PHENOCADES: Developmental neurodynamics of phenotypic cascades in autism and ADHD

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Neurodevelopmental conditions such as autism and Attention deficit hyperactivity disorder (ADHD) affect up to 10% of children and are associated with other mental health difficulties. Both conditions are associated with reduced educational attainment, occupational success and quality of life, making effective identification and intervention imperative. Although autism and ADHD are not typically recognised until school age or older, underpinning genetic and environment factors are present prenatally and behavioural and brain changes can be detected from early infancy. Thus, the causal mechanisms that underpin behavioural symptoms of autism and ADHD are clearest in early development, before the full symptom profile emerges. Within Phenocades, we will test our new theory that behavioural symptoms result from early-emerging changes in sensory processing and activity regulation that affect a child's behaviour, thus disrupting the experience-dependent specialisation of neural systems underpinning social engagement and executive attention. To do this, we will recruit a new cohort of infants with a family history of autism and/or ADHD who will complete in a multimodal protocol at 10, 14 and 24 months. For the first time, we will measure the dynamics of brain function during exploration and interaction using hyperscanning and wearable neuroimaging; collect home-based data to capture a child's interaction with their natural environment; and use behavioural shiftability experiments to yield causal insights into how early differences in behaviour shape later brain function. To examine longer-term outcomes and examine the genetic architecture of infant neurodevelopmental traits, we will conduct new analysis of existing multimodal longitudinal data from n=600 infants with a family history of autism/ADHD with outcome at 3 to 7 years. Taken together, this work will generate transformative new insights into developmental pathways to neurodevelopmental conditions.