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Inflammatory, cardio-metabolic and diabetic profiling of chronic schizophrenia

Published online by Cambridge University Press:  23 March 2020

R. Balõtšev ,
K. Koido ,
V. Vasar ,
S. Janno ,
K. Kriisa ,
R. Mahlapuu ,
U. Ljubajev ,
M. Parksepp ,
P. Veiksaar  and
V. Volke
...Show all authors
R. Balõtšev*
Affiliation:
Department of Child and Adolescent Psychiatry, Psychiatry Clinic of Tartu University Hospital, Raja 31, 50417Tartu, Estonia
K. Koido
Affiliation:
Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu, Ravila 19Tartu50411, Estonia Centre of Excellence for Genomics and Translational Medicine Ravila 19 Tartu50411, Estonia
V. Vasar
Affiliation:
Psychiatry Clinic of Tartu University Hospital, Raja 31, 50417Tartu, Estonia
S. Janno
Affiliation:
Psychiatry Clinic of Tartu University Hospital, Raja 31, 50417Tartu, Estonia
K. Kriisa
Affiliation:
Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu, Ravila 19Tartu50411, Estonia Centre of Excellence for Genomics and Translational Medicine Ravila 19 Tartu50411, Estonia
R. Mahlapuu
Affiliation:
Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu, Ravila 19Tartu50411, Estonia Centre of Excellence for Genomics and Translational Medicine Ravila 19 Tartu50411, Estonia
U. Ljubajev
Affiliation:
Psychiatry Department, Psychiatry Clinic of Tartu University Hospital, Raja 31, 50417Tartu, Estonia
M. Parksepp
Affiliation:
Department of Child and Adolescent Psychiatry, Psychiatry Clinic of Tartu University Hospital, Raja 31, 50417Tartu, Estonia
P. Veiksaar
Affiliation:
Psychiatry Department, Psychiatry Clinic of Tartu University Hospital, Raja 31, 50417Tartu, Estonia
V. Volke
Affiliation:
Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu, Ravila 19Tartu50411, Estonia Centre of Excellence for Genomics and Translational Medicine Ravila 19 Tartu50411, Estonia Endocrinology Unit, Internal Medicine Clinic, Tartu University Hospital, Puusepa 8, 50406Tartu, Estonia
A. Lang
Affiliation:
Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu, Ravila 19Tartu50411, Estonia Centre of Excellence for Genomics and Translational Medicine Ravila 19 Tartu50411, Estonia
L. Haring
Affiliation:
Department of the Out-Patient, Psychiatry Clinic of Tartu University Hospital, Raja 31, 50417Tartu, Estonia
M. Zilmer
Affiliation:
Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu, Ravila 19Tartu50411, Estonia Centre of Excellence for Genomics and Translational Medicine Ravila 19 Tartu50411, Estonia
E. Vasar
Affiliation:
Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu, Ravila 19Tartu50411, Estonia Centre of Excellence for Genomics and Translational Medicine Ravila 19 Tartu50411, Estonia
*
*Corresponding author. Tel.: +372 731 8866. E-mail address:[email protected] (R. Baloõtšev).
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Abstract

Background

There is a growing interest in low-grade inflammatory and metabolic alterations in patients with chronic schizophrenia (SCH).

Methods

Inflammatory (tumor-necrosis factor-α [TNF-α], interferon-γ [IFN-γ], interleukins [IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10], monocyte chemo-attractant protein-1 [MCP-1]) and growth factors (vascular endothelial growth factor [VEGF], epidermal growth factor [EGF]) were measured in blood serum samples of 105 SCH patients and 148 control subjects (CS). Simultaneously the clinical biomarkers (C-reactive protein [CRP], triglycerides [TG], low-density lipoprotein [LDL-c] and high-density lipoprotein [HDL-c] cholesterol, glycated hemoglobin [HbA1c]) were measured, and body mass index (BMI) was calculated for patients.

