title: 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.
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.
authors.affiliation: Research & Development Service, Portland VA Medical Center 3710 SW U.S. Veterans Hospital Rd., Portland, Oregon, 97239, USA ; Mental Health and Clinical Neurosciences Division, Portland VA Medical Center 3710 SW U.S. Veterans Hospital Rd., Portland, Oregon, 97239, USA ; Department of Psychiatry, Oregon Health & Science University 3181 SW Sam Jackson Park Rd., Portland, Oregon, 97239, USA.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Huckans
authors.affiliation: Research & Development Service, Portland VA Medical Center 3710 SW U.S. Veterans Hospital Rd., Portland, Oregon, 97239, USA ; Mental Health and Clinical Neurosciences Division, Portland VA Medical Center 3710 SW U.S. Veterans Hospital Rd., Portland, Oregon, 97239, USA.
authors.forename: Bret E
authors.initials: BE
authors.lastname: Fuller
authors.affiliation: Research & Development Service, Portland VA Medical Center 3710 SW U.S. Veterans Hospital Rd., Portland, Oregon, 97239, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Olavarria
authors.affiliation: Gastroenterology Service, Portland VA Medical Center 3710 SW US Veterans Hospital Rd., Portland, Oregon, 97239, USA ; Department of Internal Medicine, Oregon Health & Science University 3181 SW Sam Jackson Park Rd., Portland, Oregon, 97239, USA.
authors.forename: Anna W
authors.initials: AW
authors.lastname: Sasaki
authors.affiliation: Gastroenterology Service, Portland VA Medical Center 3710 SW US Veterans Hospital Rd., Portland, Oregon, 97239, USA ; Department of Internal Medicine, Oregon Health & Science University 3181 SW Sam Jackson Park Rd., Portland, Oregon, 97239, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Chang
authors.affiliation: Portland Gastroenterology Division, Oregon Clinic 9280 SE Sunnybrook Blvd., Clackamas, Oregon, 97015, USA.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Flora
authors.affiliation: School of Professional Psychology, Pacific University 190 SE 8th Ave., Hillsboro, Oregon, 97123, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kolessar
authors.affiliation: School of Professional Psychology, Pacific University 190 SE 8th Ave., Hillsboro, Oregon, 97123, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kriz
authors.affiliation: School of Professional Psychology, Pacific University 190 SE 8th Ave., Hillsboro, Oregon, 97123, USA.
authors.forename: Jeanne R
authors.initials: JR
authors.lastname: Anderson
authors.affiliation: Research & Development Service, Portland VA Medical Center 3710 SW U.S. Veterans Hospital Rd., Portland, Oregon, 97239, USA ; Department of Neurology, Oregon Health & Science University 3181 SW Sam Jackson Park Rd., Portland, Oregon, 97239, USA ; Department of Molecular Microbiology and Immunology, Oregon Health & Science University 3181 SW Sam Jackson Park Rd., Portland, Oregon, 97239, USA.
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.affiliation: Research & Development Service, Portland VA Medical Center 3710 SW U.S. Veterans Hospital Rd., Portland, Oregon, 97239, USA ; Department of Psychiatry, Oregon Health & Science University 3181 SW Sam Jackson Park Rd., Portland, Oregon, 97239, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Loftis
mesh_terms: D000328:Adult; D001007:Anxiety / Q000097:blood*; D015415:Biomarkers; D016207:Cytokines / Q000032:analysis*; D003863:Depression / Q000097:blood*; D005221:Fatigue / Q000097:blood*; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood*; D006801:Humans; D007162:Immunoproteins / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000097:blood*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007162:Immunoproteins
keywords: Anxiety; biological markers; chronic infection; cytokines; depression; fatigue; pain