Psychotic Illness as a Disorder of Subtle, Whole-body Maldevelopment: Challenges and Opportunities for Drug Discovery

Abstract

Research seeking to identify the pathobiology of and improved treatments for schizophrenia and related psychotic illness has focussed, and continues to focus, on brain dysfunction and its origins. Yet there is a wide and still increasing array of biological abnormalities in psychotic illness that appear to reflect non-cerebral involvement. This review considers the evidence for a whole-body concept of schizophrenia pathobiology, focussing particularly on anatomy, metabolism, immunity and inflammation, cancer, the gut microbiome and microRNAs. These findings reinforce a pleiotropic effect of genetic risk for schizophrenia across the whole body and indicate both challenges and opportunities for drug discovery.