Inflammation and the Metabolic Syndrome in Psychosis

INFLAMMATION AND THE METABOLIC SYNDROME IN PSYCHOSIS ABSTRACT TEXT The metabolic syndrome (MetS) is a constellation of metabolic risk factors associated with the development of atherosclerotic cardiovascular disease morbidity and mortality. The MetS is highly common in patients with psychosis, and cardiovascular disease is the leading cause of mortality in this patient population. The MetS is also associated with a state of low-grade inflammation. Blood white blood cell (WBC) counts—even within the normal range—serve as a marker of inflammation. Psychosis is associated with increased inflammation, including increased total and differential WBC counts. The adverse metabolic effects of atypical antipsychotics, which increase MetS risk, may potentiate aberrant levels of blood inflammatory markers. Several large population-based samples found that total and differential WBC counts were associated with risk of the MetS and its individual criteria. Compared to the general population, relatively less is known about associations between inflammation and the MetS in psychosis, especially whether baseline levels of inflammatory markers predict incident metabolic adverse effects of antipsychotic treatment. This application addresses these important knowledge gaps. The primary goals are to perform systematic reviews and meta-analyses of the relationship between inflammation and prevalent and incident MetS in patients with psychosis, including unpublished data from the Open Translational Science in Schizophrenia (OPTICS) Project, an open-science initiative between Janssen and the NIMH. This R03 application: 1) Has Aims congruent with NIMH's strategic focus on clinically useful biomarkers that predict change across the trajectory of illness, 2) Is a rigorously designed systematic review and meta-analysis using unpublished data from the OPTICS Project to investigate a novel potential biomarker that may identify—prior to treatment— patients with psychosis at heightened risk for incident adverse cardiometabolic effects of antipsychotics, and represents a “next-step” towards personalized medicine approaches for these patients, and 3) Supports the career transition of an L30 and K23 awardee to an R-series Investigator, consistent with the NIH's Next Generation Researchers Initiative.