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Psychiatric Quarterly

, Volume 84, Issue 4, pp 485–497 | Cite as

Measurement Methods of BDNF Levels in Major Depression: A Qualitative Systematic Review of Clinical Trials

  • Stefania Pigatto Teche
  • Gabriela Lotin Nuernberg
  • Anne Orgler Sordi
  • Lívia Hartmann de Souza
  • Lysa Remy
  • Keila Maria Mendes Ceresér
  • Neusa Sica Rocha
Original Paper

Abstract

There is evidence that the brain-derived neurotrophic factor (BDNF) has implications for the pathophysiology of major depressive disorders (MDD). Measures of BDNF levels are highly dependent on the methodologies used and these vary among different studies. Therefore, the aim of this study was to carry out a descriptive analysis of the methodologies used to measure BDNF in clinical trials (CT) in patients with the diagnosis of major depression. We conducted a qualitative systematic review of CT that included samples of subjects diagnosed with major depression and evaluated the BDNF levels as an outcome. The search was performed on Pubmed, Scielo, Psychinfo and Lilacs. The selected articles were analyzed according to the CONSORT Statement and their methods of BDNF collection and analysis were described. Twenty-eight studies were included in the final analysis. Of those, 6 trials (21.4 %) involved non-pharmacological interventions and only half had the MDD diagnosis based on structured interview. Trials used different methods to evaluate BDNF levels: most of them verified serum BDNF levels, 17 (60.7 %) trials mentioned that measured BDNF levels in duplicate and 9 (32.1 %) collected blood in fasting. A variety of methods for BDNF collection and analysis was used in the different studies, making it difficult to compare results. However, despite of the methodology, BDNF seems to increase after treatment for major depression.

Keywords

Systematic review Clinical trials Depression BDNF 

Notes

Acknowledgments

This study was supported by PPG Psychiatry UFRGS (Post-Graduation Program in Medical Sciences: Psychiatry, Universidade Federal do Rio Grande do Sul) and Hospital de Clínicas de Porto Alegre.

Conflict of interest

The authors have no potential conflict of interest pertaining to this submission.

