Role of T helper lymphokines in the immune-inflammatory pathophysiology of schizophrenia: Systematic review and meta-analysis

References

• Steinman L. Lessons learned at the intersection of immunology and neuroscience. J Clin Invest. 2012;122:1146–1148.
   PubMed Web of Science ®Google Scholar
• Gruol DL, Nelson TE. Physiological and pathological roles of interleukin-6 in the central nervous system. Mol Neurobiol. 1997;15:307–339.
   PubMed Web of Science ®Google Scholar
• Sommer IE, van Westrhenen R, Begemann MJ, de Witte LD, Leucht S, Kahn RS. Efficacy of anti-inflammatory agents to improve symptoms in patients with schizophrenia: An update. Schizophr Bull. 2014;40:181–191.
   PubMed Web of Science ®Google Scholar
• de Jong S, van Eijk KR, Zeegers DW, Strengman E, Janson E, Veldink JH, et al; PGC Schizophrenia (GWAS) Consortium. Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes. Eur J Hum Genet. 2012;20:1004–1008.
   PubMed Web of Science ®Google Scholar
• Keshavan MS. Development, disease and degeneration in schizophrenia: A unitary pathophysiological model. J Psychiatry Res. 1999;33:513–521.
   PubMed Web of Science ®Google Scholar
• Maynard TM, Sikich L, Lieberman JA, LaMantia AS. Neural development, cell-cell signaling, and the “two-hit” hypothesis of schizophrenia. Schizophr Bull. 2001;27:457–476.
   PubMed Web of Science ®Google Scholar
• Meyer U. Developmental neuroinflammation and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2013;42:20–34.
   PubMed Web of Science ®Google Scholar
• Boyajyan A, Khoyetsyan A, Tsakanova G, Sim RB. Cryoglobulins as indicators of upregulated immune response in schizophrenia. Clin Biochem. 2008;41:355–360.
   PubMed Web of Science ®Google Scholar
• Maes M, Bosmans E, Kenis G, De Jong R, Smith RS, Meltzer HY. In vivo immunomodulatory effects of clozapine in schizophrenia. Schizophr Res. 1997;26:221–225.
   PubMed Web of Science ®Google Scholar
• Anderson G, Maes M. Schizophrenia: Linking prenatal infection to cytokines, the tryptophan catabolite (TRYCAT) pathway, NMDA receptor hypofunction, neurodevelopment and neuroprogression. Prog Neuropsychopharmacol Biol Psychiatry. 2013;42:5–19.
   PubMed Web of Science ®Google Scholar
• Nottet HS, Gendelman HE. Unraveling the neuroimmune mechanisms for the HIV-1-associated cognitive/motor complex. Immunol Today. 1995;16:441–448.
   PubMedGoogle Scholar
• Kaul M, Zheng J, Okamoto S, Gendelman HE, Lipton SA. HIV-1 infection and AIDS: Consequences for the central nervous system. Cell Death Differ. 2005;12 Suppl 1:878–892.
   PubMed Web of Science ®Google Scholar
• Ibi D, Nagai T, Nabeshima T, Yamada K. PolyI:C-induced neurodevelopmental animal model for schizophrenia]. Nihon Shinkei Seishin Yakurigaku Zasshi. 2011;31:201–207.
   PubMedGoogle Scholar
• Nawa H, Yamada K. Experimental schizophrenia models in rodents established with inflammatory agents and cytokines. Methods Mol Biol. 2012;829:445–451.
   PubMedGoogle Scholar
• Henneberg AE, Horter S, Ruffert S. Increased prevalence of antibrain antibodies in the sera from schizophrenic patients. Schizophr Res. 1994;14:15–22.
   PubMed Web of Science ®Google Scholar
• Schwarz MJ, Riedel M, Gruber R, Muller N, Ackenheil M. Autoantibodies against 60-kDa heat shock protein in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 1998;248:282–288.
   PubMed Web of Science ®Google Scholar
• Arrode-Bruses G, Bruses JL. Maternal immune activation by poly(I:C) induces expression of cytokines IL-1β and IL-13, chemokine MCP-1 and colony stimulating factor VEGF in fetal mouse brain. J Neuroinflammation. 2012;9:83.
   PubMed Web of Science ®Google Scholar
• Ashdown H, Dumont Y, Ng M, Poole S, Boksa P, Luheshi GN. The role of cytokines in mediating effects of prenatal infection on the fetus: Implications for schizophrenia. Mol Psychiatry. 2006;11:47–55.
