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2000
Volume 22, Issue 1
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190

Abstract

Total white blood cell count (TWBCc), an index of chronic and low-grade inflammation, is associated with clinical symptoms and metabolic alterations in patients with schizophrenia. The effect of antipsychotics on TWBCc, predictive values of TWBCc for drug response, and role of metabolic alterations require further study.

Patients with schizophrenia were randomized to monotherapy with risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, perphenazine or haloperidol in a 6-week pharmacological trial. We repeatedly measured clinical symptoms, TWBCc, and metabolic measures (body mass index, blood pressure, waist circumference, fasting blood lipids and glucose). We used mixed-effect linear regression models to test whether TWBCc can predict drug response. Mediation analysis to investigate metabolic alteration effects on drug response.

At baseline, TWBCc was higher among patients previously medicated. After treatment with risperidone, olanzapine, quetiapine, perphenazine, and haloperidol, TWBCc decreased significantly ( < 0.05). Lower baseline TWBCc predicted greater reductions in Positive and Negative Syndrome Scale (PANSS) total and negative scores over time ( < 0.05). We found significant mediation of TWBCc for effects of waist circumference, fasting low-density lipoprotein cholesterol, and glucose on reductions in PANSS total scores and PANSS negative subscale scores ( < 0.05).

TWBCc is affected by certain antipsychotics among patients with schizophrenia, with decreases observed following short-term, but increases following long-term treatment. TWBCc is predictive of drug response, with lower TWBCc predicting better responses to antipsychotics. It also mediates the effects of certain metabolic measures on improvement of negative symptoms. This indicates that the metabolic state may affect clinical manifestations through inflammation.

Chinese Clinical Trials number: ChiCTR-TRC-10000934 (http://www.chictr.org.cn/showproj.aspx?proj=8604).