References

  1. 1.
    Brundtland GH. From the World Health Organization. Mental health: new understanding, new hope. JAMA. 2001;286(19):2391.Google Scholar
  2. 2.
    Murray CJ, Lopez AD. Evidence-based health policy–lessons from the Global Burden of Disease Study. Science. 1996;274(5288):740–3.Google Scholar
  3. 3.
    Regier DA, Narrow WE, Rae DS, Manderscheid RW, Locke BZ, Goodwin FK. The de facto US mental and addictive disorders service system. Epidemiologic catchment area prospective 1-year prevalence rates of disorders and services. Arch Gen Psychiatry. 1993;50(2):85–94.Google Scholar
  4. 4.
    Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51(1):8–19.Google Scholar
  5. 5.
    Picinelli M, Gomez Homen F. Gender differences in the epidemiology of affective disorders and schizophrenia. World Health Organization: Gevena, Switzerland; 1997.Google Scholar
  6. 6.
    Yukimasa T, Yoshimura R, Tamagawa A, Uozumi T, Shinkai K, Ueda N, et al. High-frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors. Pharmacopsychiatry. 2006;39(2):52–9.Google Scholar
  7. 7.
    Molteni R, Calabrese F, Cattaneo A, Mancini M, Gennarelli M, Racagni G, et al. Acute stress responsiveness of the neurotrophin BDNF in the rat hippocampus is modulated by chronic treatment with the antidepressant duloxetine. Neuropsychopharmacology. 2009;34(6):1523–32.Google Scholar
  8. 8.
    Yoshimura R, Mitoma M, Sugita A, Hori H, Okamoto T, Umene W, et al. Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor in depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(5):1034–7.Google Scholar
  9. 9.
    Gorgulu Y, Caliyurt O. Rapid antidepressant effects of sleep deprivation therapy correlates with serum BDNF changes in major depression. Brain Res Bull. 2009;80(3):158–62.Google Scholar
  10. 10.
    Oliveira CO, Ikuta N, Regner A. Biomarcadores prognósticos no traumatismo crânio-encefálico grave. Rev bras ter intensiva. 2008;20(4).Google Scholar
  11. 11.
    Sen S, Duman R, Sanacora G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry. 2008;64(6):527–32.Google Scholar
  12. 12.
    Brunoni AR, Lopes M, Fregni F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol. 2008;11(8):1169–80.Google Scholar
  13. 13.
    Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A, et al. Serum and plasma BDNF levels in major depression: a replication study and meta-analyses. World J Biol Psychiatry. 2010;11(6):763–73.Google Scholar
  14. 14.
    Aydemir O, Deveci A, Taneli F. The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(2):261–5.Google Scholar
  15. 15.
    Gonul AS, Akdeniz F, Taneli F, Donat O, Eker C, Vahip S. Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients. Eur Arch Psychiatry Clin Neurosci. 2005;255(6):381–6.Google Scholar
  16. 16.
    Bocchio-Chiavetto L, Zanardini R, Bortolomasi M, Abate M, Segala M, Giacopuzzi M, et al. Electroconvulsive Therapy (ECT) increases serum Brain Derived Neurotrophic Factor (BDNF) in drug resistant depressed patients. Eur Neuropsychopharmacol. 2006;16(8):620–4.Google Scholar
  17. 17.
    Lang UE, Bajbouj M, Gallinat J, Hellweg R. Brain-derived neurotrophic factor serum concentrations in depressive patients during vagus nerve stimulation and repetitive transcranial magnetic stimulation. Psychopharmacology (Berl). 2006;187(1):56–9.Google Scholar
  18. 18.
    Aydemir C, Yalcin ES, Aksaray S, Kisa C, Yildirim SG, Uzbay T, et al. Brain-derived neurotrophic factor (BDNF) changes in the serum of depressed women. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(7):1256–60.Google Scholar
  19. 19.
    Zanardini R, Gazzoli A, Ventriglia M, Perez J, Bignotti S, Rossini PM, et al. Effect of repetitive transcranial magnetic stimulation on serum brain derived neurotrophic factor in drug resistant depressed patients. J Affect Disord. 2006;91(1):83–6.Google Scholar
  20. 20.
    Huang TL, Lee CT, Liu YL. Serum brain-derived neurotrophic factor levels in patients with major depression: effects of antidepressants. J Psychiatr Res. 2008;42(7):521–5.Google Scholar
  21. 21.
    Lee HY, Kim YK. Plasma brain-derived neurotrophic factor as a peripheral marker for the action mechanism of antidepressants. Neuropsychobiology. 2008;57(4):194–9.Google Scholar
  22. 22.
    Piccinni A, Marazziti D, Catena M, Domenici L, Del Debbio A, Bianchi C, et al. Plasma and serum brain-derived neurotrophic factor (BDNF) in depressed patients during 1 year of antidepressant treatments. J Affect Disord. 2008;105(1–3):279–83.Google Scholar
  23. 23.
    Yoshimura R, Umene-Nakano W, Ueda N, Ikenouchi-Sugita A, Hori H, Nakamura J. Addition of risperidone to sertraline improves sertraline-resistant refractory depression without influencing plasma concentrations of sertraline and desmethylsertraline. Hum Psychopharmacol. 2008;23(8):707–13.Google Scholar
  24. 24.
    Hellweg R, Ziegenhorn A, Heuser I, Deuschle M. Serum concentrations of nerve growth factor and brain-derived neurotrophic factor in depressed patients before and after antidepressant treatment. Pharmacopsychiatry. 2008;41(2):66–71.Google Scholar
  25. 25.
    Machado-Vieira R, Yuan P, Brutsche N, DiazGranados N, Luckenbaugh D, Manji HK, et al. Brain-derived neurotrophic factor and initial antidepressant response to an N-methyl-D-aspartate antagonist. The Journal of clinical psychiatry. 2009;70:1662–6.Google Scholar
