Hostname: page-component-7479d7b7d-rvbq7 Total loading time: 0 Render date: 2024-07-12T01:37:44.198Z Has data issue: false hasContentIssue false
  • English
  • Français

C-reactive protein and white blood cell levels in schizophrenia, bipolar disorders and depression - associations with mortality and psychiatric outcomes: a population-based study

Published online by Cambridge University Press:  23 March 2020

H.T. Horsdal ,
O. Köhler-Forsberg ,
M.E. Benros  and
C. Gasse
H.T. Horsdal*
Affiliation:
National Centre for Register-based Research, Department of Economics and Business Economics, Aarhus BSS, Aarhus University, Fuglesangs Allé 26, DK-8210Aarhus V, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark
O. Köhler-Forsberg
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
M.E. Benros
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
C. Gasse
Affiliation:
National Centre for Register-based Research, Department of Economics and Business Economics, Aarhus BSS, Aarhus University, Fuglesangs Allé 26, DK-8210Aarhus V, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark
*
* Corresponding author. National Centre for Register-based Research, Department of Economics and Business, Aarhus BSS, Aarhus University, Fuglesangs Allé 26, DK-8210 Aarhus V, Denmark. E-mail address:horsdal@econ.au.dk (H.T. Horsdal).
Get access

Abstract

Background:

Mental disorders have been associated with increased levels of inflammatory markers, which can affect disease trajectories. We aimed to assess levels of C-reactive protein (CRP) and white blood cells (WBC) across individuals with schizophrenia, bipolar disorder, and depression, and to investigate associations with subsequent psychiatric admission and mortality.

Methods:

We identified all adults in the Central Denmark Region during 2000–2012 with a first diagnosis of schizophrenia, bipolar disorder, or depression and a baseline measurement of CRP and/or WBC count. We followed these individuals until outcome of interest (psychiatric admission or death), emigration or December 31, 2012, using Cox regression analysis to estimate hazard ratios (HRs).

Results:

Baseline median CRP differed significantly between mental disorders (P = 0.01) being highest in individuals with bipolar disorder (3.5 mg/L) (particularly during manic states, 3.9 mg/L), followed by schizophrenia (3.1 mg/L), and depression (2.8 mg/L), while baseline WBC count did not differ (median 7.1 × 109/L). Elevated CRP levels were associated with increased all-cause mortality by adjusted HRs of 1.56 (95% CI: 1.02–2.38) for levels 3–10 mg/L and 2.07 (95% CI: 1.30–3.29) for levels above 10 mg/L compared to individuals with levels below 3 mg/L. WBC counts were not associated with all-cause mortality. No association was observed between levels of the inflammatory markers and subsequent psychiatric admissions.

Conclusions:

People with severe mental disorders had increased inflammatory markers at first diagnosis, and elevated CRP levels were associated with increased mortality. Thorough screening for physical diseases is of utmost importance among individuals who are diagnosed with severe mental disorder.

Keywords

Pro-inflammatory markersSevere mental disordersPsychoimmunology
Type
Original article
Information
European Psychiatry , Volume 44 , July 2017 , pp. 164 - 172
Copyright
Copyright © European Psychiatric Association 2017

