Early Life Adversity and Adult Attention-Deficit/Hyperactivity Disorder (ADHD): Pathways to Persistence and Adult Susceptibility

Attention-Deficit/Hyperactivity Disorder (ADHD), a common neurodevelopmental disorder in childhood, often persists into adulthood, affecting around 500 million adults globally. While genetic factors play a significant role, recent studies have highlighted the contribution of environmental factors to ADHD pathogenesis. Early Life Adversity (ELA), through the impact of chronic stress, disrupts critical neurodevelopmental processes, leading to alterations in brain networks involved in attention. Viewing ADHD through ELA-shaped neurodevelopment reframes the disorder from a largely inherited liability to a partly preventable, stress-programmable phenotype, prioritizing early detection and mechanistic interventions across sensitive periods. Drawing on extensive human clinical research and advancements in ELA animal models, this review critically examines the evidence linking ELA and adult ADHD. The findings indicate that ELA significantly contributes to the persistence of ADHD and increases vulnerability to the disorder. Mechanistic insights suggest that ELA is associated with hypothalamic-pituitary-adrenal axis dysregulation, aberrant epigenetic modifications, sleep disturbances, oxidative stress, neuroinflammation, and disrupted myelination. These processes may interact synergistically, creating cascading effects that exacerbate adult ADHD pathology. This review also summarizes potential therapeutic strategies targeting these underlying mechanisms. Further research in this field is essential to enhance ELA intervention strategies and alleviate the burden of ADHD and its associated comorbidities.