NORADRENERGIC SYSTEM IN DEPRESSION
抑郁症中的去甲肾上腺素能系统
基本信息
- 批准号:2890431
- 负责人:
- 金额:$ 13.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1991
- 资助国家:美国
- 起止时间:1991-09-30 至 2001-03-31
- 项目状态:已结题
- 来源:
- 关键词:alpha adrenergic receptor amine oxidase (flavin) brain disorder diagnosis brain metabolism cell death central neural pathway /tract clinical research histology human tissue intercellular connection limbic system locus coeruleus major depression neuroanatomy neurochemistry neurotransmitter metabolism norepinephrine pathologic process postmortem psychopharmacology radioimmunoassay suicide tyrosine 3 monooxygenase western blottings
项目摘要
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.
来自多年深入研究的越来越多的证据表明
项目成果
期刊论文数量(0)
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GREGORY ALLEN ORDWAY其他文献
GREGORY ALLEN ORDWAY的其他文献
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{{ truncateString('GREGORY ALLEN ORDWAY', 18)}}的其他基金
Quillen College of Medicine Building 119 Renovation
奎伦医学院119号楼改造
- 批准号:
7900124 - 财政年份:2010
- 资助金额:
$ 13.7万 - 项目类别:
Center for Research Excellence Psychiatric Neuroscience
精神神经科学卓越研究中心
- 批准号:
6571629 - 财政年份:2002
- 资助金额:
$ 13.7万 - 项目类别:
Center for Research Excellence Psychiatric Neuroscience
精神神经科学卓越研究中心
- 批准号:
6796888 - 财政年份:2002
- 资助金额:
$ 13.7万 - 项目类别:
Center for Research Excellence Psychiatric Neuroscience
精神神经科学卓越研究中心
- 批准号:
6660398 - 财政年份:2002
- 资助金额:
$ 13.7万 - 项目类别: