NORADRENERGIC SYSTEM IN DEPRESSION

多年密集研究的证据表明， 大脑去甲肾上腺素和/或血清素的紊乱主要发生在 萧条然而，抑郁症的基本神经生物学还没有 尚未被阐明。本研究的目的是验证假设 神经化学/神经解剖学缺陷的独特组合 发生在去甲肾上腺素能系统（特别是蓝斑） 严重抑郁症实验旨在解决以下问题： (1)精确的神经化学和/或神经解剖学改变和（2） 精神疾病改变的特异性。到 解决第一个问题，一些蛋白质的浓度， 将在整个蓝斑测量物质，并在一个 主要边缘投射区（杏仁核）在死后的大脑， 患有重度抑郁症的受试者和来自精神病学正常对照组的受试者 科目特别是，一些去甲肾上腺素能和非去甲肾上腺素能的 作为抗抑郁药物作用位点的蛋白质将被 沿着研究的蛋白质水平在基因座中被调节 抗抑郁药治疗的蓝斑。初步调查结果显示， 去甲肾上腺素能细胞的数量是去甲肾上腺素能 蓝斑中的蛋白质浓度。此外，细胞损失 蓝斑与衰老、阿尔茨海默病和 帕金森氏症。因此，如果蓝斑的细胞数量改变， 在精神疾病中，这种变化可能使测量 蓝斑中的去甲肾上腺素能蛋白或导致 蓝斑神经化学改变的误解 严重抑郁症患者因此，去甲肾上腺素能神经元的密度和数量 将在所有受试者中进行体视学估计， 神经化学测量。为了解决特异性问题，4组 的受试者将接受研究：1）无精神病诊断，年龄匹配 对照组受试者死于自然或意外原因，2）自杀 重度抑郁症患者，3）非自杀受试者， 抑郁症，以及4）轴I诊断的自杀受害者， 萧条这项研究将扩大和澄清的主要发现， 第一批研究经费。生物化学和/或 蓝斑神经元的解剖学改变与主要 抑郁症可能会产生重要的信息， 有效的治疗方法

Converging evidence from years of intensive research has implicated that a disorder of brain norepinephrine and/or serotonin occurs in major depression. However, the basic neurobiology of major depression has not yet been elucidated. The goal of this research is test the hypothesis that a distinct constellation of neurochemical/neuroanatomical deficits occurs in the noradrenergic system (in particular, the locus coeruleus) in major depression. Experiments are designed to address the issues of (1) the precise neurochemical and/or neuroanatomical alterations and (2) the specificity of alterations with respect to psychiatric illness. To address the first issue, concentrations of a number of proteins and substances will be measured throughout the locus coeruleus, and in a major limbic projection area (amygdala) in post-mortem brains from subjects with major depression and from psychiatrically normal control subjects. In particular, a number of noradrenergic and non-noradrenergic proteins which are sites of action of antidepressant drugs will be studied, along with proteins of which levels are modulated in the locus coeruleus by antidepressant treatment. Preliminary findings demonstrates that noradrenergic cell number is a major determinant of noradrenergic protein concentration in the locus coeruleus. Furthermore, cell loss in the locus coeruleus is associated with aging, Alzheimer's disease, and Parkinson's disease. Thus, if cell number in locus coeruleus is altered in psychiatric disease, such a change could complicate measurements of noradrenergic proteins in the locus coeruleus or lead to misinterpretation of neurochemical alterations in the locus coeruleus from major depressives. Thus, noradrenergic neuron density and number will be estimated stereologically in all subjects in parallel with neurochemical measurements. To address the issue of specificity, 4 groups of subjects will be studied: 1) no psychiatric diagnosis, age-matched control subjects dying of natural or accidental causes, 2) suicide victims with major depression, 3) non-suicide subjects with major depression, and 4) suicide victims with Axis I diagnoses other than major depression. This research will extend and clarify major findings of research in the first grant period. Elucidation of the biochemical and/or anatomical alterations of locus coeruleus neurons associated with major depression may yield important information for the development of more effective treatments for this devastating disorder.