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.

Objective 1

Identification of adverse environmental signatures, their interaction with genetics and their relationship with brain and behaviour in citizens and patients.

Project outputs

  • Development of a prediction model for environmental impact on brain and mental health by relating transdiagnostic symptoms of mental illness from federated big cohorts through geoposition with environmental measures of urbanicity, climate/atmosphere and psychosocial stress in response to the pandemic (Figure 5) using innovative techniques, such as remote sensing satellite data, climate modelling, and digital health applications.
  • Identification of structural and functional brain features related to the environmental signatures and behavioural symptom clusters identified.
  • Characterisation of at-risk individuals by analysing gene-environment interactions and other potential risk factors such as age, existing mental illness and social deprivation.

Objective 3

Establishment of quantitative neurobiological biomarkers for prediction and stratification of environmentally-related mental illness.

Project outputs

  • Development of stratification algorithms of individuals based on multimodal brain imaging biomarkers by estimating normative models integrating the identified environmental and molecular risk signatures across the life-span in the population.
  • Development of validated multivariate environmental risk and resilience biomarkers allowing for dissection of the heterogeneous underlying pathophysiological mechanisms within mental disorders.
  • Development of clinically useful predictive biomarkers for the risk, onset, and progression of environmentally-related symptoms of depression, anxiety, stress, and substance abuse in clinical populations using federated machine learning techniques that accommodate longitudinal data.

Objective 5

Establishing a programme of responsible research and innovation.

Project outputs

  • Maintenance of the societal ‘licence to operate’ of the project by engaging in a two-way dialogue about objectives and design of the project with key stakeholders.
  • Stakeholder participation in research design and development of intervention through user focus groups, as well as s consultation on European and national public health priorities.
  • Critical reflection and consultation on ethical and societal consequences of our research programme through advisory boards, including of experts from social science and humanities.

Objective 2

Characterization of molecular, neurobiological, and cognitive mechanisms underlying the brain and behavioural changes related to environmental adversity

Project outputs

  • Characterisation of molecular signatures and biochemical pathways associated with the structural and functional brain networks and behavioural changes associated with environmental adversity and resilience through large scale -omics analyses in deep phenotyping population-based and clinical cohorts (e.g. IMAGEN and STRATIFY). These analyses involve genetics, epigenetic methylation, gene expression and proteomics that are analysed using normative modelling and AI-derived deep learning prediction models.
  • Characterisation of perturbations of signalling pathways affected by the -omics signatures identified in peripheral blood to measure the effect on cell morphology, gene expression and translation, neurotransmitter release and electrophysiology in 3D brain organoids (‘assembloids’) that reflect the neuronal composition of the brain network nodes most affected by the environmental factors identified.
  • Development of a biologically-grounded model of the neurobehavioural response to environmental adversity by integrating environmental signatures and results of the 3D organoid experiments in virtual brain models to simulate the changes in brain network activity and behaviour induced by molecular signatures.

Objective 4

Development of pharmacological, cognitive and educational interventions targeting molecular and neurobiological mechanisms of environmentally-sensitive symptoms of mental illness.

Project outputs

  • Development of a prediction model for environmental impact on brain and mental health by relating transdiagnostic symptoms of mental illness from federated big cohorts through geoposition with environmental measures of urbanicity, climate/atmosphere and psychosocial stress in response to the pandemic (Figure 5) using innovative techniques, such as remote sensing satellite data, climate modelling, and digital health applications.
  • Identification of structural and functional brain features related to the environmental signatures and behavioural symptom clusters identified.
  • Characterisation of at-risk individuals by analysing gene-environment interactions and other potential risk factors such as age, existing mental illness and social deprivation.

environMENTAL Cohorts

IMAGEN

More Information

The European IMAGEN cohort is a large-scale, longitudinal neuroimaging-genetics study that combines brain imaging, genetics, psychiatry to increase the understanding of adolescent brain development and behaviour – namely, sensitivity to rewards, impulsivity, and emotional processing. The cohort consists of 2000 adolescents from Germany, UK, France, and Ireland assessed at age 14, 16, 19 and 23 using clinical, behavioural, neuropsychological and environmental assessments as well as task-based and resting state functional neuroimaging, DTI, structural neuroimaging and genomic analyses, and clinical and behavioural assessments. The full list of assessments is available online.

Reference paper:
Schumann G, Loth E, Banaschewski T, et al. (2010). The IMAGEN study: reinforcement-related behaviour in normal brain function and psychopathology. Molecular Psychiatry, 15. doi.org/10.1038/mp.2010.4

CoMorMent

More Information

CoMorMent (Investigating comorbid mental ill-health and cardiovascular disease) is an EU Horizon 2020 project aiming to predict the risk of cardiovascular disease in people with mental disorders. Its objective is to investigate the relationship between mental disorders and cardiovascular diseases and to find new methods to reduce the risk of developing multiple diseases at the same time.

