DOPA Decarboxylase Activity in Attention Deficit Hyperactivity Disorder Adults. A [Fluorine-18]Fluorodopa Positron Emission Tomographic Study

Abstract

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.

Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB

“…Specifically, we aimed to address the following issues: (1) identify genetic susceptibility factors involved in ADHD in the serotoninergic neurotransmission system; (2) test the existence of common genetic factors in childhood and adulthood ADHD; and (3) 73 Interestingly, functional brain imaging studies showed evidence of altered DDC activity in children and adults with ADHD, also suggesting that DDC is a susceptibility factor common to both adulthood and childhood ADHD. 74,75 …”

Dopamine Transporter Genotype and Methylphenidate Dose Response in Children with ADHD

“…Furthermore, neuroimaging studies have consistently reported abnormalities in nigrostriatal dopaminergic brain structures (Aylward et al, 1996;Castellanos et al, 1996) and function (Zametkin et al, 1993;Vaidya et al, 1998;Zametkin and Liotta, 1998) in children with ADHD. Consistent with these findings, neuroimaging studies in ADHD adults have shown alterations in presynaptic dopamine storage processes (Ernst et al, 1998) and in the density of striatal dopamine transporters (DATs) (Dougherty et al, 1999;Krause et al, 2000Krause et al, , 2002, although not consistently.…”

Dopaminergic System Genes in ADHD Toward a Biological Hypothesis

“…Functional brain imaging studies (Ernst et al 1998;Ernst et al 1999) have reported increased DOPA decarboxylase activity in the midbrains of ADHD children and decreased activity in prefrontal regions in ADHD adults. The authors hypothesized that the increased subcortical activity was the primary abnormality.…”

“…DOPA decarboxylase is an enzyme involved in the syn-thesis of dopamine, noradrenaline, and serotonin. Functional imaging studies have shown altered DOPA decarboxylase activity in the midbrain of children with ADHD and in prefrontal areas in ADHD adults (Ernst et al 1998;Ernst et al 1999). There has been no published data, however, regarding the potential role of the DOPA gene as a susceptibility locus in ADHD.…”