MONOAMINE SYSTEMS IN ALCOHOLISM AND SUICIDE

5-羟色胺能系统和其他单胺能系统出现变化 与酗酒有关。酗酒者处于显著的 自杀风险高于普通人群。更改后的 5-羟色胺能功能与自杀和严重自杀有关 尝试。本研究将综合运用心理学和社会心理学的方法。 用神经生物学方法阐明脑单胺类物质的相互关系 酒精中毒和自杀行为的系统，以确定是否 与酒精中毒相关的生物变化与酒精中毒相同或相似 对于那些被视为自杀的人，可能因此解释了高自杀率 酗酒者自杀。另一种假设是， 与自杀风险相关的生物变化也容易导致 酒精中毒的发展。在5年内，18起自杀事件和18起 非自杀，符合DSM-III-R酒精依赖标准，以及18 将对所有匹配的非精神病对照进行系统调查 关于心理社会和神经生物学指数。此外, 9例急性醉酒非酒精自杀和9例急性醉酒自杀 将使用相同的指数对非酒精控制进行调查 评估酒精的急性影响。这些控件将与 根据死后时间间隔、年龄、大脑一侧用于 生化分析，性别和死亡季节。呈阳性的病例 毒物学筛查(来自外周液体或大脑)，用于非法 精神活性药物，除酒精外，将被排除在 这项研究。心理社会档案和DSM-III-R诊断将是 通过对Key进行的心理验尸获得的 告密者。通过测量将获得神经生物学特征。 死后脑组织单胺能系统的指标。(1) 5-羟色胺能系统将通过以下方式进行评估：(A)测量 特定脑区的色氨酸、5-羟色胺及其代谢物5-HIAA； (B)膜制剂中的放射性配体与5-羟色胺(1A)、5-羟色胺的结合 转运蛋白和5-羟色胺(2)结合位点建立特异性结合指数 5-羟色胺受体亚型；和(C)平行放射自显影研究 测量相同的受体位置；(2)肾上腺素能和去甲肾上腺素能 将通过测量以下指标来研究系统：(A)#年NE和MHPG水平 指定脑区；(B)膜制剂中的结合指数 研究β1-肾上腺素能受体；和(C)定量受体 高亲和力和低亲和力β2肾上腺素能受体的放射自显影； α1和α2肾上腺素能受体。(3)此外， 多巴胺和一种代谢物高香草酸将在特定的 大脑区域。酒精依赖的特定生化关联， 自杀或急性酒精影响是假设的。这项研究的发现 研究将具有理论意义，并提出新的建议 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.