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The Roles of BDNF in the Pathophysiology of Major Depression and in Antidepressant Treatment

  • Lee, Bun-Hee (Department of Psychiatry, College of Medicine, Korea University) ;
  • Kim, Yong-Ku (Department of Psychiatry, College of Medicine, Korea University)
  • Received : 2010.07.09
  • Accepted : 2010.09.07
  • Published : 2010.12.30

Abstract

Neurotrophic factors are critical regulators of the formation and plasticity of neuronal networks. Brain-derived neurotrophic factor (BD-NF) is abundant in the brain and periphery, and is found in both human serum and plasma. Animal studies have demonstrated that stress reduces BDNF expression or activity in the hippocampus and that this reduction can be prevented by treatment with antidepressant drugs. A similar change in BDNF activity occurs in the brain of patients with major depression disorder (MDD). Recently, clinical studies have indicated that serum or plasma BDNF levels are decreased in untreated MDD patients. Antidepressant treatment for at least four weeks can restore the decreased BDNF function up to the normal value. Therefore, MDD is associated with impaired neuronal plasticity. Suicidal behavior can be a consequence of severe impaired neuronal plasticity in the brain. Antidepressant treatment promotes increased BDNF activity as well as several forms of neuronal plasticity, including neurogenesis, synaptogenesis and neuronal maturation. BDNF could also play an important role in the modulation of neuronal networks. Such a neuronal plastic change can positively influence mood or recover depressed mood. These alterations of BDNF levels or neuronal plasticity in MDD patients before and after antidepressant treatment can be measured through the examination of serum or plasma BDNF concentrations. BDNF levels can therefore be useful markers for clinical response or improvement of depressive symptoms, but they are not diagnostic markers of major depression.

Keywords

References

  1. Warner-Schmidt JL, Duman RS. Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus 2006;16: 239-249. https://doi.org/10.1002/hipo.20156
  2. Mellstrom B, Torres B, Link WA, Naranjo JR. The BDNF gene: exemplifying complexity in Ca2+ -dependent gene expression. Crit Rev Neurobiol 2004;16:43-49. https://doi.org/10.1615/CritRevNeurobiol.v16.i12.40
  3. Lu B, Pang PT, Woo NH. The yin and yang of neurotrophin action. Nat Rev Neurosci 2005;6:603-614. https://doi.org/10.1038/nrn1726
  4. Miller FD, Kaplan DR. Neurotrophin signaling pathways regulating neu-ronal apoptosis. Cell Mol Life Sci 2001;58:1045-1053. https://doi.org/10.1007/PL00000919
  5. Duman RS. Pathophysiology of depression: the concept of synaptic pla-sticity. Eur Psychiatry 2002;17 Suppl 3:306-310. https://doi.org/10.1016/S0924-9338(02)00654-5
  6. Castren E, Voikar V, Rantamaki T. Role of neurotrophic factors in depression. Curr Opin Pharmacol 2007;7:18-21. https://doi.org/10.1016/j.coph.2006.08.009
  7. Smith MA, Makino S, Kvetnansky R, Post RM. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neu-rotrophin-3 mRNAs in the hippocampus. J Neurosci 1995;15:1768-1777.