   PubMed Web of Science ®Google Scholar
• Brown AS, Derkits EJ. Prenatal infection and schizophrenia: A review of epidemiologic and translational studies. Am J Psychiatry. 2010;167:261–280.
   PubMed Web of Science ®Google Scholar
• Khandaker GM, Zimbron J, Lewis G, Jones PB. Prenatal maternal infection, neurodevelopment and adult schizophrenia: A systematic review of population based studies. Psychol Med. 2012;16:1–19.
   Google Scholar
• Smith SEP, Li J, Garbett K, Mirnics K, Patterson PH. Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci. 2007;27:10695–10702.
   PubMed Web of Science ®Google Scholar
• Zuckerman L, Weiner I. Maternal immune activation leads to behavioral and pharmacological changes in the adult offspring. J Psychiatr Res. 2005;39:311–323.
   PubMed Web of Science ®Google Scholar
• Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, et al. The classical complement cascade mediates CNS synapse elimination. Cell. 2007;131:1164–1178.
   PubMed Web of Science ®Google Scholar
• Boulanger LM. Immune proteins in brain development and synaptic plasticity. Neuron. 2009;64:93–109.
   PubMed Web of Science ®Google Scholar
• Samaroo D, Dickerson F, Kasarda DD, Green PH, Briani C, Yolken RH, et al. Novel immune response to gluten in individuals with schizophrenia. Schizophr Res. 2010;118:248–255.
   PubMed Web of Science ®Google Scholar
• Mayilyan KR, Weinberger DR, Sim RB. The complement system in schizophrenia. Drug News Perspect. 2008;21:200–210.
   PubMed Web of Science ®Google Scholar
• Arakelyan A, Zakharyan R, Khoyetsyan A, Poghosyan D, Aroutiounian R, Mrazek F, et al. Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia. BMC Clin Pathol. 2011;11:10.
   PubMedGoogle Scholar
• Severance EG1, Gressitt KL, Halling M, Stallings CR, Origoni AE, Vaughan C, et al. Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia. Neurobiol Dis. 2012;48:447–453.
   PubMed Web of Science ®Google Scholar
• Shcherbakova I, Neshkova E, Dotsenko V, Platonova T, Shcherbakova E, Yarovaya G. The possible role of plasma kallikreinkinin system and leukocyte elastase in pathogenesis of schizophrenia, Immunopharmacol. 1999;43:273–279.
   PubMed Web of Science ®Google Scholar
• Hakobyan S, Boyajyan A, Sim RB. Classical pathway complement activity in schizophrenia. Neurosci Lett. 2005;374:35–37.
   PubMed Web of Science ®Google Scholar
• Powell C, Thompson L, Murtaugh RJ. Type III hypersensitivity reaction with immune complex deposition in 2 critically ill dogs administered human serum albumin. J Vet Emerg Crit Care (San Antonio). 2013;23:598–604.
   PubMed Web of Science ®Google Scholar
• Herken H, Uz E, Ozyurt H, Sogut S, Virit O, Akyol O. Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia. Mol Psychiatry. 2001;6:66–73.
   PubMed Web of Science ®Google Scholar
• Zoroglu SS, Herken H, Yurekli M, Uz E, Tutkun H, Savaþ HA, et al. The possible pathophysiological role of plasma nitric oxide and adrenomedullin in schizophrenia. J Psychiatr Res. 2002;36: 309–315.
   PubMed Web of Science ®Google Scholar
• Suzuki E, Nakaki T, Nakamura M, Miyaoka H. Plasma nitrate levels in deficit versus non-deficit forms of schizophrenia. J. Psychiatry Neurosci. 2003;28:288–292.
   PubMed Web of Science ®Google Scholar
• Akyol O, Zoroðlu SS, Armutcu F, Sahin S, Gurel A. Nitric oxide as a physiopathological factor in neuropsychiatric disorders. In Vivo. 2004;18:377–390.
   PubMed Web of Science ®Google Scholar
• Yao JK, Leonard S, Reddy RD. Increased nitric oxide radicals in postmortem brain from patients with schizophrenia. Schizophr Bull. 2004;30:923–934.
   PubMed Web of Science ®Google Scholar
• Li HC, Chen QZ, Ma Y, Zhou JF. Imbalanced free radicals and antioxidant defense systems in schizophrenia: A comparative study. J Zhejiang Univ Sci B. 2006;7:981–986.
   PubMedGoogle Scholar
• Zhang XY, Tan YL, Zhou DF, Cao LY, Wu GY, Haile CN, et al. Disrupted antioxidant enzyme activity and elevated lipid peroxidation products in schizophrenic patients with tardive dyskinesia. J Clin Psychiatry. 2007;68:754–760.
