The neurobehavioral, environmental and genetic factors impacting ADHD.

National Human Genome Research Institute

Investigators

Linked publications, trials & patents

Abstract

This report details progress towards our overarching aim of understanding the interplay between behavioral, social, genetic and brain factors in development. Much of research focuses on how attention deficit hyperactivity disorder (ADHD) may impact on brain development. In 2021-2022, our group has focused on developing a conceptual model to understand how symptoms of ADHD changes over adolescence. This has been complemented by empirical studies looking at how genetic, neural and cognitive features might help predict the likely course of ADHD symptoms throughout late childhood and adolescence. Finally, we have started a project that will integrate our findings on how brain differences are tied to ADHD with data from other, similar childhood cohorts. Recent findings. In our research we have sought to explain why symptoms of ADHD run a variable course through adolescence. While most affected individuals show some improvement, particularly of hyperactivity-impulsivity, symptoms of inattention are more persistent, and some individuals may meet diagnostic criteria for the first time during adolescence. Genetic factors affect adolescent symptom trajectories; those showing persistence likely carry a greater burden of common risk alleles. At a neural level, we have shown in several studies over the years that adolescents whose childhood ADHD symptoms have remitted are indistinguishable from neurotypical individuals. This finding could reflect the correction of early childhood anomalies with a convergence toward typical dimensions. Other studies have noted unique, possibly compensatory patterns of neural activity among adolescents whose ADHD has improved. Integrating an understanding of the neural processes with genomic risk could elucidate the mechanisms underlying the complex course of adolescent ADHD. We have summarized this integrative work and reflected upon the complexity of symptom trajectories in ADHD in the following publications. Shaw P, Sudre G. Adolescent attention-deficit/hyperactivity disorder: understanding teenage symptom trajectories. Biological psychiatry. 2021 15;89(2):152-61. Shaw P. Growing Up With ADHD Symptoms: Smooth Transitions or a Bumpy Course?. American Journal of Psychiatry. 2022 179(2):88-9. We also conducted an empirical study that attempted to predict ADHD symptom course using brain-based, genetic and cognitive features acquired on around 300 children, at an average age of 8 years. We followed these youth for an average of 4.8 years, assessing if the symptoms of ADHD improved, worsened or stayed stable. Compared to a never-affected comparison group, we find that participants with worsening symptoms carried the highest common variant (polygenic) risk for ADHD, followed by those with stable symptoms, then those whose symptoms improved. Machine-learning algorithms, trained and tested on independent groups, showed acceptable accuracy in classifying the different outcome groups (those with worsening, stable, or improving symptoms (area under the curve >0.79). Our next step is to attempt replication of these findings in other cohorts. We have reported this work in and considered some of its limitations in the following publications:- Shaw P. Polygenic risk scores in child psychiatry, research promise and potential clinical pitfalls. Journal of the American Academy of Child and Adolescent Psychiatry. 2022 Jun;61(6):747. Sudre G, Sharp W, Kundzicz P, Bouyssi-Kobar M, Norman L, Choudhury S, Shaw P. Predicting the course of ADHD symptoms through the integration of childhood genomic, neural, and cognitive features. Molecular psychiatry. 2021 Aug;26(8):4046-54. Our next step will be integrate the findings from our dataset with other cohorts, such as the Adolescent Brain and Cognitive Development cohort which is following over 11000 youth across the US.