UK Biobank

More Information

UK Biobank  is a large-scale biomedical database and research resource, containing in-depth genetic and health information from half a million UK participants. The database is regularly augmented with additional data and is globally accessible to approved researchers undertaking vital research into the most common and life-threatening diseases. It is a major contributor to the advancement of modern medicine and treatment and has enabled several scientific discoveries that improve human health.

ZIB

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The Zhangjiang International Brain Bank (ZIB) of Fudan University has six cohorts of schizophrenia, depression, autism, stroke, neurodegenerative disorders and college students. Each cohort collected a full-dimension of environmental, behavioral, genetic, brain imaging and microbiome data. The database serves basic research on brain science, clinical diagnosis and treatment of brain disorders, as well as the development of new brain-like intelligence industries.

STRATIFY/ESTRA

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STRATIFY/ESTRA are ERC- and MRC-funded studies designed to develop a framework for psychiatric nosology based on quantifiable neurobiological phenotypes. The aim of the STRATIFY/ESTRA study is to understand the relationship between Eating Disorders (EDs) and other mental health disorders. EDs include anorexia nervosa, bulimia nervosa, binge eating disorder and OSFED (other specified feeding or eating disorders). Sometimes, by treating people based on a single mental health diagnosis, other harmful symptoms and behaviours can go unnoticed. STRATIFY- ESTRA aims to measure a variety of symptoms, behaviours, and the biological mechanisms behind them to give a more holistic idea of EDs.

COVIDMENT

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COVIDMENT is a NordForsk-funded research collaboration across six nations, with the overarching aim to significantly advance current knowledge on mental morbidity trajectories associated with the coronavirus disease 2019 (COVID-19) in the general population and in specific risk groups.

NAKO

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The German National Cohort (NAKO Gesundheitsstudie/NAKO) has been inviting men and women aged between 20 and 69 to 18 study centres throughout Germany since 2014. The participants are medically examined and questioned about their living conditions. The NAKO’s aim is to investigate the causes of chronic diseases, such as cancer, diabetes, cardiovascular diseases, rheumatism, infectious diseases, and dementia to improve prevention, early diagnoses, and treatment of these very widely spread diseases. The multicenter project is funded by the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF), the participating federal states and the Helmholtz Association.

IMAGEN

The European IMAGEN cohort is a large-scale, longitudinal neuroimaging-genetics study that combines brain imaging, genetics, psychiatry to increase the understanding of adolescent brain development and behaviour – namely, sensitivity to rewards, impulsivity, and emotional processing. The cohort consists of 2000 adolescents from Germany, UK, France, and Ireland assessed at age 14, 16, 19 and 23 using clinical, behavioural, neuropsychological and environmental assessments as well as task-based and resting state functional neuroimaging, DTI, structural neuroimaging and genomic analyses, and clinical and behavioural assessments. The full list of assessments is available online.

Reference paper:
Schumann G, Loth E, Banaschewski T, et al. (2010). The IMAGEN study: reinforcement-related behaviour in normal brain function and psychopathology. Molecular Psychiatry, 15. doi.org/10.1038/mp.2010.4

STRATIFY/ESTRA

STRATIFY/ESTRA are ERC- and MRC-funded studies designed to develop a framework for psychiatric nosology based on quantifiable neurobiological phenotypes. The aim of the STRATIFY/ESTRA study is to understand the relationship between Eating Disorders (EDs) and other mental health disorders. EDs include anorexia nervosa, bulimia nervosa, binge eating disorder and OSFED (other specified feeding or eating disorders). Sometimes, by treating people based on a single mental health diagnosis, other harmful symptoms and behaviours can go unnoticed. STRATIFY- ESTRA aims to measure a variety of symptoms, behaviours, and the biological mechanisms behind them to give a more holistic idea of EDs.

CoMorMent

CoMorMent (Investigating comorbid mental ill-health and cardiovascular disease) is an EU Horizon 2020 project aiming to predict the risk of cardiovascular disease in people with mental disorders. Its objective is to investigate the relationship between mental disorders and cardiovascular diseases and to find new methods to reduce the risk of developing multiple diseases at the same time.

COVIDMENT

COVIDMENT is a NordForsk-funded research collaboration across six nations, with the overarching aim to significantly advance current knowledge on mental morbidity trajectories associated with the coronavirus disease 2019 (COVID-19) in the general population and in specific risk groups.

UK Biobank

UK Biobank  is a large-scale biomedical database and research resource, containing in-depth genetic and health information from half a million UK participants. The database is regularly augmented with additional data and is globally accessible to approved researchers undertaking vital research into the most common and life-threatening diseases. It is a major contributor to the advancement of modern medicine and treatment and has enabled several scientific discoveries that improve human health.

NAKO

The German National Cohort (NAKO Gesundheitsstudie/NAKO) has been inviting men and women aged between 20 and 69 to 18 study centres throughout Germany since 2014. The participants are medically examined and questioned about their living conditions. The NAKO’s aim is to investigate the causes of chronic diseases, such as cancer, diabetes, cardiovascular diseases, rheumatism, infectious diseases, and dementia to improve prevention, early diagnoses, and treatment of these very widely spread diseases. The multicenter project is funded by the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF), the participating federal states and the Helmholtz Association.