Neuroinflammatory Hypothesis in Major Depressive Disorder

Abstract

Faced with stress and acute instances, brain cells trigger neuroinflammation and increase inflam-mation response and can cause cell damage, cell death and thereby functional insufficiencies, behavioral disorders and autonomic imbalances. Cytokines that play an important role in inflamma-tory processes affect neurotransmitter metabolism, neuroendocrine functions and synaptic plasticity. It has been proven that inflammatory activity increases in depression. Proinflammatory cytokines such as interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α along with acute phase reactants increase in depression. If the inflammatory response becomes chronic and cannot be balanced, inflammation and cytokines may cause behavioral symptoms and neuropsychiatric disorders such as major depression and anxiety disorders. In this article, the changes that occur in inflammatory processes in depressive disorder will be summarized; the effects of pharmacologic and psychotherapeutic approaches on these changes will be reviewed.

Keywords

• Major depressive disorder, neuroinflammatory hypothesis, treatment

Major Depresif Bozuklukta Nöroinflamatuvar Hipotez

Abstract

Beyin hücreleri stres ve akut olaylar karşısında nöroinflamasyonu tetikleyerek ve inflamasyon yanıtını arttırarak hücre hasarına, ölümüne ve dolayısıyla fonksiyonel yetersizliklere, davranışsal bozukluklara ve otonomik dengesizliklere yol açabilmektedir. İnflamatuvar süreçlerde önemli rol oynayan sitokinler nörotransmitter metabolizması, nöroendokrin işlevler ve sinaptik plastisiteyi etkilemektedir. Depresyonda inflamatuvar aktivitenin artmış olduğu kanıtlanmıştır. Depresyonda interlökin (IL)-1, IL-6 ve tümör nekroz faktör (TNF)-α gibi proinflamatuvar sitokinler ve akut faz reaktanları artmaktadır. Psikososyal stresörlere yanıt olarak ortaya çıkan bu immun değişiklikler geçicidir ve anti-inflamatuvar mekanizmalarla dengelenmektedir. Bununla birlikte, inflamatuvar yanıt kronikleşirse ya da dengelenemezse inflamasyon ve sitokinler davranışsal belirtilere ve major depresyon, anksiyete bozuklukları gibi nöropsikiyatrik hastalıklara yol açabilmektedir. Bu yazıda, major depresif bozuklukta inflamatuvar süreçlerde meydana gelen değişiklikler özetlenecek, farmakolojik ve psikoterapötik yaklaşımların bu değişiklikler üzerine etkileri gözden geçirilmiştir.

Keywords

• Major depresif bozukluk, nöroinflamatuvar hipotez, tedavi

References

1. Capuron L, Miller AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther 2011; 130:226-238.
2. Raison CL, Cowles MK, Miller AH. Immune system and central nervous system interactions. In Kaplan&Sadock’s Comprehensive Textbook of Psychiatry, 9th edition (Eds BJ Sadock, VA Sadock, P Ruiz):175-197. Philadelphia, PA, Lippincott, Williams&Wilkins, 2009.
3. Tuğlu C, Kara SH. Depresyon, sitokinler ve bağışıklık sistemi. Klinik Psikofarmakoloji Bülteni 2003; 13:142-150.
4. Dinan TG. Inflammatory markers in depression. Curr Opin Psychiatry 2009; 22:32-36.
5. Schiepers OJ, Wichers MC, Maes M. Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29:201-217.
6. Gümrü S, Arıcıoğlu F. Inflammation in depression: the role of cytokines. Marmara Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 2012; 2:103-107.
7. Krishnadas R, Cavanagh J. Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry 2012; 83:495-502.
8. Raedler TJ. Inflammatory mechanisms in major depressive disorder. Curr Opin Psychiatry 2011; 24:519–525.