  26. 26.
    Gustafsson G, Lira CM, Johansson J, Wisen A, Wohlfart B, Ekman R, et al. The acute response of plasma brain-derived neurotrophic factor as a result of exercise in major depressive disorder. Psychiatry Res. 2009;169(3):244–8.Google Scholar
  27. 27.
    Matrisciano F, Bonaccorso S, Ricciardi A, Scaccianoce S, Panaccione I, Wang L, et al. Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine. J Psychiatr Res. 2009;43(3):247–54.Google Scholar
  28. 28.
    Umene-Nakano W, Yoshimura R, Ueda N, Suzuki A, Ikenouchi-Sugita A, Hori H, et al. Predictive factors for responding to sertraline treatment: views from plasma catecholamine metabolites and serotonin transporter polymorphism. J Psychopharmacol. 2010;24(12):1764–71.Google Scholar
  29. 29.
    Mackay GM, Forrest CM, Christofides J, Bridel MA, Mitchell S, Cowlard R, et al. Kynurenine metabolites and inflammation markers in depressed patients treated with fluoxetine or counselling. Clin Exp Pharmacol Physiol. 2009;36(4):425–35.Google Scholar
  30. 30.
    Basterzi AD, Yazici K, Aslan E, Delialioglu N, Tasdelen B, Tot Acar S, et al. Effects of fluoxetine and venlafaxine on serum brain derived neurotrophic factor levels in depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(2):281–5.Google Scholar
  31. 31.
    Yoshimura R, Hori H, Ikenouchi-Sugita A, Umene-Nakano W, Ueda N, Nakamura J. Higher plasma interleukin-6 (IL-6) level is associated with SSRI- or SNRI-refractory depression. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(4):722–6.Google Scholar
  32. 32.
    Shi Y, You J, Yuan Y, Zhang X, Li H, Hou G. Plasma BDNF and tPA are associated with late-onset geriatric depression. Psychiatry Clin Neurosci. 2010;64(3):249–54.Google Scholar
  33. 33.
    Hu Y, Yu X, Yang F, Si T, Wang W, Tan Y, et al. The level of serum brain-derived neurotrophic factor is associated with the therapeutic efficacy of modified electroconvulsive therapy in Chinese patients with depression. J ECT. 2010;26(2):121–5.Google Scholar
  34. 34.
    Kang RH, Chang HS, Wong ML, Choi MJ, Park JY, Lee HY, et al. Brain-derived neurotrophic factor gene polymorphisms and mirtazapine responses in Koreans with major depression. J Psychopharmacol. 2010;24(12):1755–63.Google Scholar
  35. 35.
    Rojas PS, Fritsch R, Rojas RA, Jara P, Fiedler JL. Serum brain-derived neurotrophic factor and glucocorticoid receptor levels in lymphocytes as markers of antidepressant response in major depressive patients: a pilot study. Psychiatry Res. 2011;189(2):239–45.Google Scholar
  36. 36.
    Bot M, Pouwer F, Assies J, Jansen EH, Beekman AT, de Jonge P. Supplementation with eicosapentaenoic omega-3 fatty acid does not influence serum brain-derived neurotrophic factor in diabetes mellitus patients with major depression: a randomized controlled pilot study. Neuropsychobiology. 2011;63(4):219–23.Google Scholar
  37. 37.
    Serra-Millas M, Lopez-Vilchez I, Navarro V, Galan AM, Escolar G, Penades R, et al. Changes in plasma and platelet BDNF levels induced by S-citalopram in major depression. Psychopharmacology (Berl). 2011;216(1):1–8.Google Scholar
  38. 38.
    Tadic A, Wagner S, Schlicht KF, Peetz D, Borysenko L, Dreimuller N, et al. The early non-increase of serum BDNF predicts failure of antidepressant treatment in patients with major depression: a pilot study. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(2):415–20.Google Scholar
  39. 39.
    Trajkovska V, Marcussen AB, Vinberg M, Hartvig P, Aznar S, Knudsen GM. Measurements of brain-derived neurotrophic factor: methodological aspects and demographical data. Brain Res Bull. 2007;73(1–3):143–9.Google Scholar
  40. 40.
    Rosenfeld RD, Zeni L, Haniu M, Talvenheimo J, Radka SF, Bennett L, et al. Purification and identification of brain-derived neurotrophic factor from human serum. Protein Expr Purif. 1995;6(4):465–71.Google Scholar
  41. 41.
    Yamamoto H, Gurney ME. Human platelets contain brain-derived neurotrophic factor. J Neurosci. 1990;10(11):3469–78.Google Scholar
  42. 42.
    Radka SF, Holst PA, Fritsche M, Altar CA. Presence of brain-derived neurotrophic factor in brain and human and rat but not mouse serum detected by a sensitive and specific immunoassay. Brain Res. 1996;709(1):122–301.Google Scholar
  43. 43.
    Greenberg ME, Xu B, Lu B, Hempstead BL. New insights in the biology of BDNF synthesis and release: implications in CNS function. J Neurosci. 2009;29(41):12764–7.Google Scholar
  44. 44.
    Pang PT, Teng HK, Zaitsev E, Woo NT, Sakata K, Zhen S, et al. Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science. 2004;306(5695):487–91.Google Scholar
  45. 45.
    Teng HK, Teng KK, Lee R, Wright S, Tevar S, Almeida RD, et al. ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin. J Neurosci. 2005;25(22):5455–63.Google Scholar
  46. 46.
    Woo NH, Teng HK, Siao CJ, Chiaruttini C, Pang PT, Milner TA, et al. Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat Neurosci. 2005;8(8):1069–77.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Stefania Pigatto Teche
    • 1
  • Gabriela Lotin Nuernberg
    • 1
  • Anne Orgler Sordi
    • 1
  • Lívia Hartmann de Souza
    • 1
  • Lysa Remy
    • 1
  • Keila Maria Mendes Ceresér
    • 1
  • Neusa Sica Rocha
    • 1
  1. 1.UFRGSPorto AlegreBrazil

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