Precision Medicine Care in ADHD: The Case for Neural Excitation and Inhibition

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that has become increasingly prevalent worldwide. Its core symptoms, including difficulties regulating attention, activity level, and impulses, appear in early childhood and can persist throughout the lifespan. Current pharmacological options targeting catecholamine neurotransmissions have effectively alleviated symptoms in some, but not all affected individuals, leaving clinicians to implement trial-and-error approach to treatment. In this review, we discuss recent experimental evidence from both preclinical and human studies that suggest imbalance of excitation/inhibition (E/I) in the fronto-striatal circuitry during early development may lead to enduring neuroanatomical abnormality of the circuitry, causing persistence of ADHD symptoms in adulthood. We propose a model of precision medicine care that includes E/I balance as a candidate biomarker for ADHD, development of GABA-modulating medications, and use of magnetic resonance spectroscopy and scalp electrophysiology methods to monitor the effects of treatments on shifting E/I balance throughout the lifespan.

Automated summary

ADHD is a neurodevelopmental disorder with core symptoms of difficulties regulating attention, activity level, and impulses that can persist throughout a person's lifespan. Current pharmacological options targeting catecholamine neurotransmissions have varying levels of effectiveness, leading clinicians to implement trial-and-error approaches to treatment. Recent evidence suggests an imbalance of excitation/inhibition in the fronto-striatal circuitry during early development may lead to enduring neuroanatomical abnormalities, proposing a precision medicine care model focusing on E/I balance as a candidate biomarker for ADHD.