title: Quantification of neuroreceptors in the living human brain: IV. Effect of aging and elevations of D2-like receptors in schizophrenia and bipolar illness.
abstract: 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]methyl-spiperone ([11C]NMSP), we tested four questions: Were the assumptions underlying the quantitation valid? Is there an age decline of the density of D2-like 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.
authors.affiliation: Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Wong
authors.forename: G D
authors.initials: GD
authors.lastname: Pearlson
authors.forename: L E
authors.initials: LE
authors.lastname: Tune
authors.forename: L T
authors.initials: LT
authors.lastname: Young
authors.forename: C C
authors.initials: CC
authors.lastname: Meltzer
authors.forename: R F
authors.initials: RF
authors.lastname: Dannals
authors.forename: H T
authors.initials: HT
authors.lastname: Ravert
authors.forename: J
authors.initials: J
authors.lastname: Reith
authors.forename: M J
authors.initials: MJ
authors.lastname: Kuhar
authors.forename: A
authors.initials: A
authors.lastname: Gjedde
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001479:Basal Ganglia / Q000737:chemistry / Q000000981:diagnostic imaging; D001714:Bipolar Disorder / Q000000981:diagnostic imaging / Q000378:metabolism*; D001923:Brain Chemistry; D002421:Caudate Nucleus / Q000737:chemistry / Q000000981:diagnostic imaging; D002851:Chromatography, High Pressure Liquid; D018491:Dopamine Agonists / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis*; D017448:Receptors, Dopamine D2 / Q000032:analysis*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism*; D013134:Spiperone / Q000031:analogs & derivatives / Q000097:blood; D014055:Tomography, Emission-Computed
chemical_list: D018491:Dopamine Agonists; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D013134:Spiperone; C039167:3-N-methylspiperone