Results

Several cyto-/chemokines (IFN-γ, MCP-1, IL-2, IL-6, IL-8 and IL-10) were significantly (P < 0.0000001) elevated in SCH patients compared to CS. Odds ratios, obtained from logistic regression analyses, were significantly elevated for IL-2, IL-6, IL-10, INF-γ, and decreased for TNF-α in SCH group. Among the patients, higher IL-2, IL-6, INF-γ and lower MCP-1 levels as well as male gender were together significant (P < 0.000001) predictors of higher HbA1c levels, and TG/HDL-c parameter was associated with ratios of INF-γ/IL-10 (P = 0.004), and INF-γ/IL-4 (P = 0.049), HbA1c (P = 0.005), INF-γ (P = 0.009), as well as LDL-c (P = 0.02) levels.

Conclusions

IL-2, IL-6, IL-10 and IFN-γ were the most significant SCH-related markers among the measured cytokines in our patient group. Furthermore, significant associations between pro-/anti-inflammatory imbalance and HbA1c as well as cardio-metabolic risk marker (TG/HDL-c) were observed, indicating higher risks of diabetes and cardiovascular diseases among SCH patients.

Keywords

Cytokines and growth factorsType-2 diabetesInflammationCardio-metabolic risk factors
Type
Original article
Information
European Psychiatry , Volume 39 , January 2017 , pp. 1 - 10
Copyright
Copyright © Elsevier Masson SAS 2017

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Footnotes

1

Tel.: +372 737 4337.

2

Deceased author.

3

Tel.: +372 731 8701.

4

Tel.: +372 737 4313.

5

Tel.: +372 731 8735.

6

Tel.: +372 731 8865.

7

Tel.: +372 737 4338.

8

Tel.: +372 737 4333.

9

Tel.: +372 731 8767.

10

Tel.: +372 737 4311.

11

Tel.: +372 737 4331.

