The Exposome Paradigm to Understand the Environmental Origins of Mental Disorders

Abstract

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

Keywords: Exposome; environment; epidemiology; gene-environment interaction; risk; schizophrenia.

Figure 1

The correlation globes of childhood trauma (A) and cannabis use (B) in the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2)., Only statistically significant correlations are shown (P < .05). The line thickness marks the magnitude of the correlation. The green lines indicate positive correlations. The red lines indicate negative correlations.