The Roles of BDNF in the Pathophysiology of Major Depression and in Antidepressant Treatment
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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.
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.
참고문헌 (53)
- Warner-Schmidt JL, "Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment", Hippocampus, 16, pp.239~249 (2006)
- Mellstrom B, "The BDNF gene: exemplifying complexity in Ca2+ -dependent gene expression", Crit Rev Neurobiol, 16, pp.43~49 (2004)
- Lu B, "The yin and yang of neurotrophin action", Nat Rev Neurosci, 6, pp.603~614 (2005)
- Miller FD, "Neurotrophin signaling pathways regulating neu-ronal apoptosis", Cell Mol Life Sci, 58, pp.1045~1053 (2001)
- Duman RS, "Pathophysiology of depression: the concept of synaptic pla-sticity", Eur Psychiatry, 17(3), pp.306~310 (2002)
- Castrén E, "Role of neurotrophic factors in depression", Curr Opin Pharmacol, 7, pp.18~21 (2007)
- Smith MA, "Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neu-rotrophin-3 mRNAs in the hippocampus", J Neurosci, 15, pp.1768~1777 (1995)
- Ueyama T, "Immobilization stress reduced the expression of neurotrophins and their receptors in the rat brain", Neurosci Res, 28, pp.103~110 (1997)
- Rasmusson AM, "Downregulation of BDNF mRNA in the hippocampal dentate gyrus after re-exposure to cues previously associated with footshock", Neuropsychopharmacology, 27, pp.133~142 (2002)
- Pizarro JM, "Acute social defeat reduces neurotrophin expression in brain cortical and subcortical areas in mice", Brain Res, 1025, pp.10~20 (2004)
- Roceri M, "Early maternal deprivation reduces the expression of BDNF and NMDA receptor subunits in rat hippocampus", Mol Psychiatry, 7, pp.609~616 (2002)
- Russo-Neustadt A, "Physical activity-antidepressant treatment combination: impact on brain-derived neurotro-phic factor and behavior in an animal model", Behav Brain Res, 120, pp.87~95 (2001)
- Schaaf MJ, "Downregulation of BDNF mRNA and protein in the rat hippocampus by corticosterone", Brain Res, 813, pp.112~120 (1998)
- Dwivedi Y, "Antidepressants reverse corticosterone-mediated decrease in BDNF expression: dissociation in regulation of specific exons by antidepressants and corticosterone", Neuroscience, 139, pp.1017~1029 (2006)
- Chao HM, "Adrenal steroid regulation of neurotrophic factor expression in the rat hippocampus", Endocrinology, 139, pp.3112~3118 (1998)
- Tsankova NM, "Sustained hippocampal chromatin regulation in a mouse model of depres-sion and antidepressant action", Nat Neurosci, 9, pp.519~525 (2006)
- Duman RS, "A neurotrophic model for stress-related mood disorders", Biol Psychiatry, 59, pp.1116~1127 (2006)
- Müller MB, "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", Neuropsycho-pharmacology, 23, pp.205~215 (2000)
- Altar CA, "Electroconvulsive seizures regulate gene expression of distinct neurotrophic signaling pathways", J Neurosci, 24, pp.2667~2677 (2004)
- Balu DT, "Differential regulation of central BDNF protein levels by antidepressant and non-antidepressant drug treatments", Brain Res, 1211, pp.37~43 (2008)
- Coppell AL, "Bi-phasic change in BDNF gene expression following antidepressant drug treatment", Neuropharmacology, 44, pp.903~910 (2003)
- De Foubert G, "Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment", Neuroscience, 128, pp.597~604 (2004)
- Altieri M, "Expression analysis of brain-derived neurotrophic factor (BDNF) mRNA isoforms after ch-ronic and acute antidepressant treatment", Brain Res, 1000, pp.148~155 (2004)
- Hajszan T, "Short-term treatment with the an-tidepressant fluoxetine triggers pyramidal dendritic spine synapse forResponse mation in rat hippocampus", Eur J Neurosci, 21, pp.1299~1303 (2005)
- Sairanen M, "Chronic antidepressant treatment selectively increases expression of plasticity-related proteins in the hippocampus and medial prefrontal cortex of the rat", Neuroscience, 144, pp.368~374 (2007)
