In vivo neuroreceptor imaging in attention-deficit/hyperactivity disorder: a focus on the dopamine transporter.
There is converging evidence of the role of catecholamine dysregulation in the underlying pathophysiology of attention-deficit/hyperactivity disorder (ADHD). The dopamine transporter (DAT) is known to be a key regulator of dopamine, and recent genetic, treatment, and imaging studies have highlighted the role of DAT in ADHD. There is an emerging literature on in vivo neuroreceptor imaging of DAT in ADHD and control subjects reported by a number of groups internationally. A comprehensive review of existing imaging studies of DAT binding in ADHD shows that six of eight independent studies by six different groups have reported increased DAT binding in (mostly) treatment-naïve children and adults with ADHD. Although there is fair agreement regarding the presence and direction of abnormal DAT binding, there remains disagreement as to the magnitude of the finding and the importance of many potentially confounding variables, including clinical characteristics and imaging methodology. Three studies by three different groups have reported decreased DAT binding after methylphenidate treatment. Interpretation of the latter finding awaits clarification of the issue of timing of drug administration and imaging to disentangle receptor occupancy from downregulation.
Spencer
Thomas J
TJ
Pediatric Psychopharmacology Unit, Psychiatry Service, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. spencer@helix.mgh.harvard.edu
Biederman
Joseph
J
Madras
Bertha K
BK
Faraone
Stephen V
SV
Dougherty
Darin D
DD
Bonab
Ali A
AA
Fischman
Alan J
AJ
D000367:Age Factors; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging* / Q000378:metabolism; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D003042:Cocaine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000000981:diagnostic imaging* / Q000378:metabolism; D013997:Time Factors; D014055:Tomography, Emission-Computed / Q000379:methods*
D002247:Carbon Isotopes; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C102282:N-iodoallyl-2-carbomethoxy-3-(4-fluorophenyl)tropane; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; D003042:Cocaine