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

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Abstract

Objective: The metabolic syndrome is highly prevalent in patients with schizophrenia. We previously found that blood C-reactive protein (CRP), interleukin-6 (IL-6), and leptin levels were predictors of current metabolic syndrome in schizophrenia. In the present study, we investigated whether baseline levels of total and differential white blood cell (WBC) counts, inflammatory markers, and adipokines predicted incident metabolic syndrome in schizophrenia. Method: For subjects from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial who did not have metabolic syndrome at baseline (n = 726), WBC counts, inflammatory markers, and adipokines were investigated as predictors of incident metabolic syndrome over 12 months of antipsychotic treatment. Cox proportional hazards regression models, controlling for multiple potential confounding factors, were used to investigate these associations. Results: 39% of subjects (n = 280) had incident metabolic syndrome over 12 months. After controlling for potential confounders, baseline blood IL-6 (HR = 1.12, 95% CI 1.01–1.24, p = 0.031) and leptin (HR = 1.12, 95% CI 1.01–1.24, p = 0.038) were significant predictors of incident metabolic syndrome, and there was a trend-level association with CRP (HR = 1.09, 95% CI 1.00–1.19, p = 0.059). Conclusions: Our findings provide additional evidence that measurement of inflammatory markers and adipokines are germane to the clinical care of patients with schizophrenia. Specifically, these markers may identify—prior to treatment—patients with schizophrenia at heightened risk for incident adverse cardiometabolic effects of antipsychotics. Given the tremendous burden of cardiovascular disease morbidity and mortality in schizophrenia, vigilant screening for and treatment of metabolic risk factors in this patient population are warranted.

Original languageEnglish (US)
Pages (from-to)193-197
Number of pages5
JournalSchizophrenia Research
Volume209
DOIs
StatePublished - Jul 1 2019

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Clinical Trials, Phase I
Adipokines
Leukocyte Count
Antipsychotic Agents
Schizophrenia
Leptin
C-Reactive Protein
Interleukin-6
Proportional Hazards Models
Blood Proteins
Patient Care
Cardiovascular Diseases
Clinical Trials
Morbidity
Mortality
Therapeutics
Population

Keywords

  • C-reactive protein
  • Inflammation
  • Interleukin-6
  • Leptin
  • Metabolic syndrome
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

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title = "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",
abstract = "Objective: The metabolic syndrome is highly prevalent in patients with schizophrenia. We previously found that blood C-reactive protein (CRP), interleukin-6 (IL-6), and leptin levels were predictors of current metabolic syndrome in schizophrenia. In the present study, we investigated whether baseline levels of total and differential white blood cell (WBC) counts, inflammatory markers, and adipokines predicted incident metabolic syndrome in schizophrenia. Method: For subjects from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial who did not have metabolic syndrome at baseline (n = 726), WBC counts, inflammatory markers, and adipokines were investigated as predictors of incident metabolic syndrome over 12 months of antipsychotic treatment. Cox proportional hazards regression models, controlling for multiple potential confounding factors, were used to investigate these associations. Results: 39{\%} of subjects (n = 280) had incident metabolic syndrome over 12 months. After controlling for potential confounders, baseline blood IL-6 (HR = 1.12, 95{\%} CI 1.01–1.24, p = 0.031) and leptin (HR = 1.12, 95{\%} CI 1.01–1.24, p = 0.038) were significant predictors of incident metabolic syndrome, and there was a trend-level association with CRP (HR = 1.09, 95{\%} CI 1.00–1.19, p = 0.059). Conclusions: Our findings provide additional evidence that measurement of inflammatory markers and adipokines are germane to the clinical care of patients with schizophrenia. Specifically, these markers may identify—prior to treatment—patients with schizophrenia at heightened risk for incident adverse cardiometabolic effects of antipsychotics. Given the tremendous burden of cardiovascular disease morbidity and mortality in schizophrenia, vigilant screening for and treatment of metabolic risk factors in this patient population are warranted.",
keywords = "C-reactive protein, Inflammation, Interleukin-6, Leptin, Metabolic syndrome, Schizophrenia",
author = "Kelly, {Conor W.} and McEvoy, {Joseph Patrick} and Miller, {Brian J}",
year = "2019",
month = "7",
day = "1",
doi = "10.1016/j.schres.2019.04.021",
language = "English (US)",
volume = "209",
pages = "193--197",
journal = "Schizophrenia Research",
issn = "0920-9964",
publisher = "Elsevier",

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TY - JOUR

T1 - 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

AU - Kelly, Conor W.