- Saarelainen T, "Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects", J Neurosci, 23, pp.349~357 (2003)
- Monteggia LM, "Essential role of brain-derived neurotrophic factor in adult hippocampal function", Proc Natl Acad Sci U S A, 101, pp.10827~10832 (2004)
- Altar CA, "Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain", Biol Psychiatry, 54, pp.703~709 (2003)
- MacQueen GM, "Performance of heterozygous brain-derived neurotrophic factor knockout mice on behavioral analogues of anxiety, nociception, and depression", Behav Neurosci, 115, pp.1145~1153 (2001)
- Zörner B, "Forebrain-specific trkB-receptor knockout mice: behaviorally more hyperactive than depressive", Biol Psychiatry, 54, pp.972~982 (2003)
- Chen B, "Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication", Biol Psychiatry, 50, pp.260~265 (2001)
- Dowlatshahi D, "Increased temporal cortex CREB concentrations and antidepressant treatment in major depression", Lancet, 352, pp.1754~1755 (1998)
- Fujimura H, "Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation", Thromb Haemost, 87, pp.728~734 (2002)
- Pan W, "Transport of brain-derived neurotrophic factor across the blood-brain barrier", Neuropharmacology, 37, pp.1553~1561 (1998)
- Poduslo JF, "Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF", Brain Res Mol Brain Res, 36, pp.280~286 (1996)
- Gonul AS, "Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients", Eur Arch Psychiatry Clin Neurosci, 255, pp.381~386 (2005)
- Karege F, "Decreased serum brain-derived neurotrophic factor levels in major depress-ed patients", Psychiatry Res, 109, pp.143~148 (2002)
- Karege F, "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, pp.1068~1072 (2005)
- Shimizu E, "Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants", Biol Psychiatry, 54, pp.70~75 (2003)
- Lee BH, "Decreased plasma BDNF level in depressive patients", J Affect Disord, 101, pp.239~244 (2007)
- Brunoni AR, "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, pp.1169~1180 (2008)
- Yoshimura R, "Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor in depressed patients", Prog Neuropsychopharmacol Biol Psychiatry, 31, pp.1034~1037 (2007)
- Matrisciano F, "Changes in BDNF serum levels in patients with depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine", J Psychiatr Res, 43, pp.247~254 (2009)
- Lee HY, "Plasma brain-derived neurotrophic factor as a peripheral marker for the action mechanism of antidepressants", Neuropsychobiology, 57, pp.194~199 (2008)
- Piccinni A, "Plasma and serum brain-derived neurotrophic factor (BDNF) in depressed patients during 1 year of antidepressant treatments", J Affect Disord, 105, pp.279~283 (2008)
- Dwivedi Y, "Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects", Arch Gen Psychiatry, 60, pp.804~815 (2003)
- Pandey GN, "Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims", Int J Neuropsychopharmacol, 11, pp.1047~1061 (2008)
- Ernst C, "Alternative splicing, methylation state, and expression profile of tropomyosin-related kinase B in the frontal cortex of suicide completers", Arch Gen Psychiatry, 66, pp.22~32 (2009)
- Dwivedi Y, "Neurotrophin receptor activation and expression in human postmortem brain: effect of suicide", Biol Psychiatry, 65, pp.319~328 (2009)
- Deveci A, "Serum BDNF levels in suicide attempters related to psychosocial stressors: a comparative study with depression", Neuropsychobiology, 56, pp.93~97 (2007)
- Kim YK, "Low plasma BDNF is associated with suicidal behavior in depression", Prog Neuropsychopharmacol Biol Psychiatry, 31, pp.78~85 (2007)
- Dawood T, "Reduced overflow of BDNF from the brain is linked with suicide risk in depressive illness", Mol Psychiatry, 12, pp.981~983 (2007)
- Malcangio M, "A common thread for pain and memory synapses? Brain-derived neurotrophic factor and trkB receptors", Trends Pharmacol Sci, 24, pp.116~121 (2003)
