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

Molecular Psychiatry volume 21, pages 1696–1709 (2016)Cite this article

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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.

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Acknowledgements

Author contributions

Drs Goldsmith and Miller designed the study, managed the literature searches and the analyses. Drs Goldsmith, Rapaport and Miller wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Emory University, Atlanta, GA, USA

    D R Goldsmith & M H Rapaport

  2. Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA, USA

    B J Miller

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  1. D R Goldsmith
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Correspondence to D R Goldsmith.

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Competing interests

Dr Goldsmith has nothing to disclose relevant to the present work. In the past 12 months, Dr Goldsmith received grant funding from the Janssen Academic Research Mentoring program. Dr Goldsmith has also recieved training support from the National Institute of Mental Health (R25MH101079). Dr Rapaport has nothing to disclose relevant to the present work. In the past 12 months, Dr Rapaport is a member of the scientific advisory board for Pax (unpaid) and the Depression and Bipolar Alternative Therapies Foundation, and a consultant for the American Psychiatric Association. Dr Miller has nothing to disclose relevant to present work. 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.

Additional information

Previous Presentation: This manuscript has been presented at the American College of Neuropsychopharmacology annual meeting, 7–11 December 2014, Phoenix, Arizona, the biennial International Congress on Schizophrenia Research, 28 March–1 April 2015, Colorado Springs, Colorado, the Society of Biological Psychiatry annual meeting, 14–16 May 2015, Toronto, Canada, and the American Society of Clinical Psychopharmacology annual meeting, 22–25 June 2015, Miami, FL, USA.

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Goldsmith, D., Rapaport, M. & Miller, B. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry 21, 1696–1709 (2016). https://doi.org/10.1038/mp.2016.3

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