Delivering paediatric precision medicine: Genomic and environmental considerations along the causal pathway of childhood neurodevelopmental disorders

Abstract

Precision medicine refers to treatments that are targeted to an individual's unique characteristics. Precision medicine for neurodevelopmental disorders (such as cerebral palsy, attention‐deficit/hyperactivity disorder, obsessive–compulsive disorder, Tourette syndrome, and autism spectrum disorder) in children has predominantly focused on advances in genomic sequencing technologies to increase our ability to identify single gene mutations, diagnose a multitude of rare neurodevelopmental disorders, and gain insights into pathogenesis. Although targeting specific gene variants with high penetrance will help some children with rare disease, this approach will not help most children with neurodevelopmental disorders. A ‘pathway’ driven approach targeting the cumulative influence of psychosocial, epigenetic, or cellular factors is likely to be more effective. To optimize the therapeutic potential of precision medicine, we present a biopsychosocial integrated framework to examine the ‘gene–environment neuroscience interaction’. Such an approach would be supported through harnessing the power of big data, transdiagnostic assessment, impact and implementation evaluation, and a bench‐to‐bedside scientific discovery agenda with ongoing clinician and patient engagement.

What this paper adds

• Precision medicine has predominantly focused on genetic risk factors.

• The impact of environmental risk factors, particularly inflammatory, metabolic, and psychosocial risks, is understudied.

• A holistic biopsychosocial model of neurodevelopmental disorder causal pathways is presented.

• The model will provide precision medicine across the full spectrum of neurodevelopmental disorders.

What this paper adds

• Precision medicine has predominantly focused on genetic risk factors.

• The impact of environmental risk factors, particularly inflammatory, metabolic, and psychosocial risks, is understudied.

• A holistic biopsychosocial model of neurodevelopmental disorder causal pathways is presented.

• The model will provide precision medicine across the full spectrum of neurodevelopmental disorders.

This graphical abstract represents our current limited conceptualisation of precision medicine for children with neurodevelopmental disorders and the importance of considering the gene‐ environment neuroscience interaction using a bio‐psychosocial integrated framework as key for precision medicine advances in the future. The enablers of this approach include big data, transdiagnostic assessment, bench‐to‐bedside translation and consumer engagement.