Periodic Reporting for period 1 - Youth-GEMs (Gene Environment interactions in Mental health trajectories of Youth)
Periodo di rendicontazione: 2022-06-01 al 2023-11-30
Youth mental health is heavily burdened, with life-long enduring impact on European citizens and societies. Trajectories of mental health and illness in young people are assumed to be determined by interplay between genetic, epigenetic, and environmental risk impacting during development. However, direct evidence for this is sparse and scientific progress is challenged. We recently initiated substantial advances enabling us to create necessary breakthroughs at the most pressing needs and challenges. Aiming to significantly reduce mental suffering and illness among European youth within the next 5-10 years, we will provide:
1) The world’s first, evidence-based knowledge base of functional (epi)genomics of the developing post-natal human brain in direct relation to developmental trajectories of trans-syndromal phenotypes of mental illness, providing improved risk markers and actionable biological targets,
2) Reliable predictive models, while identifying gene-environment interplay, as well as actionable markers of trajectories of mental (ill)health in young people through the use of Artificial Intelligence (AI)-based and inference-based analyses of unprecedented sets of longitudinal general population datasets,
3) The first comprehensive, validated set of evidence-based behavioural, environmental, biological, and psychological-informed instruments for the robust quantitative clinical assessment of mental health for help-seeking young people aged 12-24 years, harmonised across European clinical settings, and
4) Youth- and clinician-empowering AI-driven instruments for early (self)detection, prediction and monitoring of mental ill-health trajectories in youth.
Our multidisciplinary consortium is uniquely equipped and positioned to enforce the necessary breakthroughs for significant reduction of mental illness and suffering of young people, and to translate our findings into clinical innovation and life-long impact in Europe and beyond.
1) The world’s first, evidence-based knowledge base of functional (epi)genomics of the developing post-natal human brain in direct relation to developmental trajectories of trans-syndromal phenotypes of mental illness, providing improved risk markers and actionable biological targets,
2) Reliable predictive models, while identifying gene-environment interplay, as well as actionable markers of trajectories of mental (ill)health in young people through the use of Artificial Intelligence (AI)-based and inference-based analyses of unprecedented sets of longitudinal general population datasets,
3) The first comprehensive, validated set of evidence-based behavioural, environmental, biological, and psychological-informed instruments for the robust quantitative clinical assessment of mental health for help-seeking young people aged 12-24 years, harmonised across European clinical settings, and
4) Youth- and clinician-empowering AI-driven instruments for early (self)detection, prediction and monitoring of mental ill-health trajectories in youth.
Our multidisciplinary consortium is uniquely equipped and positioned to enforce the necessary breakthroughs for significant reduction of mental illness and suffering of young people, and to translate our findings into clinical innovation and life-long impact in Europe and beyond.
In the initial 18 months of the Youth-GEMs project, considerable progress has been made across various work packages (WPs). The Dissemination and Communication Strategy (WP2) has seen the development of key communication tools, engaging young individuals with lived experiences and the broader international research community. Preparations for a digital storytelling project and ethical considerations have been addressed, leading to the establishment of a draft ethics research agenda.
In WP3, the initial Data Management Plan has been created, outlining solutions for data accessibility and reusability. The first year involved sharing data management best practices across work packages. A task force, including representatives from each WP, is designing a sustainable data model, exploring existing models and seeking recommendations from the US-based National Institute for Mental Health. In Collaboration with WP7, a minimal set of clinical variables for the project has been defined.
In WP4 (Developmental Genomics of the Human Brain), significant advancements have been achieved in generating polygenic gene scores for predicting shared as well as diagnosis-specific disease trajectories and identifying genetic variants that moderate the molecular response to stress. Analysis of DNA methylation profiles across developmental stages has linked dynamic changes to psychiatric and neurodevelopmental disorders. Tools for functional analyses, such as cell lines and electrophysiological recording methods, are also in preparation.
WP5 (Data Inference) focuses on understanding mental health development in youth using data from the existing youth cohorts. Clustering and time series analysis techniques reveal patterns in mental health data, aiding in predicting well-being at age 17 in the UK Millennium Cohort Study Group-based trajectory modelling categorizes participants based on longitudinal symptoms, exploring environmental factors and polygenic risk components for specific disorders. In the ABCD study, we found a significant interplay between genetic and environmental risks for schizophrenia in early adolescence, impacting distressing psychotic experiences.
WP6 involves the development of an AI-powered app to predict mental health trajectories in young populations. Co-creation workshops have been organized with stakeholders to improve the app's design, and emphasizing accessibility, privacy protection, and data transparency. Model development is underway using datasets from the UK Millennium and ABCD studies.
WP7 has devised a comprehensive transdiagnostic clinical assessment protocol for youth. which has undergone translation, pilot testing, and refinement based on young people's feedback. A transdiagnostic review aims to deliver measure recommendations, with preliminary results emphasizing the need for improved assessment methods. Study initiation and registration procedures for the clinical study are currently underway.
