The Role of Brain-Derived Neurotrophic Factor in Mediating the Action of Antidepressants in the Treatment of Depression

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Abstract

According to the neurotrophic hypothesis of depression proposed two decades ago, the most important role in the pathogenesis of depressive disorders is played by abnormalities in the maintenance of neuronal plasticity regulated by brain neurotrophic factor (BDNF). Although the decline in BDNF activity in depression is now widely documented, it remains unclear whether it is a factor contributing to the onset of depression, or a consequence of the chronic course of the disease. In preclinical studies, it was found that exogenous BDNF infusions causes antidepressant-like effects, prevents the depressogenic effects of chronic stress and increases cell survival in the hippocampus and the prefrontal cortex, but the mechanisms mediating these effects have not been fully studied. The results of molecular genetic studies confirmed that BDNF is essential in mediating the therapeutic effect of antidepressants, while the role of genetic polymorphisms in predicting antidepressant efficacy in depression remains uncertain. The mechanisms of action of monoaminergic antidepressants are related to their effect on the expression of BDNF and its TrkB receptor, however, apparently, the effect size varies for different drugs. Peripheral BDNF levels increase during treatment with antidepressants, and this increase is clearly observed only during the acute phase treatment of depression, but not during the period of maintenance therapy. The serum level of BDNF is a potentially useful marker for diagnosing depression and prediction of a therapeutic response.

About the authors

Tamara I. Vazagaeva

V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology

Author for correspondence.
Email: vazagaeva@mail.ru
ORCID iD: 0000-0002-6018-402X

MD, PhD.

