, Volume 216, Issue 1, pp 1–8 | Cite as

Changes in plasma and platelet BDNF levels induced by S-citalopram in major depression

  • Montserrat Serra-Millàs
  • Irene López-Vílchez
  • Víctor Navarro
  • Ana-María Galán
  • Ginés Escolar
  • Rafael Penadés
  • Rosa Catalán
  • Lourdes Fañanás
  • Bárbara Arias
  • Cristóbal Gastó
Original Investigation



Neuroplastic processes are thought to be involved in the pathophysiology of major depression. It has been reported that serum brain-derived neurotrophic factor (BDNF) is decreased in depressed patients.


Compare BDNF levels in depressed patients and healthy controls in platelet poor plasma and in washed platelets. Observe the effects of 8- and 24-week treatment with S-citalopram on these levels.


We assessed the levels of BDNF in platelet poor plasma and in washed platelets from 18 major depression patients, and compared them with 14 healthy controls. Blood samples were obtained from patients before and during treatment (8 and 24 weeks) with a selective serotonin reuptake inhibitor, S-citalopram.


A significant decrease in severity of depressive symptoms was observed from the first month of treatment with S-citalopram, and symptoms continued decreasing until the 6th month. Plasma BDNF levels in untreated patients appeared significantly increased (p < 0.01) but reached values similar to those of controls at the 24th week. In contrast, levels of platelet BDNF appeared significantly decreased (p < 0.05), but treatment also normalized levels so that values obtained were equivalent to those of controls.


Untreated depressed patients showed increased plasma BDNF levels and decreased platelet BDNF levels, as compared with control subjects, and tend to normalize during treatment with S-citalopram for 24 weeks, with BDNF reaching levels similar to those in healthy controls at the 24th week in both samples. We observed that improvement in depressive symptoms was accompanied by normalization of plasma and platelet BDNF levels.


Major depression Brain-derived neurotrophic factor (BDNF) Serum Plasma Platelets S-citalopram. Antidepressant 



Brain-derived neurotrophic factor


Hamilton Depression Rating Scale


Enzyme-linked immunosorbent assays


BDNF in platelet poor plasma


BDNF in washed platelets



This work was partially supported by a grant from Hospital Clínic, Barcelona, by Ministerio de Ciencia e Innovación [SAF 2008-05674-C03-03 and Red HERACLES RD06/0009/1003], and by Ministerio de Sanidad [FIS CP04-00112, FIS PS09-0664] from the Spanish Government.

Registered in Current Controlled Trials as ISRCTN11216093—Changes in plasma and platelet Brain-Derived Neurotrophic Factor (BDNF) levels induced by S-citalopram in major depression

The authors report no biomedical financial interests or potential conflicts of interest.


