Precision Medicine Care in ADHD: The Case for Neural Excitation and Inhibition
Ping C Mamiya1, Anne B Arnett2, Mark A Stein2
1Institute for Learning and Brain Sciences, University of Washington, Seattle, WA 98195, USA.
Insights
Attention-deficit/hyperactivity disorder (ADHD) may stem from early developmental excitation/inhibition (E/I) imbalances in brain circuitry. Precision medicine could target E/I balance for ADHD treatment.
Area of Science:
- Neuroscience
- Developmental Psychology
- Pharmacology
Background:
- Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with persistent symptoms.
- Current ADHD treatments targeting catecholamines are not universally effective, necessitating alternative approaches.
Purpose of the Study:
- To review evidence linking early developmental excitation/inhibition (E/I) imbalances to persistent ADHD.
- To propose a precision medicine model for ADHD incorporating E/I balance biomarkers and novel therapeutics.
Main Methods:
- Review of preclinical and human studies examining fronto-striatal circuitry and E/I balance in ADHD.
- Exploration of neuroimaging and electrophysiology techniques for monitoring E/I balance.
Main Results:
- Evidence suggests early E/I imbalance in fronto-striatal circuits can cause lasting neuroanatomical abnormalities contributing to adult ADHD.
- E/I balance is proposed as a potential biomarker for ADHD diagnosis and treatment monitoring.
Conclusions:
- A precision medicine approach for ADHD should consider E/I balance.
- Development of GABA-modulating drugs and advanced monitoring techniques could personalize ADHD care.
Abstract:
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.
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