23, Kropotkinsky pereulok, 119034 Moscow

SPIN-код: 6469-6491

Russian Federation

Roman V. Akhapkin

V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology

Email: 4ahapkin@gmail.com
ORCID iD: 0000-0002-7045-0547

MD, PhD

SPIN-код: 9966-0084

Yuri A. Alexandrovsky

V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology

Email: alexandrovsky_u@mail.ru
ORCID iD: 0000-0002-4362-2921

MD, PhD, Professor

SPIN-cod: 9010-2378

References

  1. Ferrari AJ, Charlson FJ, Norman RE, et al. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med. 2013;10(11):e1001547. doi: 10.1371/journal.pmed.1001547.
  2. Wong ML, Licinio J. Research and treatment approaches to depression. Nat Rev Neurosci. 2001;2(5):343–351. doi: 10.1038/35072566.
  3. Hillhouse TM, Porter JH. A brief history of the development of antidepressant drugs: from monoamines to glutamate. Exp Clin Psychopharmacol. 2015;23(1):1–21. doi: 10.1037/a0038550.
  4. Meyer JH, Ginovart N, Boovariwala A, et al. Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression. Arch Gen Psychiatry. 2006;63(11):1209–1216. doi: 10.1001/archpsyc.63.11.1209.
  5. Lambert G, Johansson M, Agren H, Friberg P. Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: evidence in support of the catecholamine hypothesis of mood disorders. Arch Gen Psychiatry. 2000;57(8):787–793. doi: 10.1001/archpsyc.57.8.787.
  6. Savitz JB, Drevets WC. Neuroreceptor imaging in depression. Neurobiol Dis. 2013;52:49–65. doi: 10.1016/j.nbd.2012.06.001.
  7. Garcia-Garcia AL, Newman-Tancredi A, Leonardo ED. 5-HT(1A) [corrected] receptors in mood and anxiety: recent insights into autoreceptor versus heteroreceptor function. Psychopharmacology (Berl). 2013;231(4):623–636. doi: 10.1007/s00213-013-3389-x.
  8. Duman RS, Malberg J, Nakagawa S, D’Sa C. Neuronal plasticity and survival in mood disorders. Biol Psychiatry. 2000;48(8):732–739. doi: 10.1016/S0006-3223(00)00935-5.
  9. Duman RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry. 1997;54(7):597–606. doi: 10.1001/archpsyc.1997.01830190015002.
  10. Levy MJ, Boulle F, Steinbusch HW, et al. Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression. Psychopharmacology (Berl). 2018;235(8):2195–2220. doi: 10.1007/s00213-018-4950-4.
  11. Castrén E, Hen R. Neuronal plasticity and antidepressant actions. Trends Neurosci. 2013;36(5):259–267. doi: 10.1016/j.tins.2012.12.010.
  12. Cramer SC, Sur M, Dobkin BH, et al. Harnessing neuroplasticity for clinical applications. Brain. 2011;134(Pt 6):1591–1609. doi: 10.1093/brain/awr039.
  13. Barde YA, Edgar D, Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1982;1(5):549–553. doi: 10.1002/j.1460-2075.1982.tb01207.x.
  14. Cohen S, Levi-Montalcini R, Hamburger V. A nerve growth-stimulating factor isolated from sarcom as 37 and 180. Proc Natl Acad Sci U S A. 1954;40(10):1014–1018. doi: 10.1073/pnas.40.10.1014.
  15. Park H, Poo MM. Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci. 2013;14(1):7–23. doi: 10.1038/nrn3379.
  16. Hashimoto K. Regulation of brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in the brain by serotonin. Eur Arch Psychiatry Clin Neurosci. 2016;266(3):195–197. doi: 10.1007/s00406-016-0682-9.
  17. Lessmann V, Brigadski T. Mechanisms, locations, and kinetics of synaptic BDNF secretion: an update. Neurosci Res. 2009;65(1):11–22. doi: 10.1016/j.neures.2009.06.004.
  18. Leal G, Afonso PM, Salazar IL, Duarte CB. Regulation of hippocampal synaptic plasticity by BDNF. Brain Res. 2015;1621:82–101. doi: 10.1016/j.brainres.2014.10.019.
  19. Yang B, Yang C, Ren Q, et al. Regional differences in the expression of brain-derived neurotrophic factor (BDNF) pro-peptide, proBDNF and preproBDNF in the brain confer stress resilience. Eur Arch Psychiatry Clin Neurosci. 2016;266(8):765–769. doi: 10.1007/s00406-016-0693-6.
  20. Matsuda N, Lu H, Fukata Y, et al. Differential activity-dependent secretion of brain-derived neurotrophic factor from axon and dendrite. J Neurosci. 2009;29(45):14185–14198. doi: 10.1523/JNEUROSCI.1863-09.2009.
  21. Minichiello L. TrkB signalling pathways in LTP and learning. Nat Rev Neurosci. 2009;10(12):850–860. doi: 10.1038/nrn2738.
  22. Gupta VK, You Y, Gupta VB, et al. TrkB receptor signalling: implications in neurodegenerative, psychiatric and proliferative disorders. Int J Mol Sci. 2013;14(5):10122–10142. doi: 10.3390/ijms140510122.
  23. Autry AE, Monteggia LM. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev. 2012;64(2):238–258. doi: 10.1124/pr.111.005108.
  24. Nibuya M, Takahashi M, Russell DS, Duman RS. Repeated stress increases catalytic TrkB mRNA in rat hippocampus. Neurosci Lett. 1999;267(2):81–84. doi: 10.1016/S0304-3940(99)00335-3.
