123I-beta-CIT SPECT demonstrates increased presynaptic dopamine transporter binding sites in basal ganglia in vivo in schizophrenia.
BACKGROUND
The dopamine hypothesis for schizophrenia postulates overactivity of dopamine transmission in the basal ganglia. Most effective antipsychotic drugs block postsynaptic dopamine receptors, but in-vivo imaging studies have not been able to show changes in these receptors in drug-naive schizophrenics.


OBJECTIVE
The presynaptic dopamine transporter (DAT) is thought to be an important regulator of synaptic dopamine concentration. We have used SPECT with (123)I-beta-CIT, which has a high affinity for DAT, in order to further examine the dopamine hypothesis for schizophrenia.


METHODS
Six patients with chronic schizophrenia treated with classic dopamine D(2)-receptor blocking neuroleptics were investigated. The number of DAT binding sites in the basal ganglia was calculated and compared with five healthy volunteers and ten parkinsonian patients.


RESULTS
The schizophrenic patients showed a 36-63% increase in DAT binding sites compared with the volunteers, whereas the parkinsonian patients showed a 57-96% decrease. The differences between the groups were highly significant (even after correction for different age composition within the groups).


CONCLUSIONS
There was an increased number of DAT binding sites in the schizophrenic patients treated with dopamine D(2)-receptor blocking neuroleptics. This fits well with several recent reports that have shown increased volumes of basal ganglia in this patient category. It thus appears that there is an increased number of presynaptic dopamine releasing nerve terminals in the basal ganglia, possibly as a biological adaptation to counteract the postsynaptic dopamine D(2)-receptor blockade.
Sjøholm
Hans
H
Department of Neurology, University Hospital, 9038 Tromsø, Norway. hans.sjoholm@ulleval.no
Bratlid
Trond
T
Sundsfjord
Johan
J
D000328:Adult; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000378:metabolism*; D001665:Binding Sites; D001931:Brain Mapping; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000000981:diagnostic imaging* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; C493214:SLC6A3 protein, human; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine