis.2007.05.009. Epub 2007 Jul 12.

5. Nodel МR. The impact of neuropsychiatric symptoms on quality of life of patients with Parkinsons disease. Neurologicheskiy zhurnal. 2015;20(1):20-7. doi: 10.18821/1560-9545-2015-20-1-20-27 (In Russ.).

6. Pontone G, Bakker C, Chen S, et al. The longitudinal impact of depression on disability in Parkinson disease. Int J Geriatr Psychiatry. 2016 May;31(5):458-65. doi: 10.1002/gps.4350. Epub 2015 Aug 18.

7. Nodel МR, Danilova NN, Glozman GM, Yahno NN. The relationship between cognitive and emotional-affective disorders in patients with Parkinson's disease. Neurologicheskiy zhurnal. 2016;(6):338-43 (In Russ.

8. De Lau L, Verbaan D, Marinus J, van Hilten J. Survival in Parkinson's disease. Relation with motor and non-motor features. Parkinsonism Relat Disord. 2014 Jun;20(6):613-6. doi: 10.1016/j.parkreldis.2014.02.030. Epub 2014 Mar 12.

9. Castrioto A, Thobois S, Carnicella S, et al. Emotional manifestations of PD: Neurobiological basis. Mo Disord. 2016 Aug;31(8):1103-13. doi: 10.1002/mds.26587. Epub 2016 Apr 4.

10. Wang S, Mao S, Xiang D, et al. Association between depression and the subsequent risk of Parkinson's disease: A meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Aug 30;86:186-92. doi: 10.1016/j.pnpbp.2018.05.025. Epub 2018 May 31.

11. Leentjens AF. Parkinson disease: Depression-risk factor or early symptom in Parkinson disease? Nat Rev Neurol. 2015 Aug;11(8):432-3. doi: 10.1038/nrneurol.2015.126. Epub 2015 Jul 28.

12. Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson's disease. Mov Disord. 2015 Oct;30(12):1600-11. doi: 10.1002/mds.26431

13. Rojo A, Aguilar M, Garolera MT, et al. Depression in Parkinson's disease: clinical correlates and outcome. Parkinsonism Relat Disord. 2003 Oct;10(1):23-8. doi: 10.1016/s1353-8020(03)00067-1

14. Fahn S, Elton RL; UPDRS Development Committee. Unified Parkinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M, eds. Recent Developments in Parkinson’s Disease. Florham Park, NJ: Macmillan; 1987. P. 153-63.

15. Beck A, Streer R, Brown G. Depression Inventory – II. San Antonio, TX: Psychological Corporation; 1996.

16. Spielberger CD, Gorsuch RL, Lushene R. Manual for the State-Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists Press; 1983.

17. Brown RG, Dittner A, Findley L, Wessely SC. The Parkinson fatigue scale. Parkinsonism Relat Disord. 2005 Jan;11(1):49-55. doi: 10.1016/j.parkreldis.2004.07.007

18. Pedersen KF, Alves G, Larsen JP, et al. Psychometric properties of the Starkstein Apathy Scale in patients with early untreated Parkinson disease. Am J Geriatr Psychiatry. 2012 Feb;20(2):142-8. doi: 10.1097/JGP.0b013e31823038f2

19. Reiff J, Schmidt N, Riebe B. Subthreshold depression in Parkinson's disease. Mov Disord. 2011 Aug 1;26(9):1741-4. doi: 10.1002/mds.23699. Epub 2011 Mar 25.

20. Nodel МR, Yahno NN. Features of depression in Parkinson's disease. Doctоr. ru. 2013;(5):50-4 (In Russ.).

21. Nodel МR, Yahno NN. Apathy in Parkinson's disease. Nevrologicheskii zhurnal = Neurological Journal. 2014;(1):9-15 (In Russ.).

22. Nodel МR, Yahno NN. Fatigue in Parkinson's disease. Nevrologicheskii zhurnal = Neurological Journal. 2017;(5):244-51 (In Russ.).

