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Effect of treatment on serum brain–derived neurotrophic factor levels in depressed patients

European Archives of Psychiatry and Clinical Neuroscience volume 255, pages 381–386 (2005)Cite this article

Abstract

Researchers have reported that serum brain–derived neurotrophic factor (sBDNF) of drug–free depressed patients are lower than those of healthy controls and proposed that low sBDNF levels might reflect failure of neuronal plasticity in depression. In this study, we compared sBDNF levels of depressed patients (n = 28) before and after 8 weeks of antidepressant treatment, with those of healthy controls (n = 18) to test the hypothesis that initially low sBDNF levels of drug–free depressed patients will increase parallel with their clinical response to antidepressant treatment. The severity of depression and response to treatment were assessed with Hamilton Rating Scale for Depression (HAM–D). sBDNF was assayed with the sandwich ELISA method. Baseline sBDNF levels of patients (mean, 20.8 ng/ml; [S.D., 6.7]) were significantly lower than those of controls (mean, 26.8 ng/ml; [S.D., 9.3]; p = 0.015), and were negatively correlated with HAM–D scores (r = –0.49, p = 0.007). After 8 weeks of treatment, sBDNF levels of patients had increased significantly (mean, 33.3 ng/ml; [S.D., 9.9]; p < 0.001) and no longer differed from those of controls. These results support the hypothesis that BDNF might play a critical role in the pathophysiology of major depressive disorder and successful antidepressant treatment increases the attenuated BDNF levels in depressed patients.

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References

  1. American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders, 4th ed. American Psychiatric Press, Washington, DC

  2. Berchtold NC, Kesslak JP, Pike CJ, Adlard PA, Cotman CW (2001) Estrogen and exercise interact to regulate brain-derived neurotrophic factor mRNA and protein expression in the hippocampus. Eur J Neurosci 14:1992–2002

    PubMed  Article  CAS  Google Scholar 

  3. Bianchi M, Moser C, Lazzarini C, Vecchiato E, Crespi F (2002) Forced swimming test and fluoxetine treatment, in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes. Exp Brain Res 143:191–197

    PubMed  CAS  Article  Google Scholar 

  4. Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM, Delaney RC, McCarthy G, Charney DS, Innis RB (1995) MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry 152:973–981

    PubMed  CAS  Google Scholar 

  5. Chao HM, Sakai RR, Ma LY, McEwen BS (1998) Adrenal steroid regulation of neurotrophic factor expression in the rat hippocampus. Endocrinology 139:3112–3118

    PubMed  CAS  Google Scholar 

  6. Chen B, Dowlatshahi D, MacQueen GM, Wang JF, Young LT (2001) Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 50:260–265

    PubMed  Article  CAS  Google Scholar 

  7. Dias BG, Banerjee SB, Duman RS, Vaidya VA (2003) Differential regulation of brain derived neurotrophic factor transcripts by antidepressant treatments in the adult rat brain. Neuropharmacology 45:553–563

    PubMed  Article  CAS  Google Scholar 

  8. Dowlatshahi D, MacQueen GM, Wang JF, Young LT (1998) Increased temporal cortex CREB concentrations and antidepressant treatment in major depression. Lancet 352:1754–1755

    PubMed  Article  CAS  Google Scholar 

  9. D’Sa C, Duman RS (2002) Antidepressants and neuroplasticity. Bipolar Disord 4:183–194

    PubMed  CAS  Google Scholar 

  10. Duman RS, Malberg J, Nakagawa S, D’Sa C (2000) Neuronal plasticity and survival in mood disorders. Biol Psychiatry 48:732–739

    PubMed  Article  CAS  Google Scholar 

  11. Figurov A, Pozzo-Miller LD, Olafsson P, Wang T, Lu B (1996) Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature 381:706–709

    PubMed  Article  CAS  Google Scholar 

  12. Frodl T, Meisenzahl EM, Zetzsche T, Born C, Groll C, Jager M, Leinsinger G, Bottlender R, Hahn K, Moller HJ (2002) Hippocampal changes in patients with a first episode of major depression. Am J Psychiatry 159:1112–1118

    PubMed  Article  Google Scholar 

  13. Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi J, Sun B, Tandon NN (2002) Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 87:728–734

    PubMed  CAS  Google Scholar 

  14. Gould E, McEwen BS, Tanapat P, Galea LA, Fuchs E (1997) Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci 17:2492–2498

    PubMed  CAS  Google Scholar 

  15. Gould E, Tanapat P, McEwen BS, Flugge G, Fuchs E (1998) Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci USA 95: 3168–3171

    PubMed  Article  CAS  Google Scholar 

  16. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

    PubMed  CAS  Google Scholar 

  17. 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 109:143–148

    Article  CAS  Google Scholar 

  18. Karege F, Schwald M, Cisse M (2002b) Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neurosci Lett 328:261–264

    Article  CAS  Google Scholar 

  19. Korte M, Carroll P, Wolf E, Brem G, Thoenen H, Bonhoeffer T (1995) Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci USA 92:8856–8860

    PubMed  CAS  Google Scholar 

  20. Magarinos AM, McEwen BS (1995) Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons, involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience 69:89–98

    PubMed  CAS  Google Scholar 

  21. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20:9104–9110

    PubMed  CAS  Google Scholar 

  22. Markstein R, Matsumoto M, Kohler C, Togashi H, Yoshioka M, Hoyer D (1999) Pharmacological characterisation of 5-HT receptors positively coupled to adenylyl cyclase in the rat hippocampus. Naunyn Schmiedebergs Arch Pharmacol 359:454–459

