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BMC Psychiatry
Published in: BMC Psychiatry 1/2016

Open Access 01-12-2016 | Research article

The value of interleukin 6 as a peripheral diagnostic marker in schizophrenia

Authors: Kayla A. Chase, Jackson J. Cone, Cherise Rosen, Rajiv P. Sharma

Published in: BMC Psychiatry | Issue 1/2016

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Abstract

Background

Associations between a pro-inflammatory state and schizophrenia have been one of the more enduring findings of psychiatry, with various lines of evidence suggesting a compelling role for IL-6 in the underlying pathogenesis of schizophrenia.

Methods

In this study, we examined IL-6 mRNA levels by real-time RT-PCR from fresh extracted peripheral blood mononuclear cells (PBMC) in normal controls and participants with schizophrenia.

Results

We found that peripheral PBMC IL-6 mRNA levels, in the absence of any other information, reliably discriminated between a diagnosis of schizophrenia and normal controls. Furthermore, in participants with schizophrenia, we also found elevated levels of IL-6 mRNA with earlier ages of illness onset and worse positive symptom presentation, as measured by the Positive and Negative Syndrome Scale.

Conclusions

These findings provide important and continued support for a pathophysiological role of inflammation in patients with schizophrenia. Future utilization of peripheral IL-6 mRNA levels could be clinically useful during an initial diagnosis and help tailor individualized treatment plans for patients with schizophrenia.
Literature
1.
Gibney SM, Drexhage HA. Evidence for a dysregulated immune system in the etiology of psychiatric disorders. J Neuroimmune Pharmacol. 2013;8(4):900–20.CrossRefPubMed
2.
3.
Kendell RE, Kemp IW. Maternal influenza in the etiology of schizophrenia. Arch Gen Psychiatry. 1989;46(10):878–82.CrossRefPubMed
4.
Upthegrove R, Manzanares-Teson N, Barnes NM. Cytokine function in medication-naive first episode psychosis: a systematic review and meta-analysis. Schizophr Res. 2014;155(1-3):101–8.CrossRefPubMed
5.
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(8):801–8.CrossRefPubMed
6.
Kubistova A, Horacek J, Novak T. Increased interleukin-6 and tumor necrosis factor alpha in first episode schizophrenia patients versus healthy controls. Psychiatr Danub. 2012;24 Suppl 1:S153–6.PubMed
7.
Cole SW, Arevalo JM, Takahashi R, Sloan EK, Lutgendorf SK, Sood AK, Sheridan JF, Seeman TE. Computational identification of gene-social environment interaction at the human IL6 locus. Proc Natl Acad Sci U S A. 2010;107(12):5681–6.CrossRefPubMedPubMedCentral
8.
Paul-Samojedny M, Owczarek A, Kowalczyk M, Suchanek R, Palacz M, Kucia K, Fila-Danilow A, Borkowska P, Kowalski J. Association of interleukin 2 (IL-2), interleukin 6 (IL-6), and TNF-alpha (TNFalpha) gene polymorphisms with paranoid schizophrenia in a Polish population. J Neuropsychiatry Clin Neurosci. 2013;25(1):72–82.CrossRefPubMed
9.
Zakharyan R, Petrek M, Arakelyan A, Mrazek F, Atshemyan S, Boyajyan A. Interleukin-6 promoter polymorphism and plasma levels in patients with schizophrenia. Tissue Antigens. 2012;80(2):136–42.CrossRefPubMed
10.
Aaltonen R, Heikkinen T, Hakala K, Laine K, Alanen A. Transfer of proinflammatory cytokines across term placenta. Obstet Gynecol. 2005;106(4):802–7.CrossRefPubMed
