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Attenuated Tonic and Enhanced Phasic Release of Dopamine in Attention Deficit Hyperactivity Disorder.

Badgaiyan RD, Sinha S, Sajjad M, Wack DS - PLoS ONE (2015)

Bottom Line: Since indirect methods used in earlier studies have arrived at contradictory conclusions, we directly measured the tonic and phasic release of dopamine in ADHD volunteers.During task performance significantly lower ligand BP was observed in the same area, indicating increased phasic release.By characterizing the nature of dysregulated dopamine neurotransmission in ADHD, the results explain earlier findings of reduced or increased dopaminergic activity.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Functional Imaging Laboratory, Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, United States of America; Neuromodulation Program, University of Minnesota Twin City Campus, Minneapolis, Minnesota, United States of America; Laboratory of Advanced Radiochemistry, University of Minnesota Twin City Campus, Minneapolis, Minnesota, United States of America.

ABSTRACT
It is unclear whether attention deficit hyperactive disorder (ADHD) is a hypodopaminergic or hyperdopaminergic condition. Different sets of data suggest either hyperactive or hypoactive dopamine system. Since indirect methods used in earlier studies have arrived at contradictory conclusions, we directly measured the tonic and phasic release of dopamine in ADHD volunteers. The tonic release in ADHD and healthy control volunteers was measured and compared using dynamic molecular imaging technique. The phasic release during performance of Eriksen's flanker task was measured in the two groups using single scan dynamic molecular imaging technique. In these experiments volunteers were positioned in a positron emission tomography (PET) camera and administered a dopamine receptor ligand (11)C-raclopride intravenously. After the injection PET data were acquired dynamically while volunteers either stayed still (tonic release experiments) or performed the flanker task (phasic release experiments). PET data were analyzed to measure dynamic changes in ligand binding potential (BP) and other receptor kinetic parameters. The analysis revealed that at rest the ligand BP was significantly higher in the right caudate of ADHD volunteers suggesting reduced tonic release. During task performance significantly lower ligand BP was observed in the same area, indicating increased phasic release. In ADHD tonic release of dopamine is attenuated and the phasic release is enhanced in the right caudate. By characterizing the nature of dysregulated dopamine neurotransmission in ADHD, the results explain earlier findings of reduced or increased dopaminergic activity.

No MeSH data available.


Related in: MedlinePlus

Comparison of the mean ligand binding potentials (BP) estimated at rest in ADHD and healthy control volunteers (ADHD>control).The BP was significantly greater in ADHD volunteers in the right caudate suggesting reduced tonic release of dopamine in this area.
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pone.0137326.g001: Comparison of the mean ligand binding potentials (BP) estimated at rest in ADHD and healthy control volunteers (ADHD>control).The BP was significantly greater in ADHD volunteers in the right caudate suggesting reduced tonic release of dopamine in this area.

Mentions: To estimate the tonic release PET data acquired at rest were analyzed to measure values of the ligand BP in each voxel and in the caudate and putamen of each hemisphere separately. We found that the mean ligand BP in the right caudate of ADHD volunteers (3.19±0.23) was significantly higher (p<0.003; peak t = 9.02, confidence interval ±0.13 at 95% confidence level) than that of the healthy control (2.86±0.26; confidence interval ±0.15 at 95% confidence level) volunteers (Fig 1). It was higher in the other striatal regions also but the difference was not significant statistically (Table 1). The mean ligand BP of the entire striatum was 27% higher in the ADHD group (3.21±1.30) as compared to that in the healthy control group (2.53±0.85).


Attenuated Tonic and Enhanced Phasic Release of Dopamine in Attention Deficit Hyperactivity Disorder.

Badgaiyan RD, Sinha S, Sajjad M, Wack DS - PLoS ONE (2015)

Comparison of the mean ligand binding potentials (BP) estimated at rest in ADHD and healthy control volunteers (ADHD>control).The BP was significantly greater in ADHD volunteers in the right caudate suggesting reduced tonic release of dopamine in this area.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4589406&req=5

pone.0137326.g001: Comparison of the mean ligand binding potentials (BP) estimated at rest in ADHD and healthy control volunteers (ADHD>control).The BP was significantly greater in ADHD volunteers in the right caudate suggesting reduced tonic release of dopamine in this area.
Mentions: To estimate the tonic release PET data acquired at rest were analyzed to measure values of the ligand BP in each voxel and in the caudate and putamen of each hemisphere separately. We found that the mean ligand BP in the right caudate of ADHD volunteers (3.19±0.23) was significantly higher (p<0.003; peak t = 9.02, confidence interval ±0.13 at 95% confidence level) than that of the healthy control (2.86±0.26; confidence interval ±0.15 at 95% confidence level) volunteers (Fig 1). It was higher in the other striatal regions also but the difference was not significant statistically (Table 1). The mean ligand BP of the entire striatum was 27% higher in the ADHD group (3.21±1.30) as compared to that in the healthy control group (2.53±0.85).

Bottom Line: Since indirect methods used in earlier studies have arrived at contradictory conclusions, we directly measured the tonic and phasic release of dopamine in ADHD volunteers.During task performance significantly lower ligand BP was observed in the same area, indicating increased phasic release.By characterizing the nature of dysregulated dopamine neurotransmission in ADHD, the results explain earlier findings of reduced or increased dopaminergic activity.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Functional Imaging Laboratory, Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, United States of America; Neuromodulation Program, University of Minnesota Twin City Campus, Minneapolis, Minnesota, United States of America; Laboratory of Advanced Radiochemistry, University of Minnesota Twin City Campus, Minneapolis, Minnesota, United States of America.

ABSTRACT
It is unclear whether attention deficit hyperactive disorder (ADHD) is a hypodopaminergic or hyperdopaminergic condition. Different sets of data suggest either hyperactive or hypoactive dopamine system. Since indirect methods used in earlier studies have arrived at contradictory conclusions, we directly measured the tonic and phasic release of dopamine in ADHD volunteers. The tonic release in ADHD and healthy control volunteers was measured and compared using dynamic molecular imaging technique. The phasic release during performance of Eriksen's flanker task was measured in the two groups using single scan dynamic molecular imaging technique. In these experiments volunteers were positioned in a positron emission tomography (PET) camera and administered a dopamine receptor ligand (11)C-raclopride intravenously. After the injection PET data were acquired dynamically while volunteers either stayed still (tonic release experiments) or performed the flanker task (phasic release experiments). PET data were analyzed to measure dynamic changes in ligand binding potential (BP) and other receptor kinetic parameters. The analysis revealed that at rest the ligand BP was significantly higher in the right caudate of ADHD volunteers suggesting reduced tonic release. During task performance significantly lower ligand BP was observed in the same area, indicating increased phasic release. In ADHD tonic release of dopamine is attenuated and the phasic release is enhanced in the right caudate. By characterizing the nature of dysregulated dopamine neurotransmission in ADHD, the results explain earlier findings of reduced or increased dopaminergic activity.

No MeSH data available.


Related in: MedlinePlus