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

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.

Longitudinal age- and sex-related change in background aperiodic activity during early adolescence

“…Findings from recent animal ( Gao et al, 2017 , Zhang et al, 2011 ) and human research ( Donoghue et al, 2020a , Mamiya et al, 2021 , Molina et al, 2020 , Ostlund et al, 2021 , Robertson et al, 2019 , Voytek et al, 2015b ) in addition to computational models ( Gao et al, 2017 ) suggest that changes in exponent reflect changes in the ratio between excitatory (E) and inhibitory (I) currents in neural populations ( Donoghue et al, 2020a , Gao et al, 2017 ). Specifically, reductions in exponent magnitude (flatter slopes) are thought to reflect increases in E:I ratios while increases in exponent magnitude (steeper slopes) are believed to reflect decreases in E:I ratios ( Donoghue et al, 2020a , Gao et al, 2017 ).…”

“…Specifically, reductions in exponent magnitude (flatter slopes) are thought to reflect increases in E:I ratios while increases in exponent magnitude (steeper slopes) are believed to reflect decreases in E:I ratios ( Donoghue et al, 2020a , Gao et al, 2017 ). There is an increasing body of evidence to suggest that E:I imbalances are associated with neurological and psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD; Mamiya et al, 2021 ; Ostlund et al, 2021 ; Robertson et al, 2019 ) and schizophrenia ( Molina et al, 2020 ) and Fragile X Syndrome (FXS; Wilkinson and Nelson, 2021 ). This is particularly evident in instances in which pharmaceutical interventions have led to changes in E:I ratios in schizophrenia ( Molina et al, 2020 ) and possibly in ADHD ( Mamiya et al, 2021 , Robertson et al, 2019 ).…”

“…There is an increasing body of evidence to suggest that E:I imbalances are associated with neurological and psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD; Mamiya et al, 2021 ; Ostlund et al, 2021 ; Robertson et al, 2019 ) and schizophrenia ( Molina et al, 2020 ) and Fragile X Syndrome (FXS; Wilkinson and Nelson, 2021 ). This is particularly evident in instances in which pharmaceutical interventions have led to changes in E:I ratios in schizophrenia ( Molina et al, 2020 ) and possibly in ADHD ( Mamiya et al, 2021 , Robertson et al, 2019 ). These findings suggest that aberrant changes in the E:I balance found in particular disorders like ADHD and schizophrenia show that an optimal E:I balance may be of particular importance to typical and atypical brain development and function.…”

Alien Attack: A Non-Pharmaceutical Complement for ADHD Treatment

“…Although the mean SUS score was quite similar for children with and without ADHD, we also considered that, in the context of this article, the performance time for each of the minigames and the maximum level reached by our users were both important (as shown in Figures 13-22). Children with ADHD (Minigame 1) Children with ADHD (Minigame 1) Children with ADHD (Minigame 1) Children with ADHD (Minigame 1) Children without ADHD (Minigame 3) Children without ADHD (Minigame 3) Children without ADHD (Minigame 3) Children with ADHD (Minigame 4) Considering the previous figures (Figures [13][14][15][16][17][18][19][20][21][22], we can observe that, in gen time required to finish each task was somewhat less in the case of children with but in some cases the children were very excited and somewhat nervous, know they were playing Alien Attack for the first time (a new game that none of thei knew yet) and they completed the tasks very quickly.…”

“…For this reason, pharmacotherapy is often used in combination with various psychological approaches such as cognitive training, to potentiate the effect of the treatment. Cognitive training, as applied to ADHD, aims for the development of new cognitive skills, and it is based on neural plasticity, taking account of studies performed on dementia and brain-injury rehabilitation [12][13][14].…”