References

Natl Inst Ment Health NIMH n.d. National Institute of Mental Health (2016). Schizophrenia. [Retrieved January 10, 2016, from http://www.nimh.nih.gov/health/statistics/prevalence/schizophrenia.shtml].Google Scholar
van Os, JKapur, SSchizophrenia. The Lancet 2009; 374: 635–645. http://dx.doi.org/10.1016/S0140-6736(09)60995-8.CrossRefGoogle ScholarPubMed
Saraceno, BThe WHO World Health Report 2001 on mental health. Epidemiol Psichiatr Soc 2002; 11: 83–87.CrossRefGoogle ScholarPubMed
Holt, RIGBushe, CCitrome, LDiabetes and schizophrenia 2005: are we any closer to understanding the link?. J Psychopharmacol (Oxf) 2005; 19: 56–65. http://dx.doi.org/10.1177/0269881105058379.CrossRefGoogle ScholarPubMed
Brown, SKim, MMitchell, CInskip, HTwenty-five year mortality of a community cohort with schizophrenia. Br J Psychiatry J Ment Sci 2010; 196: 116–121. http://dx.doi.org/10.1192/bjp.bp.109.067512.CrossRefGoogle ScholarPubMed
McEvoy, JPMeyer, JMGoff, DCNasrallah, HADavis, SMSullivan, Let al.Prevalence of the metabolic syndrome in patients with schizophrenia: Baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res 2005; 80: 19–32. http://dx.doi.org/10.1016/j.schres.2005.07.014.CrossRefGoogle ScholarPubMed
Tiihonen, JLönnqvist, JWahlbeck, KKlaukka, TNiskanen, LTanskanen, Aet al.11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet Lond Engl 2009; 374: 620–627. http://dx.doi.org/10.1016/S0140-6736(09)60742-X.CrossRefGoogle Scholar
O’Rahilly, SHuman genetics illuminates the paths to metabolic disease. Nature 2009; 462: 307–314. http://dx.doi.org/10.1038/nature08532.CrossRefGoogle ScholarPubMed
Howes, ODBhatnagar, AGaughran, FPAmiel, SAMurray, RMPilowsky, LSA prospective study of impairment in glucose control caused by clozapine without changes in insulin resistance. Am J Psychiatry 2004; 161: 361–363. http://dx.doi.org/10.1176/appi.ajp.161.2.361.CrossRefGoogle ScholarPubMed
Mondelli, VAnacker, CVernon, ACCattaneo, ANatesan, SModo, Met al.Haloperidol and olanzapine mediate metabolic abnormalities through different molecular pathways. Transl Psychiatry 3 2013;e208. http://dx.doi.org/10.1038/tp.2012.138.CrossRefGoogle ScholarPubMed
Fernandez-Egea, EBernardo, MDonner, TConget, IParellada, EJusticia, Aet al.Metabolic profile of antipsychotic-naive individuals with non-affective psychosis. Br J Psychiatry J Ment Sci 2009; 194: 434–438. http://dx.doi.org/10.1192/bjp.bp.108.052605.CrossRefGoogle ScholarPubMed
Zajkowska, ZMondelli, VFirst-episode psychosis: an inflammatory state?. Neuroimmunomodulation 2014; 21: 102–108. http://dx.doi.org/10.1159/000356536.CrossRefGoogle Scholar
Mondelli, VHowes, OInflammation: its role in schizophrenia and the potential anti-inflammatory effects of antipsychotics. Psychopharmacology (Berl) 2014; 231: 317–318. http://dx.doi.org/10.1007/s00213-013-3383-3.CrossRefGoogle ScholarPubMed
Smith, RSMaes, MThe macrophage-T-lymphocyte theory of schizophrenia: additional evidence. Med Hypotheses 1995; 45: 135–141.CrossRefGoogle ScholarPubMed
Jia, PWang, LFanous, AHChen, XKendler, KSZhao, ZA bias-reducing pathway enrichment analysis of genome-wide association data confirmed association of the MHC region with schizophrenia. J Med Genet 2012; 49: 96–103. http://dx.doi.org/10.1136/jmedgenet-2011-100397.CrossRefGoogle ScholarPubMed
Stefansson, HOphoff, RASteinberg, SAndreassen, OACichon, SRujescu, Det al.Common variants conferring risk of schizophrenia. Nature 2009; 460: 744–747. http://dx.doi.org/10.1038/nature08186.CrossRefGoogle ScholarPubMed
Sekar, ABialas, ARde Rivera, HDavis, AHammond, TRKamitaki, Net al.Schizophrenia risk from complex variation of complement component 4. Nature 2016; 530: 177–183. http://dx.doi.org/10.1038/nature16549.CrossRefGoogle ScholarPubMed
