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Correlations between Body Mass Index, Plasma High-Sensitivity C-Reactive Protein and Lipids in Patients with Schizophrenia

  • Ted Boozalis
  • Sridevi Devaraj
  • Olaoluwa O. Okusaga
Original Paper
  • 71 Downloads

Abstract

High prevalence of obesity in individuals with schizophrenia, associated with metabolic syndrome, leads to high rate of premature deaths from cardiovascular disease (CVD) in this population. Body mass index (BMI) and C-reactive protein (CRP) are correlated in the general population but this relationship has not been fully elucidated in patients with schizophrenia. We aimed to evaluate the correlation between BMI and CRP while relating both variables to plasma lipids in patients with schizophrenia. BMI, fasting high sensitivity CRP (hs-CRP), cotinine, and lipids were measured in 106 patients with schizophrenia (diagnosis confirmed with MINI). Pearson’s and partial correlations (adjusting for age, sex, race, education and cotinine) between BMI, hs-CRP and lipids were calculated. Based on BMI, the patients were divided into normal-weight vs. overweight/obese and t-tests and linear regression were done to compare hs-CRP and lipids in the 2 groups. BMI positively correlated with hs-CRP (r = 0.29, p = 0.004). BMI and hs-CRP negatively correlated with HDL in the total sample (r = −0.29, p = 0.004; r = −0.37, p < 0.001 respectively). Furthermore, hs-CRP negatively correlated with HDL in overweight/obese patients (r = −0.41, p = 0.003), but not in normal-weight patients. hs-CRP and triglycerides were higher (1.62 ± 0.09 mg/L vs. 0.56 ± 0.08 mg/L, p < 0.001; 121.77 ± 8.96 mg/dL vs. 91.23 ± 6.52 mg/dL, p = 0.008 respectively) and HDL lower (39.55 ± 1.48 mg/dL vs. 50.68 ± 2.24 mg/dL, p < 0.001) in overweight/obese patients. Being overweight/obese is associated with increased inflammation and dyslipidemia in patients with schizophrenia. Effective interventions to prevent weight gain in schizophrenia are urgently needed.

