Multi-analyte profile analysis of plasma immune proteins: altered expression of peripheral immune factors is associated with neuropsychiatric symptom severity in adults with and without chronic hepatitis C virus infection.

Hannah Olavarria,Marilyn Huckans,Bret E Fuller,Michael Chang,Arthur A Vandenbark,Michael Kolessar,Anna W Sasaki,Daniel Kriz,Jeanne R Anderson,Kenneth D Flora,Jennifer M Loftis

doi:10.1002/brb3.200

Abstract

BackgroundThe purpose of this study was to characterize hepatitis C virus (HCV)-associated differences in the expression of 47 inflammatory factors and to evaluate the potential role of peripheral immune activation in HCV-associated neuropsychiatric symptoms—depression, anxiety, fatigue, and pain. An additional objective was to evaluate the role of immune factor dysregulation in the expression of specific neuropsychiatric symptoms to identify biomarkers that may be relevant to the treatment of these neuropsychiatric symptoms in adults with or without HCV.MethodsBlood samples and neuropsychiatric symptom severity scales were collected from HCV-infected adults (HCV+, n = 39) and demographically similar noninfected controls (HCV−, n = 40). Multi-analyte profile analysis was used to evaluate plasma biomarkers.ResultsCompared with HCV− controls, HCV+ adults reported significantly (P < 0.050) greater depression, anxiety, fatigue, and pain, and they were more likely to present with an increased inflammatory profile as indicated by significantly higher plasma levels of 40% (19/47) of the factors assessed (21%, after correcting for multiple comparisons). Within the HCV+ group, but not within the HCV− group, an increased inflammatory profile (indicated by the number of immune factors > the LDC) significantly correlated with depression, anxiety, and pain. Within the total sample, neuropsychiatric symptom severity was significantly predicted by protein signatures consisting of 4–10 plasma immune factors; protein signatures significantly accounted for 19–40% of the variance in depression, anxiety, fatigue, and pain.ConclusionsOverall, the results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity. These findings offer new biomarkers to potentially facilitate pharmacotherapeutic development and to increase our understanding of the molecular pathways associated with neuropsychiatric symptoms in adults with or without HCV.

Highlights

2–3% of adults worldwide are chronically infected with the hepatitis C virus (HCV; Lavanchy 2009)
Within the HCV+ group, but not within the HCVÀ group, number of inflammatory factors with levels ≥ the least detectable concentration (LDC) significantly correlated with several neuropsychiatric symptoms, showing that an HCV-associated increased inflammatory profile is associated with increased neuropsychiatric symptom severity, aspects of depression, anxiety, and pain
Our results indicate that it may be of interest to evaluate whether, in the context of chronic HCV, TNF-a and TNFR2 signaling could contribute toward the sensitization of neurons in a manner that enhances other neuropsychiatric symptoms

Summary

Introduction

2–3% of adults worldwide are chronically infected with the hepatitis C virus (HCV; Lavanchy 2009). Another study (n = 176) found that 10% of those about to initiate antiviral therapy for HCV met criteria for a lifetime history of an anxiety disorder (Martin-Santos et al 2008) These findings suggest that HCV is associated with a constellation or syndrome of neuropsychiatric impairments which may, stem from a common etiology (e.g., chronic immune activation on brain function). Conclusions: Overall, the results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity

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