Arion, DUnger, TLewis, DALevitt, PMirnics, KMolecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia. Biol Psychiatry 2007; 62: 711–721. http://dx.doi.org/10.1016/j.biopsych.2006.12.021.CrossRefGoogle Scholar
Fillman, SGCloonan, NCatts, VSMiller, LCWong, JMcCrossin, Tet al.Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol Psychiatry 2013; 18: 206–214. http://dx.doi.org/10.1038/mp.2012.110.CrossRefGoogle ScholarPubMed
Horváth, SMirnics, KImmune system disturbances in schizophrenia. Biol Psychiatry 2014; 75: 316–323. http://dx.doi.org/10.1016/j.biopsych.2013.06.010.CrossRefGoogle Scholar
Anderson, GMaes, MBerk, MSchizophrenia is primed for an increased expression of depression through activation of immuno-inflammatory, oxidative and nitrosative stress, and tryptophan catabolite pathways. Prog Neuropsychopharmacol Biol Psychiatry 2013; 42: 101–114. http://dx.doi.org/10.1016/j.pnpbp.2012.07.016.CrossRefGoogle ScholarPubMed
Beumer, WDrexhage, RCDe Wit, HVersnel, MADrexhage, HACohen, DIncreased level of serum cytokines, chemokines and adipokines in patients with schizophrenia is associated with disease and metabolic syndrome. Psychoneuroendocrinology 2012; 37: 1901–1911. http://dx.doi.org/10.1016/j.psyneuen.2012.04.001.CrossRefGoogle ScholarPubMed
Craddock, RMLockstone, HERider, DAWayland, MTHarris, LJWMcKenna, PJet al.Altered T-cell function in schizophrenia: a cellular model to investigate molecular disease mechanisms. Plos One 2007;2:e692. http://dx.doi.org/10.1371/journal.pone.0000692.CrossRefGoogle ScholarPubMed
Drexhage, RCPadmos, RCde Wit, HVersnel, MAHooijkaas, Hvan der Lely, A-Jet al.Patients with schizophrenia show raised serum levels of the pro-inflammatory chemokine CCL2: association with the metabolic syndrome in patients?. Schizophr Res 2008; 102: 352–355. http://dx.doi.org/10.1016/j.schres.2008.03.018.CrossRefGoogle ScholarPubMed
Drexhage, RCvan der Heul-Nieuwenhuijsen, LPadmos, RCvan Beveren, NCohen, DVersnel, MAet al.Inflammatory gene expression in monocytes of patients with schizophrenia: overlap and difference with bipolar disorder. A study in naturalistically treated patients. Int J Neuropsychopharmacol Off Sci J Coll Int Neuropsychopharmacol CINP 2010; 13: 1369–1381. http://dx.doi.org/10.1017/S1461145710000799.Google ScholarPubMed
Drexhage, RCWeigelt, Kvan Beveren, NCohen, DVersnel, MANolen, WAet al.Immune and neuroimmune alterations in mood disorders and schizophrenia. Int Rev Neurobiol 2011; 101: 169–201. http://dx.doi.org/10.1016/B978-0-12-387718-5.00007-9.CrossRefGoogle Scholar
Gibney, SMDrexhage, HAEvidence for a dysregulated immune system in the etiology of psychiatric disorders. J Neuroimmune Pharmacol Off J Soc Neuroimmune Pharmacol 2013; 8: 900–920. http://dx.doi.org/10.1007/s11481-013-9462-8.CrossRefGoogle ScholarPubMed
Müller, NWagner, JKKrause, DWeidinger, EWildenauer, AObermeier, Met al.Impaired monocyte activation in schizophrenia. Psychiatry Res 2012; 198: 341–346. http://dx.doi.org/10.1016/j.psychres.2011.12.049.CrossRefGoogle Scholar
Saetre, PEmilsson, LAxelsson, EKreuger, JLindholm, EJazin, EInflammation-related genes up-regulated in schizophrenia brains. BMC Psychiatry 7 2007. http://dx.doi.org/10.1186/1471-244X-7-46 [Art. ID: 46].CrossRefGoogle ScholarPubMed
Weigelt, KCarvalho, LADrexhage, RCWijkhuijs, Ade Wit, Hvan Beveren, NJMet al.TREM-1 and DAP12 expression in monocytes of patients with severe psychiatric disorders. EGR3, ATF3 and PU.1 as important transcription factors. Brain Behav Immun 2011; 25: 1162–1169. http://dx.doi.org/10.1016/j.bbi.2011.03.006.CrossRefGoogle ScholarPubMed
Mosmann, TRCherwinski, HBond, MWGiedlin, MACoffman, RLTwo types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986; 136: 2348–2357.Google ScholarPubMed
