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 prefrontal and nigrostriatal regions in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Using positron emission tomography (PET) with [fluorine-18]fluorodopa (F18-DOPA), we compared the integrity of the presynaptic dopaminergic function between 17 ADHD adults and 23 healthy controls. The ratio of the isotope concentration of specific regions to that of nonspecific regions reflects DOPA decarboxylase activity and dopamine storage processes. Of three composite regions (prefrontal cortex, striatum, and midbrain), only the prefrontal cortex showed significantly different F18-DOPA ratios in ADHD as compared with 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 compared 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 suggest that a prefrontal dopaminergic dysfunction mediates ADHD symptoms 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 defect in adolescents, we hypothesize that the prefrontal dopaminergic abnormality in ADHD adults is secondary and results from an interaction of the primary subcortical dopaminergic deficit with processes of neural maturation and neural adaptation.
Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
M
M
Ernst
A J
AJ
Zametkin
J A
JA
Matochik
P H
PH
Jons
R M
RM
Cohen
D000328:Adult; D000704:Analysis of Variance; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging / Q000378:metabolism*; D016022:Case-Control Studies; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D004296:Dopa Decarboxylase / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D008875:Middle Aged; D017729:Presynaptic Terminals / Q000502:physiology*; D014055:Tomography, Emission-Computed / Q000379:methods*
D005462:Fluorine Radioisotopes; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004296:Dopa Decarboxylase