Serum and gene expression profile of cytokines in first-episode psychosis

An inflammatory syndrome has been previously reported in chronic schizophrenia. The aims of this study were to investigate: (1) serum levels and leukocyte gene expression of cytokines in patients with first-episode psychosis and controls; and (2) possible causes of abnormal cytokine levels in first-episode psychosis, testing their association with psychosocial stressors, current nicotine and cannabis use, and duration of antipsychotic treatment. We recruited 24 first-episode psychosis patients and 24 healthy controls matched for age, gender, ethnicity and body mass index. Serum interleukin(IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, Tumour Necrosis Factor- α (TNF-α), Interferon- γ (IFN-γ), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and monocyte chemotactic protein-1 (MCP-1) were analysed in all subjects. Leukocyte gene expression analyses were conducted only for those cytokines that were different between-groups in the serum analyses. Patients had significantly higher serum levels of IL-1α (effect size d=0.6, p=0.03), IL-1β (d=0.4, p=0.01), IL-8 (d=0.6, p=0.01) and TNF-α (d=0.7, p=0.05) and a trend for higher IL-6 serum levels (d=0.3, p=0.09) when compared with controls. Leukocyte m-RNA levels of IL-1α (d=0.6, p=0.04), IL-6 (d=0.7, p=0.01) and TNF-α (d=1.6, p<0.001), but not IL-1β and IL-8, were also significantly higher in patients. A history of childhood trauma was associated with higher TNF-α serum levels (p=0.01), while more recent stressful life-events were associated with higher TNF-α mRNA levels in leukocytes (p=0.002). In conclusion, first-episode psychosis is characterised by a pro-inflammatory state supported, at least in part, by activation of leukocytes. Past and recent stressors contribute to this pro-inflammatory state.