Skip to main content

Advertisement

SpringerLink
Log in

Neurotrophic Factors, Clinical Features and Gender Differences in Depression

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Recent studies have evaluated the role of brain-derived neurotrophic factor (BDNF) in mood disorders; however, little is known about alterations in nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). The aim of this study was to evaluate differences among serum neurotrophic factors (BDNF, NGF and GDNF) in depressed patients and healthy controls and to verify the association between serum neurotrophic levels and clinical characteristics in a young, depressed population stratified by gender. This is a cross-sectional study with depressed patients and population controls 18–29 years of age. The concentrations of neurotrophic factors were determined by the ELISA method. The diagnosis of depression and the duration of the disease were assessed by the Structured Clinical Interview according to the diagnostic and statistical manual of mental disorders. Depression severity was measured with the 17-item Hamilton Rating Scale for Depression, and the severity of anxiety symptoms was measured using the Hamilton Anxiety Rating Scale. Serum BDNF and GDNF were lower in major depressive disorder (MDD) patients compared to controls (p ≤ 0.001). Serum NGF levels were higher in MDD patients versus controls (p ≤ 0.001). BDNF was associated with the duration of disease only in women (p = 0.005). GDNF was not associated with clinical characteristics in either gender. In women, NGF was associated with the severity of depressive symptoms (p = 0.009), anxiety (p = 0.011) and disease duration (p = 0.005). NGF was associated with disease duration in men (p = 0.026). Our results demonstrated that significant neurochemical differences in NGF and BDNF, but not in GDNF, were associated with the clinical features of MDD when patients were stratified by gender.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Jansen K, Magalhaes PV, Tavares Pinheiro R, Kapczinski F, Silva RA (2012) Early functional impairment in bipolar youth: a nested population—based case—control study. J Affect Disord 142:208–212

    Article  PubMed  Google Scholar 

  2. Jansen K, Campos Mondin T, Azevedo Cardoso T, Costa Ores L, de Mattos Souza LD, Tavares Pinheiro R, da Silva Magalhães PV, da Silva RA (2013) Quality of life and mood disorder episodes: community sample. J Affect Disord 147:123–127

    Article  PubMed  Google Scholar 

  3. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS (2003) The epidemiology of major depressive disorder results From the National Comorbidity Survey Replication (NCS-R). JAMA 289:3095–3105

    Article  PubMed  Google Scholar 

  4. Schmidt HD, Shelton RC, Duman RS (2011) Functional biomarkers of depression: diagnosis, treatment, and pathophysiology. Neuropsychopharmacology 36:2375–2394

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Hercher C, Turecki G, Mechawar N (2009) Through the looking glass: examining neuroanatomical evidence for cellular alterations in major depression. J Psychiatr Res 43:947–961

    Article  PubMed  Google Scholar 

  6. Pallavi P, Sagar R, Mehta M, Sharma S, Subramanium A, Shamshi F, Sengupta U, Qadri R, Pandey RM, Mukhopadhyay AK (2013) Serum neurotrophic factors in adolescent depression: gender difference and correlation with clinical severity. J Affect Disord 150:415–423

    Article  CAS  PubMed  Google Scholar 

  7. Martino M, Rocchi G, Escelsior A, Contini P, Colicchio S, de Berardis D, Amore M, Fornaro P, Fornaro M (2013) NGF serum levels variations in major depressed patients receiving duloxetine. Psychoneuroendocrinology 38:1824–1828

    Article  CAS  PubMed  Google Scholar 

  8. Duman RS, Voleti B (2012) Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. Trends Neurosci 35:47–56

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M (2003) Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatr 54:70–75

    Article  CAS  Google Scholar 

  10. Autry AE, Monteggia LM (2012) Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 64:238–258

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A, Giovannini C, Rillosi L, Ventriglia M, Riva MA, Gennarelli M (2010) Serum and plasma BDNF levels in major depression: a replication study and meta-analyses. World J Biol Psychiatr 11:763–773

    Article  Google Scholar 

  12. Brunoni AR, Lopes M, Fregni F (2008) 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 11:1169–1180

    Article  CAS  PubMed  Google Scholar 

  13. Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59:1116–1127

    Article  CAS  PubMed  Google Scholar 

  14. Gass P, Hellweg R (2010) Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker for affective disorders? Int J Neuropsychopharmacol 13:1–4

