MONOAMINE SYSTEMS IN ALCOHOLISM AND SUICIDE

酗酒和自杀中的单胺系统

• 批准号: 2045034
• 负责人: Victoria Arango
• 金额: $ 33.08万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2045034
• 关键词: 3 methoxy 4 hydroxyphenylethyleneglycol; alcoholic beverage consumption; alcoholism /alcohol abuse; alpha adrenergic receptor; autoradiography; behavior test; beta adrenergic receptor; brain mapping; dopamine; family; high performance liquid chromatography; human subject; hydroxyindoleacetate; interview; mental disorder diagnosis; neurochemistry; neuropsychology; neurotransmitter metabolism; norepinephrine; postmortem; radiotracer; receptor binding; serotonin; serotonin receptor; social psychology; suicide; tissue resource /registry

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.

血清素能和其他单胺能系统的改变出现 与酒精中毒有关。 酒精中毒大量 自杀的风险高于一般人口。 改变 血清素能功能与自杀和严重自杀有关 尝试。 本研究将使用综合的心理社会和 神经生物学方法阐明了脑单胺的关系 酗酒和自杀行为的系统，以确定是否是否 与酒精中毒相关的生物学变化与或类似 对于那些自杀而看到的人，因此可以解释 酗酒者中的自杀。 另一种假设是 与自杀风险相关的生物学变化也易于 酒精中毒的发展。 在5年内，18个自杀和18个 非固定剂，满足DSM-III-R酒精依赖标准，18 非精神控制均应匹配的非精神病控制 关于社会心理和神经生物学指数。 此外， 9急性陶醉的非酒精自杀和9急性陶醉 非酒精控制将使用相同的指标进行研究 评估酒精的急性影响。 控件将与 根据验尸间隔，年龄，大脑的一面自杀 生化分析，性别和死亡季节。 案例为正 毒理学筛选（来自外周液或大脑），以供非法 除酒精外，精神活性药物将被排除在外 研究。 心理社会概况和DSM-III-R诊断将是 通过心理尸检获得涉及关键采访的心理尸检 线人。 通过测量将获得神经生物学特征 验尸脑组织中单胺能系统的指标。 （1） 血清素能系统将通过：（a）测量水平 色氨酸，5-HT及其代谢物5-HIAA在特定的大脑区域中； （b）在膜制剂中与5-HT（1A），5-HT的放射性结合 转运蛋白和5-HT（2）位点，以建立特定的结合指标 5-HT受体亚型； （c）平行自显影研究 测量相同的受体位点； （2）肾上腺素和去甲肾上腺素能 将通过测量来研究系统：（a）NE和MHPG的水平 指定的大脑区域； （b）膜制剂中的结合指数 研究β1-肾上腺素受体； （c）定量受体 高亲和力β2-肾上腺素能受体的放射自显影； α1-和α2-肾上腺素受体。 （3）此外， 将在指定的 大脑区域。 酒精依赖的特定生化相关性， 假设自杀或急性酒精效应。 这个发现 研究将具有理论上的重要性，并建议新的 药理方法。

项目成果

Serotonergic and noradrenergic neurobiology of alcoholic suicide.

酒精自杀的血清素能和去甲肾上腺素能神经生物学。

• DOI: 10.1097/01.alc.0000127415.15000.ca
• 发表时间: 2004
• 期刊: Alcoholism, clinical and experimental research
• 作者: Underwood,MarkD;Mann,JJohn;Arango,Victoria
• 通讯作者: Arango,Victoria

Selective alterations of the CB1 receptors and the fatty acid amide hydrolase in the ventral striatum of alcoholics and suicides.

酗酒者和自杀者腹侧纹状体中 CB1 受体和脂肪酸酰胺水解酶的选择性改变。

• DOI: 10.1016/j.jpsychires.2009.11.013
• 发表时间: 2010
• 期刊: Journal of psychiatric research
• 影响因子: 4.8
• 作者: Vinod,KYaragudri;Kassir,SuhamA;Hungund,BasalingappaL;Cooper,ThomasB;Mann,JJohn;Arango,Victoria
• 通讯作者: Arango,Victoria

Biologic alterations in the brainstem of suicides.

自杀者脑干的生物学改变。

• DOI: 10.1016/s0193-953x(05)70331-2
• 发表时间: 1997
• 期刊: The Psychiatric clinics of North America
• 作者: Arango,V;Underwood,MD;Mann,JJ
• 通讯作者: Mann,JJ

Elevated levels of endocannabinoids and CB1 receptor-mediated G-protein signaling in the prefrontal cortex of alcoholic suicide victims.

酒精自杀受害者前额皮质内源性大麻素和 CB1 受体介导的 G 蛋白信号传导水平升高。

• DOI: 10.1016/j.biopsych.2004.11.033
• 发表时间: 2005
• 期刊: Biological psychiatry
• 影响因子: 10.6
• 作者: Vinod,KYaragudri;Arango,Victoria;Xie,Shan;Kassir,SuhamA;Mann,JJohn;Cooper,ThomasB;Hungund,BasalingappaL
• 通讯作者: Hungund,BasalingappaL

Morphometry of dorsal raphe nucleus serotonergic neurons in alcoholism.

• DOI: 10.1111/j.1530-0277.2007.00365.x
• 发表时间: 2007-05
• 期刊: Alcoholism, clinical and experimental research
• 作者: M. Underwood;J. Mann;V. Arango