    Google Scholar 

  23. McAllister AK, Katz LC, Lo DC (1999) Neurotrophins and synaptic plasticity. Annu Rev Neurosci 22:295–318

    PubMed  Article  CAS  Google Scholar 

  24. Nibuya M, Morinobu S, Duman RS (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 15:7539–7547

    PubMed  CAS  Google Scholar 

  25. Nibuya M, Nestler EJ, Duman RS (1996) Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci 16:2365–2372

    PubMed  CAS  Google Scholar 

  26. Ongur D, Drevets WC, Price JL (1998) Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 95:13290–12295

    PubMed  Article  CAS  Google Scholar 

  27. 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

    PubMed  Article  CAS  Google Scholar 

  28. Pearse HE (1980) The APUD concept and hormone production. Clin Endocrinol Metab 9:211–222

    PubMed  CAS  Google Scholar 

  29. Radka SF, Holst PA, Fritsche M, Atlar 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 709:122–130

    PubMed  Article  CAS  Google Scholar 

  30. Rajkowska G (2000) Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry 48:766–777

    PubMed  Article  CAS  Google Scholar 

  31. Roseboom PH, Klein DC (1995) Norepinephrine stimulation of pineal cyclic AMP response element-binding protein phosphorylation, primary role of a beta-adrenergic receptor/cyclic AMP mechanism. Mol Pharmacol 47:439–449

    PubMed  CAS  Google Scholar 

  32. Russo-Neustadt AA, Alejandre H, Garcia C, Ivy AS, Chen MJ (2004) Hippocampal brain-derived neurotrophic factor expression following treatment with reboxetine, citalopram, and physical exercise. Neuropsychopharmacology 29:2189–2199

    PubMed  Article  CAS  Google Scholar 

  33. Sapolsky RM (2000) Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 57:925–935

    PubMed  CAS  Google Scholar 

  34. Schaaf MJ, Sibug RM, Duurland R, Fluttert MF, Oitzl MS, De Kloet ER, Vreugdenhil E (1999) Corticosterone effects on BDNF mRNA expression in the rat hippocampus during morris water maze training. Stress 3:173–183

    PubMed  CAS  Google Scholar 

  35. Sheline YI, Sanghavi M, Mintun MA, Gado MH (1999) Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci 19:5034–5043

    PubMed  CAS  Google Scholar 

  36. Shelton RC (2000) Cellular mechanisms in the vulnerability to depression and response to antidepressants. Psychiatric Clin North Am 23:713–29

    CAS  Google Scholar 

  37. Shieh PB, Hu SC, Bobb K, Timmusk T, Ghosh A (1998) Identification of a signaling pathway involved in calcium regulation of BDNF expression. Neuron 20:727–740

    PubMed  Article  CAS  Google Scholar 

  38. 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 without or with antidepressants. Biol Psychiatry 54:70–75

    PubMed  Article  CAS  Google Scholar 

  39. Shirayama Y, Chen AC, Nakagawa S, Russell DS, Duman RS (2002) Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 22:3251–3261

    PubMed  CAS  Google Scholar 

  40. Siuciak JA, Lewis DR, Wiegand SJ, Lindsay RM (1997) Antidepressant- like effect of brain-derived neurotrophic factor (BDNF). Pharmacol Biochem Behav 56:131–137

    PubMed  Article  CAS  Google Scholar 

  41. Sofuoglu S, Dogan P, Kose K, Ese, E, Basturk M, Oguz H, Gonul AS (1995) Changes in platelet monoamine oxidase and plasma dopamine-beta-hydroxylase activities in lithium-treated bipolar patients. Psychiatry Res 59:165–170

    PubMed  Article  CAS  Google Scholar 

  42. Spitzer M (1999) Neuroplasticity. In: The Mind Within The Net, Massachusetts, Cambridge: The MIT Press, pp 137–168

  43. Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME (1998) Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20:709–726

    PubMed  Article  CAS  Google Scholar 

  44. Tapia-Arancibia L, Rage F, Givalois L, Arancibia S (2004) Physiology of BDNF: focus on hypothalamic function. Front Neuroendocrinol 25:77–107

    PubMed  CAS  Google Scholar 

  45. Thoenen H (1995) Neurotrophins and neuronal plasticity. Science 270:593–598

    PubMed  CAS  Google Scholar 

  46. Thome J, Saka N, Shin K, Steffen C, Zhang YJ, Impey S, Storm D, Duman RS (2000) cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment. J Neurosci 20:4030–4036

    PubMed  CAS  Google Scholar 

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Author information

Affiliations

  1. Ege University School of Medicine Psychiatry Department Affective Disorder Unit, 35100, Bornova Izmir, Turkey

    A. Saffet Gonul,  F. Akdeniz &  S. Vahip

  2. Celal Bayar University School of Medicine Department of Biochemistry, Manisa, Turkey

    F. Taneli

  3. Ege University School of Medicine Psychiatry Department, Bornova Izmir, Turkey

    O. Donat &  Ç. Eker

Authors
  1. A. Saffet Gonul
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  2. F. Akdeniz
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  3. F. Taneli
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  4. O. Donat
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Correspondence to A. Saffet Gonul.

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Gonul, A.S., Akdeniz, F., Taneli, F. et al. Effect of treatment on serum brain–derived neurotrophic factor levels in depressed patients. Eur Arch Psychiatry Clin Neurosci 255, 381–386 (2005). https://doi.org/10.1007/s00406-005-0578-6

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  • DOI: https://doi.org/10.1007/s00406-005-0578-6

Key words

  • antidepressants
  • biological marker
  • brain–derived neurotrophic factor (BDNF)
  • major depression
  • neuroplasticity