  1. American Psychiatric Association (APA) (2003) DSM-IV-TR Manual Diagnóstico y Estadístico de los Trastornos Mentales. Masson, BarcelonaGoogle Scholar
  2. Ataoglu A, Canan F (2009) Mean platelet volume in patients with major depression: effect of escitalopram treatment. J Clin Psychopharmacol 29(4):368–371PubMedCrossRefGoogle Scholar
  3. Atar D, Malinin A, Takserman A, Pokov A, van Zyl L, Tanguay JF et al (2006) Escitalopram, but not its major metabolites, exhibits antiplatelet activity in humans. J Clin Psychopharmacol 26(2):172–177PubMedCrossRefGoogle Scholar
  4. Atar D, Malinin A, Pokov A, van Zyl L, Frasure-Smith N, Lesperance F et al (2007) Antiplatelet properties of escitalopram in patients with the metabolic syndrome: a dose-ranging in vitro study. Neuropsychopharmacology 32(11):2369–2374PubMedCrossRefGoogle Scholar
  5. Aydemir O, Deveci A, Taneli F (2005) The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry 29:261–265PubMedCrossRefGoogle Scholar
  6. Aydemir C, Yalcin ES, Aksaray S, Kisa C, Yildirim SG, Uzbay T et al (2006) Brain derived neurotrophic factor (BDNF) changes in the serum of depressed women. Prog Neuropsychopharmacol Biol Psychiatry 30:1256–1260PubMedCrossRefGoogle Scholar
  7. Basterzi AD, Yazici K, Aslan E, Delialioğlu N, Tasdelen B, Tot Acar S et al (2009) Effects of fluoxetine and venlafaxine on serum brain derived neurotrophic factor levels in depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 33(2):281–285PubMedCrossRefGoogle Scholar
  8. Blakely RD, Berson HE, Fremeau RT Jr, Caron MG, Peek MM, Prince HK et al (1991) Cloning and expression of a functional serotonin transporter from rat brain. Nature 354(6348):66–70PubMedCrossRefGoogle Scholar
  9. Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Monteni R, Nielsen MG, Placentino A et al (2010) Serum and plasma BDNF levels in major depression: a replication study and meta-analyses. World J Biol Psychiatry 11(6):763–773PubMedCrossRefGoogle Scholar
  10. 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 11:1169–1180PubMedCrossRefGoogle Scholar
  11. Carney RM, Freedland KE (2003) Depression, mortality, and medical morbidity in patients with coronary heart disease. Biol Psychiatry 54(3):241–247PubMedCrossRefGoogle Scholar
  12. Carney RM, Blumenthal JA, Catellier D, Freedland KE, Berkman LF, Watkins LL et al (2003) Depression as a risk factor for mortality after acute myocardial infarction. Am J Cardiol 92(11):1277–1281PubMedCrossRefGoogle Scholar
  13. Carney RM, Freedland KE, Jaffe AS, Frasure-Smith N, Lesperance F, Sheps DS et al (2004) Depression as a risk factor for post-MI mortality. J Am Coll Cardiol 44(2):472–474PubMedCrossRefGoogle Scholar
  14. Diaz-Ricart M, Arderiu G, Estebanell E, Perez-Pujol S, Lozano M, White JG et al (2002) Inhibition of cytoskeletal assembly by cytochalasin B prevents signaling through tyrosine phosphosylation of Syk cortacin and focal adhesion kinase: studies under flow conditions. Am J Pathol 160:329–337PubMedCrossRefGoogle Scholar
  15. Duman R, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59:1116–1127PubMedCrossRefGoogle Scholar
  16. Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54:597–606PubMedGoogle Scholar
  17. Escolar G, Diaz-Ricart M, Gomez-Gil E, Serra M, Gasto C, Bozzo J et al (2005) Serotonergic mechanisms: a potential link between affective disorders and cardiovascular risk. Drugs Today (Barc) 41(11):721–743CrossRefGoogle Scholar
  18. First MB, Spitzer RL, Gibbon M, Williams JBW (1999) Entrevista clínica estructurada para los Trastornos del Eje I del DSM-IV-SCID I. Masson, BarcelonaGoogle Scholar
  19. Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi JI et al (2002) Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 87:728–734PubMedGoogle Scholar
  20. Galan AM, Lopez-Vilchez I, Diaz-Ricart M, Navalon F, Gomez E, Gasto C et al (2009) Serotonergic mechanisms enhance platelet-mediated thrombogenicity. Thromb Haemost 102(3):511–519PubMedGoogle Scholar