Keywords

Schizophrenia BMI Hs-CRP Plasma lipids Overweight Obese Cardiovascular disease 

Notes

Compliance with Ethical Standards

Conflicts of Interest

There are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Kirkpatrick B, Miller BJ. Inflammation and schizophrenia. Schizophr Bull. 2013;39:1174–9.CrossRefGoogle Scholar
  2. 2.
    Na K-S, Jung H-Y, Kim Y-K. The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry. 2014;48:277–86.CrossRefGoogle Scholar
  3. 3.
    Dean B. Understanding the role of inflammatory-related pathways in the pathophysiology and treatment of psychiatric disorders: evidence from human peripheral studies and CNS studies. Int J Neuropsychopharmacol. 2011;14:997–1012.CrossRefGoogle Scholar
  4. 4.
    Cameron IM, Hamilton RJ, Fernie G, MacGillivray SA. Obesity in individuals with schizophrenia: a case controlled study in Scotland. BJPsych Open. 2017;3:254–6.CrossRefGoogle Scholar
  5. 5.
    Lopresti A, Drummond P. Obesity and psychiatric disorders: commonalities in dysregulated biological pathways and their implications for treatment. Prog Neuro-Psychopharmacol Biol Psychiatry. 2013;45:92–9.CrossRefGoogle Scholar
  6. 6.
    Annamalai A, Kosir U, Tek C. Prevalence of obesity and diabetes in patients with schizophrenia. World J Diabetes. 2017;8:390–396.CrossRefGoogle Scholar
  7. 7.
    Jakobsen AS, Speyer H, Norgaard HCB, Hjorthoj C, Krogh J, Mors O, et al. Associations between clinical and psychosocial factors and metabolic and cardiovascular risk factors in overweight patients with schizophrenia spectrum disorders - baseline and two-years findings from the CHANGE trial. Schizophr Res. 2018.  https://doi.org/10.1016/j.schres.2018.02.047.CrossRefGoogle Scholar
  8. 8.
    Jeon SW, Kim YK. Unresolved issues for utilization of atypical antipsychotics in schizophrenia: Antipsychotic polypharmacy and metabolic syndrome. Int J Mol Sci. 2017;18:2174.CrossRefGoogle Scholar
  9. 9.
    Reynolds GP, Kirk SL. Metabolic side effects of antipsychotic drug treatment - pharmacological mechanisms. Pharmacol Ther. 2010;125:169–79.CrossRefGoogle Scholar
  10. 10.
    Lally J, Maccabe JH. Antipsychotic medication in schizophrenia : a review 2015:169–79.  https://doi.org/10.1093/bmb/ldv017 CrossRefGoogle Scholar
  11. 11.
    Bruijnzeel D, Suryadevara U, Tandon R. Antipsychotic treatment of schizophrenia: an update. Asian J Psychiatr. 2014;11:3–7.CrossRefGoogle Scholar
  12. 12.
    Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382:951–62.CrossRefGoogle Scholar
  13. 13.
    Raben AT, Marshe VS, Chintoh A, Gorbovskaya I, Müller DJ, Hahn MK. The complex relationship between antipsychotic-induced weight gain and therapeutic benefits: A systematic review and implications for treatment. Front Neurosci. 2018;11:741.Google Scholar
  14. 14.
    Steiner J, Bernstein H-G, Schiltz K, Muller UJ, Westphal S, Drexhage HA, et al. Immune system and glucose metabolism interaction in schizophrenia: a chicken-egg dilemma. Prog Neuro-Psychopharmacol Biol Psychiatry. 2014;48:287–94.CrossRefGoogle Scholar
  15. 15.
    Wirshing DA. Schizophrenia and obesity: impact of antipsychotic medications. J Clin Psychiatry. 2004;65(Suppl 1):13–26.PubMedGoogle Scholar
  16. 16.
    Laursen TM, Wahlbeck K, Hällgren J, Westman J, Ösby U, Alinaghizadeh 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.  https://doi.org/10.1371/journal.pone.0067133.CrossRefGoogle Scholar
  17. 17.
    Olfson M, Gerhard T, Huang C, Crystal S, Stroup TS. Premature mortality among adults with schizophrenia in the United States. JAMA Psychiat. 2015;72:1172–81.  https://doi.org/10.1001/jamapsychiatry.2015.1737.CrossRefGoogle Scholar
  18. 18.
    Chung K-H, Chen P-H, Kuo C-J, Tsai S-Y, Huang S-H, Wu W-C. Risk factors for early circulatory mortality in patients with schizophrenia. Psychiatry Res. 2018;267:7–11.CrossRefGoogle Scholar
  19. 19.
    Miller BJ, Culpepper N, Rapaport MH. C-reactive protein levels in schizophrenia: a review and meta-analysis. Clin Schizophr Relat Psychoses. 2014;7:223–30.CrossRefGoogle Scholar
  20. 20.
    Ohaeri JU, Hedo CC, Lagundoye OO. The profile of C-reactive proteins in functional psychotic states in a cohort in Nigeria. Acta Psychiatr Scand. 1993;88:252–5.CrossRefGoogle Scholar
  21. 21.