  8. Ueyama T, Kawai Y, Nemoto K, Sekimoto M, Tone S, Senba E. Immobilization stress reduced the expression of neurotrophins and their receptors in the rat brain. Neurosci Res 1997;28:103-110. https://doi.org/10.1016/S0168-0102(97)00030-8
  9. Rasmusson AM, Shi L, Duman R. Downregulation of BDNF mRNA in the hippocampal dentate gyrus after re-exposure to cues previously associated with footshock. Neuropsychopharmacology 2002;27:133-142. https://doi.org/10.1016/S0893-133X(02)00286-5
  10. Pizarro JM, Lumley LA, Medina W, Robison CL, Chang WE, Alagappan A, et al. Acute social defeat reduces neurotrophin expression in brain cortical and subcortical areas in mice. Brain Res 2004;1025:10-20. https://doi.org/10.1016/j.brainres.2004.06.085
  11. Roceri M, Hendriks W, Racagni G, Ellenbroek BA, Riva MA. Early maternal deprivation reduces the expression of BDNF and NMDA receptor subunits in rat hippocampus. Mol Psychiatry 2002;7:609-616. https://doi.org/10.1038/sj.mp.4001036
  12. Russo-Neustadt A, Ha T, Ramirez R, Kesslak JP. Physical activity-antidepressant treatment combination: impact on brain-derived neurotrophic factor and behavior in an animal model. Behav Brain Res 2001;120: 87-95. https://doi.org/10.1016/S0166-4328(00)00364-8
  13. Schaaf MJ, de Jong J, de Kloet ER, Vreugdenhil E. Downregulation of BDNF mRNA and protein in the rat hippocampus by corticosterone. Brain Res 1998;813:112-120. https://doi.org/10.1016/S0006-8993(98)01010-5
  14. Dwivedi Y, Rizavi HS, Pandey GN. Antidepressants reverse corticosterone-mediated decrease in BDNF expression: dissociation in regulation of specific exons by antidepressants and corticosterone. Neuroscience 2006;139:1017-1029. https://doi.org/10.1016/j.neuroscience.2005.12.058
  15. Chao HM, Sakai RR, Ma LY, McEwen BS. Adrenal steroid regulation of neurotrophic factor expression in the rat hippocampus. Endocrinology 1998;139:3112-3118. https://doi.org/10.1210/en.139.7.3112
  16. Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ. Sustained hippocampal chromatin regulation in a mouse model of depres-sion and antidepressant action. Nat Neurosci 2006;9:519-525. https://doi.org/10.1038/nn1659
  17. Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry 2006;59:1116-1127. https://doi.org/10.1016/j.biopsych.2006.02.013
  18. Muller MB, Toschi N, Kresse AE, Post A, Keck ME. Long-term repetitive transcranial magnetic stimulation increases the expression of brain-derived neurotrophic factor and cholecystokinin mRNA, but not neuropeptide tyrosine mRNA in specific areas of rat brain. Neuropsychopharmacology 2000;23:205-215. https://doi.org/10.1016/S0893-133X(00)00099-3
  19. Altar CA, Laeng P, Jurata LW, Brockman JA, Lemire A, Bullard J, et al. Electroconvulsive seizures regulate gene expression of distinct neurotrophic signaling pathways. J Neurosci 2004;24:2667-2677. https://doi.org/10.1523/JNEUROSCI.5377-03.2004
  20. Balu DT, Hoshaw BA, Malberg JE, Rosenzweig-Lipson S, Schechter LE, Lucki I. Differential regulation of central BDNF protein levels by antidepressant and non-antidepressant drug treatments. Brain Res 2008; 1211:37-43. https://doi.org/10.1016/j.brainres.2008.03.023
  21. Coppell AL, Pei Q, Zetterstrom TS. Bi-phasic change in BDNF gene expression following antidepressant drug treatment. Neuropharmacology 2003;44:903-910. https://doi.org/10.1016/S0028-3908(03)00077-7
  22. De Foubert G, Carney SL, Robinson CS, Destexhe EJ, Tomlinson R, Hi-cks CA, et al. Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment. Neuroscience 2004;128:597-604. https://doi.org/10.1016/j.neuroscience.2004.06.054
  23. Altieri M, Marini F, Arban R, Vitulli G, Jansson BO. Expression analysis of brain-derived neurotrophic factor (BDNF) mRNA isoforms after chronic and acute antidepressant treatment. Brain Res 2004;1000:148-155. https://doi.org/10.1016/j.brainres.2003.12.028
  24. Hajszan T, MacLusky NJ, Leranth C. Short-term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus. Eur J Neurosci 2005;21:1299-1303. https://doi.org/10.1111/j.1460-9568.2005.03968.x
  25. Sairanen M, O'Leary OF, Knuuttila JE, Castren E. Chronic antidepressant treatment selectively increases expression of plasticity-related proteins in the hippocampus and medial prefrontal cortex of the rat. Neuroscience 2007;144:368-374. https://doi.org/10.1016/j.neuroscience.2006.08.069
  26. Saarelainen T, Hendolin P, Lucas G, Koponen E, Sairanen M, MacDonald E, et al. Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J Neurosci 2003;23:349-357.