   PubMed Web of Science ®Google Scholar
• Fendri C, Mechri A, Khiari G, Othman A, Kerkeni A, Gaha L. Oxidative stress involvement in schizophrenia pathophysiology: A review. Encephale. 2006;32:244–252.
   PubMed Web of Science ®Google Scholar
• Karlsson H. Viruses and schizophrenia, connection or coincidence? Neuroreport. 2003;14:535–542.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Prasad KM, Watson AM, Dickerson FB, Yolken RH, Nimgaonkar VL. Exposure to herpes simplex virus type 1 and cognitive impairments in individuals with schizophrenia. Schizophr Bull. 2012;38:1137–1148.
   PubMed Web of Science ®Google Scholar
• Carter CJ. Schizophrenia susceptibility genes directly implicated in the life cycles of pathogens: Cytomegalovirus, influenza, herpes simplex, rubella, and Toxoplasma gondii. Schizophr Bull. 2009;35:1163–1182.
   PubMed Web of Science ®Google Scholar
• Moreno JL, Kurita M, Holloway T, López J, Cadagan R, Martínez-Sobrido L, et al. Maternal influenza viral infection causes schizophrenia-like alterations of 5-HT2A and mGlu2 receptors in the adult offspring. J Neurosci. 2011;31:1863–1872.
   PubMed Web of Science ®Google Scholar
• Muller N, Riedel M, Ackenheil M, Schwarz MJ. The role of immune function in schizophrenia: An overview. Eur Arch Psychiatry Clin Neurosci. 1999;249:62–68.
   PubMed Web of Science ®Google Scholar
• Arolt V, Weitzsch C, Wilke I, Nolte A, Pinnow M, Rothermundt M, et al. Production of interferon-gamma in families with multiple occurrence of schizophrenia. Psychiatry Res. 1997;66:145–152.
   PubMed Web of Science ®Google Scholar
• Arolt V, Rothermundt M, Wandinger KP, Kirchner H. Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment. Mol Psychiatry. 2000;5:150–158.
   PubMed Web of Science ®Google Scholar
• Avgustin B, Wraber B, Tavcar R. Increased Th1 and Th2 immune reactivity with relative Th2 dominance in patients with acute exacerbation of schizophrenia. Croat Med J. 2005;46:268–274.
   PubMed Web of Science ®Google Scholar
• Becker D, Kritschmann E, Floru S, Shlomo-David Y, Gotlieb-Stematsky T. Serum interferon in first psychotic attack. Br J Psychiatry. 1990;157:136–138.
   PubMed Web of Science ®Google Scholar
• Bessler H, Levental Z, Karp L, Modai I, Djaldetti M, Weizman A. Cytokine production in drug-free and neuroleptic-treated schizophrenic patients. Biol Psychiatry. 1995;38:297–302.
   PubMed Web of Science ®Google Scholar
• Chiang SSW, Riedel M, Muller N, Ackenheil M, Gruber R, Schwarz M. Th2-shift in schizophrenia: Primary findings from whole blood in vitro stimulation. http://www.priory.com/psych/th2.htm
   Google Scholar
• Chiang SS, Riedel M, Schwarz M, Mueller N. Is T-helper type 2 shift schizophrenia-specific? Primary results from a comparison of related psychiatric disorders and healthy controls. Psychiatry Clin Neurosci. 2013;67:228–236.
   PubMed Web of Science ®Google Scholar
• Erbagci AB, Herken H, Koyluoglu O, Yilmaz N, Tarakçioglu M. Serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha in schizophrenic patients, relation with symptomatology and responsiveness to risperidone treatment. Mediators Inflamm. 2001;10:109–115.
   PubMed Web of Science ®Google Scholar
• Gattaz WF, Dalgalarrondo P, Schröder HC. Abnormalities in serum concentrations of interleukin-2, interferon-alpha and interferon-gamma in schizophrenia not detected. Schizophr Res. 1992;6:237–241.
   PubMed Web of Science ®Google Scholar
• Hornberg M, Arolt V, Wilke I, Kruse A, Kirchner H. Production of interferons and lymphokines in leukocyte cultures of patients with schizophrenia. Schizophr Res. 1995;15:237–242.
   PubMed Web of Science ®Google Scholar
• Igue R, Potvin S, Bah R, Stip E, Bouchard RH, Lipp O, et al. Soluble interleukin-2 receptor levels correlated with positive symptoms during quetiapine treatment in schizophrenia-spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:1695–1698.
