MONOAMINE SYSTEMS IN ALCOHOLISM AND SUICIDE

在肾上腺素能和其他单胺能系统的变化出现 与酗酒有关 酗酒者在很大程度上 自杀风险高于一般人群。 改变 肾上腺素能功能与自杀和严重自杀有关 尝试. 本研究将使用一个综合的社会心理和 神经生物学方法探讨脑内单胺类神经递质 酒精中毒和自杀行为，以确定是否 与酒精中毒相关的生物学变化与酒精中毒相同或相似 自杀的人，因此可以解释高自杀率。 酗酒者自杀 另一种假设是， 与自杀风险相关的生物学变化也容易导致 酒精中毒的发展。 在五年的时间里，18起自杀事件和18起 非自杀者，符合DSM-III-R酒精依赖标准，18 将对所有匹配的非精神病对照进行系统研究 关于心理社会和神经生物学指标。 此外，本发明还提供了一种方法， 9例急性中毒非酒精性自杀和9例急性中毒 将使用相同的指数对非酒精对照进行研究， 评估酒精的急性影响。 控件将与 根据死亡时间、年龄、大脑的一侧 生化分析、性别和死亡季节。 阳性者 毒理学筛选（从外周液或大脑），非法或 精神药物，除酒精外，将被排除在 书房 心理社会概况和DSM-III-R诊断将 通过心理解剖获得，包括与关键人物的访谈， 线人 将通过测量获得神经生物学特征 死后脑组织中单胺能系统的指数。 (1)的 将通过以下方式评估能系统：（a）测量 特定脑区的色氨酸、5-HT及其代谢产物5-HIAA; (b)膜制剂中放射性配体与5-HT（1A）、5-HT的结合 转运蛋白和5-HT（2）位点，以建立特异性 5-HT受体亚型;和（c）平行放射自显影研究， 测量相同的受体位点;（2）肾上腺素能和去甲肾上腺素能 系统将通过测量进行研究：（a）NE和MHPG的水平， （B）膜制剂中的结合指数， 研究β 1-肾上腺素能受体;和（c）定量受体 高亲和力和低亲和力β 2-肾上腺素能受体的放射自显影; α 1和α 2肾上腺素能受体。(3)此外， 多巴胺和代谢产物高香草酸将在指定的时间内测量。 大脑区域。 酒精依赖的特定生化相关性， 自杀或急性酒精效应是假设的。 这项研究的结果 研究将具有理论重要性，并提出新建议 药理学方法。

Alterations in the serotonergic and other monoaminergic systems appear to be associated with alcoholism. Alcoholics are at a significantly higher risk for suicide than the general population. Altered serotonergic function is associated with suicide and serious suicide attempts. The present study will use an integrated psychosocial and neurobiological approach to elucidate the relationship of brain monoamine systems to alcoholism and suicidal behavior in order to determine if biological changes associated with alcoholism are the same as, or similar to, those seen with suicide and may therefore explain the high rate of suicide among alcoholics. An alternative hypothesis is that the biological changes associated with suicide risk also predispose toward the development of alcoholism. Over a 5 year period, 18 suicides and 18 nonsuicides, meeting DSM-III-R criteria for alcohol dependence, and 18 nonpsychiatric controls, all matched, will be systematically investigated with regard to psychosocial and neurobiological indices. In addition, 9 acutely intoxicated nonalcoholic suicides and 9 acutely intoxicated nonalcoholic controls will be investigated using the same indices to assess the acute effects of alcohol. The controls will be matched to the suicides on the basis of postmortem interval, age, side of brain used for biochemical analyses, sex and season of death. Cases with positive toxicological screens (from peripheral fluids or brain), for illicit of psychoactive drugs, with the exception of alcohol, will be excluded from the study. A psychosocial profile and DSM-III-R diagnosis will be obtained by a psychological autopsy involving interviews with key informants. A neurobiological profile will be obtained by measuring indices of monoaminergic systems in postmortem brain tissue. (1) The serotonergic system will be assessed by: (a) measuring levels of tryptophan, 5-HT and its metabolite 5-HIAA in specified brain regions; (b) radioligand binding in membrane preparations to 5-HT(1A), 5-HT transporter and 5-HT(2) sites to establish binding indices of specific 5-HT receptor subtypes; and (c) parallel autoradiographic studies to measure the same receptor sites; (2) The adrenergic and noradrenergic systems will be studied by measuring: (a) levels of NE and MHPG in specified brain regions; (b) binding indices in membrane preparations to study beta 1-adrenergic receptors; and (c) quantitative receptor autoradiography of high- and low-affinity beta 2-adrenergic receptors; alpha 1- and alpha 2-adrenergic receptors. (3) Additionally, levels of dopamine and a metabolite homovanillic acid will be measured in specified brain regions. Specific biochemical correlates of alcohol dependence, suicide or acute alcohol effects are hypothesized. The findings of this study will have theoretical importance as well as suggest new pharmacological approaches.