Inflammatory evidence for the psychosis continuum model

Background: Inflammation and immune activation have been implicated in the pathophysiology of severe mental disorders. Previous studies of inflammatory markers, however, have been limited with somewhat inconsistent results. Aims: We aimed to determine the effect sizes of inflammatory marker alterations across diagnostic groups of the psychosis continuum and investigate association to antipsychotic medications. Methods: Plasma levels of soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), osteoprotegerin (OPG), and von Willebrand factor (vWf) were measured in patients (n = 992) with schizophrenia spectrum (SCZ, n = 584), schizoaffective disorder (SA, n = 93), affective spectrum disorders (AFF, n = 315), and healthy controls (HC, n = 638). Results: Levels of sTNF-R1 (p = 1.8 x 10(-8), d = 0.23) and IL-1Ra (p = 0.002, d = 0.16) were increased in patients compared to HC. The SCZ group had higher levels of sTNF-R1 (p = 8.5 x 10-8, d = 0.27) and IL-1Ra (p = 5.9 x 10(-5), d = 0.25) compared to HC, and for sTNF-R1 this was also seen in the SA group (p = 0.01, d = 0.3) and in the AFF group (p = 0.002, d = 0.12). Further, IL-1Ra (p = 0.004, d = 0.25) and vWf (p = 0.02, d = 0.21) were increased in the SCZ compared to the AFF group. There was no significant association between inflammatory markers and use of antipsychotic medication. Conclusion: We demonstrate a small increase in sTNF-R1 and IL-1Ra in patients with severe mental disorders supporting a role of inflammatory mechanisms in disease pathophysiology. The increase was more pronounced in SCZ compared to AFF supporting a continuum psychosis model related to immune factors. (C) 2016 Elsevier Ltd. All rights reserved.