Prefrontal and Striatal Dopamine Release Are Inversely Correlated in Schizophrenia

The dopamine (DA) hypothesis postulates hyperactivity of subcortical DA transmission and hypoactivity of cortical DA in schizophrenia (SCH). Positron emission tomography provides the ability to assess this hypothesis in humans. However, no studies have examined the relationship between cortical DA and striatal DA in this illness.Dsub2/3/subreceptor radiotracer [sup11/supC]FLB457 BPsubND/sub(binding potential relative to nondisplaceable uptake) was measured in 14 off-medication subjects with SCH and 14 healthy control (HC) subjects at baseline and after the administration of 0.5 mg/kg oral d-amphetamine. The amphetamine-induced change in BPsubND/sub(ΔBPsubND/sub) was calculated as the difference between BPsubND/subin the postamphetamine condition and BPsubND/subin the baseline condition and expressed as a percentage of BPsubND/subat baseline. DA release in the striatum using the radiotracer [sup11/supC]NPA was also measured in these subjects.[sup11/supC]FLB457 ΔBPsubND/subwas greater in the HC group compared with the SCH group (Fsub1,26/sub = 5.7; p = .02) with significant differences in [sup11/supC]FLB457 ΔBPsubND/subseen across cortical brain regions. Only in the SCH group was a significant negative correlation observed between [sup11/supC]FLB457 ΔBPsubND/subin the dorsolateral prefrontal cortex and [sup11/supC]NPA ΔBPsubND/subin the dorsal caudate (r = -0.71, p = .005).Subjects with SCH demonstrated deficits of DA release in cortical brain regions relative to HC subjects. Examining both cortical and striatal DA release in the same subjects demonstrated an inverse relationship between cortical DA release and striatal DA release in SCH not present in HC subjects, providing support for the current DA hypothesis of SCH.