  27. Monteggia LM, Barrot M, Powell CM, Berton O, Galanis V, Gemelli T, et al. Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc Natl Acad Sci U S A 2004;101:10827-10832. https://doi.org/10.1073/pnas.0402141101
  28. Altar CA, Whitehead RE, Chen R, Wortwein G, Madsen TM. Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain. Biol Psychiatry 2003;54:703-709. https://doi.org/10.1016/S0006-3223(03)00073-8
  29. MacQueen GM, Ramakrishnan K, Croll SD, Siuciak JA, Yu G, Young LT, et al. Performance of heterozygous brain-derived neurotrophic factor knockout mice on behavioral analogues of anxiety, nociception, and depression. Behav Neurosci 2001;115:1145-1153. https://doi.org/10.1037/0735-7044.115.5.1145
  30. Zorner B, Wolfer DP, Brandis D, Kretz O, Zacher C, Madani R, et al. Forebrain-specific trkB-receptor knockout mice: behaviorally more hyperactive than "depressive". Biol Psychiatry 2003;54:972-982. https://doi.org/10.1016/S0006-3223(03)00418-9
  31. Chen B, Dowlatshahi D, MacQueen GM, Wang JF, Young LT. Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 2001;50:260-265. https://doi.org/10.1016/S0006-3223(01)01083-6
  32. Dowlatshahi D, MacQueen GM, Wang JF, Young LT. Increased temporal cortex CREB concentrations and antidepressant treatment in major depression. Lancet 1998;352:1754-1755. https://doi.org/10.1016/S0140-6736(05)79827-5
  33. Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi J, et al. Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 2002;87:728-734.
  34. Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 1998;37:1553-1561. https://doi.org/10.1016/S0028-3908(98)00141-5
  35. Poduslo JF, Curran GL. Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF. Brain Res Mol Brain Res 1996;36:280-286. https://doi.org/10.1016/0169-328X(95)00250-V
  36. 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;255:381-386. https://doi.org/10.1007/s00406-005-0578-6
  37. Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM. Decreased serum brain-derived neurotrophic factor levels in major depress-ed patients. Psychiatry Res 2002;109:143-148. https://doi.org/10.1016/S0165-1781(02)00005-7
  38. Karege F, Bondolfi G, Gervasoni N, Schwald M, Aubry JM, Bertschy G. 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 2005;57:1068-1072. https://doi.org/10.1016/j.biopsych.2005.01.008
  39. Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, et al. Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 2003;54:70-75. https://doi.org/10.1016/S0006-3223(03)00181-1
  40. Lee BH, Kim H, Park SH, Kim YK. Decreased plasma BDNF level in depressive patients. J Affect Disord 2007;101:239-244. https://doi.org/10.1016/j.jad.2006.11.005
  41. 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;11:1169-1180. https://doi.org/10.1017/S1461145708009309
  42. 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;31:1034-1037. https://doi.org/10.1016/j.pnpbp.2007.03.001
  43. Matrisciano F, Bonaccorso S, Ricciardi A, Scaccianoce S, Panaccione I, Wang L, et al. Changes in BDNF serum levels in patients with depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine. J Psychiatr Res 2009;43:247-254. https://doi.org/10.1016/j.jpsychires.2008.03.014
  44. Lee HY, Kim YK. Plasma brain-derived neurotrophic factor as a peripheral marker for the action mechanism of antidepressants. Neuropsychobiology 2008;57:194-199. https://doi.org/10.1159/000149817
  45. 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;105:279-283. https://doi.org/10.1016/j.jad.2007.05.005
  46. Dwivedi Y, Rizavi HS, Conley RR, Roberts RC, Tamminga CA, Pandey GN. Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiatry 2003;60:804-815. https://doi.org/10.1001/archpsyc.60.8.804
  47. Pandey GN, Ren X, Rizavi HS, Conley RR, Roberts RC, Dwivedi Y. Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims. Int J Neuropsychopharmacol 2008;11:1047-1061. https://doi.org/10.1017/S1461145708009000