    Article  CAS  PubMed  Google Scholar 

  15. Hascimoto K, Shimizu E, Iyo M (2004) Critical how of brain-derived neurotrophic factor in mood disorders. Brain Res Rev 45:104–114

    Article  Google Scholar 

  16. Sen S, Duman R, Sanacora G (2008) Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatr 64:527–532

    Article  CAS  Google Scholar 

  17. Piccinni A, Marazziti D, Del Debbio A, Bianchi C, Roncaglia I, Mannari C, Origlia N, Catena Dell’Osso M, Massimetti G, Domenici L, Dell’Osso L (2008) Diurnal variation of plasma brain-derived neurotrophic factor (BDNF) in humans: an analysis of sex differences. Chronobiol Int 25:819–826

    Article  CAS  PubMed  Google Scholar 

  18. Lommatzsch M, Zingler D, Schuhbaeck K, Schloetcke K, Zingler C, Schuff-Werner P, Virchow JC (2005) The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging 26:115–123

    Article  CAS  PubMed  Google Scholar 

  19. Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM (2002) Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 109:143–148

    Article  CAS  PubMed  Google Scholar 

  20. Lommatzsch M, Hornych K, Zingler C, Schuff-Werner P, Höppner J, Virchow JC (2006) Maternal serum concentrations of BDNF and depression in the perinatal period. Psychoneuroendocrinology 31:388–394

    Article  CAS  PubMed  Google Scholar 

  21. Mondin TC, de Azevedo Cardoso T, Jansen K, Coiro Spessato B, de Mattos Souza LD, da Silva RA (2013) Effects of cognitive psychotherapy on the biological rhythm of patients with depression. J Affect Disord

  22. Del-Ben CM, Vilela AA, Crippa JAS, Hallaka JEC, Labate CM, Zuardi AW (2001) Confiabilidade da “Entrevista Clínica Estruturada para o DSM-IV - Versão Clínica” traduzida para o português. Rev Bras Psiq 23:156–159

    Article  Google Scholar 

  23. Hamilton M (1967) Development of a rating scale for primary depressive illness. British Journal of Social and Clin Psychol 278–96

  24. Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50–55

    Article  CAS  PubMed  Google Scholar 

  25. Henrique IF, De Micheli D, Lacerda RB, Lacerda LA, Formigoni ML (2004) Validation of the Brazilian version of Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Rev Assoc Med Bras 50:199–206

    Article  PubMed  Google Scholar 

  26. Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ (1998) Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 37:1553–1561

    Article  CAS  PubMed  Google Scholar 

  27. Pardridge WM, Wu D, Sakane T (1998) Combined use of carboxyl-directed protein pegylation and vector-mediated blood-brain barrier drug delivery system optimizes brain uptake of brain-derived neurotrophic factor following intravenous administration. Pharm Res 15:576–582

    Article  CAS  PubMed  Google Scholar 

  28. Autry AE, Adachi M, Cheng P, Monteggia LM (2009) Gender-specific impact of brain-derived neurotrophic factor signaling on stress-induced depression-like behavior. Biol Psyhciatry 66:84–90

    Article  CAS  Google Scholar 

  29. Cavus I, Duman R (2003) Influence of estradiol, stress, and 5-HT2A agonist treatment on brain-derived neurotrophic factor expression in female rats. Biol Psychiatry 54:59–69

    Article  CAS  PubMed  Google Scholar 

  30. Karege F, Bondolfi G, Gervasoni N, Schwald M, Aubry JM, Bertschy G (2005) Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowred platelet BDNF release unrelated to platelet reactivity. Biol Psychiatry 57:1068–1072

    Article  CAS  PubMed  Google Scholar 

  31. Lotrich F (2012) Inflammatory cytokines, growth factors, and depression. Curr Pharm Des 18:5920–5935

    Article  CAS  PubMed  Google Scholar 

  32. Frodl T, Schüle C, Schmitt T, Born C, Baghai T, Zill P, Bottlender R, Rupprecht R, Bondy B, Reiser M, Möller HJ, Meisenzahl EM (2007) Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression. Arch Gen Psychiatry 64:410–416

    Article  CAS  PubMed  Google Scholar 

  33. Montag C, Weber B, Fliessbach K, Elger C, Reuter M (2009) The BDNF Val66Met polymorphism impacts parahippocampal and amygdala volume in healthy humans: incremental support for a genetic risk factor for depression. Psychol Med 39:1831–1839

