A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression

• Type of Material: Article
• Authors: Mark Hyman Rapaport, Emory University; David R. Goldsmith, Emory University; BJ Miller, Augusta University
• Language: English
• Date: 2016-12-01
• Publisher: Springer Nature [academic journals on nature.com]: Hybrid Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Copyright © 2016, Springer Nature
• Final Published Version (URL): http://dx.doi.org/10.1038/mp.2016.3
• Title of Journal or Parent Work: Molecular Psychiatry
• ISSN: 1359-4184
• Volume: 21
• Issue: 12
• Start Page: 1696
• End Page: 1709
• Grant/Funding Information: In the past 12 months, Dr Miller has received grant support from the National Institute of Mental Health (1K23MH098014-01) and the American Psychiatric Association; Research support from the National Institutes of Health Clinical Loan Repayment Program and Georgia Regents University; Honoraria from Psychiatric Times; and Speaker fees for lectures from the University of Nevada, Reno and Emory University.; Dr Goldsmith has also recieved training support from the National Institute of Mental Health (R25MH101079).; In the past 12 months, Dr Goldsmith received grant funding from the Janssen Academic Research Mentoring program.
• Keywords: INTERLEUKIN-1 RECEPTOR ANTAGONIST; PRO-INFLAMMATORY CYTOKINES; CELL-MEDIATED-IMMUNITY; SOLUBLE IL-2 RECEPTOR; Neurosciences; NECROSIS-FACTOR-ALPHA; 1ST EPISODE SCHIZOPHRENIA; Psychiatry; Life Sciences & Biomedicine; DRUG-NAIVE SCHIZOPHRENIA; MAJOR DEPRESSION; Neurosciences & Neurology; REUPTAKE INHIBITOR THERAPY; Science & Technology; Biochemistry & Molecular Biology; INCREASED SERUM INTERLEUKIN-6
• Research Categories: Biology, Molecular; Chemistry, Biochemistry; Health Sciences, Medicine and Surgery

Abstract

Schizophrenia, bipolar disorder and major depressive disorder (MDD) have all been associated with aberrant blood cytokine levels; however, neither the pattern of cytokine alterations nor the impact of clinical status have been compared across disorders. We performed a meta-analysis of blood cytokines in acutely and chronically ill patients with these major psychiatric disorders. Articles were identified by searching the PubMed, PsycInfo and Web of Science, and the reference lists of these studies. Sixty-eight studies met the inclusion criteria (40 schizophrenia, 10 bipolar disorder and 18 MDD) for acutely ill patients. Forty-six studies met the inclusion criteria (18 schizophrenia, 16 bipolar disorder and 12 MDD) for chronically ill patients. Levels of two cytokines (interleukin- 6 (IL-6), tumor necrosis factor-α (TNF-α)), one soluble cytokine receptor (sIL-2R), and one cytokine receptor antagonist (IL-1RA) were significantly increased in acutely ill patients with schizophrenia, bipolar mania and MDD compared with controls (P < 0.01). Following treatment of the acute illness, IL-6 levels significantly decreased in both schizophrenia and MDD (P < 0.01); sIL-2R levels increased in schizophrenia; and IL-1RA levels in bipolar mania decreased. In chronically ill patients, the levels of IL-6 were significantly increased in schizophrenia, euthymic (but not depressed) bipolar disorder and MDD compared with controls (P< 0.01). The levels of IL-1β and sIL-2R were significantly increased in both chronic schizophrenia and euthymic bipolar disorder. Overall, there were similarities in the pattern of cytokine alterations in schizophrenia, bipolar disorder and MDD during acute and chronic phases of illness, raising the possibility of common underlying pathways for immune dysfunction. Effects of treatment on cytokines were more robust for schizophrenia and MDD, but were more frequently studied than for acute mania. These findings have important implications for our understanding of the pathophysiology and treatment of major psychiatric disorders.