Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia.
Both dopaminergic neurotransmission and prefrontal cortex (PFC) function are known to be abnormal in schizophrenia. To test the hypothesis that these phenomena are related, we measured presynaptic dopaminergic function simultaneously with regional cerebral blood flow during the Wisconsin Card Sorting Test (WCST) and a control task in unmedicated schizophrenic subjects and matched controls. We show that the dopaminergic uptake constant Ki in the striatum was significantly higher for patients than for controls. Patients had significantly less WCST-related activation in PFC. The two parameters were strongly linked in patients, but not controls. The tight within-patient coupling of these values, with decreased PFC activation predicting exaggerated striatal 6-fluorodopa uptake, supports the hypothesis that prefrontal cortex dysfunction may lead to dopaminergic transmission abnormalities.
Meyer-Lindenberg
Andreas
A
Unit on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, 10-4C101, 9000 Rockville Pike, Bethesda, Maryland 20892-1365, USA. andreasml@nih.gov
Miletich
Robert S
RS
Kohn
Philip D
PD
Esposito
Giuseppe
G
Carson
Richard E
RE
Quarantelli
Mario
M
Weinberger
Daniel R
DR
Berman
Karen Faith
KF
D002560:Cerebrovascular Circulation / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000378:metabolism; D006801:Humans; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D013223:Statistics as Topic; D013569:Synapses / Q000378:metabolism; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004298:Dopamine