    Article  CAS  PubMed  Google Scholar 

  34. Nagahara AH, Tuszynski MH (2011) Potential therapeutic uses of BDNF in neurological and psychiatry disorders. Nat Rev Drug Discov 10:209–219

    Article  CAS  PubMed  Google Scholar 

  35. Roca M, Armengol S, Garcia-Garcia M, Rodriguez-Bayón A, Ballesta I, Serrano MJ, Comas A, Gili M (2011) Clinical Differences between first and recurrent episodes in depressive patients. Compr Psychiatry 52:26–32

    Article  PubMed  Google Scholar 

  36. Wang X, Hou Z, Yuan Y, Hou G, Liu Y, Li H, Zhang Z (2008) Association study between plasma GDNF and cognitive function in late-onset depression. J Affect Disord 132:418–421

    Article  Google Scholar 

  37. Diniz BS, Teixeira AL, Miranda AS, Talib LL, Gattaz WF, Forlenza OV (2012) Circulating Glial-derived neurotrophic factor is reduced in late-life depression. J Psychiatr Res 46:135–139

    Article  PubMed  Google Scholar 

  38. Takebayashi M, Hisaoka K, Nishida A, Tsuchioka M, Miyoshi I, Kozuru T, Hikasa S, Okamoto Y, Shinno H, Morinobu S, Yamawaki S (2006) Decreased levels of whole blood glial cell line-derived neurotrophic factor (GDNF) in remitted patients with mood disorder. Int J Neuropsychopharmacol 9:607–612

    Article  CAS  PubMed  Google Scholar 

  39. Otsuki K, Ushida S, Watanuki T, Wakabayashai Y, Fujimoto M, Matsubara T, Funato H, Watanabe Y (2008) Altered expression of nerotrophic factors in patients with major depression. J Psychiatr Res 42:1145–1153

    Article  PubMed  Google Scholar 

  40. Zhang X, Zhang Z, Xie C, Xi G, Zhou H, Zhang Y, Sha W (2008) Effect of treatment on serum glial cell line-derived neurotrophic factor in depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 32:886–890

    Article  CAS  PubMed  Google Scholar 

  41. Hadjiconstantinou M, McGuire L, Duchemin AM, Laskowski B, Kiecolt-Glaser J, Glaser R (2001) Changes in plasma nerve growth factor levels in older adults associated with chronic stress. J Neuroimmunol 116:102–106

    Article  CAS  PubMed  Google Scholar 

  42. Fontenelle LF, Barbosa IG, Luna JV, Rocha NP, Miranda AS, Teixeira AL (2012) Neurotrophic fators in obsessive-compulsive disorder. Psychiatry Res 199:195–200

    Article  CAS  PubMed  Google Scholar 

  43. Barbosa IG, Huguet RB, Neves FS, Reis HJ, Bauer ME, Janka Z, Palotás A, Teixeira AL (2011) Impaired nerve growth factor homeostasis in patients with bipolar disorder. World J Biol Psychiatry 12:228–232

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was partly funded by the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Programa de Pós-Graduação em Saúde e Comportamento, Universidade Católica de Pelotas, Jean Pierre Oses, Rua Gonçalves Chaves 373, Sala 418C, Centro, Pelotas, CEP 96015-560, Brazil

    Taiane de Azevedo Cardoso, Thaise Campos Mondin, Carolina David Wiener, Melina Bazili Marques, Briane de Ávila Fucolo, Ricardo Tavares Pinheiro, Luciano Dias Mattos de Souza, Ricardo Azevedo da Silva, Karen Jansen & Jean Pierre Oses

Authors
  1. Taiane de Azevedo Cardoso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thaise Campos Mondin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carolina David Wiener
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Melina Bazili Marques
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Briane de Ávila Fucolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ricardo Tavares Pinheiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Luciano Dias Mattos de Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ricardo Azevedo da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Karen Jansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jean Pierre Oses
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jean Pierre Oses.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Azevedo Cardoso, T., Mondin, T.C., Wiener, C.D. et al. Neurotrophic Factors, Clinical Features and Gender Differences in Depression. Neurochem Res 39, 1571–1578 (2014). https://doi.org/10.1007/s11064-014-1349-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-014-1349-4

Keywords

Search

Navigation