  25. Yang C, Shirayama Y, Zhang JC, et al. Regional differences in brain-derived neurotrophic factor levels and dendritic spine density confer resilience to inescapable stress. Int J Neuropsychopharmacol. 2015;18(7):pyu121. doi: 10.1093/ijnp/pyu121.
  26. Qiao H, An SC, Xu C, Ma XM. Role of proBDNF and BDNF in dendritic spine plasticity and depressive-like behaviors induced by an animal model of depression. Brain Res. 2017;1663:29–37. doi: 10.1016/j.brainres.2017.02.020.
  27. Yang B, Yang C, Ren Q, et al. Regional differences in the expression of brain-derived neurotrophic factor (BDNF) pro-peptide, proBDNF and preproBDNF in the brain confer stress resilience. Eur Arch Psychiatry Clin Neurosci. 2016;266(8):765–769. doi: 10.1007/s00406-016-0693-6.
  28. Tripp A, Oh H, Guilloux JP, et al. Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder. Am J Psychiatry. 2012;169(11):1194–1202. doi: 10.1176/appi.ajp.2012.12020248.
  29. Dwivedi Y. Brain-derived neurotrophic factor and suicide pathogenesis. Ann Med. 2010;42(2):87–96. doi: 10.3109/07853890903485730.
  30. Molendijk ML, Bus BA, Spinhoven P, et al. Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment. Mol Psychiatry. 2010;16(11):1088–1095. doi: 10.1038/mp.2010.98.
  31. Polyakova M, Stuke K, Schuemberg K, et al. BDNF as a biomarker for successful treatment of mood disorders: a systematic & quantitative meta-analysis. J Affect Disord. 2015;174:432–440. doi: 10.1016/j.jad.2014.11.044.
  32. Lee BH, Kim H, Park SH, Kim YK. Decreased plasma BDNF level in depressive patients. J Affect Disord. 2007;101(1–3):239–244. doi: 10.1016/j.jad.2006.11.005.
  33. Bus BA, Molendijk ML, Tendolkar I, et al. Chronic depression is associated with a pronounced decrease in serum brain-derived neurotrophic factor over time. Mol Psychiatry. 2015;20(5):602–608. doi: 10.1038/mp.2014.83.
  34. McKinnon MC, Yucel K, Nazarov A, MacQueen GM. A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. J Psychiatry Neurosci. 2009;34(1):41–54.
  35. Siuciak JA, Lewis DR, Wiegand SJ, Lindsay RM. Antidepressant-like effect of brain-derived neurotrophic factor (BDNF). Pharmacol Biochem Behav. 1997;56(1):131–137. doi: 10.1016/S0091-3057(96)00169-4.
  36. Shirayama Y, Chen AC, Nakagawa S, et al. Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci. 2002;22(8):3251–3261. doi: 10.1523/JNEUROSCI.22-08-03251.2002.
  37. Hoshaw BA, Malberg JE, Lucki I. Central administration of IGF-I and BDNF leads to long-lasting antidepressant-like effects. Brain Res. 2005;1037(1–2):204–208. doi: 10.1016/j.brainres.2005.01.007.
  38. Schmidt HD, Duman RS. Peripheral BDNF produces antidepressant-like effects in cellular and behavioral models. Neuropsychopharmacology. 2010;35(12):2378–2391. doi: 10.1038/npp.2010.114.
  39. Pan W, Banks WA, Fasold MB, et al. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology. 1998;37(12):1553–1561. doi: 10.1016/S0028-3908(98)00141-5.
  40. Saarelainen T, Hendolin P, Lucas G, et al. Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J Neurosci. 2003;23(1):349–357. doi: 10.1523/JNEUROSCI.23-01-00349.2003.
  41. Altar CA, Whitehead RE, Chen R, et al. Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain. Biol Psychiatry. 2003;54(7):703–709. doi: 10.1016/S0006-3223(03)00073-8.
  42. Monteggia LM, Barrot M, Powell CM, et al. Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc Natl Acad Sci U S A. 2004;101(29):10827–10832. doi: 10.1073/pnas.0402141101.
  43. Adachi M, Barrot M, Autry AE, et al. Selective loss of brain-derived neurotrophic factor in the dentate gyrus attenuates antidepressant efficacy. Biol Psychiatry. 2007;63(7):642–649. doi: 10.1016/j.biopsych.2007.09.019.
  44. Colle R, Deflesselle E, Martin S, et al. BDNF/TRKB/P75NTR polymorphisms and their consequences on antidepressant efficacy in depressed patients. Pharmacogenomics. 2015;16(9):997–1013. doi: 10.2217/pgs.15.56.
  45. Chen ZY, Jing D, Bath KG, et al. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science. 2006;314(5796):140–143. doi: 10.1126/science.1129663.
  46. Bath KG, Jing DQ, Dincheva I, et al. BDNF Val66Met impairs fluoxetine-induced enhancement of adult hippocampus plasticity. Neuropsychopharmacology. 2012;37(5):1297–1304. doi: 10.1038/npp.2011.318.
  47. Pattwell SS, Bath KG, Perez-Castro R, et al. The BDNF Val66Met polymorphism impairs synaptic transmission and plasticity in the infralimbic medial prefrontal cortex. J Neurosci. 2012;32(7):2410–2421. doi: 10.1523/JNEUROSCI.5205-11.2012.