11.
Hsiao EY, Patterson PH. Activation of the maternal immune system induces endocrine changes in the placenta via IL-6. Brain Behav Immun. 2011;25(4):604–15.CrossRefPubMedPubMedCentral
12.
Smith SE, Li J, Garbett K, Mirnics K, Patterson PH. Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci. 2007;27(40):10695–702.CrossRefPubMedPubMedCentral
13.
O’Rourke RW, Kay T, Lyle EA, Traxler SA, Deveney CW, Jobe BA, Roberts CT,Jr, Marks D, Rosenbaum JT. Alterations in peripheral blood lymphocyte cytokine expression in obesity. Clin Exp Immunol. 2006;146(1):39–46.
14.
Danivas V, Venkatasubramanian G. Current perspectives on chlorpromazine equivalents: Comparing apples and oranges! Indian J Psychiatry. 2013;55(2):207–8.CrossRefPubMedPubMedCentral
15.
Gardner DM, Murphy AL, O’Donnell H, Centorrino F, Baldessarini RJ. International consensus study of antipsychotic dosing. Am J Psychiatry. 2010;167(6):686–93.CrossRefPubMed
16.
Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261–76.CrossRefPubMed
17.
Jayaraman S, Castro M, O’Sullivan M, Bragdon MJ, Holtzman MJ. Resistance to Fas-mediated T cell apoptosis in asthma. J Immunol. 1999;162(3):1717–22.PubMed
18.
Mannhalter C, Koizar D, Mitterbauer G. Evaluation of RNA isolation methods and reference genes for RT-PCR analyses of rare target RNA. Clin Chem Lab Med. 2000;38(2):171–7.CrossRefPubMed
19.
Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3(7):RESEARCH0034.
20.
Chase KA, Gavin DP, Guidotti A, Sharma RP. Histone methylation at H3K9: evidence for a restrictive epigenome in schizophrenia. Schizophr Res. 2013;149(1-3):15–20.CrossRefPubMedPubMedCentral
21.
Pasieka TJ, Woolson RF, Grose C. Viral induced fusion and syncytium formation: measurement by the Kolmogorov-Smirnov statistical test. J Virol Methods. 2003;111(2):157–61.CrossRefPubMed
22.
Naudin J, Mege JL, Azorin JM, Dassa D. Elevated circulating levels of IL-6 in schizophrenia. Schizophr Res. 1996;20(3):269–73.CrossRefPubMed
23.
Frydecka D, Misiak B, Pawlak-Adamska E, Karabon L, Tomkiewicz A, Sedlaczek P, Kiejna A, Beszlej JA. Interleukin-6: the missing element of the neurocognitive deterioration in schizophrenia? The focus on genetic underpinnings, cognitive impairment and clinical manifestation. Eur Arch Psychiatry Clin Neurosci. 2014;265(6):449–59.PubMedPubMedCentral
24.
Karstoft K, Pedersen BK: Skeletal muscle as a gene regulatory endocrine organ. Curr Opin Clin Nutr Metab Care 2016.
25.
Ikeda S, Tamura Y, Kakehi S, Sanada H, Kawamori R, Watada H. Exercise-induced increase in IL-6 level enhances GLUT4 expression and insulin sensitivity in mouse skeletal muscle. Biochem Biophys Res Commun. 2016;473(4):947–52.CrossRefPubMed
26.
O’Connell KE, Thakore J, Dev KK. Pro-inflammatory cytokine levels are raised in female schizophrenia patients treated with clozapine. Schizophr Res. 2014;156(1):1–8.CrossRefPubMed
27.
Hori H, Yoshimura R, Yamada Y, Ikenouchi A, Mitoma M, Ida Y, Nakamura J. Effects of olanzapine on plasma levels of catecholamine metabolites, cytokines, and brain-derived neurotrophic factor in schizophrenic patients. Int Clin Psychopharmacol. 2007;22(1):21–7.PubMed
28.
