Models and mechanisms
Neuropsychological research has demonstrated heterogeneity in the deficits associated with ADHD and has led to a multiple pathway model emphasizing executive dysfunction and motivational deficits involving the brain's reward system3. Brain imaging studies of adolescents and adults have implicated frontostriatal and frontoparietal neurocircuitry in ADHD4 . Preliminary studies comparing animal and human genes and behavior have identified common genetic predispositions that substantially increase the risk for ADHD.
Psychopharmacological investigations have traditionally focused on the dopamine pathways. Recent research is examining the noradrenergic, serotonergic, and cholinergic (e.g., nicotinic) neurotransmission and interactions among these systems. Experimental animal work is helping inform optimal dosing in humans. Rat studies show that low dose methylphenidate targets norepinephrine and dopamine neurotransmission preferentially within prefrontal cortex, providing a likely basis for enhancing cognition and calming behavior5.
