Study aims and hypotheses
psychotic disorder, anhedonia, immune dysfunction, inflammation, psychosis, amotivation, psychotic symptoms
INFLAMMATION, SECONDARY, OXIDATIVE STRESS
The primary aim of this trial is to examine potential mechanisms by which IL-6 affects anhedonia, psychotic symptoms and cognition. Our primary hypothesis is that inhibition of IL-6 signalling with a single intravenous infusion of anti-IL6R mAb, tocilizumab, in individuals with psychosis and elevated IL-6 at baseline, will attenuate symptoms of anhedonia and amotivation in patients with psychosis, relative to placebo. This will provide further evidence for a potential causal role of inflammation in psychosis. Our secondary hypothesis is that reduction in peripheral inflammation after tocilizumab infusion in patients with psychosis and evidence of inflammation will be associated with central measures of oxidative stress and relevant resting state brain function.We will also conduct deep immunophenotyping of peripheral blood mononuclear cell subsets (CD4A secondary objective is to carry out an observational study to examine clinical and biomarker differences and similarities between patients with psychotic disorder with and without evidence of inflammation and healthy controls (HCs). We hypothesise that individuals with psychotic disorder and evidence of inflammation, compared with those without evidence of inflammation and HCs, will have increased symptoms of anhedonia and amotivation, poorer cognitive functioning, and cellular and brain-based measures of immune dysfunction.