High Midbrain [ 18 F]DOPA Accumulation in Children With Attention Deficit Hyperactivity Disorder

Ernst, Monique; Zametkin, Alan J.; Matochik, John A.; Pascualvaca, Daisy; Jons, Peter H.; Cohen, Robert M.

doi:10.1176/ajp.156.8.1209

Cited by 257Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology Studies

High Midbrain [ 18 F]DOPA Accumulation in Children With Attention Deficit Hyperactivity Disorder

Ernst, Monique, Zametkin, Alan J., Matochik, John A., Pascualvaca, Daisy, Jons, Peter H., Cohen, Robert M.·1999·American Journal of Psychiatry

DOI 10.1176/ajp.156.8.1209

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Abstract

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a highly prevalent childhood psychiatric disorder characterized by impaired attention, excessive motor activity, and impulsivity. Despite extensive investigation of the neuropathophysiology of ADHD by a wide array of methodologies, the neurobiochemical substrate of this disorder is still unknown. Converging evidence, however, suggests a primary role of the dopaminergic system. METHOD: This study examined the integrity of presynaptic dopaminergic function in children with ADHD through use of positron emission tomography and the tracer [18F]fluorodopa ([18F]DOPA). Accumulation of [18F]DOPA in synaptic terminals, a measure of dopa decarboxylase activity, was quantified in regions rich in dopaminergic innervation, including caudate nucleus, putamen, frontal cortex, and midbrain (i.e., substantia nigra and ventral tegmentum). RESULTS: Accumulation of [18F]DOPA in the right midbrain was higher by 48% in 10 children with ADHD than in 10 normal children. Despite its magnitude, this difference would not have reached statistical significance if corrected by the Bonferroni test for multiple comparisons. However, [18F]DOPA in the right midbrain was correlated with symptom severity. No other dopamine-rich regions significantly differed between groups. CONCLUSIONS: These findings are suggestive of dopaminergic dysfunction at the level of the dopaminergic nuclei in children with ADHD. Abnormality in dopa decarboxylase activity may be primary or secondary to deficits in other functional units of the dopamine pathway (e.g., receptor, uptake transporter, vesicular transporter, degradation enzymes). Efforts toward defining the origin of this abnormality should help delineate mechanisms of midbrain control of attention and motor behavior important for the understanding of the causes and treatment of ADHD.

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Ernst et al. found relatively higher right midbrain accumulation of 18F-DOPA in children with ADHD, correlated with symptom severity.
“Ernst and colleagues [494] found relatively higher right midbrain accumulation of 18 F-DOPA in children with ADHD, that was correlated with symptom severity”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [494]
Neurochemical studies have demonstrated alterations in dopaminergic signaling in the striatum and midbrain in ADHD, and linked such alterations with inattention symptoms and motivation problems in children and adults with ADHD.
“Neurochemical studies have demonstrated alterations in dopaminergic signaling in the striatum and the midbrain in ADHD, and linked such alterations with inattention symptoms and motivation problems in children and adults with ADHD.5,27–29”
From Striatal sensitivity during reward processing in attention-deficit/hyperactivity disorder (2012) · cites this paper as [29]
Findings for both juvenile and adult ADHD have implicated functional and structural midbrain abnormalities in the pathophysiology of the disorder.
“This question is particularly relevant because findings for both juvenile and adult ADHD have implicated functional and structural midbrain abnormalities in the pathophysiology of the disorder (Ernst et al., 1999; Jucaite et al., 2005; Volkow et al., 2009; Romanos et al., 2010), also consistent with experimental animal models of ADHD (Leo et al., 2003).”
From A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment (2013) · cites this paper as Ernst et al., 1999

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DOPA Decarboxylase Activity in Attention Deficit Hyperactivity Disorder Adults. A [Fluorine-18]Fluorodopa Positron Emission Tomographic Study
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Self-citation
DOPA decarboxylase activity in attention deficit hyperactivity disorder adults. A [flourine-18]flourodopa positron emission tomographic study
Monique Ernst, D., Zametkin, A. J., Matochik, J. A., Jons, P. H., & Cohen, R. M. (1998)
Self-citation
Altered pattern of brain dopamine synthesis in male adolescents with attention deficit hyperactivity disorder.
Forssberg, H., Fernell, E., Waters, N., Waters, N., & Tedroff, J. (2006) · Behavioral and Brain Functions · doi:10.1186/1744-9081-2-40 · Cited by 61 · see citing works
Reduced midbrain dopamine transporter binding in male adolescents with attention-deficit/hyperactivity disorder: Association between striatal dopamine markers and motor hyperactivity
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Authors: Ernst, M., Zametkin, A. J., Matochik, J. A., Pascualvaca, D., Jons, P. H., & Cohen, R. M.
Affiliations: National Institutes of Health (US)
Venue: American Journal of Psychiatry
Publisher: American Psychiatric Association Publishing
Published: 1999-08-01
Volume: 156
Issue: 8
Pages: 1209-1215
ISSN: 0002-953X (ISSN-L)
1535-7228
DOI: 10.1176/ajp.156.8.1209
OpenAlex: W2148955566
Cited by: 256
References: 52
Citations by year: 2026: 4 · 2025: 7 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 3 · 2016: 6 · 2015: 2 · 2014: 7 · 2013: 6 · 2012: 13
FWCI: 10.94
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Psychiatry (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: attention deficit hyperactivity disorder, [18F]fluorodopa, midbrain, substantia nigra, ventral tegmental area, dopaminergic dysfunction, symptom severity, children
MeSH terms: Adolescent, Attention Deficit Disorder with Hyperactivity, Caudate Nucleus, Child, Dihydroxyphenylalanine, Dopa Decarboxylase, Dopamine, Female, Fluorine Radioisotopes, Frontal Lobe, Humans, Functional Laterality, Male, Mesencephalon, Putamen, Severity of Illness Index, Tomography, Emission-Computed, Presynaptic Terminals

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High Midbrain [ 18 F]DOPA Accumulation in Children With Attention Deficit Hyperactivity Disorder

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