Neurobiology of Attention Deficit/Hyperactivity Disorder

Abstract

Attention deficit/hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder, has been associated with various structural and functional CNS abnormalities but findings about neurobiological mechanisms linking genes to brain phenotypes are just beginning to emerge. Despite the high heritability of the disorder and its main symptom dimensions, common individual genetic variants are likely to account for a small proportion of the phenotype's variance. Recent findings have drawn attention to the involvement of rare genetic variants in the pathophysiology of ADHD, some being shared with other neurodevelopmental disorders. Traditionally, neurobiological research on ADHD has focused on catecholaminergic pathways, the main target of pharmacological treatments. However, more distal and basic neuronal processes in relation with cell architecture and function might also play a role, possibly accounting for the coexistence of both diffuse and specific alterations of brain structure and activation patterns. This article aims to provide an overview of recent findings in the rapidly evolving field of ADHD neurobiology with a focus on novel strategies regarding pathophysiological analyses. A ttention deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental condition, characterized by symptoms of inattention and impulsivity/ hyperactivity to a degree that is inconsistent with developmental level. ADHD symptoms persist into adulthood in a majority of patients (1) and are associated with functional impairment and increased risk of depression, substance abuse, and antisocial behavior. Clinical presentation is heterogeneous with three subtypes identified according to the most prevalent symptoms (primarily inattentive, primarily hyperactive/ impulsive, and combined) and with a relative contextdependence of symptom expression although the condition has a chronic course. ADHD is associated with cognitive impairments in inhibitory control and executive function but neuropsychological profiles of subjects with ADHD, despite significantly differing from controls in group comparisons, also show considerable inter-and intraindividual variability. This clinical heterogeneity is likely to reflect the multiplicity of causal pathways leading to the development of the disorder and of a series of moderating and mediating factors involved in symptom expression. Treatment of ADHD involves pharmacologic and nonpharmacologic strategies. Catecholaminergic systems are the main targets of stimulant and nonstimulant medications used to alleviate ADHD symptoms. Convergent studies support that genetic factors are involved in the liability of ADHD symptoms (OMIM 143465). The last decade's research has pointed out various CNS abnormalities in ADHD patients, confirming the neurobiological basis of the disorder. However, there is still a lack of insight into the mechanisms linking genotypes, neural processes, and cognitive/behavioral symptoms. Recent findings point out that other neurodevelopmental disorders like aut...

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