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Baumeister, DRussell, APariante, CMMondelli, VInflammatory biomarker profiles of mental disorders and their relation to clinical, social and lifestyle factors. Soc Psychiatry Psychiatr Epidemiol 2014; 49: 841–849.CrossRefGoogle ScholarPubMed
Benros, MENielsen, PRNordentoft, MEaton, WWDalton, SOMortensen, PBAutoimmune diseases and severe infections as risk factors for schizophrenia: a 30-year population-based register study. Am J Psychiatry 2011; 168: 1303–1310.CrossRefGoogle ScholarPubMed
Benros, MEWaltoft, BLNordentoft, MOstergaard, SDEaton, WWKrogh, J, et al.Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study. JAMA Psychiatry 2013; 70: 812–820.CrossRefGoogle ScholarPubMed
Foldager, LKohler, OSteffensen, RThiel, SKristensen, ASJensenius, JC, et al.Bipolar and panic disorders may be associated with hereditary defects in the innate immune system. J Affect Disord 2014; 164: 148–154.CrossRefGoogle ScholarPubMed
Sekar, ABialas, ARde, RHDavis, AHammond, TRKamitaki, N, et al.Schizophrenia risk from complex variation of complement component 4. Nature 2016; 530: 177–183.CrossRefGoogle ScholarPubMed
Fernandes, BSSteiner, JBernstein, HGDodd, SPasco, JADean, OM, et al.C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications. Mol Psychiatry 2016; 21: 554–564.CrossRefGoogle Scholar
Akanji, AOOhaeri, JUAl-Shammri, SFatania, HRAssociation of blood levels of C-reactive protein with clinical phenotypes in Arab schizophrenic patients. Psychiatry Res 2009; 169: 56–61.CrossRefGoogle ScholarPubMed
Dickerson, FStallings, COrigoni, AVaughan, CKhushalani, SYang, S, et al.C-reactive protein is elevated in schizophrenia. Schizophr Res 2013; 143: 198–202.CrossRefGoogle Scholar
Fawzi, MHFawzi, MMFawzi, MMSaid, NSC-reactive protein serum level in drug-free male Egyptian patients with schizophrenia. Psychiatry Res 2011; 190: 91–97.CrossRefGoogle ScholarPubMed
Inoshita, MNumata, STajima, AKinoshita, MUmehara, HNakataki, M, et al.A significant causal association between C-reactive protein levels and schizophrenia. Sci Rep 2016;6:26105.CrossRefGoogle Scholar
Lin, CCChang, CMLiu, CYHuang, TLIncreased high-sensitivity C-reactive protein levels in Taiwanese schizophrenic patients. Asia Pac Psychiatry 2013;5:E58–E63.CrossRefGoogle ScholarPubMed
Wium-Andersen, MKOrsted, DDNordestgaard, BGElevated C-reactive protein associated with late- and very-late-onset schizophrenia in the general population: a prospective study. Schizophr Bull 2014; 40: 1117–1127.CrossRefGoogle ScholarPubMed
De Berardis, DConti, CMCampanella, DCarano, AScali, MValchera, A, et al.Evaluation of C-reactive protein and total serum cholesterol in adult patients with bipolar disorder. Int J Immunopathol Pharmacol 2008; 21: 319–324.CrossRefGoogle ScholarPubMed
Dickerson, FStallings, COrigoni, ABoronow, JYolken, RElevated serum levels of C-reactive protein are associated with mania symptoms in outpatients with bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31: 952–955.CrossRefGoogle ScholarPubMed
Dickerson, FStallings, COrigoni, AVaughan, CKhushalani, SYolken, RElevated C-reactive protein and cognitive deficits in individuals with bipolar disorder. J Affect Disord 2013; 150: 456–459.CrossRefGoogle ScholarPubMed
Fernandes, BSSteiner, JMolendijk, MLDodd, SNardin, PGoncalves, CA, et al.C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry 2016; 3: 1147–1156.CrossRefGoogle ScholarPubMed
Wium-Andersen, MKOrsted, DDNordestgaard, BGElevated C-reactive protein and late-onset bipolar disorder in 78,809 individuals from the general population. Br J Psychiatry 2016; 208: 138–145.CrossRefGoogle ScholarPubMed
