The role of astrocytes in attention-deficit hyperactivity disorder: An update

Attention-deficit hyperactivity disorder (ADHD), the most prevalent neurodevelopmental disorder, is characterized by inattention, hyperactivity, and impulsivity, manifesting in distinct symptoms and varying degrees of severity among patients. While the cellular processes underlying the neurobiology of ADHD are still being explored, in vitro studies suggest the involvement of certain cellular pathways in its clinical manifestations. Neurodevelopmental disorders such as ADHD are caused by malfunctions in numerous cells in the central nervous system (CNS) throughout development; nevertheless, most of the research focuses on neuronal dysfunction. In the last decade, it has become evident that glia and astrocytes play a crucial role in neurodevelopmental processes, which, if deficient, may result in neurodevelopmental disorders. Besides contributing to homeostatic maintenance of the blood-brain barrier (BBB) and other glial cell types, astrocytes provide neurons with structural, trophic, and metabolic support, which is indispensable for their proper functionality. Emerging evidence implicates that astrocytes are involved in processes associated with the etiopathology of ADHD, including oxidative stress, aberrant synaptic formation, neuroinflammation, and excitatory/inhibitory imbalance. This review will summarize the current knowledge addressing astrocyte dysfunction in ADHD, the remaining caveats in clinical data, and the possibilities for drug therapy. Findings substantiated by in vivo, in vitro, and genetic data will be provided, along with the impact of methylphenidate on astrocyte condition.