Attention-Deficit Hyperactivity Disorder (ADHD): A Comprehensive Overview of the Mechanistic Insights from Human...

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition marked by persistent inattention, hyperactivity, and impulsivity. Despite its considerable global prevalence, key gaps remain in our understanding of the structural and molecular changes underlying ADHD which complicate adult diagnosis, as symptoms present differently from those observed during childhood ADHD. On the other hand, while psychostimulants effectively mitigate some symptoms, significant controversy surrounds their long-term effects on cognition, learning, and memory, and day-to-day living. Moreover, our understanding of how various medications given to alleviate ADHD symptoms during pregnancy impact the developing fetal brain also remains largely unexplored. Here, we discuss the subtle differences between ADHD in children and adults and how these symptoms alter brain development and maturation. We further examine changes in monoamine signaling in ADHD and how psychostimulant and non-pharmacological treatments modulate these neural networks. We evaluate and discuss findings as they pertain to the long-term use of ADHD medications, including in utero exposure, on cognitive outcomes, and contextualize these findings with mechanistic insights from animal models.