Polygenic and environmental contributions to ADHD trajectory and outcome from childhood through adolescence

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Project Summary This project will map the co-development of multiple clinical and neurocognitive functional domains of ADHD from childhood to late adolescence. It proposes a novel mix of geospatial coded and other exposure risks along with multiple polygenic scores to identify etiological mechanisms of course and outcome related to ADHD. The functional and trait domains to be examined include inattention, hyperactivity-impulsivity (the two ADHD domains), irritability, executive functioning, vigilance, and reward delay discounting (an aspect of impulsivity). They will be examined over an age span of 7-19 in the first data set (called the Oregon-ADHD- 1000, of some 1450 youth) and ages 9-17 in the second data set (the longitudinal national Adolescent Brain, Cognition, and Development or ABCD study of some 11,800 children). The behavioral trajectories will be related to both baseline PRS and exposure metrics (including those available via geo-spatial address coding), as well as to time-varying changes and cumulative exposure metrics. Exposures or environmental influences are conceptualized both at a neighborhood level (neighborhood disadvantage, pollution exposure risk) as well as a within-family level (socio-economic indicators, parent or parenting characteristics). The developmental trajectories and their genetic and environmental influences will also be related to critical outcomes of mood and conduct disorder, suicidality, drug and alcohol use, all of which are elevated in relation to ADHD symptoms. The study is significant in its potential to introduce up-to-date combined exposure-PRS models of ADHD development that have not been done in a genotype and environment (GxE or G+E) context before using the methods or follow up density proposed here. It is also significant in its potential to bring clarity to the question of why ADHD so often leads to deleterious outcomes and to potential preventable moderator influences. It is innovative in its combining of PRS scores and geospatial coding measures as well as in the density and length of time development will be able to be examined using these measures. The aims directly target NIMH Strategic Priorities with a design that will include evaluation of generalizability and add knowledge about development, etiology, and mechanism. If successful the project will help to isolate actionable causal and outcome moderators as intervention targets for adolescent risk, including the important priority of suicide risk.