The Exposome Paradigm to Understand theEnvironmental Origins of Mental Disorders

Abstract

There is an active interest in understanding the relationship between mental disordersand modifiable and potentially preventable exposures. However, the complexity of theenvironment, involving many causal and noncausal pathways, makes research extremelychallenging. To tackle these challenges, we have recently proposed the use of the expo some paradigm. The exposome represents the totality of exposures in a lifetime fromconception onward. The framework offers a solution to handle the complexity of all“non-genetic” factors. The exposome approach has recently been adopted to constructan exposome score for schizophrenia (ES-SCZ). Findings demonstrate that ES-SCZ canbe used for risk stratification, adjusting for cumulative environmental load in statisticaltesting, and collecting risk enriched cohorts. Increasing data availability will help improveES-SCZ that can be used in staging models to enhance clinical characterization and out come forecasting. Although an ES-SCZ already provides several practical benefits forresearch practice, the exposome paradigm offers much more. Agnostic exposure-wideanalyses might be the first step to mapping the exposome of mental disorders. Theseanalyses help distinguish genuine signals from selective reporting and uncover novel riskand resilience factors. The exposome approach will also increase our understanding ofthe differential impact of the environment on mental health across geographical settingsand ethnic communities. We are in the early phases of exposome research in psychiatry;however, if successfully applied, exposome framework is poised to embrace complexityand enable advanced analytical solutions to harness ever-growing data to gain insightinto the complex dynamic network of exposures.