Nörotrofik faktörler ve depresyon: Patofizyoloji ve ötesi

Depresyon toplumda yaygın bir psikiyatrik bozukluk olmasına rağmen, patofizyolojisi henüz aydınlatılamamıştır. 1970’li yıllardan beri depresyon üzerine birçok hipotez tartışılmış; son yıllarda bu alanda birçok yeni görüş ortaya çıkmıştır. Majör depresyon hipokampus ve prefrontal kortekste hacim azalmalarıyla belirgindir ve antidepresan ilaçlar hipokampusta nörojenez, sinaptojenez ve nöronal matürasyon dahil nöronal plastisitenin pek çok çeşidini tetiklemektedir. Son yıllarda elde edilen bazı bulgular, nörotrofik faktörlerin nöronal plastisiteyi çift yönlü olarak düzenleyebildiğini göstermektedir. Bu durum, nörotrofik faktörlerin depresyonun hem patofizyolojisinde, hem de tedavisinde rol oynuyor olduğu şeklinde yorumlanabilir.Anahtar Kelimeler : Nörotrofik faktörler, beyin-kaynaklı nörotrofik faktör (BDNF), plastisite, depresyon 

Neurotrophic factors and depression: pathophysiology and beyond

Although depression is one of major psychiatric disorders in society, its neurobiology remains still unclear. Since 1970’s, many hypotheses on depression have been discussed. In recent years, many new points of view have emerged in this research area. Major depression is associated with reduced volumes in the hippocampus and prefrontal cortex, and antidepressant drugs promote many forms of neuronal plasticity, including neurogenesis, synaptogenesis and neuronal maturation in hippocampus. Recent evidences indicate that neurotrophic factors may regulate neuronal plasticity bidirectionally, meaning they may play role in pathophysiology and treatment of depression.
Keywords:

-,

___

  • Ustün TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJ. Global burden of depressive disorders in the year 2000. Br J Psychiatry. 2004;184: 386-392.
  • Kotan Z, Sarandöl A, Saygın Eker S, Akkaya C. Depresyon, Nöroplastisite ve Nörotrofik Faktörler: Psikiyatride Güncel Yaklaşımlar. Current Approaches in Psychiatry. 2009;1: 22-35.
  • Belmaker RH, Agam G. Major depressive disorder. N Engl J Med. 2008;358: 55-68.
  • Sofroniew MV, Howe CL, Mobley WC. Nerve growth factor signaling neuroprotection, and neural repair. Annu Rev Neurosci. 2001;24: 1217-1281.
  • Frodl T, Meisenzahl E, Zill P, Baghai T, Rujescu D, Leinsinger G, Bottlender R, Schüle C, Zwanzger P, Engel RR, Rupprecht R, Bondy B, Reiser M, Möller HJ. Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression. Arch Gen Psychiatry. 2004;61: 177-183.
  • Castrén E, Võikar V, Rantamäki T. Role of neurotrophic factors in depression. Curr Opin Pharmacol. 2007;7: 18-21.
  • Stahl SM. Essential Psychopharmacology Neuroscientific Basis & Practical Applications. 2nd Edition. Cambridge University Press; 2002. p.179-188.
  • Rot M, Mathew S, Charney DS. Neurobiological mechanisms in major depressive disorder. CMAJ. 2009;180: 305-313.
  • Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24: 677-736.
  • Castrén E, Rantamäki T. Neurotrophins in depression and antidepressant effects. Novartis Found Symp. 2008;289: 43-52.
  • Levi-Montalcini R. The nerve growth factor: thirty-five years later. EMBO J 1987;6: 1145-1154.
  • Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006;59: 1116-1127.
  • Drevets WC. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol. 2001;11: 240-249.
  • Berton O, Nestler EJ. New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci. 2006;7: 137-151.
  • Lu B. BDNF and activity-dependent synaptic modulation. Learn Mem. 2003;10: 86-98.
  • Huang EJ, Reichardt LF. Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem. 2003;72: 609-642.
  • Furmaga H, Carreno FR, Frazer A. Vagal Nerve Stimulation Rapidly Activates Brain-Derived Neurotrophic Factor Receptor TrkB in Rat Brain. PLoS One. 2012;7: e34844.
  • Doksat MK. Evrimsel Perspektiften Depresyon ve Sitokinler. Klinik Psikofarmakoloji Bülteni. 2003;13: 97-108.
  • Allen SJ, Dawbarn D. Clinical relevance of the neurotrophins and their receptors. Clinical Scinece; 2006;110: 175-191.
  • Rantamaki T, Knuuttila JE, Hokkanen ME, Castren E. The effects of acute and long-term lithium treatments on TrkB neurotrophin receptor activation in the mouse hippocampus and anterior cingulate cortex. Neuropharmacology. 2006;50: 421-427.
  • Saarelainen T, Hendolin P, Lucas G, Koponen E, Sairanen M, MacDonald E, Agerman K, Haapasalo A, Nawa H, Aloyz R. Ernfors B, Castrén E. Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressantinduced behavioral effects. J Neurosci. 2003;23: 349-357.
  • Gürpınar D, Erol A, Mete L. Depresyon ve nöroplastisite. Klinik Psikofarmakoloji Bülteni. 2007;17: 100-110.
  • Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology. 1988;37: 1553-1561.
  • Thorne RG, Pronk GJ, Padmanabhan V, Frey II WH. Delivery of insulin- like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience. 2004;127: 481-96.
  • Kooijman R, Sarre S, Michotte Y, De Keyser J. Insulin-like growth factor I: a potential neuroprotective compound for the treatment of acute ischemic stroke? Stroke. 2009;40: 83-88.
  • Tsai SJ. Increased central brain-derived neurotrophic factor activity could be a risk factor for substance abuse: Implications for treatment. Medical Hypotheses. 2007;68: 410-414.