Wium-Andersen, MKOrsted, DDNordestgaard, BGElevated C-reactive protein, depression, somatic diseases, and all-cause mortality: a mendelian randomization study. Biol Psychiatry 2014; 76: 249–257.CrossRefGoogle ScholarPubMed
Wium-Andersen, MKOrsted, DDNielsen, SFNordestgaard, BGElevated C-reactive protein levels, psychological distress, and depression in 73,131 individuals. JAMA Psychiatry 2013; 70: 176–184.CrossRefGoogle ScholarPubMed
Liukkonen, TSilvennoinen-Kassinen, SJokelainen, JRasanen, PLeinonen, MMeyer-Rochow, VB, et al.The association between C-reactive protein levels and depression: results from the northern Finland 1966 birth cohort study. Biol Psychiatry 2006; 60: 825–830.CrossRefGoogle ScholarPubMed
Liu, YAl-Sayegh, HJabrah, RWang, WYan, FZhang, JAssociation between C-reactive protein and depression: modulated by gender and mediated by body weight. Psychiatry Res 2014; 219: 103–108.CrossRefGoogle ScholarPubMed
Wysokinski, AMargulska, AStrzelecki, DKloszewska, ILevels of C-reactive protein (CRP) in patients with schizophrenia, unipolar depression and bipolar disorder. Nord J Psychiatry 2015; 69: 346–353.CrossRefGoogle ScholarPubMed
Kohler, OSylvia, LGBowden, CLCalabrese, JRThase, MShelton, RC, et al. White blood cell count correlates with mood symptom severity and specific mood symptoms in bipolar disorder. Aust N Z J Psychiatry 2016CrossRefGoogle Scholar
Uher, RTansey, KEDew, TMaier, WMors, OHauser, J, et al.An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. Am J Psychiatry 2014; 171: 1278–1286.CrossRefGoogle ScholarPubMed
Strawbridge, RArnone, DDanese, APapadopoulos, AHerane, VACleare, AJInflammation and clinical response to treatment in depression: a meta-analysis. Eur Neuropsychopharmacol 2015; 25: 1532–1543.CrossRefGoogle ScholarPubMed
Nordentoft, MWahlbeck, KHallgren, JWestman, JOsby, UAlinaghizadeh, H, et al.Excess mortality, causes of death and life expectancy in 270,770 patients with recent onset of mental disorders in Denmark, Finland and Sweden. Plos One 2013;8:e55176.CrossRefGoogle ScholarPubMed
Pedersen, CBThe Danish civil registration system. Scand J Public Health 2011; 39: 22–25.CrossRefGoogle ScholarPubMed
Mors, OPerto, GPMortensen, PBThe Danish psychiatric central research register. Scand J Public Health 2011; 39: 54–57.CrossRefGoogle ScholarPubMed
Grann, AFErichsen, RNielsen, AGFroslev, TThomsen, RWExisting data sources for clinical epidemiology: The clinical laboratory information system (LABKA) research database at Aarhus university, Denmark. Clin Epidemiol 2011; 3: 133–138.CrossRefGoogle ScholarPubMed
Lynge, ESandegaard, JLRebolj, MThe Danish National Patient Register. Scand J Public Health 2011; 39: 30–33.CrossRefGoogle ScholarPubMed
Charlson, MEPompei, PAles, KLMacKenzie, CRA new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373–383.CrossRefGoogle ScholarPubMed
Reuter, MBSoegaard, BNordentoft, MErlangsen, A Incidence rates of deliberate self-harm in Denmark 1994–2011. Crisis 2016; 1–9.Google Scholar
Jensen, VMRasmussen, AWDanish education registers. Scand J Public Health 2011; 39: 91–94.CrossRefGoogle ScholarPubMed
Petersson, FBaadsgaard, MThygesen, LCDanish registers on personal labour market affiliation. Scand J Public Health 2011; 39: 95–98.CrossRefGoogle ScholarPubMed
Kildemoes, HWSorensen, HTHallas, JThe Danish National prescription registry. Scand J Public Health 2011; 39: 38–41.CrossRefGoogle ScholarPubMed
Sundhedsstyrelsen, CfEoMTReference program for skizofreni København: Sundhedsstyrelsen; 2004Google Scholar