  48. Yan T, Wang L, Kuang W, et al. Brain-derived neurotrophic factor Val66Met polymorphism association with antidepressant efficacy: a systematic review and meta-analysis. Asia Pac Psychiatry. 2014;6(3):241–251. doi: 10.1111/appy.12148.
  49. Niitsu T, Fabbri C, Bentini F, Serretti A. Pharmacogenetics in major depression: a comprehensive meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2013;45:183–194. doi: 10.1016/j.pnpbp.2013.05.011.
  50. Licinio J, Dong C, Wong ML. Novel sequence variations in the brain-derived neurotrophic factor gene and association with major depression and antidepressant treatment response. Arch Gen Psychiatry. 2009;66(5):488–497. doi: 10.1001/archgenpsychiatry.2009.38.
  51. Xu G, Lin K, Rao D, et al. Brain-derived neurotrophic factor gene polymorphism (Val66Met) and the early response to antidepressant in Chinese Han population. Psychiatr Genet. 2012;22(4):214–215. doi: 10.1097/YPG.0b013e32834c0c87.
  52. Colle R, Gressier F, Verstuyft C, et al. Brain-derived neurotrophic factor Val66Met polymorphism and 6-month antidepressant remission in depressed Caucasian patients. J Affect Disord. 2015;175:233–240. doi: 10.1016/j.jad.2015.01.013.
  53. Benmansour S, Deltheil T, Piotrowski J, et al. Influence of brain-derived neurotrophic factor (BDNF) on serotonin neurotransmission in the hippocampus of adult rodents. Eur J Pharmacol. 2008;587(1–3):90–98. doi: 10.1016/j.ejphar.2008.03.048.
  54. Björkholm C, Monteggia LM. BDNF — a key transducer of antidepressant effects. Neuropharmacology. 2015;102:72–79. doi: 10.1016/j.neuropharm.2015.10.034.
  55. Nibuya M, Morinobu S, Duman RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci. 1995;15(11):7539–7547. doi: 10.1523/JNEUROSCI.15-11-07539.1995.
  56. Larsen MH, Hay-Schmidt A, Rønn LC, Mikkelsen JD. Temporal expression of brain-derived neurotrophic factor (BDNF) mRNA in the rat hippocampus after treatment with selective and mixed monoaminergic antidepressants. Eur J Pharmacol. 2008;578(2–3):114–122. doi: 10.1016/j.ejphar.2007.08.050.
  57. Lepack AE, Fuchikami M, Dwyer JM, et al. BDNF release is required for the behavioral actions of ketamine. Int J Neuropsychopharmacol. 2014;18(1):pyu033. doi: 10.1093/ijnp/pyu033.
  58. Rantamaki T, Hendolin P, Kankaanpaa A, et al. Pharmacologically diverse antidepressants rapidly activate brain-derived neurotrophic factor receptor TrkB and induce phospholipase-Cgamma signaling pathways in mouse brain. Neuropsychopharmacology. 2007;32(10):2152–2162. doi: 10.1038/sj.npp.1301345.
  59. Saarelainen T, Vaittinen S, Castrén E. trkB-receptor activation contributes to the kainate-induced increase in BDNF mRNA synthesis. Cell Mol Neurobiol. 2001;21(4):429–435. doi: 10.1023/A:1012775808253.
  60. Rantamaki T, Vesa L, Antila H, et al. Antidepressant drugs transactivate TrkB neurotrophin receptors in the adult rodent brain independently of BDNF and monoamine transporter blockade. PLoS One. 2011;6(6):e20567. doi: 10.1371/journal.pone.0020567.
  61. 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):261–265. doi: 10.1016/j.pnpbp.2004.11.009.
  62. Mikoteit T, Beck J, Eckert A, et al. High baseline BDNF serum levels and early psychopathological improvement are predictive of treatment outcome in major depression. Psychopharmacology (Berl). 2014;231(15):2955–2965. doi: 10.1007/s00213-014-3475-8.
  63. Matrisciano F, Bonaccorso S, Ricciardi A, 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. 2008;43(3):247–254. doi: 10.1016/j.jpsychires.2008.03.014.
  64. Başterzi AD, Yazici K, Aslan E, et al. Effects of fluoxetine and venlafaxine on serum brain derived neurotrophic factor levels in depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(2):281–285. doi: 10.1016/j.pnpbp.2008.11.016.
  65. Zhou C, Zhong J, Zou B, et al. Meta-analyses of comparative efficacy of antidepressant medications on peripheral BDNF concentration in patients with depression. PLoS One. 2017;12(2):e0172270. doi: 10.1371/journal.pone.0172270.
  66. Piccinni A, Del Debbio A, Medda P, et al. Plasma Brain-Derived Neurotrophic Factor in treatment-resistant depressed patients receiving electroconvulsive therapy. Eur Neuropsychopharmacol. 2009;19(5):349–355. doi: 10.1016/j.euroneuro.2009.01.002.
  67. Dreimüller N, Schlicht KF, Wagner S, et al. Early reactions of brain-derived neurotrophic factor in plasma (pBDNF) and outcome to acute antidepressant treatment in patients with Major Depression. Neuropharmacology. 2012;62(1):264–269. doi: 10.1016/j.neuropharm.2011.07.017.
  68. Tadić A, Wagner S, Schlicht KF, 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):415–420. doi: 10.1016/j.pnpbp.2010.08.011.

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