  21. Gervasoni N, Aubry JM, Bondolfi G, Osiek C, Schwald M, Bertschy G et al (2005) Partial normalization of serum brain-derived neurotrophic factor in remitted patients after a major depressive episode. Neuropsychobiology 51:234–238PubMedCrossRefGoogle Scholar
  22. Gonul AS, Akdeniz F, Taneli F, Donat O, Eker C, Vahip S (2005) Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients. Eur Arch Psychiatry Clin Neurosci 255:267–268CrossRefGoogle Scholar
  23. Grassi-Oliveira R, Stein LM, Lopes RP, Teixeira AL, Bauer ME (2008) Low plasma brain-derived neurotrophic factor and childhood physical neglect are associated with verbal memory impairment in major depression-a preliminary report. Biol Psychiatry 64(4):281–285PubMedCrossRefGoogle Scholar
  24. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62PubMedCrossRefGoogle Scholar
  25. Hoffman BJ, Mezey E, Brownstein MJ (1991) Cloning of a serotonin transporter affected by antidepressants. Science 254(5031):579–580PubMedCrossRefGoogle Scholar
  26. Hoyer D, Hannon JP, Martin GR (2002) Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 71(4):533–554PubMedCrossRefGoogle Scholar
  27. Huang TL, Lee CT, Liu YL (2008) Serum brain-derived neurotrophic factor levels in patients with major depression: effects of antidepressants. J Psychiatr Res 42(7):521–525PubMedGoogle Scholar
  28. Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM (2002a) Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 109(2):143–148PubMedCrossRefGoogle Scholar
  29. Karege F, Schwald M, Cisse M (2002b) Postnatal developmental profile of brain derived neurotrophic factor in rat brain and platelets. Neurosci Lett 328(3):261–264PubMedCrossRefGoogle 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 lowered platelet BDNF release unrelated to platelet reactivity. Biol Psychiatry 57:1068–1072PubMedCrossRefGoogle Scholar
  31. Kishino A, Katayama N, Ishige Y, Yamamoto Y, Ogo H, Tatsuno T et al (2001) Analysis of effects and pharmacokinetics of subcutaneously administered BDNF. NeuroReport 12(5):1067–1072PubMedCrossRefGoogle Scholar
  32. Lee BH, Kim YK (2009) Reduced platelet BDNF level in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry 33(5):849–853PubMedCrossRefGoogle Scholar
  33. Lee BH, Kim H, Park SH, Kim YK (2007) Decreased plasma BDNF level in depressive patients. J Affect Disord 101:239–244PubMedCrossRefGoogle Scholar
  34. Lesch KP, Wolozin BL, Murphy DL, Reiderer P (1993) Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem 60(6):2319–2322PubMedCrossRefGoogle Scholar
  35. Lindsay RM, Wiegand SJ, Altar CA, DiStefano PS (1994) Neurotrophic factors: from molecule to man. Trends Neurosci 17:182–190PubMedCrossRefGoogle Scholar
  36. Lommatzsch M, Braun A, Mannsfeldt A, Botchkarev VA, Botchkareva NV, Paus R et al (1999) Abundant production of brain-derived neurotrophic factor by adult visceral epithelia Implications paracrine target derived Neurotrophic functions. Am J Pathol 155(4):1183–1193PubMedCrossRefGoogle Scholar
  37. Lommatzsch M, Zingler D, Schuhbaeck K, Schloetcke K, Zingler C, Schuff-Werner P et al (2005) The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging 26:115–123PubMedCrossRefGoogle Scholar
  38. Lommatzsch M, Niewerth A, Klotz J, Schulte-Herbrüggen O, Zingler C, Schuff-Werner P et al (2007) Platelet and plasma BDNF in lower respiratory tract infections of the adult. Respir Med 101(7):1493–1499PubMedCrossRefGoogle Scholar
  39. Matrisciano F, Bonaccorso S, Ricciardi A, Scaccianoce S, Panaccione I, Wang L et al (2009) Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine. J Psychiatr Res 43(3):247–254PubMedCrossRefGoogle Scholar
  40. Maurer-Spurej E, Pittendreigh C, Solomons K (2004) The influence of selective serotonin reuptake inhibitors on human platelet serotonin. Thromb Haemost 91(1):119–128PubMedGoogle Scholar
  41. Nakahashi T, Fujimura H, Altar CA, Li J, Kambayashi J, Tandon NN et al (2000) Vascular endothelial cells synthesize and secrete brain-derived neurotrophic factor. FEBS Lett 470(2):113–117PubMedCrossRefGoogle Scholar
  42. Pan W, Banks WA, Kastin AJ (1998) Permeability of the blood-brain barrier to neurotrophins. Brain Res 788:94–97CrossRefGoogle Scholar