Schwarz, MJChiang, SMüller, NAckenheil, MT-helper-1 and T-helper-2 Responses in Psychiatric Disorders. Brain Behav Immun 2001; 15: 340–370. http://dx.doi.org/10.1006/brbi.2001.0647.CrossRefGoogle ScholarPubMed
Miller, BJBuckley, PSeabolt, WMellor, AKirkpatrick, BMeta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry 2011; 70: 663–671. http://dx.doi.org/10.1016/j.biopsych.2011.04.013.CrossRefGoogle ScholarPubMed
Potvin, SStip, ESepehry, AAGendron, ABah, RKouassi, EInflammatory Cytokine Alterations in Schizophrenia: A Systematic Quantitative Review. Biol Psychiatry 2008; 63: 801–808. http://dx.doi.org/10.1016/j.biopsych.2007.09.024.CrossRefGoogle ScholarPubMed
Upthegrove, RManzanares-Teson, NBarnes, NMCytokine function in medication-naive first episode psychosis: a systematic review and meta-analysis. Schizophr Res 2014; 155: 101–108. http://dx.doi.org/10.1016/j.schres.2014.03.005.CrossRefGoogle ScholarPubMed
Di Nicola, MCattaneo, AHepgul, NDi Forti, MAitchison, KJJaniri, Let al.Serum and gene expression profile of cytokines in first-episode psychosis. Brain Behav Immun 2013; 31: 90–95. http://dx.doi.org/10.1016/j.bbi.2012.06.010.CrossRefGoogle ScholarPubMed
WH Organization, The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines; 1992.Google Scholar
Kay, SRFiszbein, AOpler, LAThe positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261–276. http://dx.doi.org/10.1093/schbul/13.2.261.CrossRefGoogle Scholar
StataCorp., Stata Statistical Software: Release 12 College Station, TX: StataCorp LP. n.d; 2011Google Scholar
Haring, LKoido, KVasar, VLeping, VZilmer, KZilmer, Met al.Antipsychotic treatment reduces psychotic symptoms and markers of low-grade inflammation in first episode psychosis patients, but increases their body mass index. Schizophr Res 2015; 169: 22–29. http://dx.doi.org/10.1016/j.schres.2015.08.027.CrossRefGoogle ScholarPubMed
Liu, LJia, FYuan, GChen, ZYao, JLi, Het al.Tyrosine hydroxylase, interleukin-1beta and tumor necrosis factor-alpha are overexpressed in peripheral blood mononuclear cells from schizophrenia patients as determined by semi-quantitative analysis. Psychiatry Res 2010; 176: 1–7. http://dx.doi.org/10.1016/j.psychres.2008.10.024.CrossRefGoogle ScholarPubMed
Beutler, BCerami, AThe biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol 1989; 7: 625–655. http://dx.doi.org/10.1146/annurev.iy.07.040189.003205.CrossRefGoogle ScholarPubMed
Kim, Y-KMyint, A-MVerkerk, RScharpe, SSteinbusch, HLeonard, BCytokine changes and tryptophan metabolites in medication-naïve and medication-free schizophrenic patients. Neuropsychobiology 2009; 59: 123–129. http://dx.doi.org/10.1159/000213565.CrossRefGoogle ScholarPubMed
O’Brien, SMScully, PDinan, TGIncreased tumor necrosis factor-alpha concentrations with interleukin-4 concentrations in exacerbations of schizophrenia. Psychiatry Res 2008; 160: 256–262. http://dx.doi.org/10.1016/j.psychres.2007.11.014.CrossRefGoogle ScholarPubMed
Reale, MPatruno, ADe Lutiis, MAPesce, MFelaco, MDi Giannantonio, Met al.Dysregulation of chemo-cytokine production in schizophrenic patients versus healthy controls. BMC Neurosci 2011;12. http://dx.doi.org/10.1186/1471-2202-12-13.CrossRefGoogle ScholarPubMed
Xu, HMWei, JHemmings, GPChanges of plasma concentrations of interleukin-1 alpha and interleukin-6 with neuroleptic treatment for schizophrenia. Br J Psychiatry J Ment Sci 1994; 164: 251–253. http://dx.doi.org/10.1192/bjp.164.2.251.CrossRefGoogle Scholar
Lv, MTan, YYan, STian, LChen, DTan, Set al.Decreased serum TNF-alpha levels in chronic schizophrenia patients on long-term antipsychotics: correlation with psychopathology and cognition. Psychopharmacology (Berl) 2015; 232: 165–172. http://dx.doi.org/10.1007/s00213-014-3650-y.CrossRefGoogle ScholarPubMed