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References

  1. McGrathJ. SahaS. ChantD. WelhamJ. Schizophrenia: a concise overview of incidence, prevalence, and mortality.Epidemiol. Rev.2008301677610.1093/epirev/mxn00118480098
    [Google Scholar]
  2. MullerN. Inflammation in schizophrenia: pathogenetic aspects and therapeutic considerations.Schizophr. Bull.201844597398210.1093/schbul/sby024
    [Google Scholar]
  3. KrokenR.A. SommerI.E. SteenV.M. DiesetI. JohnsenE. Constructing the immune signature of schizophrenia for clinical use and research; An integrative review translating descriptives into diagnostics.Front. Psychiatry2019975310.3389/fpsyt.2018.0075330766494
    [Google Scholar]
  4. JacksonA.J. MillerB.J. Meta-analysis of total and differential white blood cell counts in schizophrenia.Acta Psychiatr. Scand.20201421182610.1111/acps.13140
    [Google Scholar]
  5. MoodyG. MillerB.J. Total and differential white blood cell counts and hemodynamic parameters in first-episode psychosis.Psychiatry Res.201826030731210.1016/j.psychres.2017.11.08629223800
    [Google Scholar]
  6. FanX. LiuE.Y. FreudenreichO. Higher white blood cell counts are associated with an increased risk for metabolic syndrome and more severe psychopathology in non-diabetic patients with schizophrenia.Schizophr. Res.20101181-321121710.1016/j.schres.2010.02.1028
    [Google Scholar]
  7. LiemburgE.J. NolteI.M. KleinH.C. KnegteringH. Relation of inflammatory markers with symptoms of psychotic disorders: a large cohort study.Prog. Neuropsychopharmacol. Biol. Psychiatry201886899410.1016/j.pnpbp.2018.04.00629778547
    [Google Scholar]
  8. MylesN. MylesH. XiaS. A meta-analysis of controlled studies comparing the association between clozapine and other antipsychotic medications and the development of neutropenia.Aust. N. Z. J. Psychiatry201953540341210.1177/0004867419833166
    [Google Scholar]
  9. MauriM.C. VolonteriL.S. Dell’OssoB. Predictors of clinical outcome in schizophrenic patients responding to clozapine.J. Clin. Psychopharmacol.2003236660664
    [Google Scholar]
  10. OdaE. KawaiR. The prevalence of metabolic syndrome and diabetes increases through the quartiles of white blood cell count in japanese men and women.Intern. Med.200948131127113410.2169/internalmedicine.48.2138
    [Google Scholar]
  11. NilssonG. HedbergP. JonasonT. White blood cell counts associate more strongly to the metabolic syndrome in 75-year-old women than in men: A population based study.Metab. Syndr. Relat. Disord.200754359364
    [Google Scholar]
  12. PrestwoodT.R. AsgariroozbehaniR. WuS. AgarwalS.M. LoganR.W. BallonJ.S. HahnM.K. FreybergZ. Roles of inflammation in intrinsic pathophysiology and antipsychotic drug-induced metabolic disturbances of schizophrenia.Behav. Brain Res.202140211310110.1016/j.bbr.2020.11310133453341
    [Google Scholar]
  13. AndersenC.J. MurphyK.E. FernandezM.L. Impact of obesity and metabolic syndrome on immunity.Adv. Nutr.201671667510.3945/an.115.010207
    [Google Scholar]
  14. Pavlović M.; Babić D.; Rastović P.; Babić R.; Vasilj, M. Metabolic syndrome, total and differential white blood cell counts in patients with schizophrenia.Psychiatr. Danub.201628Suppl. 221622228035126
    [Google Scholar]
  15. KellyC.W. McEvoyJ.P. MillerB.J. Total and differential white blood cell counts, inflammatory markers, adipokines, and incident metabolic syndrome in phase 1 of the clinical antipsychotic trials of intervention effectiveness study.Schizophr. Res.201920919319710.1016/j.schres.2019.04.02131118157
    [Google Scholar]
  16. HonigG.J. Schizophrenia and antipsychotics: Metabolic alterations and therapeutic effectivity.Vertex201829138139147
    [Google Scholar]
  17. PillingerT. McCutcheonR.A. VanoL. MizunoY. ArumuhamA. HindleyG. BeckK. NatesanS. EfthimiouO. CiprianiA. HowesO.D. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: A systematic review and network meta-analysis.Lancet Psychiatry202071647710.1016/S2215‑0366(19)30416‑X31860457
    [Google Scholar]
  18. DetryM.A. MaY. Analyzing repeated measurements using mixed models.JAMA2016315440740810.1001/jama.2015.19394
    [Google Scholar]
  19. FennigS. CraigT. LavelleJ. KovasznayB. BrometE.J. Best-estimate versus structured interview-based diagnosis in first-admission psychosis.Compr. Psychiatry199435534134810.1016/0010‑440X(94)90273‑9
    [Google Scholar]
  20. WangQ. ManW.H. YueW. Effect of damaging rare mutations in synapse-related gene sets on response to short-term antipsychotic medication in chinese patients with schizophrenia: A randomized clinical trial.Jama Psychiatry201875121261126910.1001/jamapsychiatry.2018.3039
    [Google Scholar]
  21. KayS.R. FiszbeinA. OplerL.A. The positive and negative syndrome scale (panss) for schizophrenia.Schizophr. Bull.1987132261276
    [Google Scholar]
  22. NittaM. KishimotoT. MullerN. Adjunctive use of nonsteroidal anti-inflammatory drugs for schizophrenia: A meta-analytic investigation of randomized controlled trials.Schizophr. Bull.20133961230124110.1093/schbul/sbt070
    [Google Scholar]
  23. ChoM. LeeT.Y. KwakY.B. YoonY.B. KimM. KwonJ.S. Adjunctive use of anti-inflammatory drugs for schizophrenia: A meta-analytic investigation of randomized controlled trials.Aust. N. Z. J. Psychiatry201953874275910.1177/000486741983502830864461
    [Google Scholar]
  24. ZhengL.T. HwangJ. OckJ. The antipsychotic spiperone attenuates inflammatory response in cultured microglia via the reduction of proinflammatory cytokine expression and nitric oxide production.J. Neurochem.2008107512251235
    [Google Scholar]
  25. KatoT. MonjiA. HashiokaS. KanbaS. Risperidone significantly inhibits interferon-gamma-induced microglial activation in vitro.Schizophr. Res.2007921-3108115
