NEURONAL ORGANIZATION OF FRONTAL CORTEX IN DEPRESSION

描述(摘自申请者摘要)：最近的神经成像 研究表明，大体形态和代谢活性存在变化 受试者左侧前额叶皮质(眶前和/或背外侧) 患有抑郁症和精神分裂症。这位调查员最近的研究表明 显示出前额叶皮质细胞结构的变化 与精神分裂症有关，提供了一种形态病理学基础 精神分裂症皮质的神经影像研究中报告的异常。 然而，前额叶皮质的细胞构筑学研究还没有 到目前为止，他一直在治疗抑郁症。因此，基于神经成像研究 显示前额叶皮质的大体形态和代谢变化 在抑郁的大脑中，研究人员假设细胞构筑 重度抑郁症患者左侧前额叶皮质发生改变。此外， 多条证据表明单胺类系统功能障碍 情感障碍的病理学。额叶皮质可能是这种情况的一个部位 病理，因为该区域是单胺类突触后的重要靶点 投影系统。因此，调查员还假设 额叶皮质细胞构筑的改变伴随着改变 在这一地区单胺系统的神经化学组织中。这个 本项目的具体目标将：1)审查量化 死后脑背外侧前额叶皮质的细胞构筑 抑郁症自杀者的组织并与自杀者进行比较 非自杀的主要抑郁对象，非抑郁的精神分裂症患者和年龄- 和性别匹配的非精神病对照；2)建立量化 正常人眶前叶皮质的细胞构筑标准 并在四种诊断方法中检查大脑皮质的细胞结构 3)揭示儿茶酚胺能和 4)四组前额叶皮质的5-羟色胺能受体 比较各个皮质层的神经元密度和受体密度。至 为了实现这些目标，调查员将使用直接的、三维的 用于测量细胞结构参数(神经元和神经胶质细胞)的图像分析仪 密度、细胞大小、层宽)和计算机化成像设备 对大脑皮层各层的受体进行密度分析 相同受试者中相同的前额叶区域。拟议的项目将 检测神经元结构(细胞结构和/或 前额叶皮质的化学结构)，这可能是 抑郁症的神经病理学。这一信息可能会阐明潜在的 用于开发新的抗抑郁药物治疗的神经元部位。在……里面 此外，该项目将支持调查员的特殊性 先前关于精神分裂症和精神分裂症的形态病理学发现 定义前额叶区域是相同的还是不同的 精神分裂症和抑郁症的神经病理学。

DESCRIPTION (Adapted from applicant's abstract): Recent neuroimaging studies indicate changes exist in gross morphology and metabolic activity of the left prefrontal cortex (orbitofrontal and/or dorsolateral) of subjects with depression and schizophrenia. The investigator's recent studies have demonstrated changes in cell architecture in prefrontal cortex which are associated with schizophrenia, providing a morphopathological basis for abnormalities reported in neuroimaging studies on schizophrenic cortex. However, cytoarchitectonic studies of the prefrontal cortex have not been undertaken on depression to date. Thus, based on neuroimaging studies demonstrating gross morphological and metabolic changes in prefrontal cortex in depressive brains the investigator hypothesizes that cytoarchitectonic changes occur in left prefrontal cortex in major depression. Furthermore, multiple lines of evidences implicate dysfunction of monoamine systems in the pathology of affective disorders. Frontal cortex may be a site of this pathology since this region is an important postsynaptic target of monoamine projection systems. Therefore, the investigator also hypothesizes that cytoarchitectonic changes in frontal cortex are accompanied by alterations in neurochemical organization of monoamine systems in this region. The specific aims of this project will: 1) examine the quantitative cytoarchitecture of the dorsolateral prefrontal cortex in postmortem brain tissue of suicide victims with major depression and compare it to that of nonsuicide major depressive subjects, nondepressed schizophrenics and age- and sex-matched nonpsychiatric controls; 2) establish quantitative cytoarchitectonic criteria for the orbitofrontal cortex in normal human brain and examine the cytoarchitecture of this cortex in the four diagnostic groups; 3) reveal the autoradiographic densitometry of catecholaminergic and serotonergic receptors in prefrontal cortex of the four groups; 4) and compare neuronal and receptor densities for individual cortical layers. To accomplish these aims the investigator will use a direct, 3-dimensional image analyzer to measure cytoarchitectonic parameters (neuronal and glial density, cell size, laminar width) and a computerized imaging device to conduct densitometric analyses of receptors in individual layers of the very same prefrontal regions in the same subjects. The proposed project will detect alterations in neuronal organization (cytoarchitecture and/or chemoarchitecture) of prefrontal cortex which may underlie the neuropathology of depression. This information may elucidate potential neuronal sites for the development of novel antidepressant treatments. In addition, this project will support specificity of the investigator's previous morphopathological findings with respect to schizophrenia and define whether the same or different prefrontal regions are involved in the neuropathology of schizophrenia and major depression.