Schroder, KInterferon-γ: an overview of signals, mechanisms and functions. J Leukoc Biol 2003; 75: 163–189. http://dx.doi.org/10.1189/jlb.0603252.CrossRefGoogle ScholarPubMed
Schloot, NCHanifi-Moghaddam, PGoebel, CShatavi, SVFlohé, SKolb, Het al.Serum IFN-gamma and IL-10 levels are associated with disease progression in non-obese diabetic mice. Diabetes Metab Res Rev 2002; 18: 64–70. http://dx.doi.org/10.1002/dmrr.256.CrossRefGoogle ScholarPubMed
Wu, C-CSytwu, H-KLu, K-CLin, Y-FRole of T cells in type 2 diabetic nephropathy. Exp Diabetes Res 2011;38. http://dx.doi.org/10.1155/2011/514738.Google Scholar
Ijzermans, JNMarquet, RLInterferon-gamma: a review. Immunobiology 1989; 179: 456–473. http://dx.doi.org/10.1016/S0171-2985(89)80049-X.CrossRefGoogle ScholarPubMed
Chiang, SSWRidel, MMüller, NAckenheil, MGruber, RSchwarz, MTh2-shift in schizophrenia: primary findings from whole blood in vitro stimulation. Psychiatry Onl 2004, http://www.priory.com/psych/th2.htm.Google Scholar
Na, K-SKim, Y-KMonocytic, Th1 and th2 cytokine alterations in the pathophysiology of schizophrenia. Neuropsychobiology 2007; 56: 55–63. http://dx.doi.org/10.1159/000111535.CrossRefGoogle ScholarPubMed
Ouyang, WRutz, SCrellin, NKValdez, PAHymowitz, SGRegulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 2011; 29: 71–109. http://dx.doi.org/10.1146/annurev-immunol-031210-101312.CrossRefGoogle ScholarPubMed
Opp, MRSmith, EMHughes, TKInterleukin-10 (cytokine synthesis inhibitory factor) acts in the central nervous system of rats to reduce sleep. J Neuroimmunol 1995; 60: 165–168. http://dx.doi.org/10.1016/0165-5728(95)00066-B.CrossRefGoogle ScholarPubMed
Maes, MIncreased serum interleukin-8 and interleukin-10 in schizophrenic patients resistant to treatment with neuroleptics and the stimulatory effects of clozapine on serum leukemia inhibitory factor receptor. Schizophr Res 2002; 54: 281–291. http://dx.doi.org/10.1016/S0920-9964(00)00094-3.CrossRefGoogle ScholarPubMed
Rothermundt, MArolt, VWeitzsch, CEckhoff, DKirchner, HProduction of cytokines in acute schizophrenic psychosis. Biol Psychiatry 1996; 40: 1294–1297. http://dx.doi.org/10.1016/S0006-3223(96)00360-5.CrossRefGoogle ScholarPubMed
Shibata, MEndo, SInada, KKuriki, SHarada, MTakino, Tet al.Elevated plasma levels of interleukin-1 receptor antagonist and interleukin-10 in patients with acute myocardial infarction. J Interferon Cytokine Res 2009; 17(3): 145–15010.1089/jir.1997.17.145CrossRefGoogle Scholar
Chiavetto, LBBoin, FZanardini, RPopoli, MMichelato, ABignotti, Set al.Association between promoter polymorphic haplotypes of interleukin-10 gene and schizophrenia. Biol Psychiatry 2002; 51: 480–484. http://dx.doi.org/10.1016/S0006-3223(01)01324-5.CrossRefGoogle Scholar
Yu, LAn association between polymorphisms of the interleukin-10 gene promoter and schizophrenia in the Chinese population. Schizophr Res 2004; 71: 179–183. http://dx.doi.org/10.1016/j.schres.2004.01.001.CrossRefGoogle ScholarPubMed
Wright, PSham, PCGilvarry, CMJones, PBCannon, MSharma, Tet al.Autoimmune diseases in the pedigrees of schizophrenic and control subjects. Schizophr Res 1996; 20: 261–267. http://dx.doi.org/10.1016/0920-9964(96)82950-1.CrossRefGoogle ScholarPubMed
Eaton, WWByrne, MEwald, HMors, OChen, C-YAgerbo, Eet al.Association of schizophrenia and autoimmune diseases: linkage of Danish National Registers. Am J Psychiatry 2006; 163: 521–528. http://dx.doi.org/10.1176/appi.ajp.163.3.521.CrossRefGoogle ScholarPubMed
