DISRUPTED PATTERN OF D-2 DOPAMINE-RECEPTORS IN THE TEMPORAL-LOBE IN SCHIZOPHRENIA - A POSTMORTEM STUDY

Background: Anatomical substrates for the clinical efficacy of D-2 dop amine receptor antagonism in ameliorating positive symptoms, including auditory hallucinations, in schizophrenia are not fully known. We pre viously identified a modular organization of D-2 receptors unique to t he temporal lobe. The dense bands of D-2 receptors showed highest freq uency in auditory and speech association cortices (Brodmann areas 22, 39, and 42) and auditory-visual association areas (Brodmann areas 20 a nd 37) but were rarely found in Somatosensory association regions (Bro dmann area 21). Since the anatomical localization of these bands mirro rs the presumed sites underlying hallucinations in schizophrenia, the modular and laminar distribution of D-2 receptors was studied in the t emporal cortex in the brains of schizophrenic and control subjects. Me thods: Tissue obtained post mortem from 12 elderly schizophrenic subje cts and 13 controls matched for age and postmortem interval was examin ed by quantitative receptor autoradiography for D-2 receptor binding w ith [I-125]epidepride. All regions of the temporal lobe were sampled i n all cases. Results: Schizophrenic cases exhibited significantly disr upted patterns of D-2 receptors in the perirhinal, superior, and infer ior temporal cortices, including disrupted patterns in the modular D-2 receptor bands. The schizophrenic cases had reduced concentrations of D-2 receptors in the supragranular layers and elevated concentrations of D-2 receptors in the granular layer in isocortical regions of the temporal lobe. This disruption does not appear to be due to long-term treatment with antipsychotic drugs and is regionally specific as there were no differences between groups for concentrations or patterns of expression in the hippocampal complex. Conclusions: Blockade of the di srupted distribution of D-2 receptors in auditory and auditory-visual association cortices is a likely mechanism for the clinical efficacy o f D-2 antagonists in reducing hallucinations. The regionally specific, aberrant pattern of D-2 receptors may be a symptom of anomalous corti cal development in these regions.