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5-HTTLPR polymorphism and depression risk in Parkinson's disease: an updated meta-analysis

Acta Neurologica Belgica volume 121, pages 933–940 (2021)Cite this article

Abstract

The relationship between the 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) and depression in Parkinson's disease (PD) has remained controversial. Therefore, we conducted this meta-analysis to evaluate the relationship between 5-HTTLPR polymorphisms and depression in PD. Relevant online databases were searched for cross-sectional, case–control or cohort studies examining relations between 5-HTTLPR polymorphisms (S/L) and the risk of developing depression of PD using a meta-analysis. Odd ratios (ORs) of 5-HTTLPR polymorphisms (S/L allele genotype) were calculated between depression in PD and PD for each study. Five observational studies were identified. Overall ORs for 5-HTTLPR S-Allele genotype was 1.98 (95% CI 0.92–4.26) in the dominant model, 1.43 (95% CI 1.08–1.90) in the recessive model, 2.64 (95% CI 1.01–6.88) in the additive model, independently. The overall ORs of S-Allele genotype was 1.51 (95% CI 0.63–3.64) for the Caucasian subgroup, and 1.44 (95% CI 1.05–1.98) for the non-Caucasian subgroup in the recessive model. This meta-analysis indicates that the 5-HTTLPR genotype (S/S-Allele) is correlated with an increased depression risk in PD, and this highlights the needs for these people to take some effective approaches (if any) in prevention of depression of PD before its onset.

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References

  1. Aarsland D, Påhlhagen S, Ballard CG, Ehrt U, Svenningsson P (2012) Depression in Parkinson disease epidemiology, mechanisms and management. Nat Rev Neurol 8(1):35–47

    CAS  Article  Google Scholar 

  2. Tremblay C, Achim AM, Macoir J, Monetta L (2013) The heterogeneity of cognitive symptoms in Parkinson's disease: a meta-analysis. J Neurol Neurosurg Psychiatry 84(11):1265–1272

    Article  Google Scholar 

  3. Morgante L, Colosimo C, Antonini A, Marconi R, Meco G, Pederzoli M et al (2012) Psychosis associated to Parkinson's disease in the early stages: relevance of cognitive decline and depression. J Neurol Neurosurg Psychiatry 83(1):76–82

    Article  Google Scholar 

  4. Ravina B, Elm J, Camicioli R, Como PG, Marsh L, Jankovic J et al (2009) The course of depressive symptoms in early Parkinson's disease. Mov Disord 24(9):1306–1311

    Article  Google Scholar 

  5. Starkstein SE, Mayberg HS, Leiguarda R, Preziosi TJ, Robinson RG (1992) A prospective longitudinal study of depression, cognitive decline, and physical impairments in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry 55(5):377–382

    CAS  Article  Google Scholar 

  6. Vriend C, Raijmakers P, Veltman DJ, van Dijk KD, van der Werf YD, Foncke EM et al (2014) Depressive symptoms in Parkinson's disease are related to reduced [123I] FP-CIT binding in the caudate nucleus. J Neurol Neurosurg Psychiatry 85(2):159–164

    Article  Google Scholar 

  7. Sagna A, Gallo JJ, Pontone GM (2014) Systematic review of factors associated with depression and anxiety disorders among older adults with Parkinson's disease. Parkinsonism Relat Disord 20(7):708–715

    Article  Google Scholar 

  8. Committee GPsDSS (2002) Factors impacting on quality of life in Parkinson's disease: results from an international survey. Mov Disord 17(1):60

    Article  Google Scholar 

  9. Leentjens AF, Moonen AJ, Dujardin K, Marsh L, Martinez-Martin P, Richard IH et al (2013) Modeling depression in Parkinson disease Disease-specific and nonspecific risk factors. Neurology 81(12):1036–1043

    Article  Google Scholar 

  10. Reijnders JS, Ehrt U, Weber WE, Aarsland D, Leentjens AF (2008) A systematic review of prevalence studies of depression in Parkinson's disease. Mov Disord 23(2):183–189

    Article  Google Scholar 

  11. Schrag A (2006) Quality of life and depression in Parkinson's disease. J Neurol Sci 248(1):151–157

    Article  Google Scholar 

  12. Tamminga CA, Nemeroff CB, Blakely RD, Brady L, Carter CS, Davis KL et al (2002) Developing novel treatments for mood disorders: accelerating discovery. Biol Psychiatry 52(6):589–609

    Article  Google Scholar 

  13. Burn DJ (2002) Beyond the iron mask: towards better recognition and treatment of depression associated with Parkinson's disease. Mov Disord 17(3):445–454

    Article  Google Scholar 

  14. Nakamura M, Ueno S, Sano A, Tanabe H (2000) The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants. Mol Psychiatry 5(1):32–38

    CAS  Article  Google Scholar 

  15. Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS et al (1993) Antidepressant-and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci USA 90(6):2542–2546

    CAS  Article  Google Scholar 

  16. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H et al (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301(5631):386–389

