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Depression, Neuroplasticity and Neurotrophic Factors

Year 2009, Volume: 1 Issue: 1, 36 - 44, 01.03.2009

Abstract

Depression is a common psychiatric disorder. There is still very little known about the neurobiological alterations that underlie the pathophysiology of depression. Recently, neuroplasticity hypothesis is added to monoamine hypothesis and neurotransmitter receptor hypothesis which are among the theories about the biological etiology of depression. Neuroplasticity can be defined as alterations in structural properties and functions of neurons and synapses depending on various internal and external stimuli. Neurotrophic factors are molecules important for development and protection of neurons. The neuron needs the neurotrophic factors synthesized by itself for survival, differentiation and neuroplasticity. Hippocampus is one of the brain regions with highest level of neuroplasticity. Brain imaging studies reveal that there is hippocampal volume reduction in depression. This reduction may be due to stress induced alterations in neurogenesis and neurotrophic factor expression in hippocampus. Pharmacologic and somatic antidepressant treatments increase adult hippocampal neurogenesis and neurotrophic factor expression and reverse effects of stress on hippocampal atrophy. Brain derived neurotrophic factor (BDNF) is the mostly studied neurotrophic factor in depression. There are data about decreased levels of BDNF in depression. Many studies suggest that BDNF is the "common final pathway" for actions of different antidepressants and chronic antidepressant treatment can enhance neurogenesis in adult hippocampus regulating plasticity and neurotrophin signalling pathways important in neuronal survival.

