Goldsmith S K, Shapiro R M, Joyce J N
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, USA.
Arch Gen Psychiatry. 1997 Jul;54(7):649-58. doi: 10.1001/archpsyc.1997.01830190077008.
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.
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.
Schizophrenia 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 of antipsychotic drugs and is regionally specific as there were no differences between groups for concentrations or patterns of expression in the hippocampal complex.
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.
D2多巴胺受体拮抗作用改善精神分裂症阳性症状（包括幻听）的临床疗效的解剖学基础尚不完全清楚。我们之前发现了颞叶特有的D2受体模块化组织。D2受体密集带在听觉和言语联合皮质（布罗德曼区22、39和42）以及听觉-视觉联合区（布罗德曼区20和37）中出现频率最高，但在体感联合区（布罗德曼区21）中很少见。由于这些带的解剖定位反映了精神分裂症幻觉潜在的部位，因此我们研究了精神分裂症患者和对照者大脑颞叶皮质中D2受体的模块化和层状分布。
通过定量受体放射自显影术，用[125I]表哌啶检测12例老年精神分裂症患者和13例年龄及死后间隔相匹配的对照者死后获得的组织中的D2受体结合情况。所有病例均对颞叶的所有区域进行采样。
精神分裂症患者在梨状叶周围、颞上和颞下皮质中表现出明显的D2受体分布紊乱模式，包括模块化D2受体带的紊乱模式。精神分裂症患者颞叶等皮质区域颗粒上层的D2受体浓度降低，颗粒层的D2受体浓度升高。这种紊乱似乎不是由于抗精神病药物的长期治疗所致，并且具有区域特异性，因为海马复合体中两组的浓度或表达模式没有差异。
阻断听觉和听觉-视觉联合皮质中D2受体的紊乱分布可能是D2拮抗剂减少幻觉临床疗效的机制。D2受体区域特异性的异常模式可能是这些区域皮质发育异常的一种症状。