  48. Ernst C, Deleva V, Deng X, Sequeira A, Pomarenski A, Klempan T, et al. Alternative splicing, methylation state, and expression profile of tropomyosin-related kinase B in the frontal cortex of suicide completers. Arch Gen Psychiatry 2009;66:22-32. https://doi.org/10.1001/archpsyc.66.1.22
  49. Dwivedi Y, Rizavi HS, Zhang H, Mondal AC, Roberts RC, Conley RR, et al. Neurotrophin receptor activation and expression in human postmortem brain: effect of suicide. Biol Psychiatry 2009;65:319-328. https://doi.org/10.1016/j.biopsych.2008.08.035
  50. Deveci A, Aydemir O, Taskin O, Taneli F, Esen-Danaci A. Serum BDNF levels in suicide attempters related to psychosocial stressors: a comparative study with depression. Neuropsychobiology 2007;56:93-97. https://doi.org/10.1159/000111539
  51. Kim YK, Lee HP, Won SD, Park EY, Lee HY, Lee BH, et al. Low plasma BDNF is associated with suicidal behavior in depression. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:78-85. https://doi.org/10.1016/j.pnpbp.2006.06.024
  52. Dawood T, Anderson J, Barton D, Lambert E, Esler M, Hotchkin E, et al. Reduced overflow of BDNF from the brain is linked with suicide risk in depressive illness. Mol Psychiatry 2007;12:981-983. https://doi.org/10.1038/sj.mp.4002059
  53. Malcangio M, Lessmann V. A common thread for pain and memory synapses? Brain-derived neurotrophic factor and trkB receptors. Trends Pharmacol Sci 2003;24:116-121. https://doi.org/10.1016/S0165-6147(03)00025-7

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  62. Peritoneal endometriosis induces time-related depressive- and anxiety-like alterations in female rats: involvement of hippocampal pro-oxidative and BDNF alterations vol.34, pp.3, 2010, https://doi.org/10.1007/s11011-019-00397-1
  63. What do DNA methylation studies tell us about depression? A systematic review vol.9, pp.1, 2010, https://doi.org/10.1038/s41398-019-0412-y
  64. Alterations in the Levels of Growth Factors in Adolescents with Major Depressive Disorder: A Longitudinal Study during the Treatment with Fluoxetine vol.2019, pp.None, 2010, https://doi.org/10.1155/2019/9130868
  65. Decoding the Mechanism of Action of Rapid-Acting Antidepressant Treatment Strategies: Does Gender Matter? vol.20, pp.4, 2010, https://doi.org/10.3390/ijms20040949
  66. The Low Molecular Weight Brain-derived Neurotrophic Factor Mimetics with Antidepressant-like Activity vol.25, pp.6, 2010, https://doi.org/10.2174/1381612825666190329122852
  67. Low serum brain-derived neurotrophic factor is associated with suicidal ideation in major depressive disorder vol.273, pp.None, 2019, https://doi.org/10.1016/j.psychres.2019.01.013
  68. Direct and indirect evidences of BDNF and NGF as key modulators in depression: role of antidepressants treatment vol.129, pp.3, 2019, https://doi.org/10.1080/00207454.2018.1527328
  69. Differential associations of depression‐related phenotypes with cardiometabolic risks: Polygenic analyses and exploring shared genetic variants and pathways vol.36, pp.4, 2010, https://doi.org/10.1002/da.22861
  70. Effect of probiotic interventions on depressive symptoms: A narrative review evaluating systematic reviews vol.73, pp.4, 2010, https://doi.org/10.1111/pcn.12804
  71. Stress – (self) eating: Epigenetic regulation of autophagy in response to psychological stress vol.286, pp.13, 2010, https://doi.org/10.1111/febs.14826
  72. Elucidation of the Molecular Mechanism Underlying Lippia citriodora(Lim.)-Induced Relaxation and Anti-Depression vol.20, pp.14, 2010, https://doi.org/10.3390/ijms20143556
  73. Linking unfolded protein response to inflammation and depression: potential pathologic and therapeutic implications vol.24, pp.7, 2010, https://doi.org/10.1038/s41380-018-0241-z
  74. The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress‐induced depression in mice vol.33, pp.8, 2010, https://doi.org/10.1096/fj.201802359rr
  75. Paeoniflorin attenuates impairment of spatial learning and hippocampal long-term potentiation in mice subjected to chronic unpredictable mild stress vol.236, pp.9, 2010, https://doi.org/10.1007/s00213-019-05257-5