References

  • Ongur D, Drevets WC, Price JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 1998; 95:13290–13295
  • Rajkowska G. Postmortem studies in brain disorders indicate altered number of neurons and glial cells. Biol Psychiatry 2000; 48:766–777
  • McEwen BS. Stress and hippocampal plasticity. Annu Rev Neurosci 1999; 22:105–122
  • Kendler KS, Karkowski LM, Prescott CA. Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 1999; 156:837– 841
  • Horner H, Packan D, Sapolsky R. Glucocorticoids inhibit glucose transport in cultured hippocampal neurons and glia. Neuroendocrinology 1990; 52:57–62
  • Sapolsky RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 2000; 57:925–935
  • Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry 2000; 47:305–313
  • Krystal JH, Sanacora G, Blumberg H, et al. Glutamate and GABA systems as targets for novel antidepressants and mood-stabilizing treatments. Mol Psychiatry 2002; 7:71–80
  • Schmidt WJ, Reith MEA. Dopamine and Glutamate in Psychiatric Disorders. (Glutamate and Depression - Joaquin Del Rio and Diana Frechilla) Totowa, NJ: Humana Pres Inc. 2005; 215–234
  • During MJ, Spencer DD. Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 1993; 341:1607– 1610
  • Coyle JT, Schwarcz R. Mind glue: implications of glial cell biology for psychiatry. Arch Gen Psychiatry 2000; 57:90–93
  • Lowy M, Gault L, Yammamato B. Adrenalectomy attenuates stress induced elevation in extracellular glutamate concentration in hippocampus. J Neurosci 1993; 61:1957–1960
  • Moghaddam B. Stress activation of glutamate neurotransmission in the prefrontal cortex: implications for dopamine-associated psychiatric disorders. Biol Psychiatry 2002; 51:775–787
  • Dugan LL, Choi DW. Hypoxic-ischemic brain injury and oxidative stress. In: Siegel GJ, ed. Basic Neurochemistry. Molecular, Cellular and Medical Aspects. 6th ed. Philadelphia: Lippincot- Raven, 1999:712–729
  • Dixon JF, Hokin LE. Lithium acutely inhibits and chronically upregulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. Proc Natl Acad Sci USA 1998; 95:8363–8368
  • Walden J, Normann C, Langosch J, Berger M, Grunze H. Differential treatment of bipolar disorder with old and new antiepileptic drugs. Neuropsychobiology 1998; 38:181–184
  • Michael-Titus AT, Bains S, Jeetle J, Whelpton R. Imipramine and phenelzine decrease glutamate overflow in the prefrontal cortex—a possible mechanism of neuroprotection in major depression? Neuroscience 2000; 100:681–684
  • Banasr M, Chowdhury GM, Terwilliger R, Newton SS, Duman RS, Behar KL, Sanacora G. Glia pathology in an animal model of depression: reversal of stres- induced cellular, metabolic and behavioral deficits by the glutamate- modulating drug riluzole. Mol Psychiatry 2008, doi: 10.1038/mp.2008.106
  • Pittenger C, Coric V, Banasr M, Bloch M, Krystal JH, Sanacora G. Riluzole in the treatment of mood and anxiety disorders. CNS Drugs 2008;22(9):761–786
  • Nowak G, Ordway GA, Paul IA. Alterations in the N-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims. Brain Res 1995; 675:157–164
  • Holemans S, De Paermentier F, Horton RW, Crompton MR, Katona CLE, Maloteaux J. NMDA glutamatergic receptors labelled with [3H]MK–801 in brain samples from drug-free depressed suicides. Brain Res 1993; 616:138–143
  • Gould E, Tanapat P, McEwen BS, Flugge G, Fuchs E. Proliferation of granule cell precursors in the dentate gyrus of hippocampus is diminished by stress. Proc Natl Acad Sci USA 1998; 95:3168–3171
  • Gould E, Cameron HA, McEwen BS. Blockade of NMDA receptors increases cell death and birth in the developing dentate gyrus. J Comp Neurol 1994; 340; 551–565
  • 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; 15:7539–7547
  • Skolnick P, Layer RT, Popik P, Nowak G, Paul IA, Trullas R. Adaptation of N- methyl-Daspartate receptors following antidepressant treatment: implications for the pharmacotherapy of depression. Pharmacopsychiatry 1996; 29:23–26
  • Paul IA, Nowak G, Layer RT, Popik P, Skolnick P. Adaptation of the N-methyl-D- aspartate receptor complex following chronic antidepressant treatments. J Pharmacol Exp Ther 1994; 269:95–102