AU - McEvoy, Joseph Patrick

AU - Miller, Brian J

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Objective: The metabolic syndrome is highly prevalent in patients with schizophrenia. We previously found that blood C-reactive protein (CRP), interleukin-6 (IL-6), and leptin levels were predictors of current metabolic syndrome in schizophrenia. In the present study, we investigated whether baseline levels of total and differential white blood cell (WBC) counts, inflammatory markers, and adipokines predicted incident metabolic syndrome in schizophrenia. Method: For subjects from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial who did not have metabolic syndrome at baseline (n = 726), WBC counts, inflammatory markers, and adipokines were investigated as predictors of incident metabolic syndrome over 12 months of antipsychotic treatment. Cox proportional hazards regression models, controlling for multiple potential confounding factors, were used to investigate these associations. Results: 39% of subjects (n = 280) had incident metabolic syndrome over 12 months. After controlling for potential confounders, baseline blood IL-6 (HR = 1.12, 95% CI 1.01–1.24, p = 0.031) and leptin (HR = 1.12, 95% CI 1.01–1.24, p = 0.038) were significant predictors of incident metabolic syndrome, and there was a trend-level association with CRP (HR = 1.09, 95% CI 1.00–1.19, p = 0.059). Conclusions: Our findings provide additional evidence that measurement of inflammatory markers and adipokines are germane to the clinical care of patients with schizophrenia. Specifically, these markers may identify—prior to treatment—patients with schizophrenia at heightened risk for incident adverse cardiometabolic effects of antipsychotics. Given the tremendous burden of cardiovascular disease morbidity and mortality in schizophrenia, vigilant screening for and treatment of metabolic risk factors in this patient population are warranted.

AB - Objective: The metabolic syndrome is highly prevalent in patients with schizophrenia. We previously found that blood C-reactive protein (CRP), interleukin-6 (IL-6), and leptin levels were predictors of current metabolic syndrome in schizophrenia. In the present study, we investigated whether baseline levels of total and differential white blood cell (WBC) counts, inflammatory markers, and adipokines predicted incident metabolic syndrome in schizophrenia. Method: For subjects from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial who did not have metabolic syndrome at baseline (n = 726), WBC counts, inflammatory markers, and adipokines were investigated as predictors of incident metabolic syndrome over 12 months of antipsychotic treatment. Cox proportional hazards regression models, controlling for multiple potential confounding factors, were used to investigate these associations. Results: 39% of subjects (n = 280) had incident metabolic syndrome over 12 months. After controlling for potential confounders, baseline blood IL-6 (HR = 1.12, 95% CI 1.01–1.24, p = 0.031) and leptin (HR = 1.12, 95% CI 1.01–1.24, p = 0.038) were significant predictors of incident metabolic syndrome, and there was a trend-level association with CRP (HR = 1.09, 95% CI 1.00–1.19, p = 0.059). Conclusions: Our findings provide additional evidence that measurement of inflammatory markers and adipokines are germane to the clinical care of patients with schizophrenia. Specifically, these markers may identify—prior to treatment—patients with schizophrenia at heightened risk for incident adverse cardiometabolic effects of antipsychotics. Given the tremendous burden of cardiovascular disease morbidity and mortality in schizophrenia, vigilant screening for and treatment of metabolic risk factors in this patient population are warranted.

KW - C-reactive protein

KW - Inflammation

KW - Interleukin-6

KW - Leptin

KW - Metabolic syndrome

KW - Schizophrenia

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U2 - 10.1016/j.schres.2019.04.021

DO - 10.1016/j.schres.2019.04.021

M3 - Article

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SP - 193

EP - 197

JO - Schizophrenia Research

JF - Schizophrenia Research

SN - 0920-9964

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