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

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

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: The 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. Methods: Blood 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. Results: Compared 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. Conclusions: Overall, 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. This study characterized HCV-associated differences in the expression of a large array of immune proteins and evaluated the potential role of peripheral immune activation in neuropsychiatric impairments-depression, anxiety, fatigue, and pain. Compared with noninfected and demographically similar HCV- controls, HCV+ adults presented with increased neuropsychiatric symptoms including aspects of depression, anxiety, fatigue, and pain; neuropsychiatric symptoms were associated with changes in inflammatory factors, independent of HCV status. Overall, these results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity, which may be relevant to the discovery and development of new treatments for neuropsychiatric symptoms in adults with and without HCV.

Original languageEnglish (US)
Pages (from-to)123-142
Number of pages20
JournalBrain and Behavior
Volume4
Issue number2
DOIs
StatePublished - 2014

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Immunologic Factors
Chronic Hepatitis C
Virus Diseases
Hepacivirus
Blood Proteins
Anxiety
Fatigue
Depression
Pain
Biomarkers
Protein Array Analysis
Proteins

Keywords

  • Anxiety
  • Biological markers
  • Chronic infection
  • Cytokines
  • Depression
  • Fatigue
  • Pain

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

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

In: Brain and Behavior, Vol. 4, No. 2, 2014, p. 123-142.

Research output: Contribution to journalArticle

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abstract = "Background: The 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. Methods: Blood 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. Results: Compared 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. Conclusions: Overall, 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. This study characterized HCV-associated differences in the expression of a large array of immune proteins and evaluated the potential role of peripheral immune activation in neuropsychiatric impairments-depression, anxiety, fatigue, and pain. Compared with noninfected and demographically similar HCV- controls, HCV+ adults presented with increased neuropsychiatric symptoms including aspects of depression, anxiety, fatigue, and pain; neuropsychiatric symptoms were associated with changes in inflammatory factors, independent of HCV status. Overall, these results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity, which may be relevant to the discovery and development of new treatments for neuropsychiatric symptoms in adults with and without HCV.",
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AU - Chang, Michael

AU - Flora, Kenneth D.

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