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.
Highlights
Need for Precision Medicine Care in ADHDAttention-deficit/hyperactivity disorder (ADHD) is a common, impairing neurodevelopmental disorder affecting more than six million children in the United States, many of whom will continue to experience symptoms and associated dysfunction well into adolescence and adulthood [1].In addition to core symptoms of ADHD, individuals are at increased risk of psychiatric comorbidity, including substance use, and impaired academic, occupational, and health maintenance [2,3]
We recently demonstrated that adults with ADHD showed reduced GABA and glutamate concentrations in the anterior cingulate cortex (ACC) and the caudate nucleus while people directed their attention to monitor and report conflicts [54]
The literature reviewed here supports a model in which interactions among GABA, glutamate, and catecholamine neurotransmissions underlie E/I imbalance in the brains of very young children with ADHD
Summary
Attention-deficit/hyperactivity disorder (ADHD) is a common, impairing neurodevelopmental disorder affecting more than six million children in the United States (https://www.cdc.gov/ncbddd/adhd/data.html), many of whom will continue to experience symptoms and associated dysfunction well into adolescence and adulthood [1]. In adults with ADHD, both GABA and glutamate concentrations are reduced in the anterior cingulate cortex and the striatum [40,41,42], and, see [43]. We recently demonstrated that adults with ADHD showed reduced GABA and glutamate concentrations in the ACC and the caudate nucleus while people directed their attention to monitor and report conflicts [54]. This body of research indicates that the balance of GABA and glutamate signaling in the fronto-striatal circuitry is crucial for attention control, and deficient GABA signaling in this circuitry may be related to impaired attention control in ADHD. Spectral slope as a candidate biomarker for ADHD remains uncertain and deserves further investigation
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