  • Nowak G, Trullas R, Layer RT, Skolnick P, Paul IA. Adaptive changes in the N- methyl-Daspartatereceptor complex after chronic treatment with imipramine and 1-aminocyclopropanecarboxylic acid. J Pharmacol Exp Ther 1993; 265:1380–1386
  • Mjellem N, Lund A, Hole K. reduction of NMDA-induced behavior after acute and chronic administration of desipramine in mice. Neuropharmacology 1993; 32:591–595
  • Brandoli C, Sanna A, De Bernardi MA, Follesa P, Brooker G, Mocchetti I. Brain- derived neurotrophic factor and basic fibroblast growth factor downregulate NMDA receptor function in cerebellar granule cells. J Neurosci 1998; 18:7953– 7961
  • Skolnick P, Legutko B, Li X, Bymaster FP. Current perspectives on the development of non-biogenic amine-based antidepressants. Pharmacol Res 2001; 43:411–422
  • Uzbay İT, Oglesby MW. Nitric oxide and substance dependence. Neurosci Biobehav Rev 2001; 25:43–52
  • Zoroğlu SS, Herken H, Yürekli M, Uz E, Tutkun H, Savaș HA ve ark. The possible pathophysiological role of plasma nitric oxide and adrenomedullin in schizophrenia. J Psychiatr Res 2002; 36:309–315
  • Savaș HA, Herken H, Yürekli M, Uz E, Tutkun H, Zoroğlu SS ve ark. Possible role of nitric oxide and adrenomedullin in bipolar affective disorder. Neuropsychobiology 2002; 45:57–61
  • Yanık M, Vural H, Koçyiğit A, Tutkun H, Zoroğlu SS, Herken H, ve ark. Is the arginine-nitric oxide pathway involved in the pathogenesis of schizophrenia? Neuropsychology 2003; 47:61–65
  • Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 1991; 14:60–67
  • Dhir A, Kulkarni SK. Possible involvement of nitric oxide (NO) signaling pathway in the antidepressant-like effect of MK–801 (dizocilpine), a NMDA receptor antagonist in mouse forced swim test. Indian Journal of Experimental Biology 2008; 46:164-170
  • Wegener G, Volke V, Harvey BH, Rosenberg R. Local, but not systemic, administration of serotonergic antidepressants decreases hippocampal nitric oxide synthase activity. Brain Res 2003; 959:128–134
  • Uzbay İT. Nöroplastisite ve Depresyon. 1.Baskı, Çizgi: Ankara, 2005; 53–74
  • Ulak G, Mutlu O, Akar FY, Komșuoğlu FI, Tanyeri P, Erden BF. Neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole augment the effects of antidepressants acting via serotonergic system in the forced swimming test in rats. Pharmacol Biochem Behav. 2008; 90:563–568.
  • Mutlu O, Ulak G, Laugeray A, Belzung C. Effects of neuronal and inducible NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole (TRIM) in unpredictable chronic mild stress procedure in mice. Pharmacol Biochem Behav. 2009; 92(1):82–87
  • Cooper JR, Bloom FE, Roth RH. The Biochemical Basis of Neuropharmacology. Oxford University Press: New York, 1996; vol.48
  • Khairova RA, Machado-Vieira R, Du J, Manji HK. A potential role for pro- inflammatory cytokines in regulating synaptic plasticity in major depressive disorder. Int J Neuropsychopharmacol 2009; 12:561–578
  • Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL–1, and IL–6: a meta-analysis. Psychosom Med 2009; 71:171–186
  • Dinan TG. Inflammatory markers in depression. Curr Opin Psychiatry 2009; 22:32–36.
  • Sütcigil L, Öktenli C, Musabak U, Bozkurt A, Cansever A, Uzun O ve ark. Pro- and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy. Clin Dev Immunol. 2007; 76396.
  • McNally L, Bhagwagar Z, Hannestad J. Inflammation, glutamate, and glia in depression: a literature review. CNS Spectr. 2008; 13:501–510
  • Shibakawa YS, Sasaki Y, Goshima Y, Echigo N, Kamiya Y, Kurahashi K, Yamada Y, Andoh T. Effects of ketamine and propofol on inflammatory responses of primary glial cell cultures stimulated with lipopolysaccharide. Br J Anaesth. 2005; 95:803–810
  • Rosi S, Vazdarjanova A, Ramirez-Amaya V, Worley PF, Barnes CA, Wenk GL. Memantine protects against LPS-induced neuroinflammation, restores behaviorally-induced gene expression and spatial learning in the rat. Neuroscience 2006; 142:1303–1315
  • Pitt D, Nagelmeier IE, Wilson HC, Raine CS. Glutamate uptake by oligodendrocytes: Implications for excitotoxicity in multiple sclerosis. Neurology 2003 Oct 28;61(8):1113–1120
  • Valentine GV, Sanacora G. Targeting glial physiology and glutamate cycling in the treatment of depression. Biochem Pharmacol 2009 (baskıda)

