Immune system and glucose metabolism interaction in schizophrenia: a chicken-egg dilemma

Abstract

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.

Keywords: 5HT2C receptor; AITD; ARC; AgRP; Akt1; BMI; Body-Mass-Index; C-reactive protein; C-terminal PDZ domain ligand of neuronal nitric oxide synthase; CAPON; CART; CCK; CD; CRH; CRP; CSF; DCs; FDG-PET; GLP-1; GLUT4; Glucose metabolism; IFN-γ; IGF-1; IL; Immune system; LMNA; Lymphocytes; MCH; MHC; MPS; Major Histocompatibility Complex; Microglia; Mononuclear phagocyte system; NPY; NTS; PBMCs; POMC; PYY; PolyI:C; RGS4; S100B; Schizophrenia; TGF-β; TNF-α; TRH; a calcium-binding member of a family of proteins that are 100% soluble in ammonium sulfate at neutral pH; a serine–threonine protein kinase; a subtype of 5-hydroxytryptamine receptor that binds the neurotransmitter serotonin; agouti-related peptide; autoimmune thyroid disease; cerebrospinal fluid; cholecystokinin; cluster of differentiation; cocaine- and amphetamine-regulated transcript; corticotropin-releasing hormone; dendritic cells; fMRI; fluorodeoxyglucose positron emission tomography; functional magnetic resonance imaging; gene encoding lamin A/C; glucagon-like peptide-1; hypothalamic arcuate nucleus; insulin-like growth factor-1; insulin-sensitive glucose transporter 4; interferon-gamma; interleukin; melanin-concentrating hormone; mononuclear phagocyte system; neuropeptide Y; nucleus tractus solitarii; peptide YY; peripheral blood mononuclear cells; polyriboinosinic–polyribocytidilic acid; pro-opiomelanocortin; regulator of G-protein signaling 4; sIL-2R; sRAGE; soluble IL-2 receptor; soluble receptor for advanced glycation products; thyrotropin releasing hormone; transforming growth factor-beta; tumor necrosis factor-alpha.