  76. Off-label Antidepressant Use for Treatment and Management of Chronic Pain: Evolving Understanding and Comprehensive Review vol.23, pp.9, 2010, https://doi.org/10.1007/s11916-019-0803-z
  77. Neuroprotective Benefits of Antidepressants in Multiple Sclerosis: Are We Missing the Mark? vol.31, pp.4, 2010, https://doi.org/10.1176/appi.neuropsych.18070164
  78. Behavioural characterisation of chronic unpredictable stress based on ethologically relevant paradigms in rats vol.9, pp.1, 2010, https://doi.org/10.1038/s41598-019-53624-1
  79. The Impact of Social and Behavioral Factors on Reproducibility in Terrestrial Vertebrate Models vol.60, pp.2, 2019, https://doi.org/10.1093/ilar/ilaa005
  80. Flaxseed oil supplementation on severity of depression and brain-derived neurotrophic factor: a randomized, double blind placebo controlled clinical trial vol.23, pp.1, 2010, https://doi.org/10.1080/10942912.2020.1812639
  81. Among Adolescents, BDNF and Pro-BDNF Lasting Changes with Alcohol Use Are Stage Specific vol.2020, pp.None, 2010, https://doi.org/10.1155/2020/3937627
  82. FGF21 Attenuated LPS-Induced Depressive-Like Behavior via Inhibiting the Inflammatory Pathway vol.11, pp.None, 2010, https://doi.org/10.3389/fphar.2020.00154
  83. New Insights on the Role of N 6 -Methyladenosine RNA Methylation in the Physiology and Pathology of the Nervous System vol.7, pp.None, 2010, https://doi.org/10.3389/fmolb.2020.555372
  84. Curcumin in Depression: Potential Mechanisms of Action and Current Evidence—A Narrative Review vol.11, pp.None, 2010, https://doi.org/10.3389/fpsyt.2020.572533
  85. Analyzing the genes and pathways related to major depressive disorder via a systems biology approach vol.10, pp.2, 2010, https://doi.org/10.1002/brb3.1502
  86. The Effect of Probiotic Intervention in Ameliorating the Altered Central Nervous System Functions in Neurological Disorders: A Review vol.14, pp.None, 2020, https://doi.org/10.2174/1874285802014010018
  87. Brain‐derived neurotrophic factor and post‐stroke depression vol.98, pp.3, 2010, https://doi.org/10.1002/jnr.24510
  88. Is There a Future for PPARs in the Treatment of Neuropsychiatric Disorders? vol.25, pp.5, 2020, https://doi.org/10.3390/molecules25051062
  89. Inflammatory, Structural, and Pain Biochemical Biomarkers May Reflect Radiographic Disc Space Narrowing: The Johnston County Osteoarthritis Project vol.38, pp.5, 2010, https://doi.org/10.1002/jor.24534
  90. The Novel Role of PPAR Alpha in the Brain: Promising Target in Therapy of Alzheimer’s Disease and Other Neurodegenerative Disorders vol.45, pp.5, 2010, https://doi.org/10.1007/s11064-020-02993-5
  91. Cellular mechanisms and molecular signaling pathways in stress-induced anxiety, depression, and blood-brain barrier inflammation and leakage vol.28, pp.3, 2010, https://doi.org/10.1007/s10787-020-00712-8
  92. Polyphenols selectively reverse early-life stress-induced behavioural, neurochemical and microbiota changes in the rat vol.116, pp.None, 2010, https://doi.org/10.1016/j.psyneuen.2020.104673
  93. State-of-the-Art: Inflammatory and Metabolic Markers in Mood Disorders vol.10, pp.6, 2020, https://doi.org/10.3390/life10060082
  94. Peripheral Biomarkers in DSM-5 Anxiety Disorders: An Updated Overview vol.10, pp.8, 2010, https://doi.org/10.3390/brainsci10080564
  95. Neuroinflammation and microglia/macrophage phenotype modulate the molecular background of post-stroke depression: A literature review vol.20, pp.3, 2010, https://doi.org/10.3892/etm.2020.8933
  96. Dance and Parkinson's: Biological perspective and rationale vol.1, pp.2, 2010, https://doi.org/10.1002/lim2.15
  97. Folic acid ameliorates depression-like behaviour in a rat model of chronic unpredictable mild stress vol.21, pp.1, 2020, https://doi.org/10.1186/s12868-020-0551-3
  98. Asparagus cochinchinensis extract ameliorates menopausal depression in ovariectomized rats under chronic unpredictable mild stress vol.20, pp.1, 2010, https://doi.org/10.1186/s12906-020-03121-0
  99. Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes, BDNF, and astrocytes vol.54, pp.2, 2010, https://doi.org/10.1590/1414-431x202010107