Depresyon, Nöroplastisite ve Nörotrofik Faktörler

Year 2009, Volume: 1 Issue: 1, 36 - 44, 01.03.2009

Abstract

Yaygın bir psikiyatrik bozukluk olan depresyon patofizyolojisinin altında yatan nörobiyolojik değişiklikler hakkında halen çok az şey bilinmektedir. Depresyonun biyolojik etiyolojisi hakkında geliştirilen kuramlardan monoamin hipotezi ve nörotransmitter reseptör hipotezine son yıllarda depresyonun nöroplastisite hipotezi eklenmiştir. Nöroplastisite, çeşitli iç ve dış uyaranlara bağlı olarak beyindeki nöronların ve bunların oluşturduğu sinapsların yapısal özellikleri ve işlevlerindeki değişiklikler olarak tanımlanabilir. Nörotrofik faktörler; nöronların gelişimi ve korunması için büyük öneme sahip olan moleküllerdir. Nöron yaşamak, farklılaşmak ve nöroplastisite için kendi salgıladığı nörotrofik faktörlere gereksinim duymaktadır. Hipokampus nöroplastisitesi en yüksek beyin bölgelerinden biridir. Beyin görüntüleme çalışmaları; depresyonlu olgularda hipokampal hacim azalması olduğunu göstermektedir. Bu durum hipokampustaki nörogenez ve nörotrofik faktör ekspresyonunda stresle indüklenen değişikliklere bağlı olabilir. Farmakolojik ve somatik antidepresan tedaviler erişkin hipokampal nörogenezi ve nörotrofik faktör ekspresyonunu arttırmakta, dolayısıyla stresin hipokampal atrofi üzerine olan etkisini durdurup geriye döndürebilmektedir. Depresyonda üzerinde en çok çalışılan nörotrofik faktör olan beyin kaynaklı nörotrofik faktör (BDNF) düzeylerinin depresyon durumunda azaldığı yönünde veriler mevcuttur. Pek çok araştırma, BDNF'nin farklı antidepresan yaklaşımlar için "son ortak yol" olduğunu ileri sürmekte ve kronik antidepresan tedavinin erişkin hipokampusunda nörogenezi hızlandırdığını; plastisite ve nöronal hayatta kalımda rolü olan nörotrofin iletici yolakları düzenlediğini göstermektedir