   PubMed Web of Science ®Google Scholar
• Kamiñska T1, Wysocka A, Marmurowska-Michalowska H, Dubas-Slemp H, Kandefer-Szerszeñ M. Investigation of serum cytokine levels and cytokine production in whole blood cultures of paranoid schizophrenic patients. Arch Immunol Ther Exp (Warsz). 2001;49:439–445.
   PubMed Web of Science ®Google Scholar
• Kim YK, Lee MS, Suh KY. Decreased interleukin-2 production in Korean schizophrenic patients. Biol Psychiatry. 1998;43:701–704.
   PubMed Web of Science ®Google Scholar
• Kim YK, Myint AM, Lee BH, Han CS, Lee HJ, Kim DJ, et al. Th1, Th2 and Th3 cytokine alteration in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:1129–1134.
   PubMed Web of Science ®Google Scholar
• Krause D, Weidinger E, Dippel C, Riedel M, Schwarz MJ, Müller N, et al. Impact of different antipsychotics on cytokines and tryptophan metabolites in stimulated cultures from patients with schizophrenia. Psychiatr Danub. 2013;25:389–397.
   PubMed Web of Science ®Google Scholar
• Lin CC, Chang CM, Chang PY, Huang TL. Increased interleukin-6 level in Taiwanese schizophrenic patients. Chang Gung Med J. 2011;34:375–381.
   PubMedGoogle Scholar
• Na KS, Kim YK. Monocytic, Th1 and th2 cytokine alterations in the pathophysiology of schizophrenia. Neuropsychobiol. 2007;56:55–63.
   PubMed Web of Science ®Google Scholar
• O’Brien SM, Scully P, Dinan TG. Increased tumor necrosis factor-alpha concentrations with interleukin-4 concentrations in exacerbations of schizophrenia. Psychiatry Res. 2008;160:256–262.
   PubMed Web of Science ®Google Scholar
• Rothermundt M, Arolt V, Weitzsch C, Eckhoff D, Kirchner H. Production of cytokines in acute schizophrenic psychosis. Biol Psychiatry. 1996;40:1294–1297.
   PubMed Web of Science ®Google Scholar
• Singh B, Bera NK, Nayak CR, Chaudhuri TK. Decreased serum levels of interleukin-2 and interleukin-6 in Indian Bengalee schizophrenic patients. Cytokine. 2009;47:1–5.
   PubMed Web of Science ®Google Scholar
• Wilke I, Arolt V, Rothermundt M, Weitzsch C, Hornberg M, Kirchner H. Investigations of cytokine production in whole blood cultures of paranoid and residual schizophrenic patients. Eur Arch Psychiatry Clin Neurosci. 1996;246:279–284.
   PubMed Web of Science ®Google Scholar
• 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;70:663–671.
   PubMed Web of Science ®Google Scholar
• Potvin S, Stip E, Sepehry AA, Gendron A, Bah R, Kouassi E. Inflammatory cytokine alterations in schizophrenia: A systematic quantitative review. Biol Psychiatry. 2008;63:801–808.
   PubMed Web of Science ®Google Scholar
• Romagnani S. Th1/Th2 cells. Inflamm Bowel Dis. 1999;5:285–294.
   PubMed Web of Science ®Google Scholar
• Berger A. Science commentary: Th1 and Th2 responses: What are they? BMJ. 2000;321:424.
   PubMed Web of Science ®Google Scholar
• Said WM, Saleh R, Jumaian N. Prevalence of hepatitis B virus among chronic schizophrenia patients. East Mediterr Health J. 2001;7:526–530.
   PubMedGoogle Scholar
• Hung CC, Loh el-W, Hu TM, Chiu HJ, Hsieh HC, Chan CH, et al. Prevalence of hepatitis B and hepatitis C in patients with chronic schizophrenia living in institutions. J Chin Med Assoc. 2012;75:275–280.
   PubMed Web of Science ®Google Scholar
• Xue Y, Sun X, Li Y, Liu X, Dong C. Increased risk of hepatitis E virus infection in schizophrenia. Arch Virol. 2013;158:359–365.
   PubMed Web of Science ®Google Scholar
• Hornig M, Briese T, Licinio J, Khabbaz RF, Altshuler LL, Potkin SG, et al. Absence of evidence for bornavirus infection in schizophrenia, bipolar disorder and major depressive disorder. Mol Psychiatry. 2012;17:486–493.
   PubMed Web of Science ®Google Scholar
• Oldstone MB. The game's afoot: Seeking viruses that cause chronic and degenerative neurologic and psychiatric disorder. Mol Psychiatry. 2012;17:472–473.
   PubMed Web of Science ®Google Scholar