In WP3, the initial Data Management Plan has been created, outlining solutions for data accessibility and reusability. The first year involved sharing data management best practices across work packages. A task force, including representatives from each WP, is designing a sustainable data model, exploring existing models and seeking recommendations from the US-based National Institute for Mental Health. In Collaboration with WP7, a minimal set of clinical variables for the project has been defined.
In WP4 (Developmental Genomics of the Human Brain), significant advancements have been achieved in generating polygenic gene scores for predicting shared as well as diagnosis-specific disease trajectories and identifying genetic variants that moderate the molecular response to stress. Analysis of DNA methylation profiles across developmental stages has linked dynamic changes to psychiatric and neurodevelopmental disorders. Tools for functional analyses, such as cell lines and electrophysiological recording methods, are also in preparation.
WP5 (Data Inference) focuses on understanding mental health development in youth using data from the existing youth cohorts. Clustering and time series analysis techniques reveal patterns in mental health data, aiding in predicting well-being at age 17 in the UK Millennium Cohort Study Group-based trajectory modelling categorizes participants based on longitudinal symptoms, exploring environmental factors and polygenic risk components for specific disorders. In the ABCD study, we found a significant interplay between genetic and environmental risks for schizophrenia in early adolescence, impacting distressing psychotic experiences.
WP6 involves the development of an AI-powered app to predict mental health trajectories in young populations. Co-creation workshops have been organized with stakeholders to improve the app's design, and emphasizing accessibility, privacy protection, and data transparency. Model development is underway using datasets from the UK Millennium and ABCD studies.
WP7 has devised a comprehensive transdiagnostic clinical assessment protocol for youth. which has undergone translation, pilot testing, and refinement based on young people's feedback. A transdiagnostic review aims to deliver measure recommendations, with preliminary results emphasizing the need for improved assessment methods. Study initiation and registration procedures for the clinical study are currently underway.
Although scientific knowledge indicates that the entire period of 12-24 years of age is an important continuous period of transition, mental health services across most European and non-European countries is dichotomously organized using 18 years of age as the cut-off. This creates artificial boundaries and transition gaps for health care and research. Mental health problems are first experienced during youth and usually persist into adulthood, leading to massive economic burden.
To address the European youth mental crisis, Youth-GEMs has concluded that:
• There is urgency and momentum to better understand mental health trajectories, detect early markers of trajectories towards mental ill-health, and intervene early in youth at-risk for transitioning into mental illness;
• Progress at the scientific frontiers on youth mental health is influenced by important needs and halted by several important challenges which should be addressed to make impactful progress.
• The project team has identified five central needs of contemporary research, which will be tackled by the project, thereby opening the gateway to innovation, translation, and impact.
o 1: Studying mental illness from a neurodevelopmental perspective.
o 2: Operationalization of a mental health/illness concept that goes beyond symptom-based criteria.
o 3: Understanding genetic architecture in a trans-syndromal, neurodevelopmental, environmentally influenced, and neurobiological meaningful context.
o 4: Embracing the complexity of the exposome.
o 5: Engagement with young people, care givers, clinicians, and policymakers.
Youth-GEMs will generate a body of new knowledge constituting a solid basis for a better and deeper molecular neurobiological understanding of brain development and brain (dys)functioning as well as for understanding genetic architecture in a trans-syndromal, neurodevelopmental, environmentally influenced and neurobiological meaningful context. Engaging young people throughout the process, Youth-GEMs will furthermore develop (self) assessment instruments for help-seeking young people and clinical tools for transdiagnostic assessments.
To address the European youth mental crisis, Youth-GEMs has concluded that:
• There is urgency and momentum to better understand mental health trajectories, detect early markers of trajectories towards mental ill-health, and intervene early in youth at-risk for transitioning into mental illness;
• Progress at the scientific frontiers on youth mental health is influenced by important needs and halted by several important challenges which should be addressed to make impactful progress.
• The project team has identified five central needs of contemporary research, which will be tackled by the project, thereby opening the gateway to innovation, translation, and impact.
o 1: Studying mental illness from a neurodevelopmental perspective.
o 2: Operationalization of a mental health/illness concept that goes beyond symptom-based criteria.
o 3: Understanding genetic architecture in a trans-syndromal, neurodevelopmental, environmentally influenced, and neurobiological meaningful context.
o 4: Embracing the complexity of the exposome.
o 5: Engagement with young people, care givers, clinicians, and policymakers.
Youth-GEMs will generate a body of new knowledge constituting a solid basis for a better and deeper molecular neurobiological understanding of brain development and brain (dys)functioning as well as for understanding genetic architecture in a trans-syndromal, neurodevelopmental, environmentally influenced and neurobiological meaningful context. Engaging young people throughout the process, Youth-GEMs will furthermore develop (self) assessment instruments for help-seeking young people and clinical tools for transdiagnostic assessments.