Mengozzi M, Fantuzzi G, Faggioni R, Marchant A, Goldman M, Orencole S, Clark BD, Sironi M, Benigni F, Ghezzi P. Chlorpromazine specifically inhibits peripheral and brain TNF production, and up-regulates IL-10 production, in mice. Immunology. 1994;82(2):207–10.PubMedPubMedCentral
29.
Dimitrov DH, Lee S, Yantis J, Valdez C, Paredes RM, Braida N, Velligan D, Walss-Bass C. Differential correlations between inflammatory cytokines and psychopathology in veterans with schizophrenia: potential role for IL-17 pathway. Schizophr Res. 2013;151(1-3):29–35.CrossRefPubMed
30.
Frommberger UH, Bauer J, Haselbauer P, Fraulin A, Riemann D, Berger M. Interleukin-6-(IL-6) plasma levels in depression and schizophrenia: comparison between the acute state and after remission. Eur Arch Psychiatry Clin Neurosci. 1997;247(4):228–33.CrossRefPubMed
31.
Ganguli R, Yang Z, Shurin G, Chengappa KN, Brar JS, Gubbi AV, Rabin BS. Serum interleukin-6 concentration in schizophrenia: elevation associated with duration of illness. Psychiatry Res. 1994;51(1):1–10.CrossRefPubMed
32.
Haas GL, Sweeney JA. Premorbid and onset features of first-episode schizophrenia. Schizophr Bull. 1992;18(3):373–86.CrossRefPubMed
33.
Hoff AL, Harris D, Faustman WO, Beal M, DeVilliers D, Mone RD, Moses JA, Csernansky JG. A neuropsychological study of early onset schizophrenia. Schizophr Res. 1996;20(1-2):21–8.CrossRefPubMed
34.
DeLisi LE. The significance of age of onset for schizophrenia. Schizophr Bull. 1992;18(2):209–15.CrossRefPubMed
35.
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):663–71.CrossRefPubMedPubMedCentral
36.
Garcia de Guadiana-Romualdo L, Espanol-Morales I, Cerezuela-Fuentes P, Consuegra-Sanchez L, Hernando-Holgado A, Esteban-Torrella P, Jimenez-Santos E, Viqueira-Gonzalez M, de Bejar-Almira A, Albaladejo-Oton MD. Value of lipopolysaccharide binding protein as diagnostic marker of infection in adult cancer patients with febrile neutropenia: comparison with C-reactive protein, procalcitonin, and interleukin 6. Support Care Cancer. 2015;23(7):2175–82.CrossRefPubMed
37.
Sun XY, Lu J, Zhang L, Song HT, Zhao L, Fan HM, Zhong AF, Niu W, Guo ZM, Dai YH, Chen C, Ding YF, Zhang LY. Aberrant microRNA expression in peripheral plasma and mononuclear cells as specific blood-based biomarkers in schizophrenia patients. J Clin Neurosci. 2015;22(3):570–4.CrossRefPubMed
38.
Lai CY, Yu SL, Hsieh MH, Chen CH, Chen HY, Wen CC, Huang YH, Hsiao PC, Hsiao CK, Liu CM, Yang PC, Hwu HG, Chen WJ. MicroRNA expression aberration as potential peripheral blood biomarkers for schizophrenia. PLoS One. 2011;6(6):e21635.CrossRefPubMedPubMedCentral
39.
Stojanovic A, Martorell L, Montalvo I, Ortega L, Monseny R, Vilella E, Labad J. Increased serum interleukin-6 levels in early stages of psychosis: associations with at-risk mental states and the severity of psychotic symptoms. Psychoneuroendocrinology. 2014;41:23–32.CrossRefPubMed
40.
Guest FL, Guest PC, Martins-de-Souza D. The emergence of point-of-care blood-based biomarker testing for psychiatric disorders: enabling personalized medicine. Biomark Med. 2016;10(4):431–43.CrossRefPubMed
Metadata
Title
The value of interleukin 6 as a peripheral diagnostic marker in schizophrenia
Authors
Kayla A. Chase
Jackson J. Cone
Cherise Rosen
Rajiv P. Sharma
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2016
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-016-0866-x

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