Attention deficit hyperactivity disorder: Last in, first out - delayed brain maturation with an accelerated decline?

Abstract

While early neurodevelopmental processes during the emergence of ADHD in childhood received considerable attention, the neurobiological mechanisms that underlie the changes in ADHD in adulthood remain largely unaddressed. We wanted to delineate neurodevelopmental changes in adult ADHD using an electrophysiological measure, the fronto-central NoGo P3 event-related potential (ERP), which is an important neurophysiological index of brain functioning in ADHD, and biomarker for response inhibition and aging. ERPs were obtained from 45 ADHD and 41 healthy subjects using a 128-channel BioSemi recording-system, applying emotionally-valenced and neutral stimuli in a response inhibition task. Our results indicated that ADHD subjects manifested delayed developmental P3-trajectory in young-adulthood as compared to controls; they also showed P3 reduction across all emotional valences, and the reduction was most pronounced at younger ages. The differences in P3 diminished by mid-adulthood, and started to increase again at more advanced ages. Thus, similar to structural-MRI indices, developmental brain differences in the fronto-central NoGo P3 in ADHD largely normalize in young-adulthood. However, a reduction of P3 occurs again starting from mid-adulthood. As the fronto-central NoGo P3 reflects the functioning of the frontal areas (which show delayed maturation in ADHD), our findings are consistent with the ‘‘last in, first out’’ hypothesis, which refers to a mirroring pattern of brain development and aging, and posits that brain regions that develop relatively late degenerate relatively early with age. Thus, ADHD may not only be associated with delayed neurodevelopment, but also with a premature age-related deterioration, at least in some measures of electrophysiological functioning.