Association of baseline inflammatory markers and the development of negative symptoms in individuals at clinical high risk for psychosis

• Type of Material: Article
• Authors: David Goldsmith, Emory University; Ebrahim Haroon, Emory University; Andrew Miller, Emory University; Jean Addington, University of Calgary; Carrie Bearden, University of California Los Angeles; Kristin Cadenhead, University of California San Diego; Tyrone Cannon, Yale University; Barbara Cornblatt, Zucker Hillside Hospital; Daniel Mathalon, University of California San Francisco; Thomas McGlashan, Yale University; Larry Seidman, Harvard Medical School; Ming Tsuang, University of California San Diego; Scott W. Woods, Yale University; Elaine Walker, Emory University; Diana O. Perkins, University of North Carolina
• Language: English
• Date: 2019-02-01
• Publisher: Academic Press Inc, Elsevier Science
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbi.2018.11.315
• Title of Journal or Parent Work: Brain Behavior and Immunity
• Volume: 76
• Start Page: 268
• End Page: 274
• Grant/Funding Information: This study has also been funded by a collaborative U01 award from the National Institute of Mental Health at the National Institutes of Health (MH081902 to TDC and CB; MH081857 to BAC; MH081988 to EW; MH081928 to LS; MH082004 to DP; MH081944 to KC; MH081984 to JA; MH082022 to SWW; and MH076989 TO DM).; Dr. Goldsmith has received research support from an NIMH K23 MH114037 as well as from the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers UL1TR002378 and KL2TR002381.
• Keywords: Psychosis; Neurosciences & Neurology; Life Sciences & Biomedicine; ULTRA-HIGH RISK; CYTOKINE ALTERATIONS; Clinical high risk; Science & Technology; Inflammation; STATE; 1ST-EPISODE; DEPRESSION; SCHIZOPHRENIA; Neurosciences; 1ST EPISODE PSYCHOSIS; INTERRATER RELIABILITY; Negative symptoms; Cytokines; PRODROMAL SYNDROMES; Psychiatry; Immunology; SERUM-LEVELS; Schizophrenia
• Research Categories: Biology, Neuroscience

Abstract

Negative symptoms are common in individuals at clinical high-risk (CHR) for psychosis and are associated with worse functional outcomes. Inflammation may be one mechanism underlying negative symptoms. Inflammatory markers are altered in individuals at CHR and are associated with negative symptoms in patients with schizophrenia. We thus hypothesized that baseline inflammatory markers would predict the development of negative symptoms in individuals at CHR for psychosis. Thirty seven individuals from the North American Prodromal Longitudinal Study who met CHR criteria were included in the study. Inflammatory cytokines, including interferon (IFN)-λ, Interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF) were measured at baseline. Negative symptoms as measured by the Scale of Prodromal Symptoms, were measured at baseline and six and twelve months. Associations between inflammatory markers and the trajectory of negative symptoms (slope) over the first year of follow-up, were assessed using linear regression models controlling for age, sex, race and depressive symptom severity (as assessed by the Calgary Depression Scale for Schizophrenia). Baseline TNF (beta = 0.361, p = 0.007) and IL-6 (beta = −0.306, p = 0.026) predicted negative symptoms slopes, along with depressive symptom severity at baseline (beta = −0.596, p = 0.000). These findings demonstrate that inflammatory cytokines may underlie the development of negative symptoms in some individuals at CHR for psychosis. TNF predicted the development of negative symptoms independent of baseline depression. Given the heterogeneity of the CHR population, the comorbidity of negative symptoms and depression in this population, and the particular challenges in treating negative symptoms, immune markers could represent potential biomarkers that underlie the development of negative symptoms, representing a potential treatment target.