DOPA DECARBOXYLASE ACTIVITY IN ATTENTION-DEFICIT HYPERACTIVITY DISORDER ADULTS - A [FLUORINE-18]FLUORODOPA POSITRON EMISSION TOMOGRAPHIC STUDY

Converging evidence implicates the dopaminergic system and the prefron tal and nigrostriatal regions in the pathophysiology of attention defi cit hyperactivity disorder (ADHD). Using positron emission tomography (PET) with [fluorine-18]fluorodopa (F18-DOPA), we compared the integri ty of the presynaptic dopaminergic function between 17 ADHD adults and 23 healthy controls. The ratio of the isotope concentration of specif ic regions to that of nonspecific regions reflects DOPA decarboxylase activity and dopamine storage processes. Of three composite regions (p refrontal cortex, striatum, and midbrain), only the prefrontal cortex showed significantly different F18-DOPA ratios in ADHD as compared wit h control adults (p < 0.01). The medial and left prefrontal areas were the most altered (lower F18-DOPA ratios by 52 and 51% in ADHD as comp ared with controls). Similarly, the interaction [sex x diagnosis] was significant only in the prefrontal cortex (p < 0.02). lower ratios in men than in women in ADHD and vice versa in controls. These findings s uggest that a prefrontal dopaminergic dysfunction mediates ADHD sympto ms in adults and that gender influences this abnormality. On the basis of previous neuroimaging findings in ADHD showing discrepant findings in adults and adolescents and on evidence for midbrain dopaminergic d efect in adolescents, we hypothesize that the prefrontal dopaminergic abnormality in ADHD adults is secondary and results from an interactio n of the primary subcortical dopaminergic deficit with processes of ne ural maturation and neural adaptation.