    Fernandes BS, Steiner J, Bernstein H-G, Dodd S, Pasco JA, Dean OM, et al. C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications. Mol Psychiatry. 2016;21:554–64.CrossRefGoogle Scholar
  22. 22.
    van Berckel BN, Bossong MG, Boellaard R, Kloet R, Schuitemaker A, Caspers E, et al. Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study. Biol Psychiatry. 2008;64:820–2.CrossRefGoogle Scholar
  23. 23.
    Boozalis T, Teixeira AL, Cho RY-J, Okusaga O. C-reactive protein correlates with negative symptoms in patients with schizophrenia. Front Public Heal. 2018;5:360.CrossRefGoogle Scholar
  24. 24.
    Misiak B, Stańczykiewicz B, Kotowicz K, Rybakowski JK, Samochowiec J, Frydecka D. Cytokines and C-reactive protein alterations with respect to cognitive impairment in schizophrenia and bipolar disorder: a systematic review. Schizophr Res. 2018;192:16–29.CrossRefGoogle Scholar
  25. 25.
    Horsdal HT, Köhler-Forsberg O, Benros ME, Gasse C. C-reactive protein and white blood cell levels in schizophrenia, bipolar disorders and depression - associations with mortality and psychiatric outcomes: a population-based study. Eur Psychiatry. 2017;44:164–72.CrossRefGoogle Scholar
  26. 26.
    Barzilay R, Lobel T, Krivoy A, Shlosberg D, Weizman A, Katz N. Elevated C-reactive protein levels in schizophrenia inpatients is associated with aggressive behavior. Eur Psychiatry. 2016;31:8–12.CrossRefGoogle Scholar
  27. 27.
    Szortyka MFV, Cristiano VB, Ceresér KM, Francesconi LP, Lobato MI, Gama C, et al. Physical functional capacity and C-reactive protein in schizophrenia. Front Psych. 2016;7:131.Google Scholar
  28. 28.
    Choi J, Joseph L, Pilote L. Obesity and C-reactive protein in various populations: a systematic review and meta-analysis. Obes Rev. 2013;14:232–44.CrossRefGoogle Scholar
  29. 29.
    Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999;282:2131–5.CrossRefGoogle Scholar
  30. 30.
    Firdous S. Correlation of CRP, fasting serum triglycerides and obesity as cardiovascular risk factors. J Coll Physicians Surg Pak. 2014;24:308–15.PubMedGoogle Scholar
  31. 31.
    Bonamichi BDSF, Lee J. Unusual suspects in the development of obesity-induced inflammation and insulin resistance: NK cells, iNKT cells, and ILCs. Diabetes Metab J. 2017;41:229–50.CrossRefGoogle Scholar
  32. 32.
    Gutierrez J, Alloubani A, Mari M, Alzaatreh M. Cardiovascular disease risk factors: Hypertension, diabetes mellitus and obesity among Tabuk Citizens in Saudi Arabia. Open Cardiovasc Med J. 2018;12:41–9.CrossRefGoogle Scholar
  33. 33.
    Devaraj S, Valleggi S, Siegel D, Jialal I. Role of C-reactive protein in contributing to increased cardiovascular risk in metabolic syndrome. Curr Atheroscler Rep. 2010;12:110–8.CrossRefGoogle Scholar
  34. 34.
    Rhainds D, Brodeur MR, Tardif J-C. Lipids, apolipoproteins and inflammatory biomarkers of cardiovascular risk. What have we learned? Clin Pharmacol Ther. 2018;104:244–56.CrossRefGoogle Scholar
  35. 35.
    Wang J, Tan G-J, Han L-N, Bai Y-Y, He M, Liu H-B. Novel biomarkers for cardiovascular risk prediction. J Geriatr Cardiol. 2017;14:135–50.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Abraham J, Campbell CY, Cheema A, Gluckman TJ, Blumenthal RS, Danyi P. C-reactive protein in cardiovascular risk assessment: a review of the evidence. J Cardiometab Syndr. 2007;2:119–23.CrossRefGoogle Scholar
  37. 37.
    Joseph J, Depp C, Martin AS, Daly RE, Glorioso DK, Palmer BW, et al. Associations of high sensitivity C-reactive protein levels in schizophrenia and comparison groups. Schizophr Res. 2015;168:456–60.CrossRefGoogle Scholar
  38. 38.
    Dieset I, Hope S, Ueland T, Bjella T, Agartz I, Melle I, et al. Cardiovascular risk factors during second generation antipsychotic treatment are associated with increased C-reactive protein. Schizophr Res. 2012;140:169–74.CrossRefGoogle Scholar
  39. 39.
    Vuksan-Cusa B, Sagud M, Jakovljevic M, Peles AM, Jaksic N, Mihaljevic S, et al. Association between C-reactive protein and homocysteine with the subcomponents of metabolic syndrome in stable patients with bipolar disorder and schizophrenia. Nord J Psychiatry. 2013;67:320–5.CrossRefGoogle Scholar
  40. 40.
    Fawzi MH, Fawzi MM, Fawzi MM, Said NS. C-reactive protein serum level in drug-free male Egyptian patients with schizophrenia. Psychiatry Res. 2011;190:91–7.CrossRefGoogle Scholar
