Farzad Salehpour, F. Gonzalez‐Lima
Introduction The conceptualization of attention-deficit/hyperactivity disorder (ADHD) has evolved from early moral interpretations into a complex, multidimensional neurodevelopmental syndrome. This review traces the progressive convergence of clinical observation, developmental psychopathology, genetics, and behavioral neuroscience across history. Methods We synthesized historical literature, clinical milestones, neuroimaging data, and molecular genetics from the 18th century to the present. The evolution of diagnostic terminology and successive revisions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) were evaluated alongside emerging therapeutic trends and computational models. Results Early 20th-century observations of encephalitis lethargica shifted the field toward neurobiological paradigms. Catecholaminergic theories and family studies in the 1970s and 1980s established biological underpinnings, moving focus from mere hyperactivity to core deficits in executive functioning. The subsequent neuroscience-driven era used structural and functional neuroimaging to implicate fronto-striatal, fronto-parietal, and cerebellar circuits. Distributed functional networks have replaced single-deficit models, while large-scale genome-wide association studies suggest that ADHD may be highly polygenic. Concurrently, therapeutics have expanded beyond stimulants to non-stimulants, behavioral therapies, and non-invasive neuromodulation techniques like prefrontal photobiomodulation. Discussion Despite significant progress, critical gaps remain. Future research must transition from categorical diagnostic models to dimensional, biologically informed frameworks that capture individual heterogeneity. Identifying reproducible biomarkers through multimodal data integration and machine learning is a high priority. Furthermore, longitudinal studies are essential to clarify lifespan trajectories, symptom persistence into adulthood, and late-life manifestations. Improving sample representativeness by actively including females, adults, and ethnically diverse populations is vital for generalizability. Finally, investigating overlapping or distinct non-hyperactive phenotypes, such as cognitive disengagement syndrome, will refine future nosology. An interdisciplinary, precision psychiatry approach is necessary to transform ADHD from a symptom-based diagnosis into a personalized, biologically informed neurodevelopmental disorder.