    [Google Scholar]
  26. ChenM.L. TsaiT.C. WangL.K. Clozapine inhibits th1 cell differentiation and causes the suppression of ifn-gamma production in peripheral blood mononuclear cells.Immunopharmacol. Immunotoxicol.2012344686694
    [Google Scholar]
  27. StapelB. SieveI. FalkC.S. BleichS. Hilfiker-KleinerD. KahlK.G. Second generation atypical antipsychotics olanzapine and aripiprazole reduce expression and secretion of inflammatory cytokines in human immune cells.J. Psychiatr. Res.20181059510210.1016/j.jpsychires.2018.08.01730216787
    [Google Scholar]
  28. UranovaN.A. BonartsevP.D. AndrosovaL.V. RakhmanovaV.I. KaledaV.G. Impaired monocyte activation in schizophrenia: ultrastructural abnormalities and increased IL-1beta production.Eur. Arch. Psychiatry Clin. Neurosci.2017267541742610.1007/s00406‑017‑0782‑1
    [Google Scholar]
  29. CapannoloM. FascianiI. RomeoS. The atypical antipsychotic clozapine selectively inhibits interleukin 8 (IL-8)-induced neutrophil chemotaxis.Eur. Neuropsychopharmacol.2015253413424
    [Google Scholar]
  30. ComerA.L. CarrierM. TremblayM.È. Cruz-MartínA. The inflamed brain in schizophrenia: the convergence of genetic and environmental risk factors that lead to uncontrolled neuroinflammation.Front. Cell. Neurosci.20201427410.3389/fncel.2020.0027433061891
    [Google Scholar]
  31. WicinskiM. WeclewiczM.M. Clozapine-induced agranulocytosis/granulocytopenia: mechanisms and monitoring.Curr. Opin. Hematol.20182512228
    [Google Scholar]
  32. MomtazmaneshS. Zare-ShahabadiA. RezaeiN. Cytokine alterations in Schizophrenia: An updated review.Front. Psychiatry20191089210.3389/fpsyt.2019.0089231908647
    [Google Scholar]
  33. ZhangY. RenH. WangQ. DengW. YueW. YanH. TanL. ChenQ. YangG. LuT. WangL. ZhangF. YangJ. LiK. LvL. TanQ. ZhangH. MaX. YangF. LiL. WangC. ZhangD. ZhaoL. WangH. LiX. GuoW. HuX. TianY. MaX. LiT. Testing the role of genetic variation of the mc4r gene in chinese population in antipsychotic-induced metabolic disturbance.Sci. China Life Sci.201962453554310.1007/s11427‑018‑9489‑x30929193
    [Google Scholar]
  34. MondelliV. CiufoliniS. BelvederiM.M. Cortisol and inflammatory biomarkers predict poor treatment response in first episode psychosis.Schizophr. Bull.20154151162117010.1093/schbul/sbv028
    [Google Scholar]
  35. ChenY.Q. LiX.R. ZhangL. ZhuW.B. WuY.Q. GuanX.N. XiuM.H. ZhangX.Y. Therapeutic response is associated with antipsychotic-induced weight gain in drug-naive first-episode patients with schizophrenia: an 8-week prospective study.J. Clin. Psychiatry202182320m1346910.4088/JCP.20m1346934004092
    [Google Scholar]
  36. KimD.D. BarrA.M. FredriksonD.H. HonerW.G. ProcyshynR.M. Association between serum lipids and antipsychotic response in schizophrenia.Curr. Neuropharmacol.201917985286010.2174/1570159X17666190228113348
    [Google Scholar]
  37. ZhangY. WangQ. ReynoldsG.P. YueW. DengW. YanH. TanL. WangC. YangG. LuT. WangL. ZhangF. YangJ. LiK. LvL. TanQ. LiY. YuH. ZhangH. MaX. YangF. LiL. ChenQ. WeiW. ZhaoL. WangH. LiX. GuoW. HuX. TianY. RenH. MaX. CoidJ. ZhangD. LiT. Metabolic effects of 7 antipsychotics on patients with schizophrenia: A short-term, randomized, open-label, multicenter, pharmacologic trial.J. Clin. Psychiatry202081319m1278510.4088/JCP.19m1278532237292
    [Google Scholar]
  38. DunleavyC. ElsworthyR.J. UpthegroveR. WoodS.J. AldredS. Inflammation in first-episode psychosis: the contribution of inflammatory biomarkers to the emergence of negative symptoms, a systematic review and meta-analysis.Acta Psychiatr. Scand.2022146162010.1111/acps.1341635202480
    [Google Scholar]
  39. JeppesenR. ChristensenR.H.B. PedersenE.M.J. NordentoftM. HjorthøjC. Köhler-ForsbergO. BenrosM.E. Efficacy and safety of anti-inflammatory agents in treatment of psychotic disorders - A comprehensive systematic review and meta-analysis.Brain Behav. Immun.20209036438010.1016/j.bbi.2020.08.02832890697
    [Google Scholar]
  40. ZunszainP.A. AnackerC. CattaneoA. Interleukin-1beta: A new regulator of the kynurenine pathway affecting human hippocampal neurogenesis.Neuropsychopharmacol.2012374939949
    [Google Scholar]
  41. CakiciN. van BeverenN. Judge-HundalG. KoolaM.M. SommerI. An update on the efficacy of anti-inflammatory agents for patients with schizophrenia: A meta-analysis.Psychol. Med.2019491423072319
    [Google Scholar]
  42. PollakT.A. DrndarskiS. StoneJ.M. The blood-brain barrier in psychosis.Lancet Psychiatry201851799210.1016/S2215‑0366(17)30293‑6
    [Google Scholar]
  43. CarvalheiraJ.B. QiuY. ChawlaA. Blood spotlight on leukocytes and obesity.Blood2013122193263326710.1182/blood‑2013‑04‑459446
    [Google Scholar]
  44. TalukdarS. OhD.Y. BandyopadhyayG. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase.Nat. Med.20121891407141210.1038/nm.2885
    [Google Scholar]
  45. CipollettaD. FeuererM. LiA. Ppar-gamma is a major driver of the accumulation and phenotype of adipose tissue treg cells.Nature20124867404549553
    [Google Scholar]
  46. WeinstockA. MouraS.H. MooreK.J. SchmidtA.M. FisherE.A. Leukocyte heterogeneity in adipose tissue, including in obesity.Circ. Res.2020126111590161210.1161/CIRCRESAHA.120.316203
    [Google Scholar]
  47. HealdA. MontejoA.L. MillarH. De HertM. McCraeJ. CorrellC.U. Management of physical health in patients with schizophrenia: Practical recommendations.Eur. Psychiatry201025S2Suppl. 2S41S4510.1016/S0924‑9338(10)71706‑520620887
    [Google Scholar]
  48. MazzaM.G. CapellazziM. LucchiS. Monocyte count in schizophrenia and related disorders: A systematic review and meta-analysis.Acta Neuropsychiatr.202032522923610.1017/neu.2020.12
    [Google Scholar]
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