Abstract
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.
Highlights
In the past two decades, several studies have investigated the relevance of cytokine alterations in the multifactorial pathogenesis of schizophrenia (Erbagci et al, 2001; Cazzullo et al, 2001; Zhang et al, 2002; Na and Kim, 2007)
Gene expression analyses conducted only in those cytokines that were different in the serum (IL-1a, IL-1b, IL-6, IL-8 and TNFa) revealed significantly increased mRNA levels of IL-1a (d = 0.6), IL-6 (d = 0.7) and tumor necrosis factor-a (TNF-a) (d = 1.6) in first-episode psychosis patients when compared with controls
When looking at correlations between serum levels and mRNA levels of each of the above cytokines, we found a significant correlation between serum and mRNA levels only for IL-6 (r = 0.553, p = 0.005), and a trend for TNF-a (r = 0.375, p = 0.07); no significant correlation was found between serum and mRNA
Summary
In the past two decades, several studies have investigated the relevance of cytokine alterations in the multifactorial pathogenesis of schizophrenia (Erbagci et al, 2001; Cazzullo et al, 2001; Zhang et al, 2002; Na and Kim, 2007). In order to reduce the role of these possible confounding factors, it is important to study cytokine network alterations in subjects with a first-episode of psychosis. First-episode psychosis subjects have a short exposure to antipsychotic drugs, with fewer metabolic effects and immunological changes associated to these drugs. Only few studies have investigated cytokine levels in subjects with first-episode psychosis, reporting higher serum or plasma levels of IL-1b, IL-6, IL-12, INF-
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