Periodic Reporting for period 1 - R2D2-MH (Risk and Resilience in Developmental Diversity and Mental Health)
Reporting period: 2022-09-01 to 2024-02-29
Mental health (MH) conditions impact 38.2% of the EU population, costing EU economies €600 billion annually. A significant portion, €180 billion, is allocated to neurodevelopmental disorders (NDDs) due to their high prevalence (10%-15% of the population), early onset and persistence, frequent co-occurrence with MH conditions (e.g. anxiety and mood disorders, substance use disorders), increased risks for suicide, and medical comorbidities like epilepsy. NDDs encompass conditions such as autism, attention deficit/hyperactivity disorder (ADHD), intellectual disabilities (ID), and language/motor impairments. Individuals with NDDs and their families face greater discrimination and stigma, impacting mental well-being, functioning and quality of life. We need better approaches to diagnostics and interventions for NDDs and a better understanding of the factors contributing to MH outcomes. The R2D2-MH Project (https://www.r2d2-mh.eu/) is a 5-year initiative co-funded by the European Commission. Its primary aim is to identify risk and resilience factors associated with NDD and associated outcomes (Figure 1). The consortium comprises 27 partners with diverse expertise worldwide. R2D2-MH has four main objectives: 1. Promote participatory research/medicine and reduce stigma surrounding MH. 2. Establish the largest European multi-scale dataset on early brain and MH diversity in humans. 3. Co-develop a first-generation predictive model for developmental diversities. 4. Identify biological mechanisms of resilience associated with diverse outcomes in developmental diversities.
R2D2-MH's research strategy integrates both risk factors, such as genetic variations and preterm birth, and resilience factors to better understand trajectories of individuals with NDDs and deliver tailored tools. The project comprises seven Work Packages (WP, Figure 2): In WP1, we explore the genetic/environmental influences on risk and resilience in neurodiversity. Leveraging data augmentation and standardization on existing large-scale datasets, we seek to pinpoint genetic/environmental factors that offer protection or resilience against MH challenges. Our investigation extends to understanding how various factors during developmental stages modulate MH outcomes among carriers of genetic variations associated with NDD and/or individuals born preterm. In WP2, we employ brain imaging to uncover neurobiological markers indicative of both risk/resilience in the developing brain. Simultaneously, we embark on establishing brain organoid models to elucidate mechanisms that could be targeted for treatment or intervention. Moving to WP3, we use participatory research with stakeholders to co-produce new measures of MH. Our approach aligns with the bio-psycho-social framework outlined in the WHO’s International Classification of Functioning Disability and Health (ICF). In WP4, we develop the CareConnect platform, innovative digital phenotyping tools, alongside a positive psychology app tailored for parents of children with NDDs. These device aim to enhance family well-being and parenting styles. Additionally, we analyze the influence of genetic variations on responses to interventions for NDDs. In WP5, we aim to develop predictive models for NDDs that encompass both risk and resilience factors, offering a comprehensive understanding of these conditions. In WP6, we strive to engage stakeholders effectively, disseminate findings, foster communication, and facilitate training initiatives to ensure widespread impact and knowledge exchange. Lastly, in WP7 we coordinate the R2D2-MH project.
During the initial 18 months, R2D2-MH teams focused on data acquisition/augmentation and cocreation processes. We established a consolidated data repository and harmonized data from over half a million participants. Key publications include advancements in understanding autism through the lens of neurodiversity, the development of predictive models for autism, and insights into brain patterns and genetic variants associated with NDDs. We discussed the transition from a diagnosis-based research approach to one centered on developmental diversity, aiming to redefine well-being and functioning across developmental trajectories in a more nuanced manner (Hens and Van Goidsenhoven, Front. Psychiatry 2023). Our research yielded two papers focused on utilizing the ICF framework to examine autism from a neurodiversity perspective (Black et al., J Autism Dev Disord 2023) and to consider positive functional outcomes for identifying resilience factors (Black et al., Neurodiversity 2023). Additionally, we conducted investigations into the development of language and motor skills, revealing that early language abilities predicted later fine motor skills, and vice versa (Leyan et al., Autism Research 2023). In a cohort study involving 1.2 million children, we successfully developed prediction models utilizing information from routine developmental assessments to accurately forecast the likelihood of autism (Amit et al., JAMA Netw Open. 2024). Furthermore, our research efforts extended to brain imaging. One study examined the shared and distinct cortical thickness patterns in autism and ADHD (Berg et al., Molecular Autism 2023), while another explored the structural connectivity in autism and its correlation with specific gene expression in the human brain (Leyhausen et al., Biol Psychiatry 2023). We also concluded a large-scale study on the phenotypic impact of genetic variations associated with autism (Rolland et al., Nature Medicine 2023), highlighting the necessity of studying these variants beyond categorical diagnosis. Ongoing studies include research on genetic variations in NDD genes such as NRXN1, the interaction between genetics and preterm birth, and the genetic/environmental factors influencing the age at diagnosis in autism. Furthermore, we are currently codeveloping digital tools such as the CareConnect platform and a positive psychology app to enhance support for individuals and families concerned by NDD.