Reduced midbrain dopamine transporter binding in male adolescents with attention-deficit/hyperactivity disorder: association between striatal dopamine markers and motor hyperactivity.
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.
Jucaite
Aurelija
A
Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden. aurelija.jucaite@kbh.ki.se
Fernell
Elisabeth
E
Halldin
Christer
C
Forssberg
Hans
H
Farde
Lars
L
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism* / Q000503:physiopathology; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000494:pharmacology; D002648:Child; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008636:Mesencephalon / Q000378:metabolism*; D009043:Motor Activity / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D009662:Nortropanes / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D020891:Raclopride / Q000494:pharmacology; D011869:Radioligand Assay / Q000379:methods; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D002247:Carbon Isotopes; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009419:Nerve Tissue Proteins; D009662:Nortropanes; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D020891:Raclopride