Quantification of neuroreceptors in the living human brain: IV. Effect of aging and elevations of D₂-like receptors in schizophrenia and bipolar illness

In a previous study of 10 drug-naive schizophrenic patients, the density of D₂ dopamine receptors was found to be elevated in the caudate nucleus. The study raised questions about the influence of the age of the patients, the relationship of receptor density to psychosis, and the accuracy of the method used to obtain this evidence. Using positron emission tomography and constrained analysis of the brain uptake of the radioligand N- [¹¹C]methylspiperone ([¹¹C]NMSP), we tested four questions: Were the assumptions underlying the quantitation valid? Is there an age decline of the density of D₂-1ike dopamine receptors in drug-naive schizophrenia and bipolar illness? If so, is it different from that observed in normal aging'? Are D₂-like dopamine receptors elevated at any age in either drug-naive schizophrenic or psychotic bipolar illness patients? NMSP and haloperidol partition volumes and plasma protein fractions were not significantly different among patient groups and normal volunteers. The model-derived assay of radioligand metabolites in plasma was confirmed by high-performance liquid chromatography in the patient groups. D₂-like dopamine receptors declined with age, and the slope did not differ significantly between the schizophrenic patients, bipolar affective illness patients, and normal controls. Taking the effect of age into account, increases in D₂ dopamine receptor density were found in seven psychotic patients with bipolar affective illness compared with seven nonpsychotic patients and 24 control subjects as well as in 22 drug-naive schizophrenic patients compared with the 24 control subjects.