The Netherlands Autism Register: A longitudinal clinical cohort study

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition, characterized by impaired social skills and inflexibility and high rates of co-occurring disorders. There is no “cure” for ASD, but adequate care can improve functioning, enhance quality of life and reduce societal costs [1]. Mechanisms that influence the course of ASD are poorly understood. Longitudinal research is crucial to link these mechanisms to development and intervention outcomes. The Netherlands Autism Register (NAR), founded by applicant SB and the Dutch Autism Society (NVA), is a unique and diverse clinical longitudinal cohort, including >3300 autistic individuals (aged 2 to 84 years) and over 700 controls. Since 2013, the NAR included yearly measurements (see https://www.nederlandsautismeregister.nl/onderzoek/onderzoek/). Covering 15 years (7 retro-, 8 prospectively), we aim to 1) enlarge and enrich the NAR with genetic and environmental data and innovative online assessments to map lifespan trajectories of individuals with and without ASD and assess their ability to predict diagnostic status and quality of life 2) embed digital interventions in the NAR aimed at the core ASD symptoms and the most prevalent and disabling co-occurring mental health conditions to optimize personalized care, and 3) implement the findings and make online screening and digital interventions available. The NAR is well-known for its close collaboration with and dissemination to individuals with ASD. Work package 1. Enlarging and enriching the NAR with genetic and environmental risk factors and online objective assessments Genetic and environmental risk factors ASD is strongly heritable [2] and highly heterogeneous [3]. Linking genetic and environmental risk factors to life-course development and intervention outcomes [4, 5] is essential to unravel underlying mechanisms. Apart from rare genetic variants (e.g., Rett syndrome), ASD has a polygenic basis, involving many genetic loci. Of the 2019 NAR participants (n = 1459), 77% reported to appreciate genetic research. Environmental factors also impact on occurrence, development and wellbeing in ASD [6]. However, findings are inconsistent so far [7]. Examining polygenic and environmental risk factors contributes to understanding predictive factors for ASD and intervention responses. We have accumulated a wealth of person- and context information and will include matched longitudinal control data (Appendix 4). Online tests We enrich the NAR with online behavioral tests on social and non-social capacities. ASD diagnoses strongly rely on subjective methods (interviews and observations [1]), which can be complemented with objective assessments. Online tests will be used for social (perspective taking, reciprocity and emotion understanding) and non-social (sensory processing, central coherence, executive functioning) capacities, using validated tests, partly developed or adapted by applicants. Evolutionary algorithms and machine learning will be applied to investigate output. Tests are online (via Gorilla and Collector, data quality similar to lab data [8]). In-house knowledge and previous results from independent studies make this project highly feasible. Work package 2. Digital interventions in NAR ASD interventions focus on support and prevention of comorbid symptoms [1]. However, the social demands of traditional interventions may pose a barrier for autistic individuals. Internet based interventions provide innovative, suitable solutions [9]. Individuals with ASD appreciate internet-based communication. We will adapt digital interventions (internet- and mobile based), with proven effectiveness for depression and anxiety to autistic individuals, aimed at ASD deficits (social skills) and the most prevalent (50 to 80%) and disabling comorbidities (mood- and sleep problems). We will, in close collaboration with autistic individuals, 1) study effects of digital interventions and 2) use stratified data to determine who benefits most from the interventions. This will lead to more cost-effective mental health care. Work package 3. Dissemination and implementation We disseminate and implement findings in clinical practice, care facilities and policy, to accelerate ASD support. We extend active dissemination with actual implementation activities by 1) professionalizing accessibility of data for the general public and media using visualizations of NAR data compared to existing control data (CBS, GGD), providing perspectives on ASD and general population statistics (Appendix 6); 2) sharing information on polygenic risk by developing a toolkit for application of this type of information, which benefits clinicians and ASD families; 3) sharing digital interventions using health platforms (https://mindway.nl/); 4) pilot implementing interventions in routine practice building on knowledge and products developed within EU H2020 projects for implementing and upscaling of digital interventions.