Dorph-Petersen Karl-Anton, Pierri Joseph N, Sun Zhuoxin, Sampson Allan R, Lewis David A
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
J Comp Neurol. 2004 May 10;472(4):449-62. doi: 10.1002/cne.20055.
The mediodorsal thalamic nucleus (MD) is the principal relay nucleus for the prefrontal cortex, a brain region thought to be dysfunctional in schizophrenia. Several, but not all, postmortem studies of the MD in schizophrenia have reported decreased volume and total neuronal number. However, it is not clear whether the findings are specific for schizophrenia nor is it known which subtypes of thalamic neurons are affected. We studied the left MD in 11 subjects with schizophrenia, 9 control subjects, and 12 subjects with mood disorders. Based on morphological criteria, we divided the neurons into two subclasses, presumably corresponding to projection neurons and local circuit neurons. We estimated MD volume and the neuron number of each subclass using methods based on modern unbiased stereological principles. We also estimated the somal volumes of each subclass using a robust, but biased, approach. In addition, we investigated the left MD in four cynomolgus monkeys chronically exposed to haloperidol and in four control monkeys in order to assess the possible effects of antipsychotic medications. The three human subject groups did not differ in any of the measures. In addition, no differences were observed between the two groups of monkeys. Thus, these findings do not support the hypothesis that the MD is a locus of pathology in schizophrenia, although they cannot rule out important functional or structural changes in parameters not measured. Like other studies, this investigation is subject to the limitations involved in sampling from a heterogeneous population emphasizing the need to continue to improve the application of robust, unbiased techniques to quantitative studies of this complex brain disorder.
丘脑背内侧核（MD）是前额叶皮质的主要中继核，前额叶皮质是一个被认为在精神分裂症中功能失调的脑区。一些（但不是全部）对精神分裂症患者丘脑背内侧核的尸检研究报告称其体积和神经元总数减少。然而，尚不清楚这些发现是否是精神分裂症所特有的，也不清楚哪些丘脑神经元亚型受到影响。我们研究了11名精神分裂症患者、9名对照受试者和12名情绪障碍患者的左侧丘脑背内侧核。根据形态学标准，我们将神经元分为两个亚类，可能分别对应投射神经元和局部回路神经元。我们使用基于现代无偏立体学原理的方法估计丘脑背内侧核的体积和每个亚类的神经元数量。我们还使用一种稳健但有偏差的方法估计每个亚类的体细胞体积。此外，我们研究了长期服用氟哌啶醇的4只食蟹猴和4只对照猴的左侧丘脑背内侧核，以评估抗精神病药物的可能影响。这三组人类受试者在任何测量指标上均无差异。此外，两组猴子之间也未观察到差异。因此，这些发现不支持丘脑背内侧核是精神分裂症病理位点的假设，尽管它们不能排除未测量参数中存在重要的功能或结构变化。与其他研究一样，这项调查受到从异质人群中抽样所涉及的局限性的影响，强调需要继续改进将稳健、无偏技术应用于这种复杂脑部疾病的定量研究。