  41. 41.
    Akanji AO, Ohaeri JU, Al-Shammri S, Fatania HR. Association of blood levels of C-reactive protein with clinical phenotypes in Arab schizophrenic patients. Psychiatry Res. 2009;169:56–61.CrossRefGoogle Scholar
  42. 42.
    Sheehan D. The Mini international neuropsychiatric interview (MINI): the development and validation of a structured diagnostic psychiatric interview. J Clin Psychiatry. 1998;59:22.PubMedGoogle Scholar
  43. 43.
    Hicks M, Gebicki J. A spectrophotometric method for the determination of lipid hydroperoxides. Anal Biochem. 1979;99:249–53.CrossRefGoogle Scholar
  44. 44.
    Field PA, Vasan RS. LDL-cholesterol is not the only clinically relevant biomarker for coronary artery disease or acute coronary syndrome. Clin Pharmacol Ther. 2018;104:232–4.CrossRefGoogle Scholar
  45. 45.
    Al-Hakeim HK, Al-Rammahi DA, Al-Dujaili AH. IL-6, IL-18, sIL-2R, and TNFα proinflammatory markers in depression and schizophrenia patients who are free of overt inflammation. J Affect Disord. 2015;182:106–14.CrossRefGoogle Scholar
  46. 46.
    Moore JX, Chaudhary N, Akinyemiju T. Metabolic syndrome prevalence by race/ethnicity and sex in the United States, National Health and nutrition examination survey, 1988-2012. Prev Chronic Dis. 2017;14:E24.CrossRefGoogle Scholar
  47. 47.
    Jeong SH, Lee NY, Kim SH, Chung IW, Youn T, Kang UG, et al. Long-term evolution of metabolic status in patients with schizophrenia stably maintained on second-generation antipsychotics. Psychiatry Investig. 2018;15:628–37.CrossRefGoogle Scholar
  48. 48.
    Kucerova J, Babinska Z, Horska K, Kotolova H. The common pathophysiology underlying the metabolic syndrome, schizophrenia and depression. A review. Biomed Pap Med Fac Univ Palacký, Olomouc, Czechoslov. 2015;159:208–14.CrossRefGoogle Scholar
  49. 49.
    Correll CU, Robinson DG, Schooler NR, Brunette MF, Mueser KT, Rosenheck RA, et al. Cardiometabolic risk in patients with first-episode schizophrenia spectrum disorders: Baseline results from the RAISE-ETP Study. JAMA Psychiatry 2. 2014;71:1350–63.CrossRefGoogle Scholar
  50. 50.
    Ringen PA, Engh JA, Birkenaes AB, Dieset I, Andreassen OA. Increased mortality in schizophrenia due to cardiovascular disease - a non-systematic review of epidemiology, possible causes, and interventions. Front Psych. 2014;5:137.Google Scholar
  51. 51.
    Zhao S, Xia H, Mu J, Wang L, Zhu L, Wang A, et al. 10-year CVD risk in Han Chinese mainland patients with schizophrenia. Psychiatry Res. 2018;264:322–6.CrossRefGoogle Scholar
  52. 52.
    Khan IM, Pokharel Y, Dadu RT, Lewis DE, Hoogeveen RC, Wu H, et al. Postprandial monocyte activation in individuals with metabolic syndrome. J Clin Endocrinol Metab. 2016;101:4195–204.CrossRefGoogle Scholar
  53. 53.
    Devaraj S, Kumaresan PR, Jialal I. C-reactive protein induces release of both endothelial microparticles and circulating endothelial cells in vitro and in vivo: further evidence of endothelial dysfunction. Clin Chem. 2011;57:1757–61.CrossRefGoogle Scholar
  54. 54.
    Scaini G, Quevedo J, Velligan D, Roberts DL, Raventos H, Walss-Bass C. Second generation antipsychotic-induced mitochondrial alterations: implications for increased risk of metaboloic syndrome in patients with schizophrenia. Eur Neuropsychopharmacol. 2018;28:369–80.CrossRefGoogle Scholar
  55. 55.
    Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353:1209–23.CrossRefGoogle Scholar
  56. 56.
    Aas M, Dieset I, Hope S, Hoseth E, Mørch R, Reponen E, et al. Childhood maltreatment severity is associated with elevated C-reactive protein and body mass index in adults with schizophrenia and bipolar diagnoses. Brain Behav Immun. 2017;65:342–9.CrossRefGoogle Scholar

Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2018

Authors and Affiliations

  • Ted Boozalis
    • 1
  • Sridevi Devaraj
    • 2
    • 3
  • Olaoluwa O. Okusaga
    • 1
    • 4
  1. 1.Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Lee and Joe Jamail Specialty Care CenterHoustonUSA
  2. 2.Department of pathology & Immunology Baylor College of MedicineHoustonUSA
  3. 3.Department of Pathology and ImmunologyTexas Children’s HospitalHoustonUSA
  4. 4.Michael E. DeBakey Veterans Affairs Medical CenterHoustonUSA

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