Immune system and glucose metabolism interaction in schizophrenia: A chicken–egg dilemma

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2014-01, Vol.48, p.287-294
• Main Authors: Steiner, Johann, Bernstein, Hans-Gert, Schiltz, Kolja, Müller, Ulf J., Westphal, Sabine, Drexhage, Hemmo A., Bogerts, Bernhard
• Format: Article
• Language: English
• Subjects: Cytokines - metabolism; Glucose metabolism; Glucose Metabolism Disorders - etiology; Humans; Immune system; Immune System - metabolism; Immune System - physiopathology; Lymphocytes; Microglia; Mononuclear phagocyte system; Schizophrenia; Schizophrenia - complications; Schizophrenia - immunology; Schizophrenia - metabolism
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2012.09.016

Impaired glucose metabolism and the development of metabolic syndrome contribute to a reduction in the average life expectancy of individuals with schizophrenia. It is unclear whether this association simply reflects an unhealthy lifestyle or whether weight gain and impaired glucose tolerance in patients with schizophrenia are directly attributable to the side effects of atypical antipsychotic medications or disease-inherent derangements. In addition, numerous previous studies have highlighted alterations in the immune system of patients with schizophrenia. Increased concentrations of interleukin (IL)-1, IL-6, and transforming growth factor-beta (TGF-β) appear to be state markers, whereas IL-12, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and soluble IL-2 receptor (sIL-2R) appear to be trait markers of schizophrenia. Moreover, the mononuclear phagocyte system (MPS) and microglial activation are involved in the early course of the disease. This review illustrates a “chicken–egg dilemma”, as it is currently unclear whether impaired cerebral glucose utilization leads to secondary disturbances in peripheral glucose metabolism, an increased risk of cardiovascular complications, and accompanying pro-inflammatory changes in patients with schizophrenia or whether immune mechanisms may be involved in the initial pathogenesis of schizophrenia, which leads to disturbances in glucose metabolism such as metabolic syndrome. Alternatively, shared underlying factors may be responsible for the co-occurrence of immune system and glucose metabolism disturbances in schizophrenia. ► Impaired glucose utilization may induce inflammatory changes in schizophrenia. ► Immune alterations may trigger impaired glucose tolerance in schizophrenia. ► Immune / glucose metabolism disturbances may co-occur in schizophrenia.