9. Janssen DG, Caniato RN, Verster JC, Baune BT. A psychoneuroimmunological review on cytokines involved in antidepressant treatment response. Hum Psychopharmacol 2010; 25: 201-215.
10. 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.
11. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK et al. A meta-analysis of cytokines in major depression. Biol Psychiatry 2010; 67:446-457.
12. Duivis HE, Vogelzangs N, Kupper N, de Jonge P, Penninx BW. Differential association of somatic and cognitive symptoms of depression and anxiety with inflammation: findings from the Netherlands Study of Depression and Anxiety (NESDA). Psychoneuroendocrinology 2013; 38:1573-1585.
13. Kocabaşoğlu N, Konuk N, Öztürk S, Bayar R. Akut faz proteinleri, immünite ve depresyon ilişkisi üzerine kontrollü bir çalışma. Yeni Symposium 2000; 36:83-87.
14. Hocaoğlu Ç, Kural B, Aliyazıcıoglu R, Deger O, Cengiz S. IL-1 β , IL-6, IL-8, IL-10, IFN- γ, TNF- α and its relationship with lipid parameters in patients with major depression. Metab Brain Dis 2012; 27:425 -4
15. Doksat MK. Evrimsel perspektiften depresyon ve sitokinler. Klinik Psikofarmakoloji Bülteni 2003; 13:97-108.
16. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 2009; 65:732-741.
17. Jones KA, Thomsen C. The role of the innate immune system in psychiatric disorders. Mol Cell Neurosci 2013; 53:52-62.
18. Doksat K, Savrun M. Duygudurum bozukluklarının patofizyolojisi ile ilgili son gelişmeler. Yeni Symposium 2002; 40:90-99. Maes M, Ringel K, Kubera M, Berk M, Rybakowski J. Increased autoimmune activity against 5-HT: a key component of depression that is associated with inflammation and activation of cell-mediated immunity, and with severity and staging of depression. J Affect Disord 2012; 136:386-392.
19. Drevets WC. Functional neuroimaging studies of depression: the anatomy of melancholia. Annu Rev Med 1998; 49:3413
20. Mayberg HS. Brain imaging. In Textbook of Mood Disorders (Eds. DJ Stein, DJ Kupfer, AF Schatzberg):219-234. Arlington, VA, American Psychiatry Publishing, 2006.
21. Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD. Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry 2009; 66:407-414.
22. Eisenberger NI, Lieberman MD. Why rejection hurts: a common neural alarm system for physical and social pain. Trends Cogn Sci 2004; 8:294-300.
23. Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 2000; 22:370-379.
24. Piletz JE, Halaris A, Iqbal O, Hoppensteadt D, Fareed J, Zhu H et al. Pro-inflammatory biomakers in depression: treatment with venlafaxine. World J Biol Psychiatry 2009; 10:313-323.
25. Fornaro M, Martino M, Battaglia F, Colicchio S, Perugi G. Increase in IL-6 levels among major depressive disorder patients after a 6-week treatment with duloxetine 60 mg/day: a preliminary observation. Neuropsychiatr Dis Treat 2011; 7:51-56. Eller T, Vasar V, Shlik J, Maron E. Pro-inflammatory cytokines and treatment response to escitalopram in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32:445-450.
26. Eller T, Vasar V, Shlik J, Maron E. Effects of bupropion augmentation on pro-inflammatory cytokines in escitalopramresistant patients with major depressive disorder. J Psychopharmacol 2009; 23:854-858.
27. Sutcigil L, Oktenli C, Musabak U, Bozkurt A, Cansever A, Uzun O et al. Pro- and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy. Clin Dev Immunol 2007; 2007:76396.
28. Tuglu C, Kara SH, Caliyurt O, Vardar E, Abay E. Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder. Psychopharmacology 2003; 170:429-433.
29. Kagaya A, Kugaya A, Takebayashi M, Fukue-Saeki M, Saeki T, Yamawaki S et al. Plasma concentrations of interleukin1beta, interleukin-6, soluble interleukin-2 receptor and tumor necrosis factor alpha of depressed patients in Japan. Neuropsychobiology 2001; 43:59-62.
30. O'Brien SM, Scott LV, Dinan TG. Antidepressant therapy and C-reactive protein levels. Br J Psychiatry 2006; 188:449-452. Hannestad J, DellaGioia N, Bloch M. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology 2011; 36:2452-2459.
31. Musselman DL, Lawson DH, Gumnick JF, Manatunga AK, Penna S, Goodkin RS et al. Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med 2001; 344:961-966.
32. Landmann R, Schaub B, Link S, Wacker HR. Unaltered monocyte function in patients with major depression before and after three months of antidepressive therapy. Biol Psychiatry 1997; 41:675-681.
33. Brambilla F, Maggioni M. Blood levels of cytokines in elderly patients with major depressive disorder. Acta Psychiatr Scand 1998; 97:309-313.
34. Castanon N, Leonard BE, Neveu PJ, Yirmiya R. Effects of antidepressants on cytokine production and actions. Brain Behav Immun 2002; 16:569-574.
35. Tyring S, Gottlieb A, Papp K, Gordon K, Leonardi C, Wang A et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 2006; 367:29-35.
36. Müller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Müller B et al. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry 2006; 11:680-684. Gülfizar Sözer Varma, Yrd. Doç. Dr., Pamukkale Üniversitesi Tıp Fakültesi Psikiyatri AD, Denizli. Yazışma Adresi/Correspondence: Gülfizar Sözer-Varma, Pamukkale Üniversitesi Tıp Fakültesi Psikiyatri AD, Denizli, Turkey. E-mail: [e-mail] Yazar bu makale ile ilgili herhangi bir çıkar çatışması bildirmemiştir. The author reported no conflict of interest related to this article. Çevrimiçi adresi / Available online at: www.cappsy.org/archives/vol6/no1/ Çevrimiçi yayım / Published online 07 Mayıs/May 07, 2013; doi:10.5455/cap.20130507091423