References

  • Ongur D, Drevets WC, Price JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 1998; 95:13290–13295
  • Rajkowska G. Postmortem studies in brain disorders indicate altered number of neurons and glial cells. Biol Psychiatry 2000; 48:766–777
  • McEwen BS. Stress and hippocampal plasticity. Annu Rev Neurosci 1999; 22:105–122
  • Kendler KS, Karkowski LM, Prescott CA. Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 1999; 156:837– 841
  • Horner H, Packan D, Sapolsky R. Glucocorticoids inhibit glucose transport in cultured hippocampal neurons and glia. Neuroendocrinology 1990; 52:57–62
  • Sapolsky RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 2000; 57:925–935
  • Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry 2000; 47:305–313
  • Krystal JH, Sanacora G, Blumberg H, et al. Glutamate and GABA systems as targets for novel antidepressants and mood-stabilizing treatments. Mol Psychiatry 2002; 7:71–80
  • Schmidt WJ, Reith MEA. Dopamine and Glutamate in Psychiatric Disorders. (Glutamate and Depression - Joaquin Del Rio and Diana Frechilla) Totowa, NJ: Humana Pres Inc. 2005; 215–234
  • During MJ, Spencer DD. Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 1993; 341:1607– 1610
  • Coyle JT, Schwarcz R. Mind glue: implications of glial cell biology for psychiatry. Arch Gen Psychiatry 2000; 57:90–93
  • Lowy M, Gault L, Yammamato B. Adrenalectomy attenuates stress induced elevation in extracellular glutamate concentration in hippocampus. J Neurosci 1993; 61:1957–1960
  • Moghaddam B. Stress activation of glutamate neurotransmission in the prefrontal cortex: implications for dopamine-associated psychiatric disorders. Biol Psychiatry 2002; 51:775–787
  • Dugan LL, Choi DW. Hypoxic-ischemic brain injury and oxidative stress. In: Siegel GJ, ed. Basic Neurochemistry. Molecular, Cellular and Medical Aspects. 6th ed. Philadelphia: Lippincot- Raven, 1999:712–729
  • Dixon JF, Hokin LE. Lithium acutely inhibits and chronically upregulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. Proc Natl Acad Sci USA 1998; 95:8363–8368
  • Walden J, Normann C, Langosch J, Berger M, Grunze H. Differential treatment of bipolar disorder with old and new antiepileptic drugs. Neuropsychobiology 1998; 38:181–184
  • Michael-Titus AT, Bains S, Jeetle J, Whelpton R. Imipramine and phenelzine decrease glutamate overflow in the prefrontal cortex—a possible mechanism of neuroprotection in major depression? Neuroscience 2000; 100:681–684
  • Banasr M, Chowdhury GM, Terwilliger R, Newton SS, Duman RS, Behar KL, Sanacora G. Glia pathology in an animal model of depression: reversal of stres- induced cellular, metabolic and behavioral deficits by the glutamate- modulating drug riluzole. Mol Psychiatry 2008, doi: 10.1038/mp.2008.106
  • Pittenger C, Coric V, Banasr M, Bloch M, Krystal JH, Sanacora G. Riluzole in the treatment of mood and anxiety disorders. CNS Drugs 2008;22(9):761–786
  • Nowak G, Ordway GA, Paul IA. Alterations in the N-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims. Brain Res 1995; 675:157–164
  • Holemans S, De Paermentier F, Horton RW, Crompton MR, Katona CLE, Maloteaux J. NMDA glutamatergic receptors labelled with [3H]MK–801 in brain samples from drug-free depressed suicides. Brain Res 1993; 616:138–143
  • Gould E, Tanapat P, McEwen BS, Flugge G, Fuchs E. Proliferation of granule cell precursors in the dentate gyrus of hippocampus is diminished by stress. Proc Natl Acad Sci USA 1998; 95:3168–3171
  • Gould E, Cameron HA, McEwen BS. Blockade of NMDA receptors increases cell death and birth in the developing dentate gyrus. J Comp Neurol 1994; 340; 551–565
  • 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; 15:7539–7547
  • Skolnick P, Layer RT, Popik P, Nowak G, Paul IA, Trullas R. Adaptation of N- methyl-Daspartate receptors following antidepressant treatment: implications for the pharmacotherapy of depression. Pharmacopsychiatry 1996; 29:23–26
  • Paul IA, Nowak G, Layer RT, Popik P, Skolnick P. Adaptation of the N-methyl-D- aspartate receptor complex following chronic antidepressant treatments. J Pharmacol Exp Ther 1994; 269:95–102
  • Nowak G, Trullas R, Layer RT, Skolnick P, Paul IA. Adaptive changes in the N- methyl-Daspartatereceptor complex after chronic treatment with imipramine and 1-aminocyclopropanecarboxylic acid. J Pharmacol Exp Ther 1993; 265:1380–1386
  • Mjellem N, Lund A, Hole K. reduction of NMDA-induced behavior after acute and chronic administration of desipramine in mice. Neuropharmacology 1993; 32:591–595
