Overview of environMENTAL

Mission

Mental illness accounts for almost 30% of disease burden among non-communicable diseases worldwide. In the WHO European Region, mental illness is the leading cause of disability and the third leading cause of overall disease burden with an estimated prevalence of 110 million individuals, equivalent to 12% of the entire population. It is well known that environmental factors can account for more than 50% of the attributable risk for mental disorders. In the last decades, we have witnessed the emergence of environmental challenges affecting Europe and the world. The most relevant include urbanicity, changes in climate and atmosphere and the COVID-19 pandemic.

The impact of these changes on mental health and brain, their molecular and cognitive mechanisms remain unresolved. While rates of depression, anxiety, stress and substance use are known to be sensitive to changes in the environment it is unclear how living conditions defined by environmental factors related to urbanicity, climate/atmosphere and response to the COVID-19 pandemic affect individuals across Europe during the lifespan, and how they interact with their socioeconomic and individual psychosocial environment. It is also unclear how this exposure alters molecular and cognitive pathways that influence mental health. In the absence of this knowledge, it has not been possible to identify accurate risk biomarkers and develop targeted interventions to treat existing symptoms of environmentally-related mental illness, and to prevent the transition from mental health to mental illness.

The environMENTAL project aims to investigate the molecular and cognitive characteristics of mental illness related to global environmental changes, and to develop targeted interventions to cope with these challenges. To achieve this effect the project will enrich European cohorts of over 1.5M individuals through digital health apps. Environmental signatures related to mental illness will be identified by relating mental illness symptoms and brain structure and function through geoposition to comprehensive geospatial environmental information. Further analyses, including comprehensive multimodal -omics data, enable unprecedented precision in the characterisation of molecular signatures. Capitalising on the environmental signatures identified and the molecular and cognitive models established, we will develop targeted pharmacological, and cognitive interventions based on virtual reality programmes.

Objectives

The environMENTAL consortium has committed itself to five central project objectives. These will cover the leverage of federated cohort data of over 1 million European citizens and patients enriched with deep phenotyping data form large scale behavioural neuroimaging cohorts and the identification of brain mechanisms related to environmental adversity underlying symptoms of depression, anxiety, stress, and substance abuse. By linking population and patient data via geo-location to environmental data derived from remote sensing satellite measures, climate models as well as digital health applications, our interdisciplinary team will develop a neurocognitive model of multimodal environmental influences defined by transdiagnostic symptom groups of mental illness and their brain correlates. We will uncover the molecular mechanisms underlying this model using multi-modal omics analyses, 3D-brain organoid aggregates and virtual brain simulations. This work will provide an integrated perspective for each individual that incorporates the genetic and environmental influences on brain systems and psychopathology and behaviour, across the lifespan and spectrum of functioning, which we will apply to develop risk biomarkers and stratification markers for different disease mechanisms. Based on the mechanistic knowledge generated, we will then identify compounds targeting causal mechanisms of disease and develop in close collaborations with stakeholders adapted digital health interventions using virtual reality that target symptom clusters defined by shared brain mechanisms. Together, this project will lead to the development of objective biomarkers and evidence-based interventions that will significantly improve outcomes of environmentally related mental illness.