Neuropathological studies on the vulnerability to mood disorders and refractoriness to antidepressant treatment.

为了阐明原发性情绪障碍中神经元的易感性，我们研究了在长期服用抗抑郁药和情绪稳定剂的原发性情绪障碍患者死后脑组织中，是否会观察到左前额叶皮层BA 9的细胞结构改变。左侧前额叶皮层ba9是病理生理脑区之一，我们已经清楚地证明FDG-PET估计左侧前额叶皮层ba9的葡萄糖摄取活性降低，以抑郁状态依赖的方式。左ba9的第1、第3、第4层小细胞神经元密度降低，第2层小细胞神经元密度降低。与正常对照组相比，左脑9区的胶质细胞密度和大神经元细胞密度没有变化，但通过脑9区的皮质深度可以观察到胶质细胞密度和大神经元密度的下降。有趣的是，原发性情绪障碍患者死后大脑第II层血清素(5-HT)-2A受体免疫细胞数量显著增加，而左BA 9第I、III、IV层细胞数量明显增加。众所周知，在亚慢性给药后，大鼠大脑皮层中5-HT-2A受体结合位点的密度下调。因此，位于左侧前额叶皮层的第二层ba9在原发性情绪障碍的易感性和抗抑郁药物治疗的难耐性中具有特殊的作用。

To clarify a neuronal vulnerability in primary mood disorder, we have investigated if cytoarchitectural alterations would be observed in the left prefrontal cortex, BA 9 in postmortem brain tissue from subjects with primary mood disorder, who were under long-term treatment with antidepressant and mood stabilizers. The left prefrontal cortex, BA 9 is documented to be one of the pathophysiological brain regions, and we have clearly demonstrated that the lowered glucose uptake activity was estimated by FDG-PET, in the left prefrontal cortex, BA 9, in depressive state-depended manner. Reduction in the density of small cell neurons has been observed in layer II, but not in I, III, IV in the left BA 9. There are no changes in glial density and large neuronal cell density in the left BA 9, although the decrease was observed through the depth of cortex of BA 9, compared with normal controls. Interestingly, the number of serotonin (5-HT)-2A receptor immunorecative cells was significantly increased in layer II, but not in I, III, IV in the left BA 9 in postmortem brain from subjects with primary mood disorder. The density of 5-HT-2A receptor binding sites is well-known to be down-regulated after subchronic administration of antidepressant agents in rat cerebral cortex. Therefore, the layer II in the left prefrontal cortex, BA 9 is of special interest in the vulnerability in primary mood disorder and refractoriness to antidepressant treatment.