Jones, ALMowry, BJPender, MPGreer, JMImmune dysregulation and self-reactivity in schizophrenia: do some cases of schizophrenia have an autoimmune basis?. Immunol Cell Biol 2005; 83: 9–17. http://dx.doi.org/10.1111/j.1440-1711.2005.01305.x.CrossRefGoogle ScholarPubMed
Rothermundt, MArolt, VBayer, TAReview of immunological and immunopathological findings in schizophrenia. Brain Behav Immun 2001; 15: 319–339. http://dx.doi.org/10.1006/brbi.2001.0648.CrossRefGoogle Scholar
Arolt, VRothermundt, MWandinger, KPKirchner, HDecreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment. Mol Psychiatry 2000; 5: 150–158.CrossRefGoogle ScholarPubMed
Apte, SHBaz, AGroves, PKelso, AKienzle, NInterferon- and interleukin-4 reciprocally regulate CD8 expression in CD8+ T cells. Proc Natl Acad Sci 2008; 105: 17475–17480. http://dx.doi.org/10.1073/pnas.0809549105.CrossRefGoogle ScholarPubMed
Chiang, SS-WRiedel, MSchwarz, MMueller, NIs 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. http://dx.doi.org/10.1111/pcn.12040.CrossRefGoogle ScholarPubMed
Eskandari, FWebster, JISternberg, EMNeural immune pathways and their connection to inflammatory diseases. Arthritis Res Ther 2003; 5: 251–265. http://dx.doi.org/10.1186/ar1002.CrossRefGoogle ScholarPubMed
Yao, YTsirka, SEMonocyte chemoattractant protein-1 and the blood–brain barrier. Cell Mol Life Sci 2014; 71: 683–697. http://dx.doi.org/10.1007/s00018-013-1459-1.CrossRefGoogle ScholarPubMed
Stamatovic, SMShakui, PKeep, RFMoore, BBKunkel, SLVan Rooijen, Net al.Monocyte chemoattractant protein-1 regulation of blood–brain barrier permeability. J Cereb Blood Flow Metab 2005; 25: 593–606. http://dx.doi.org/10.1038/sj.jcbfm.9600055.CrossRefGoogle ScholarPubMed
Bernstein, H-GSteiner, JBogerts, BGlial cells in schizophrenia: pathophysiological significance and possible consequences for therapy. Expert Rev Neurother 2009; 9: 1059–1071. http://dx.doi.org/10.1586/ern.09.59.CrossRefGoogle ScholarPubMed
Monji, AKato, TKanba, SCytokines and schizophrenia: Microglia hypothesis of schizophrenia: Cytokines and schizophrenia. Psychiatry Clin Neurosci 2009; 63: 257–265. http://dx.doi.org/10.1111/j.1440-1819.2009.01945.x.CrossRefGoogle Scholar
Devlin, MJYanovski, SZWilson, GTObesity: what mental health professionals need to know. Am J Psychiatry 2000; 157: 854–866. http://dx.doi.org/10.1176/appi.ajp.157.6.854.CrossRefGoogle ScholarPubMed
Gregor, MFHotamisligil, GSInflammatory Mechanisms in Obesity. Annu Rev Immunol 2011; 29: 415–445. http://dx.doi.org/10.1146/annurev-immunol-031210-101322.CrossRefGoogle ScholarPubMed
International Diabetes Federation Guideline Development Group Global guideline for type 2 diabetes. Diabetes Res Clin Pract 2014; 104: 1–52. http://dx.doi.org/10.1016/j.diabres.2012.10.001.CrossRefGoogle Scholar
Fan, XLiu, EYHoffman, VPPotts, AJSharma, BHenderson, DCTriglyceride/high-density lipoprotein cholesterol ratio: a surrogate to predict insulin resistance and low-density lipoprotein cholesterol particle size in nondiabetic patients with schizophrenia. J Clin Psychiatry 2011; 72: 806–812. http://dx.doi.org/10.4088/JCP.09m05107yel.CrossRefGoogle ScholarPubMed
da Luz, PLFavarato, DFaria-Neto Junior, JRLemos, PChagas, ACPHigh ratio of triglycerides to hdl-cholesterol predicts extensive coronary disease. Clinics 2008;63. http://dx.doi.org/10.1590/S1807-59322008000400003.Google ScholarPubMed
Gaziano, JMHennekens, CHO’Donnell, CJBreslow, JLBuring, JEFasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation 1997; 96: 2520–2525. http://dx.doi.org/10.1161/01.CIR.96.8.2520.CrossRefGoogle ScholarPubMed
Pearson, TAMarkers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003; 107: 499–511. http://dx.doi.org/10.1161/01.CIR.0000052939.59093.45.CrossRefGoogle ScholarPubMed
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