A comprehensive overview of the biological foundations of ADHD

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition marked by persistent and impairing patterns of inattention, hyperactivity, and impulsivity. Evidence from neurochemical, pharmacological, and genetic research supports the hypothesis that ADHD involves alterations in neurotransmission, primarily within dopaminergic and noradrenergic systems, with contributions from other neurotransmitter pathways and their interactions. Neuroimaging studies identify structural and functional differences in regions such as the frontal cortex and subcortical structures, although findings remain heterogeneous. Genomic research indicates a polygenic basis, with common and rare variants influencing synaptic transmission, neuronal development, regulatory pathways, and related biological processes. These studies also point to shared genetic influences between ADHD and psychological, social, and somatic traits. Additional omics approaches have further expanded these insights, although larger and more integrative studies across multiple layers remain needed. Environmental factors not only influence the onset of ADHD but also shape its course and prognosis, with emerging evidence highlighting complex gene-environment correlations and interactions. Together, the heterogeneity of findings across neuroimaging, genomic, and multi-omics studies underscores the importance of integrative approaches that embrace diversity across populations, methodologies, and biological systems. The present review provides a comprehensive overview of ADHD's biological foundations, highlighting central nervous system mechanisms, their interplay with genetic and environmental factors, and recent advances from multi-omics research with translational potential. We also discuss key methodological considerations, emphasizing that the biological architecture of ADHD is complex, highly polygenic, and spans multiple levels of analysis.