    CAS  Article  Google Scholar 

  17. Hariri AR, Mattay VS, Tessitore A, Kolachana B, Fera F, Goldman D et al (2002) Serotonin transporter genetic variation and the response of the human amygdala. Science 297(5580):400–403

    CAS  Article  Google Scholar 

  18. Lesch K-P, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S et al (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274(5292):1527–1531

    CAS  Article  Google Scholar 

  19. Mak KK, Kong WY, Mak A, Sharma VK, Ho RC (2013) Polymorphisms of the serotonin transporter gene and post-stroke depression: a meta-analysis. J Neurol Neurosurg Psychiatry 84(3):322–328

    Article  Google Scholar 

  20. Murphy DL, Lesch K-P (2008) Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev Neurosci 9(2):85–96

    CAS  Article  Google Scholar 

  21. Risch N, Herrell R, Lehner T, Liang K-Y, Eaves L, Hoh J et al (2009) Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 301(23):2462–2471

    CAS  Article  Google Scholar 

  22. Gao L, Gao H (2014) Association between 5-HTTLPR polymorphism and Parkinson’s disease: a meta analysis. Mol Biol Rep 41(9):6071–6082

    CAS  Article  Google Scholar 

  23. Dissanayaka NN, Silburn PA, O'Sullivan JD, Mellick GD (2009) Serotonin and dopamine transporter genes do not influence depression in Parkinson's disease. Mov Disord 24(1):111–115

    Article  Google Scholar 

  24. Wang J-Y, Fan Q-Y, He J-H, Zhu S-G, Huang C-P, Zhang X et al (2019) SLC6A4 repeat and single-nucleotide polymorphisms are associated with depression and rest tremor in Parkinson’s disease: An exploratory study. Front Neurol 10:333

    Article  Google Scholar 

  25. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605

    Article  Google Scholar 

  26. Menza MA, Palermo B, DiPaola R, Sage JI, Ricketts MH (1999) Depression and anxiety in Parkinson's disease: possible effect of genetic variation in the serotonin transporter. J Geriatr Psychiatry Neurol 12(2):49–52

    CAS  Article  Google Scholar 

  27. Mossner R, Henneberg A, Schmitt A, Syagailo Y, Grassle M, Hennig T et al (2001) Allelic variation of serotonin transporter expression is associated with depression in Parkinson’s disease. Mol Psychiatry 6(3):350–352

    CAS  Article  Google Scholar 

  28. Zhang J-L, Yang J-F, Chan P (2009) No association between polymorphism of serotonin transporter gene and depression in Parkinson's disease in Chinese. Neurosci Lett 455(3):155–158

    CAS  Article  Google Scholar 

  29. Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, Kolachana BS et al (2005) 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci 8(6):828–834

    CAS  Article  Google Scholar 

  30. Iurescia S, Seripa D, Rinaldi M (2016) Role of the 5-HTTLPR and SNP promoter polymorphisms on serotonin transporter gene expression: a closer look at genetic architecture and in vitro functional studies of common and uncommon allelic variants. Mol Neurobiol 53(8):5510–5526

    CAS  Article  Google Scholar 

  31. Perrin AJ, Nosova E, Co K, Book A, Iu O, Silva V et al (2017) Gender differences in Parkinson's disease depression. Parkinsonism Relat Disord 36:93–97

    Article  Google Scholar 

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Acknowledgements

This study was supported by research grants from the National Natural Science Foundation of China (Grant No. 81871034), the Natural Science Foundation of Heilongjiang Province (Grant no. H2016087), the Natural Science Program of Health and Family Planning Commission of Heilongjiang Province (Grant no. 2016-280), and the Natural Science Program of Jiamusi University (Grant no. JMSURCGG2016-004).

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  1. Pengfei Cheng, Junxiang Zhang and Yu Wu contributed equally to this manuscript.

Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Jiamusi University, 348 Xuefu Street, Xiangyang District, Jiamusi, 154002, Heilongjiang Province, People’s Republic of China

    Pengfei Cheng, Junxiang Zhang, Wenting Liu & Jiaying Zhu

  2. Institute of Clinical Research and Translational Medicine, Gansu Provincial Hospital, Lanzhou, People’s Republic of China

    Yu Wu

  3. School of Basic Medicine, Jiamusi University, Jiamusi, People’s Republic of China

    Ze Chen, Jiarui Zhang, Songwen Guan, Yiming Sun & Jingxia Wang

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  1. Pengfei Cheng
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  2. Junxiang Zhang
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Correspondence to Pengfei Cheng.

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Cheng, P., Zhang, J., Wu, Y. et al. 5-HTTLPR polymorphism and depression risk in Parkinson's disease: an updated meta-analysis. Acta Neurol Belg 121, 933–940 (2021). https://doi.org/10.1007/s13760-020-01342-1

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  • DOI: https://doi.org/10.1007/s13760-020-01342-1

Keywords

  • 5-Hydroxytryptamine transporter
  • 5-HTTLPR
  • Gene
  • Depression
  • Parkinson's disease