Şizofreni’de inflamatuvar mekanizmaların yeri

Yıl 2015, Cilt: 5 Sayı: 2, 134 - 139, 01.10.2015

Tuğba Erkmen Ceren Şahin Feyza Arıcıoğlu

Öz

Şizofreni, psikososyal fonksiyonlarda belirgin bozukluklara yol açan kronik semptomlar gösteren, dünya popülasyonunun %1’inde görülen, ciddi bir psikotik bozukluktur. Yaşamın erken dönemlerinde çevresel stresörlere maruz kalınması, genetik yatkınlık ve nörodejenerasyon; şizofreninin gelişmesinde önemli rol oynamaktadır. Güncel yaklaşımlar sitokinler aracılı gelişen inflamatuvar yanıtların, şizofreniyi de içeren birçok psikiyatrik hastalığın gelişmesinde rol oynayabileceğini ileri sürmektedir. Pro-inflamatuvar sitokinlerin ve mikrogliaların kontrolsüz aktiviteleri, genetik eğilim ve nörotransmitter fonksiyonlarındaki bozukluklar günümüzde şizofreni hastalığının gelişmesinde rol oynadığı düşünülen faktörler arasındadır. Santral sinir sisteminde pro-inflamatuvar sitokinler aracılı meydana gelen mikroglia aktivasyonu; inflamasyon sürecinin başlaması, ilerlemesi ve ayrıca nörodejenerasyon gelişmesi ile yakından ilişkilidir. Bu gözden geçirme çalışmasında, şizofreni tablosunda özellikle sitokin aracılı gelişen periferal ve santral immün yanıtlara ilişkin güncel bulguların ele alınması amaçlanmıştır.

Anahtar Kelimeler

Şizofreni, sitokin, nöroinflamasyon

The inflammatory mechanisms in schizophrenia

Öz

Schizophrenia is a serious mental illness that affects approximately 1% of the population worldwide, with chronic symptoms and significant impairment in psychosocial functioning. Interactions between genetic susceptibility and environmental stressors at the early stages of life, subsequently neurodegeneration process are important in the development of schizophrenia. Current approaches suggest that cytokines might have a role in the development of several psychiatric disorders, including schizophrenia. Uncontrolled activity of pro-inflammatory cytokines and microglia can induce schizophrenia in tandem with genetic vulnerability and neurotransmitter dysfunctions. Microglial activation induced by pro-inflammatory cytokines in central nervous system is responsible for the initiation and proceeding of inflammatory process and consequently developing neurodegeneration. Here in this review, we aimed to provide an overview to the latest findings related to the cytokines-mediated peripheral and central immune responses in the development of schizophrenia.

