Disrupted Pattern of D2 Dopamine Receptors in the Temporal Lobe in Schizophrenia

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Abstract
Background: Anatomical substrates for the clinical efficacy of D2 dopamine receptor antagonism in ameliorating positive symptoms, including auditory hallucinations, in schizophrenia are not fully known. We previously identified a modular organization of D2 receptors unique to the temporal lobe. The dense bands of D2 receptors showed highest frequency in auditory and speech association cortices (Brodmann areas 22,39,and 42) and auditory-visual association areas (Brodmann areas 20 and 37) but were rarely found in somatosensory association regions (Brodmann area 21). Since the anatomical localization of these bands mirrors the presumed sites underlying hallucinations in schizophrenia, the modular and laminar distribution of D2 receptors was studied in the temporal cortex in the brains of schizophrenic and control subjects. Methods: Tissue obtained post mortem from 12 elderly schizophrenic subjects and 13 controls matched for age and postmortem interval was examined by quantitative receptor autoradiography for D2 receptor binding with [125I] epidepride. All regions of the temporal lobe were sampled in all cases. Results: Schizophrenic cases exhibited significantly disrupted patterns of D2 receptors in the perirhinal, superior, and inferior temporal cortices, including disrupted patterns in the modular D2 receptor bands. The schizophrenic cases had reduced concentrations of D2 receptors in the supragranular layers and elevated concentrations of D2 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 disrupted distribution of D2 receptors in auditory and auditory-visual association cortices is a likely mechanism for the clinical efficacy of D2 antagonists in reducing hallucinations. The regionally specific, aberrant pattern of D2 receptors may be a symptom of anomalous cortical development in these regions.