Bimodal Distribution of Dopamine Receptor Densities in Brains of Schizophrenics

Abstract

The dopamine hypothesis of schizophrenia was examined by measuring the density of dopamine receptors in the postmortem brains of 81 control subjects and 59 schizophrenics from four different countries. The densities of dopamine receptors in the tissues from the schizophrenic patients had a bimodal distribution in the caudate nucleus, putamen, and nucleus accumbens. One mode occurred 25 percent above the control density, and a second mode occurred at a density 2.3 times that of the control density for all three regions. Although almost all the patients had been medicated with neuroleptics, the two modes had the same dissociation constant for the labeled ligand used, suggesting that the neuroleptic doses were similar for the two populations of schizophrenics. The results thus provide direct evidence for two distinct categories of schizophrenia.

Subjective Effects of AMPT-induced Dopamine Depletion in Schizophrenia Correlation between Dysphoric Responses and Striatal D2 Binding Ratios on SPECT Imaging

“…Is it possible that the one third of schizophrenic patients without elevated dopamine levels are the same one third who tend to develop dysphoric responses during antipsychotic drug therapy? Our study supports a growing notion that dopaminergic function may differ vastly, across different people with schizophrenia (Seeman et al 1984;Zakzanis and Hansen 1998), and at different stages of illness (Laruelle et al 1999), but also indicated that schizophrenic patients with little or no elevation of synaptic dopamine at the baseline were indeed at an increased risk to experience dysphoric responses with AMPT.…”

Subjective tolerability of antipsychotic medications and the emerging science of subjective tolerability disorders

“…In other words, those patients who have lower dopamine functioning are the ones who are vulnerable for dysphoric responses when further given potent dopamine blocking antipsychotics. This observation has also clarified why not all persons with schizophrenia develop negative subjective responses on antipsychotic medications, confirming early observations that not all persons with schizophrenia have high dopamine D 2 functioning [28].…”

Dopamine transporter density of striatum showed to be increased in Schizophrenia first-episode drug-naïve patients

“…Dopaminergic nigrostriatal pathway has a role in movement control, so the study of the dopamine transporter (DaT) may be of great value to determine its effect in the appearance of Drug-induced parkinsonism [8][9][10][11].…”