S33. REDUCTION IN PERIPHERAL C-REACTIVE PROTEIN LEVELS WITH CANAKINUMAB ADMINISTRATION IS RELATED TO REDUCED POSITIVE SYMPTOM SEVERITY IN PATIENTS WITH SCHIZOPHRENIA AND INFLAMMATION

摘要

Schizophrenia is characterized by positive and negative symptoms and cognitive deficits related to functional disability. Approved treatments targeting small molecule neurotransmitter receptors are limited in their effectiveness and often leave residual symptoms and debilitating side effects. Psychotic symptoms, cognitive deficits, and treatment response are variable in schizophrenia, highlighting heterogeneity in the etiology and presentation of the illness. There is a critical need for novel treatments targeting subgroups related to underlying biology that can be identified by biomarkers. A substantial subgroup (40%) of people with schizophrenia can be distinguished by cytokines in both peripheral blood and in brain. The cytokine interleukin 1-beta (IL-1β) mRNA and protein levels are significantly increased in serum, plasma, white blood cells, cerebrospinal fluid and brain in chronically ill patients and in first episode psychosis. Canakinumab is an approved human anti-IL-1β monoclonal antibody that interferes with the bioactivity of IL-1β and interrupts excessive immune response. However, the extent to which IL-1β blockade by canakinumab can reduce peripheral markers of an overactive immune system (e.g., high sensitivity C-reactive protein: hsCRP) and reduce psychotic symptom severity in schizophrenia is unknown.