Anahtar Kelimeler

Schizophrenia, cytokine, neuroinflammation

Kaynakça

• Na KS, Jung HY, Kim YK. The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2014; 48: 277-286.
• Karamustafalıoğlu KO. Şizofreni tedavisinde karşılanmamış ihtiyaçlar: psikofarmakolojik boyutlar. Klinik Psikofarmakoloji Bülteni. 2009; 19(Ek 2): 311-315.
• Meyer U. Anti-inflammatory signaling in schizophrenia. Brain Behav Immun. 2011; 25(8): 1507-1518.
• Yavaşçı E, Akkaya C. Şizofrenide Serotoninin Rolü. Psiyatride Güncel Yaklaşımlar. 2012; 4(2): 237-59.
• Fiş NP, Berkem M. Nörotransmitter sistemlerinin gelişimi ve psikopatolojiye yansımaları. Bull Clin Psychopharmacol. 2009; 19(3): 312-321.
• Howes OD, Kapur S. The dopamine hypothesis of schizophrenia version 3: the final common pathway. Schizophr Bull. 2009; 35(3): 549-562.
• Laruelle M. Schizophrenia: from dopaminergic to glutamatergic interventions. Curr Opin Pharmacol. 2014; 14: 97-102.
• Tamam L, Zeren T. Depresyonda serotonerjik düzenekler. Klinik Psikiyatri. 2002; 5(Ek sayı 4): 11-18.
• Eggers AE. A serotonin hypothesis of schizophrenia. Med Hypotheses. 2013; 80(6): 791-794.
• Meyer U, Schwarz MJ, Müller N. Inflammatory processes in schizophrenia: a promising neuroimmunological target for the treatment of negative/cognitive symptoms and beyond. Pharmacol Ther. 2011; 132(1): 96-110.
• Şahin C, Ünal G, Arıcıoğlu F. Akt-GSK-3 İlişkisi: İki Ayrı Yolak İki Ayrı Hastalık. MUSBED 2014; 4(1): 51-57.
• Fineberg AM, Ellman, LM. Cytokines and neurological and neurocognitive alterations in the course of schizophrenia. Biol Psychiatry. 2013; 73: 951-966.
• Altamura AC, Pozzoli S, Fiorentini A, Dell’Osso B. Neurodevelopment and inflammatory patterns in schizophrenia in relation to pathophysiology. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 42: 63-70.
• Feigenson K, Kusnecov A, Silverstein S. Inflammation and two-hit hypothesis of schizophrenia. Neurosci Biobehav Rev. 2014; 38: 72-93.
• Brown AS. Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism. Dev Neurobiol. 2012; 72(10): 1272-1276.
• Fatemi SH, Reutiman TJ, Folsom TD, Huang H, Oishi K, Mori S, Smee DF, Pearce DA, Winter C, Sohr R, Juckel G. Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: implications for genesis of neurodevelopmental disorders. Schizophr Res. 2008; 99(1-3): 56-70.
• Meyer U. Developmental neuroinflammation and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 42: 20-34.
• Dantzer R. Cytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity. Eur J Pharmacol. 2004; 500(1-3): 399-411.
• Meyer U, Feldon J. Prenatal exposure to infection: a primary mechanism for abnormal dopaminergic development in schizophrenia. Psychopharmacology. 2009; 206(4): 587-602.
• Meyer U, Feldon J. To poly(I:C) or not to poly(I:C): advancing preclinical schizophrenia research through the use of prenatal immune activation models. Neuropharmacology. 2012; 62(3): 1308- 1321.
• Meyer U, Nyffeler M, Schwendener S, Knuesel I, Yee BK, Feldon J. Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after in utero immune challenge. Neuropsychopharmacol. 2008; 33(2): 441-456.
• Brown AS, Derkits EJ. Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry. 2010; 167(3): 261-280.
• Kim YK, Myint AM, Lee BH, Han CS, Lee HJ, Kim DJ, Leonard BE. Th1, Th2 and Th3 cytokine alteration in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28(7): 1129-1134.
• Potvin S, Stip E, Sepehry A, Gendron A, Bah R, Kouassi E. Inflammatory cytokine alterations in schizophrenia: A systematic quantitative Review. Biol Psychiatry. 2008; 63(8): 801-808.
• Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B. Meta- analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry. 2011; 70(7): 663-671.
• Song XQ, Lv LX, Li WQ, Hao YH, Zhao JP. The interaction of nuclear factor-kappa B and cytokines is associated with schizophrenia. Biol Psychiatry. 2009; 65(6): 481-488.
• Martínez-Gras I, Rodríguez-Jiménez R, Palomo T, Rubio G, García- Sánchez F, Andrés-Esteban E, Palomo T, Rubio G, Borrell J. Altered immune function in unaffected first-degree biological relatives of schizophrenia patients. Psychiatry Res. 2012; 200(2-3): 1022-1025.
• Curfs JH, Meis JF, Hoogkamp-Korstanje JA. A Primer on cytokines: sources, receptors, effects, and inducers. Clin Microbiol Rev. 1997; 10: 742-780.
• Wittea L, Tomasikb J, Schwarzb E, Guestb PC, Rahmouneb H, Kahna RS, Bahnb S. Cytokine alterations in first-episode schizophrenia patients before and after antipsychotic treatment. Schizophr Res. 2014; 154(1-3): 23-29.
• Maes M, Meltzer HY, Bosmans E. Immune-inflammatory markers in schizophrenia: comparison to normal controls and effects of clozapine. Acta Psychiatr Scand.1994; 89: 346-351.
• Layé S, Parnet P, Goujon E, Dantzer R. Peripheral administration of lipopolysaccharide induces the expression of cytokine transcripts in the brain and pituitary of mice. Brain Res Mol Brain Res.1994; 27(1): 157-162.
• Layé S, Gheusi G, Cremona S, Combe C, Kelley K, Dantzer R, Parnet P. Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression. Am J Physiol Regul Integr Comp Physiol. 2000; 279(1): 93-98.
• Ransohoff RM, Perry VH. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol. 2009; 27: 119-145.
• Bilbo S, Schwarz J. Ealy-life programming of later-life brain and behaviour: a critical role for the immune system. Front Behav Neurosci. 2009; 3: 14.
• Monji A, Kato T, Mizoguchi Y, Horikawa H, Seki Y, Kasai M et al. Neuroinflammation in schizophrenia especially focused on the role of microglia. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 42: 115-121.
• Bayer TA, Buslei R, Havas L, Falkai P. Evidence for activation of microglia in patients with psychiatric illnesses. Neurosci Lett. 1999; 271: 126-128.
• Bernstein HG, Steiner J , Bogerts B. Glial cells in schizophrenia: Pathophysiological significance and possible consequences for therapy. Expert Rev Neurother. 2009; 9(7): 1059-1071.
• Müller N. Immunological and infectious aspects in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2004; 254(1): 1-3.
• Kuloglu M, Bayik Y, Unal A, Gecici Ö, Ustundag, B. Serum IL–1β, IL–2, IL–6 and IL–8 Levels in Schizophrenia Subtypes. Bull Clin Psychopharmacol. 2011; 21(3): 193-200.
• Takahashi N, Sakurai T. Roles of glial cells in schizophrenia: possible targets for therapeutic approaches. Neurobiol Dis. 2013; 53: 49-60.
• Gümüştaş K, Atukeren P. Oksidatif ve nitrozatif stresin psikiyatrik bozukluklarla ilişkisi. İ.Ü. Cerrahpaşa Tıp Fakültesi Sürekli Eğitim Etkinlikleri Türkiye’de Sık Karşılaşılan Hastalıklar Sempozyum Dizisi. 2008; 62: 329-340.
• Rothermundt M, Ahn JN, Jörgens S. S100B in schizophrenia: an update. Gen Physiol Biophys. 2009; 28: 76-81.