Psychiatry Investig.  2019 Aug;16(8):607-614. 10.30773/pi.2019.04.14.

Distinct Inflammation Biomarkers in Healthy Individuals and Patients with Schizophrenia: A Reliability Testing of Multiplex Cytokine Immunoassay by Bland-Altman Analysis

Affiliations
  • 1Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
  • 2Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China. lcsyfw@gmail.com
  • 3Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
  • 4Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.

Abstract


OBJECTIVE
Since the inflammatory process has been implicated in the pathophysiology of psychiatric disorder, an important issue emerging is to assess the test-retest reliability of cytokine measurement in healthy individuals and patients with schizophrenia. The objective of the present study was to investigate the test-retest reliability of bead-based multiplex immunoassay technology (BMIT) for cytokine measurement by using a Bland-Altman plot (BAP).
METHODS
Twenty healthy individuals and twenty patients with schizophrenia were enrolled, and a 17-plex cytokine assay was used to measure inflammatory biomarkers at baseline and two weeks later. The test-retest reliability was examined by BAP, 95% limits of agreement (LOA), intraclass correlation coefficient (ICC), and coefficient of repeatability (CoR).
RESULTS
In the healthy controls, only interleukin (IL)-2, IL-13, IL-10, IL-17, and macrophage inflammatory protein-1β showed excellent ICC. The BAP with 95% LOA determined that 13 cytokines showed acceptable 95% LOA for a 2-week test-retest reliability, and only IL-1β, IL-12 and tumor necrosis factor (TNF)-α had significant test-retest bias. The CoR of cytokines varied significantly, ranging from 1.72 to 218.1. Compared with healthy controls, patients with schizophrenia showed significantly higher levels of IL-5, IL-13, and TNF-α and significantly lower levels of IL-4, IL-12, and interferon-gamma (IFN-γ). Of these six cytokines, IL-12 and TNF-α were considered suboptimal reliability.
CONCLUSION
The findings from ICC and CoR implied that the test-retest reliability of BMIT for cytokine measurement were suboptimal. However, the BAP with 95% LOA confirmed that BMIT can reliably distinguish schizophrenia from healthy individuals in cytokine measurement, while significant within-subject variation and between-group overlapping were evident in cytokine expression.

Keyword

Multiplex immunoassay; Cytokine; Reliability; Inflammation; Schizophrenia

MeSH Terms

Bias (Epidemiology)
Biomarkers*
Cytokines
Humans
Immunoassay*
Inflammation*
Interferon-gamma
Interleukin-10
Interleukin-12
Interleukin-13
Interleukin-17
Interleukin-4
Interleukin-5
Interleukins
Loa
Macrophages
Reproducibility of Results
Schizophrenia*
Tumor Necrosis Factor-alpha
Biomarkers
Cytokines
Interferon-gamma
Interleukin-10
Interleukin-12
Interleukin-13
Interleukin-17
Interleukin-4
Interleukin-5
Interleukins
Tumor Necrosis Factor-alpha
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