  • Brandoli C, Sanna A, De Bernardi MA, Follesa P, Brooker G, Mocchetti I. Brain- derived neurotrophic factor and basic fibroblast growth factor downregulate NMDA receptor function in cerebellar granule cells. J Neurosci 1998; 18:7953– 7961
  • Skolnick P, Legutko B, Li X, Bymaster FP. Current perspectives on the development of non-biogenic amine-based antidepressants. Pharmacol Res 2001; 43:411–422
  • Uzbay İT, Oglesby MW. Nitric oxide and substance dependence. Neurosci Biobehav Rev 2001; 25:43–52
  • Zoroğlu SS, Herken H, Yürekli M, Uz E, Tutkun H, Savaș HA ve ark. The possible pathophysiological role of plasma nitric oxide and adrenomedullin in schizophrenia. J Psychiatr Res 2002; 36:309–315
  • Savaș HA, Herken H, Yürekli M, Uz E, Tutkun H, Zoroğlu SS ve ark. Possible role of nitric oxide and adrenomedullin in bipolar affective disorder. Neuropsychobiology 2002; 45:57–61
  • Yanık M, Vural H, Koçyiğit A, Tutkun H, Zoroğlu SS, Herken H, ve ark. Is the arginine-nitric oxide pathway involved in the pathogenesis of schizophrenia? Neuropsychology 2003; 47:61–65
  • Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 1991; 14:60–67
  • Dhir A, Kulkarni SK. Possible involvement of nitric oxide (NO) signaling pathway in the antidepressant-like effect of MK–801 (dizocilpine), a NMDA receptor antagonist in mouse forced swim test. Indian Journal of Experimental Biology 2008; 46:164-170
  • Wegener G, Volke V, Harvey BH, Rosenberg R. Local, but not systemic, administration of serotonergic antidepressants decreases hippocampal nitric oxide synthase activity. Brain Res 2003; 959:128–134
  • Uzbay İT. Nöroplastisite ve Depresyon. 1.Baskı, Çizgi: Ankara, 2005; 53–74
  • Ulak G, Mutlu O, Akar FY, Komșuoğlu FI, Tanyeri P, Erden BF. Neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole augment the effects of antidepressants acting via serotonergic system in the forced swimming test in rats. Pharmacol Biochem Behav. 2008; 90:563–568.
  • Mutlu O, Ulak G, Laugeray A, Belzung C. Effects of neuronal and inducible NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole (TRIM) in unpredictable chronic mild stress procedure in mice. Pharmacol Biochem Behav. 2009; 92(1):82–87
  • Cooper JR, Bloom FE, Roth RH. The Biochemical Basis of Neuropharmacology. Oxford University Press: New York, 1996; vol.48
  • Khairova RA, Machado-Vieira R, Du J, Manji HK. A potential role for pro- inflammatory cytokines in regulating synaptic plasticity in major depressive disorder. Int J Neuropsychopharmacol 2009; 12:561–578
  • Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL–1, and IL–6: a meta-analysis. Psychosom Med 2009; 71:171–186
  • Dinan TG. Inflammatory markers in depression. Curr Opin Psychiatry 2009; 22:32–36.
  • Sütcigil L, Öktenli C, Musabak U, Bozkurt A, Cansever A, Uzun O ve ark. Pro- and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy. Clin Dev Immunol. 2007; 76396.
  • McNally L, Bhagwagar Z, Hannestad J. Inflammation, glutamate, and glia in depression: a literature review. CNS Spectr. 2008; 13:501–510
  • Shibakawa YS, Sasaki Y, Goshima Y, Echigo N, Kamiya Y, Kurahashi K, Yamada Y, Andoh T. Effects of ketamine and propofol on inflammatory responses of primary glial cell cultures stimulated with lipopolysaccharide. Br J Anaesth. 2005; 95:803–810
  • Rosi S, Vazdarjanova A, Ramirez-Amaya V, Worley PF, Barnes CA, Wenk GL. Memantine protects against LPS-induced neuroinflammation, restores behaviorally-induced gene expression and spatial learning in the rat. Neuroscience 2006; 142:1303–1315
  • Pitt D, Nagelmeier IE, Wilson HC, Raine CS. Glutamate uptake by oligodendrocytes: Implications for excitotoxicity in multiple sclerosis. Neurology 2003 Oct 28;61(8):1113–1120
  • Valentine GV, Sanacora G. Targeting glial physiology and glutamate cycling in the treatment of depression. Biochem Pharmacol 2009 (baskıda)
There are 50 citations in total.

Details

Primary Language Turkish
Journal Section Review
Authors

Zeynep Kotan This is me

Aslı Sarandöl This is me

Salih Saygın Eker This is me

Cengiz Akkaya This is me

Publication Date March 1, 2009
Published in Issue Year 2009 Volume: 1 Issue: 1

Cite

AMA Kotan Z, Sarandöl A, Eker SS, Akkaya C. Depresyon, Nöroplastisite ve Nörotrofik Faktörler. Psikiyatride Güncel Yaklaşımlar - Current Approaches in Psychiatry. March 2009;1(1):36-44.

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