  100. Comparison of Brain-derived Neurotrophic Factor Level in Depressed Patients Treated with Fluoxetine and Sertraline vol.9, pp.t3, 2010, https://doi.org/10.3889/oamjms.2021.6348
  101. Mechanism of Intermittent Theta-Burst Stimulation in Synaptic Pathology in the Prefrontal Cortex in an Antidepressant-Resistant Depression Rat Model vol.31, pp.1, 2021, https://doi.org/10.1093/cercor/bhaa244
  102. Plasma BDNF concentrations and the antidepressant effects of six ketamine infusions in unipolar and bipolar depression vol.9, pp.None, 2010, https://doi.org/10.7717/peerj.10989
  103. Blood Brain-Derived Neurotrophic Factor (BDNF) and Major Depression: Do We Have a Translational Perspective? vol.15, pp.None, 2010, https://doi.org/10.3389/fnbeh.2021.626906
  104. Hederagenin Protects PC12 Cells Against Corticosterone-Induced Injury by the Activation of the PI3K/AKT Pathway vol.12, pp.None, 2021, https://doi.org/10.3389/fphar.2021.712876
  105. The anti-inflammatory role of SSRI and SNRI in the treatment of depression: a review of human and rodent research studies vol.29, pp.1, 2010, https://doi.org/10.1007/s10787-020-00777-5
  106. Cardiac glycosaminoglycans and structural alterations during chronic stress-induced depression-like behavior in mice vol.320, pp.5, 2021, https://doi.org/10.1152/ajpheart.00635.2020
  107. Correlations between serum BDNF levels and neurodevelopmental outcomes in infants of mothers with gestational diabetes vol.62, pp.3, 2010, https://doi.org/10.1016/j.pedneo.2020.12.012
  108. Potential depression and antidepressant-response biomarkers in human lymphoblast cell lines from treatment-responsive and treatment-resistant subjects: roles of SSRIs and omega-3 polyunsaturated fatty vol.26, pp.6, 2010, https://doi.org/10.1038/s41380-020-0724-6
  109. Comparative Analysis of Pathobiochemical Changes in Major Depression and Post-Traumatic Stress Disorder vol.86, pp.6, 2021, https://doi.org/10.1134/s0006297921060109
  110. Changes of BDNF exon IV DNA methylation are associated with methamphetamine dependence vol.13, pp.12, 2010, https://doi.org/10.2217/epi-2020-0463
  111. Maternal diabetes-induced alterations in the expression of brain-derived neurotrophic factor in the developing rat hippocampus vol.114, pp.None, 2021, https://doi.org/10.1016/j.jchemneu.2021.101946
  112. Allopregnanolone in mood disorders: Mechanism and therapeutic development vol.169, pp.None, 2021, https://doi.org/10.1016/j.phrs.2021.105682
  113. The Effect of Blockade of Androgen Receptors by Flutamide on Learning and Memory, Synaptic Plasticity and Behavioral Performances: A Review Study vol.15, pp.4, 2010, https://doi.org/10.1134/s1990519x21040088
  114. The long-term bio-behavioural effects of juvenile sildenafil treatment in Sprague-Dawley versus flinders sensitive line rats vol.33, pp.4, 2010, https://doi.org/10.1017/neu.2021.4
  115. The PPARg System in Major Depression: Pathophysiologic and Therapeutic Implications vol.22, pp.17, 2010, https://doi.org/10.3390/ijms22179248
  116. Potential biomarkers of major depression diagnosis and chronicity vol.16, pp.9, 2010, https://doi.org/10.1371/journal.pone.0257251
  117. Genotype-expression interactions for BDNF across human brain regions vol.22, pp.1, 2021, https://doi.org/10.1186/s12864-021-07525-1
  118. Emerging Role of Flavonoids as the Treatment of Depression vol.11, pp.12, 2010, https://doi.org/10.3390/biom11121825
  119. Psychobiotics as treatment for anxiety, depression, and related symptoms: a systematic review vol.24, pp.12, 2010, https://doi.org/10.1080/1028415x.2019.1701220
  120. Dietary Intake of Flavonoids and Carotenoids Is Associated with Anti-Depressive Symptoms: Epidemiological Study and In Silico-Mechanism Analysis vol.11, pp.1, 2010, https://doi.org/10.3390/antiox11010053
  121. Cortisol and development of depression in adolescence and young adulthood – a systematic review and meta-analysis vol.136, pp.None, 2010, https://doi.org/10.1016/j.psyneuen.2021.105625