Pas si paradoxal … Neurobiologie du trouble déficit de l’attention–hyperactivité (TDAH) et mode d’action thérapeutique des psychostimulants

Abstract

Background

Attention deficit hyperactivity disorder (ADHD) is characterized by impairments in attention and executive functions, potentially associated with hyperactivity and impulsivity. Psychostimulants, which have a dopaminergic action, are the main pharmacological class of drugs used to treat ADHD, both in adults and children. However, psychostimulant intoxication is known to cause attentional problems and psychomotor agitation. It may therefore seem paradoxical to treat ADHD symptoms with molecules whose use may cause the same type of symptoms.

Methods

In this narrative review, based on a selection of scientific articles, we aim to highlight how recent neurobiological data, addressing the dopaminergic mechanisms of attentional and executive functions, the dopaminergic abnormalities found in ADHD, as well as the pharmacological mode of action of psychostimulants, converge to explain this apparent paradox.

Results

For some fifteen years now, it has been suggested that there is an “inverted U-shape” relationship between dopamine levels in the prefrontal cortex (PFC) on the one hand, and attentional and executive performances on the other hand. Both too much and too little dopamine lead to the same result, i.e. disrupted executive functions and reduced cognitive performance. In ADHD, studies show that there is an abnormally low level of dopamine in the PFC, providing a potential explanation for ADHD symptomatology. Psychostimulants act primarily by blocking the presynaptic transporters of catecholamines (i.e., dopamine and noradrenaline). Thus, by raising dopamine levels in the CPF of subjects with ADHD, they bring them back to a range that supports adequate cognitive performance, whereas in subjects without ADHD, Psychostimulants are more likely to bring dopamine concentrations to high levels, where executive functions are also suboptimal.

Conclusions

The “inverted U-shape” model of the relationship between dopamine levels and attentional and executive performances elegantly resolves the apparent paradox of psychostimulant efficacy in ADHD, and helps explain a number of clinical situations frequently met in this disorder. It is important to educate patients, caregivers, as well as the media and the lay public, about these neurobiological explanations, especially to combat the frequent misrepresentations associated with the use of psychostimulants in ADHD.