Norepinephrine and Impulsivity

去甲肾上腺素和冲动

基本信息

批准号：
7588818
负责人：
Alan C Swann
金额：
$ 29.92万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2011-03-31
项目状态：
已结题

项目摘要

This is a proposal to study mechanisms of state-dependent change in impulsivity. Understanding of the mechanisms of short term changes in impulsivity will be important in designing means for diagnosis, monitoring, and treatment of the potentially destructive disorders where impulsivity is prominent or where even small changes in impulsivity may have dire consequences. Most existing knowledge concerns impulsivity as a stable trait rather than the near term likelihood of impulsive behavior. The overall hypothesis of this proposal is that state-dependent flucutations in impulsivity are related to changes in noradrenergic function and occur against the backgrand of stable trait-related impulsivity that may depend on serotonergic function. Bipolar disorder provides a model for state-dependent change since increased impulsivity is closely linked to the manic state. Antisocial personality provides a comparison group where impulsivity is less related to affective state. Norepinephrine and its neurophysiological effects are also increased in mania. Effects on event-related potentials provide an objective and readily available measure that is directly related to the CNS. Based on this model, we will investigate whether short term changes in impulsivity are related to changes in noradrenergic activity and its neurophpysiological consequences. State-related changes in impulsivity will be measured using behavioral laboratory methods that our group has developed. The Specific Aims are 1) to compare state and trait measures of impulsivity, noradrenergic function, and event-related potentials (sensory gating) in euthymic and manic subjects with bipolar disorder, subjects with antisocial personality disorder, and healthy control subjects, 2) to investigate effects of pharmacologically decreasing noradrenergic function with clonidine in manic subjects with bipolar disorder and in subjects with antisocial personality disorder, with the hypothesis that there will be parallel reductions in plasma MHPG, state-related impulsivity, and sensory gating impairment, 3) to investigate effects of pharmacologically increased noradrenergic activity by yohimbine in subjects with antisocial personality disorder and healthy controls, with the hypothesis that there will be parallel increases in the same parameters reduced in manic subjects by clonidine in AIM 2, and 4) in AIMS 2 and 3 we will investigate the relationship between baseline trait-like impulsivity and the sensitivity of impulsivity to changes in noradrenergic function. The results of these experiments may suggest means for monitoring risk for impulsive behavior and for a rational treatment schema for impulsivity.

这是一项研究冲动性中依赖于状态的变化机制的提议。了解冲动短期变化的机制对于设计诊断、监测和治疗潜在破坏性疾病的方法非常重要，在这些疾病中，冲动很突出，或者即使冲动的微小变化也可能产生可怕的后果。大多数现有知识都将冲动视为一种稳定的特征，而不是近期发生冲动行为的可能性。该提议的总体假设是，冲动性的状态依赖性波动与去甲肾上腺素能功能的变化有关，并且是在可能依赖于血清素能功能的稳定特征相关冲动性的背景下发生的。双相情感障碍提供了状态依赖性变化的模型，因为冲动性的增加与躁狂状态密切相关。反社会人格提供了一个比较群体，其中冲动是与情感状态关系不大。去甲肾上腺素及其神经生理学作用在躁狂症中也会增加。对事件相关电位的影响提供了一种与中枢神经系统直接相关的客观且易于使用的测量方法。基于这个模型，我们将研究冲动的短期变化是否与去甲肾上腺素能活动的变化及其神经生理学后果有关。与状态相关的冲动变化将使用我们小组开发的行为实验室方法来测量。具体目标是 1) 比较正常和躁狂双相情感障碍受试者、反社会人格障碍受试者和健康对照受试者的冲动、去甲肾上腺素能功能和事件相关电位（感觉门控）的状态和特征测量，2)研究可乐定在药理学上降低去甲肾上腺素能功能对双相情感障碍躁狂受试者和反社会人格障碍受试者的影响，假设去甲肾上腺素能功能会平行减少血浆 MHPG、状态相关冲动和感觉门控障碍，3) 研究育亨宾在药理学上增加去甲肾上腺素活性对反社会人格障碍和健康受试者的影响对照，假设在 AIM 2 和 4 中，躁狂受试者中通过可乐定减少的相同参数会平行增加，在 AIMS 2 和 3 中，我们将研究基线特质样冲动性与冲动性敏感性之间的关系。去甲肾上腺素能功能的变化。这些实验的结果可能会提出监测冲动行为风险的方法以及针对冲动的合理治疗方案。