Inflammatory profile in the general population: transdiagnostic dimensions in the context of the psychosis continuum

Abstract

According to theories of a psychosis continuum, Psychotic-Like Experiences (PLEs) are present in a significant proportion of the general population, increasing in 5 to 16 times the future risk of transiting toward a schizophrenia-spectrum disorder. Growing body of evidence suggests a role of the immune system in psychosis; hitherto, little is known about alterations of inflammatory markers prior to the onset of psychosis. Aim: To investigate innate and adaptive immune-related markers (monocyte type-1: IL-1², TNF-±, IL-6; T helper 1: IFN-³; monocyte type-2: IL-10; T helper 2: IL-4; and T regulatory: IL-10, TGF-²) as predictors of the positive, negative, depressive and total dimensions of PLEs, as well as associations with the degree of suffering caused by such experiences, in non-psychotic population-based participants and unaffected siblings of first-episode psychosis patients, while adjusting for potential confounders (age, gender, BMI, tobacco smoking, psychoactive substances, years of study). Methods: This study is part of the epidemiological investigation named STREAM (Schizophrenia and other psychoses translational research: environment and molecular biology), conducted in the Ribeirão Preto-SP (Brazil) catchment area. The STREAM study is part of the international multicentre consortium EU-GEI (European Network of National Schizophrenia Networks Studying Gene-Environment Interactions). We will include 257 population-based controls and 75 unaffected siblings of patients with psychosis, aged between 16 and 64 years for both sexes. The three dimensions of PLEs will be evaluated by the Community Assessment of Psychic Experiences, and cytokines will be measured using the multiplex technology. The investigation of inflammatory mediators in phases that precede psychosis can potentially assist in the identification of high-risk subjects and in the prediction of transition to psychosis, facilitating target intervention strategies. Research Abroad (BEPE): In a subsample of participants, we plan to investigate the association between the aforementioned inflammatory markers and the network connectivity through resting-state fMRI. Linking blood-based biomarkers with neuroimage will help in the understanding of possible neuroanatomic and functional implications underlying the inflammatory processes as well as the understanding of the location and participation of inflammation in psychosis. (AU)