The Exposome Paradigm: Applications in Psychopathology and Psychopharmacology

Mental disorders derive from a complex interaction between genetic and environmental risk factors. Despite the rapid expansion of the psychiatric genetics knowledge base, precise genetic prediction in clinical psychiatry and psychopharmacology has not been achieved yet. Meanwhile, interest toward potentially preventable environmental exposures has been growing among both clinicians and researchers. The present chapter will start with introducing the exposome paradigm—i.e., the totality of exposures from conception onward—which has been recently proposed to study the role of environment in the pathoetiology and course of mental disorders. Next, we will present the exposome score for schizophrenia (ES-SCZ), an index of cumulative environmental liability to schizophrenia, and findings on its predictive performance in clinical and nonclinical populations. Indeed, our research has shown that the ES-SCZ can be useful for risk stratification and outcome prediction in schizophrenia spectrum disorders, as well as in the general population. More specifically, ES-SCZ is associated with poorer mental and physical outcomes, global functioning, and cognition in clinical and nonclinical populations. Finally, we will describe the potential utility of the exposome paradigm in understanding psychopathology in the general population, with a specific focus on developmental trajectories in adolescents and youths. We are in the early phases of exposome research in psychiatry. However, if successfully applied, the exposome paradigm is poised to embrace complexity and enable advanced analytical solutions to gain insight into the complex dynamic network of environmental exposures. Increasing data availability will help improve the utilization of the exposome paradigm in staging, clinical characterization, and outcome forecasting, including prediction of response to psychopharmacological treatment.