  43. Pandey GN, Dwivedi Y, Rizavi HS, Ren X, Zhang H, Pavuluri MN (2010) Brain derived neurotrophic factor gene and protein expression in pediatric and adult depressed subjects. Prog Neuropsychopharmacol Biol Psychiatry 34:645–651PubMedCrossRefGoogle Scholar
  44. Piccinni A, Marazziti D, Catena M, Domenici L, Del Debbio A, Bianchi C et al (2008) Plasma and serum brain derived neurotrophic factor (BDNF) in depressed patients during 1 year of antidepressant treatments. J Affect Disord 105:279–283PubMedCrossRefGoogle Scholar
  45. Pliego-Rivero FB, Bayatti N, Giannakoulopoulos X, Glover V, Bradford HF, Stern G et al (1997) Brain-derived neurotrophic factor in human platelets. Biochem Pharmacol 54(1):207–209PubMedCrossRefGoogle Scholar
  46. Poduslo JF, Curran GL (1996) Permeability at the blood–brain and blood–nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF. Brain Res Mol Brain Res 36(2):280–286PubMedCrossRefGoogle Scholar
  47. Radka SF, Holst PA, Fristche M, Altar CA (1996) 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 709:122–130PubMedCrossRefGoogle Scholar
  48. 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):2542–2546PubMedCrossRefGoogle Scholar
  49. Rosenfeld RD, Zeni L, Haniu M, Talvenheimo J, Radka SF, Bennett L et al (1995) Purification and identification of brain-derived neurotrophic factor from human serum. Protein Expr Purif 6(4):465–471PubMedCrossRefGoogle Scholar
  50. Sauer WH, Berlin JA, Kimmel SE (2003) Effect of antidepressants and their relative affinity for the serotonin transporter on the risk of myocardial infarction. Circulation 108(1):32–36PubMedCrossRefGoogle Scholar
  51. Schlienger RG, Meier CR (2003) Effect of selective serotonin reuptake inhibitors on platelet activation: can they prevent acute myocardial infarction? Am J Cardiovasc Drugs 3(3):149–162PubMedCrossRefGoogle Scholar
  52. Sen S, Duman R, Sanacora G (2008) Serum brain-derived neurotrophic factor, depression, and antidepressant medications: Meta-analyses and implications. Biol Psychiatry 64:527–532PubMedCrossRefGoogle Scholar
  53. Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumadiri C et al (2003) Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 54:70–75PubMedCrossRefGoogle Scholar
  54. Stratz C, Trenk D, Bhatia HS, Valina C, Neumann FJ, Fiebich BL (2008) Identification of 5-HT3 receptors on human platelets: increased surface immunoreactivity after activation with adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP). Thromb Haemost 99(4):784–786PubMedGoogle Scholar
  55. Trajkovska V, Marcussen AB, Vinberg M, Hartvig P, Aznar S, Knudsen GM (2007) Measurements of brain-derived neurotrophic factor: methodological aspects and demographical data. Brain Res Bull 73(1–3):143–149PubMedCrossRefGoogle Scholar
  56. Yamamoto H, Gurney ME (1990) Human platelets contain brain-derived neurotrophic factor. J Neurosci 10(11):3469–3478PubMedGoogle Scholar
  57. Yoshimura R, Mitoma M, Sugita A, Hori H, Okamoto T, Umene W et al (2007) Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor in depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 31(5):1034–1037PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Montserrat Serra-Millàs
    • 1
  • Irene López-Vílchez
    • 2
  • Víctor Navarro
    • 3
  • Ana-María Galán
    • 2
  • Ginés Escolar
    • 2
  • Rafael Penadés
    • 3
  • Rosa Catalán
    • 3
  • Lourdes Fañanás
    • 4
  • Bárbara Arias
    • 4
  • Cristóbal Gastó
    • 3
  1. 1.Servei de Salut MentalConsorci Hospitalari de VicVic BarcelonaSpain
  2. 2.Servei d’Hemoteràpia i Hemostàsia, Hospital ClínicCentre de Diagnòstic Biomèdic, IDIBAPS, Universitat de BarcelonaBarcelonaSpain
  3. 3.Institut de Neurociències, Hospital ClínicUniversitat de Barcelona, IDIBAPS, CIBERSAMBarcelonaSpain
  4. 4.Unitat d’Antropologia, Departament de Biologia Animal, Facultat de Biologia i Institut de Biomedicina (IBUB)Universitat de Barcelona, CIBERSAM, Instituto de Salud Carlos IIIBarcelonaSpain

Personalised recommendations