23. Ehrt U, Bronnick K, Leentjens AFG, 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. doi: 10.1002/gps.1456

24. Smulevich AB. Depressii pri psikhicheskikh i somaticheskikh zabolevaniyakh [Depressions in mental and somatic diseases]. Moscow: Medical information Agency; 2015. 640 p. (In Russ.).

25. Klepac N, Hajnsek S, Trkulja V. Impact of pre-morbid depression on health-related quality of life in non-demented Parkinson's disease patients. Parkinsonism Relat Disord. 2010 Jan;16(1):21-7. doi: 10.1016/j.parkreldis.2009.07.003. Epub 2009 Jul 28.

26. Braak H, Del Tredici K, Rub U, et al. Staging of brain pathology related to sporadic Parkinsons disease. Neurol Aging. Mar-Apr 2003;24(2):197-211. doi: 10.1016/s0197-4580(02)00065-9

27. Ishihara L, Brayne C. What is the evidence for a premorbid parkinsonian personality: a systematic review. Mov Disord. 2006 Aug;21(8):1066-72. doi: 10.1002/mds.20980

28. Faustino PR, Duarte GS, Chendo I, et al. Risk of Developing Parkinson Disease in Bipolar Disorder. A Systematic Review and Meta-analysis. JAMA Neurol. 2020 Feb 1;77(2):192-8. doi: 10.1001/jamaneurol.2019.3446

29. 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

30. Wilson H, Dervenoulas G, Pagano G, et al. Serotonergic Pathology and Disease Burden in the Premotor and Motor Phase of A53T α-Synuclein Parkinsonism: A Cross-Sectional Study. Lancet Neurol. 2019 Aug;18(8):748-59. doi: 10.1016/S1474-4422(19)30140-1. Epub 2019 Jun 19.

31. Maillet A, Krack P, Lhommee E, et al. The Prominent Role of Serotonergic Degeneration in Apathy, Anxiety and Depression in De Novo Parkinson's Disease. Brain. 2016 Sep;139(Pt9):2486-502. doi: 10.1093/brain/aww162. Epub 2016 Aug 17.

32. 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):2964-73. doi: 10.1093/brain/awv215. Epub 2015 Jul 23.

33. Pasquini J, Ceravolo R, Brooks DJ, et al. Progressive Loss of Raphe Nuclei Serotonin Transporter in Early Parkinson's Disease: A Longitudinal 123I-FP-CIT SPECT Study. Parkinsonism Relat Disord. 2019 Apr 5;1353- 8020(19):30185-3. doi: 10.1016/j.parkreldis.2019.03.025. Online ahead of print.

34. Remy P, Doder M, Lees A, et al. Depression in Parkinson's Disease: Loss of Dopamine and Noradrenaline Innervation in the Limbic System. Brain. 2005 Jun;128(Pt 6):1314-22. doi: 10.1093/brain/awh445. Epub 2005 Feb 16.

35. Barone P, Poewe W, Albrecht S, et al. Pramipexole for the treatment of depressive symptoms in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010 Jun;9(6):573-80. doi: 10.1016/S1474-4422(10)70106-X. Epub 2010 May 7.

36. Nodel MR, Yakhno NH. Mirapex (pramipexol) in the treatment of non-motor disorders in Parkinson's disease. Zhurnal neurologii i psychiatrii im. S. S. Korsakova. 2008;108(5):32-8 (In Russ.).

37. Wu Y-H, Lee W-J, Chen Y-H, et al. Premotor Symptoms as Predictors of Outcome in Parkinsons Disease: A Case-Control Study. PLoS One. 2016 Aug 17;11(8):e0161271. doi: 10.1371/journal.pone.0161271. eCollection 2016.

38. Zhang Q, Yang X, Song H, et al. Cognitive behavioral therapy for depression and anxiety of Parkinson's disease: A systematic review and meta-analysis. Complement Ther Clin Pract. 2020 May;39:101111. doi: 10.1016/j.ctcp.2020.101111. Epub 2020 Jan 30.