Reduced midbrain dopamine transporter binding in male adolescents with attention-deficit/hyperactivity disorder: Association between striatal dopamine markers and motor hyperactivity

Jucaite, Aurelija; Fernell, Elisabeth; Halldin, Christer; Forssberg, Hans; Farde, Lars

doi:10.1016/j.biopsych.2004.11.009

Cited by 238Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorSchizophrenia research and treatment

Reduced midbrain dopamine transporter binding in male adolescents with attention-deficit/hyperactivity disorder: Association between striatal dopamine markers and motor hyperactivity

Jucaite, Aurelija, Fernell, Elisabeth, Halldin, Christer, Forssberg, Hans, Farde, Lars·2005·Biological Psychiatry

DOI 10.1016/j.biopsych.2004.11.009

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Abstract

Background The hypothesis that altered dopamine transmission underlies hyperactive-inattentive behavior in children with attention-deficit/hyperactivity disorder (ADHD) is based on genetic studies and the efficacy of psychostimulants. Most of previous positron emission tomography (PET) and single photon emission tomography (SPET) studies have shown altered binding of dopamine markers in the basal ganglia. Yet, the functional role of the neurochemical disturbances are poorly understood. The purpose of our study was to examine dopamine transporter (DAT) and dopamine D2 receptor (D2R) binding in adolescents with ADHD and to search for its relationship with cognitive functions as well as locomotor hyperactivity.Methods Twelve adolescents with ADHD and 10 young adults were examined with PET using the selective radioligands [11C]PE2I and [11C]raclopride, indexing DAT and D2R density. The simplified reference tissue model was used to calculate binding potential (BP) values. Attention and motor behavior were investigated with a continuous performance task (CPT) and motion measurements.Results The BP value for [11C]PE2I and [11C]raclopride in the striatum of children with ADHD did not differ from that of the young adult control subjects. In the midbrain, however, the BP values for DAT were significantly lower (16%; p = .03) in children with ADHD. Dopamine D2 receptor binding in the right caudate nucleus correlated significantly with increased motor activity (r = .70, p = .01).Conclusions The lower BP values for DAT in the midbrain suggest that dopamine signaling in subjects with ADHD is altered. Altered dopamine signaling might have a causal relationship to motor hyperactivity and might be considered as a potential endophenotype of ADHD.

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DAT knockout mice provide an extreme model because only a mild reduction in midbrain DAT binding has been seen in human adolescents with ADHD, and the model does not agree with several studies that found increased DAT in the striatum of children and adults with ADHD.
“However, DAT knockout mice provide an extreme model because only a mild reduction in midbrain DAT binding has been seen in human adolescents with ADHD [447], and the model also does not agree with several studies have that found increased DAT in the striatum of children and adults in ADHD [448,449].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [447]
Some PET studies suggest the opposite, finding reduced DAT binding in ADHD.
“Some studies suggest the reverse.For example, in a PET study Jucaite et al (2005) observed reduced DAT binding in the midbrain of adolescents with ADHD.”
From Understanding the Effects of Stimulant Medications on Cognition in Individuals with Attention-Deficit Hyperactivity Disorder: A Decade of Progress (2011) · cites this paper as Jucaite et al (2005)
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 Jucaite et al., 2005

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Authors: Jucaite, A., Fernell, E., Halldin, C., Forssberg, H., & Farde, L.
Affiliations: Karolinska Institutet (SE)
ORCID: Fernell, Elisabeth
Halldin, Christer
Forssberg, Hans
Farde, Lars
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2005-02
Volume: 57
Issue: 3
Pages: 229-238
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2004.11.009
OpenAlex: W1983779361
Cited by: 236
References: 80
Citations by year: 2026: 3 · 2025: 3 · 2024: 1 · 2023: 6 · 2022: 5 · 2021: 3 · 2020: 9 · 2019: 6 · 2018: 4 · 2017: 9 · 2016: 6 · 2015: 7 · 2014: 14 · 2013: 13 · 2012: 21
FWCI: 14.44
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological 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
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords: attention deficit hyperactivity disorder, dopamine transporter, dopamine D2 receptor, midbrain, striatum, caudate nucleus, motor hyperactivity, adolescents, dopamine signaling, endophenotypes, [11C]PE2I, [11C]raclopride, binding potential
MeSH terms: Adolescent, Adult, Age Factors, Attention, Attention Deficit Disorder with Hyperactivity, Brain Mapping, Carbon Isotopes, Child, Corpus Striatum, Humans, Image Processing, Computer-Assisted, Functional Laterality, Magnetic Resonance Imaging, Male, Membrane Glycoproteins, Mesencephalon, Motor Activity, Nerve Tissue Proteins, Neuropsychological Tests, Nortropanes, Protein Binding, Radioligand Assay, Time Factors, Tomography, Emission-Computed, Single-Photon, Linear Models, Receptors, Dopamine D2, Dopamine Antagonists, Raclopride, Membrane Transport Proteins, Positron-Emission Tomography, Dopamine Plasma Membrane Transport Proteins

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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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