Periodic Reporting for period 2 - Youth-GEMs (Gene Environment interactions in Mental health trajectories of Youth)
Berichtszeitraum: 2023-12-01 bis 2025-05-31
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 first 36 months, the Youth-GEMs project has made strong progress across key areas. A dissemination strategy was implemented with a focus on youth engagement, international visibility, and cross-consortium collaboration. Ethical approvals were secured in six countries, and research into the ethics of AI in youth mental health was conducted. Training materials and partnerships with external projects supported researcher exchange and early-career development.
Data governance (WP3) advanced through an updated FAIR-compliant Data Management Plan, a harmonized clinical–digital data model, and a federated learning simulation to enable decentralized analysis. Efforts to enhance data discoverability are also underway.
WP4 contributed new insights into genetic and epigenetic mechanisms in youth mental health, developing brain cell-type-specific regulatory maps and polygenic risk scores, with ongoing validation of genetic variants in lab models.
WP5 combined genomic and environmental data to uncover early predictors of mental health difficulties, showing strong links between environmental risk and psychotic experiences, as well as the influence of puberty and inflammation.
AI tools for mental health monitoring (WP6) were co-developed with users, including a mobile app and clinical dashboard now in use. Digital biomarkers were extracted from wearable data, and initial predictive models showed promising performance.
Clinical translation (WP7) was advanced through the deployment of a harmonized protocol at six European sites, the launch of a digital assessment app, and recruitment of over 200 young participants. Data collection is ongoing, with AI tool evaluation planned next.
Data governance (WP3) advanced through an updated FAIR-compliant Data Management Plan, a harmonized clinical–digital data model, and a federated learning simulation to enable decentralized analysis. Efforts to enhance data discoverability are also underway.
WP4 contributed new insights into genetic and epigenetic mechanisms in youth mental health, developing brain cell-type-specific regulatory maps and polygenic risk scores, with ongoing validation of genetic variants in lab models.
WP5 combined genomic and environmental data to uncover early predictors of mental health difficulties, showing strong links between environmental risk and psychotic experiences, as well as the influence of puberty and inflammation.
AI tools for mental health monitoring (WP6) were co-developed with users, including a mobile app and clinical dashboard now in use. Digital biomarkers were extracted from wearable data, and initial predictive models showed promising performance.
Clinical translation (WP7) was advanced through the deployment of a harmonized protocol at six European sites, the launch of a digital assessment app, and recruitment of over 200 young participants. Data collection is ongoing, with AI tool evaluation planned next.
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.