Uggerby, POstergaard, SDRoge, RCorrell, CUNielsen, JThe validity of the schizophrenia diagnosis in the Danish psychiatric central research register is good. Dan Med J 2013;60:A4578.Google Scholar
Bock, CBukh, JDVinberg, MGether, UKessing, LVValidity of the diagnosis of a single depressive episode in a case register. Clin Pract Epidemiol Ment Health 2009;5:4.CrossRefGoogle Scholar
Kessing, LValidity of diagnoses and other clinical register data in patients with affective disorder. Eur Psychiatry 1998; 13: 392–398.CrossRefGoogle ScholarPubMed
Andersen, CLSiersma, VDKarlslund, WHasselbalch, HCFelding, PBjerrum, OW, et al.The Copenhagen primary care differential count (CopDiff) database. Clin Epidemiol 2014; 6: 199–211.CrossRefGoogle ScholarPubMed
Hope, SMelle, IAukrust, PSteen, NEBirkenaes, ABLorentzen, S, et al.Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor. Bipolar Disord 2009; 11: 726–734.CrossRefGoogle ScholarPubMed
Vuksan-Cusa, BSagud, MJakovljevic, MC-reactive protein and metabolic syndrome in patients with bipolar disorder compared to patients with schizophrenia. Psychiatr Danub 2010; 22: 275–277.Google ScholarPubMed
Woloshin, SSchwartz, LMDistribution of C-reactive protein values in the United States. N Engl J Med 2005; 352: 1611–1613.CrossRefGoogle ScholarPubMed
Kao, TWLu, ISLiao, KCLai, HYLoh, CHKuo, HKAssociations between body mass index and serum levels of C-reactive protein. S Afr Med J 2009; 99: 326–330.Google ScholarPubMed
Lakryc, EMMachado, RBSoares, JM Jr.Fernandes, CE IIIBaracat, ECWhat is the influence of hormone therapy on homocysteine and CRP levels in postmenopausal women?. Clinics (Sao Paulo) 2015; 70: 107–113.CrossRefGoogle ScholarPubMed
Norouzi, VSeifi, MFallah, SKorani, MSamadikuchaksaraei, AEffect of oral contraceptive therapy on homocysteine and C-reactive protein levels in women: an observational study. Anadolu Kardiyol Derg 2011; 11: 698–702.Google ScholarPubMed
Diaz, FJPerez-Iglesias, RMata, IMartinez-Garcia, OVazquez-Barquero, JLde, LJ, et al.Possible effects of some antipsychotic drugs on C-reactive protein in a drug-naive psychotic sample. Schizophr Res 2010; 121: 207–212.CrossRefGoogle Scholar
Barzilay, RLobel, TKrivoy, AShlosberg, DWeizman, AKatz, NElevated C-reactive protein levels in schizophrenia inpatients is associated with aggressive behavior. Eur Psychiatry 2016; 31: 8–12.CrossRefGoogle ScholarPubMed
Fan, XPristach, CLiu, EYFreudenreich, OHenderson, DCGoff, DCElevated serum levels of C-reactive protein are associated with more severe psychopathology in a subgroup of patients with schizophrenia. Psychiatry Res 2007; 149: 267–271.CrossRefGoogle Scholar
Lagrand, WKVisser, CAHermens, WTNiessen, HWVerheugt, FWWolbink, GJ, et al.C-reactive protein as a cardiovascular risk factor: more than an epiphenomenon?. Circulation 1999; 100: 96–102.CrossRefGoogle ScholarPubMed
Li, YZhong, XCheng, GZhao, CZhang, LHong, Y, et al.Hs-CRP and all-cause, cardiovascular, and cancer mortality risk: a meta-analysis. Atherosclerosis 2017; 259: 75–82.CrossRefGoogle ScholarPubMed
Laursen, TMWahlbeck, KHallgren, JWestman, JOsby, UAlinaghizadeh, H, et al.Life expectancy and death by diseases of the circulatory system in patients with bipolar disorder or schizophrenia in the Nordic countries. Plos One 2013;8:e67133.CrossRefGoogle ScholarPubMed
Balukova, SMHaarman, BCRiemersma-van der Lek, RFSchoevers, RADoes CRP predict outcome in bipolar disorder in regular outpatient care?. Int J Bipolar Disord 2016;4:14.CrossRefGoogle ScholarPubMed
Supplementary material: File

Horsdal et al. supplementary material

Table A1-A2

Download Horsdal et al. supplementary material(File)
File 25.7 KB
Submit a response

Comments

No Comments have been published for this article.