Norepinephrine and Impulsivity

去甲肾上腺素和冲动

• 批准号: 7201666
• 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
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7201666
• 关键词: Acute; Affective; Antisocial Personality Disorder; Behavior; Behavioral; Bipolar Disorder; Characteristics; Clonidine; Data; Diagnosis; Disease; Event-Related Potentials; Future; Impairment; Impulsive Behavior; Impulsivity; Knowledge; Laboratories; Link; Manic; Measurable; Measures; Mental disorders; Methods; Methoxyhydroxyphenylglycol; Modeling; Monitor; Nature; Norepinephrine; Plasma; Range; Research Personnel; Risk; Role; Series; TNFRSF5 gene; Time; Yohimbine; base; comparison group; design; neurophysiology; noradrenergic; prevent; programs; research study; sensory gating; trait

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.

这是研究冲动性国家依赖性变化机制的建议。理解冲动性变化的机制对于设计诊断，监测和治疗冲动很突出的潜在破坏性疾病的方法将很重要，或者冲动性的少量变化也可能带来可怕的后果。大多数现有的知识将冲动性视为稳定的特征，而不是冲动行为的近期可能性。该提议的总体假设是，冲动性的状态依赖性抗性与去甲肾上腺素能功能的变化有关，并且发生在可能取决于血清素能功能的稳定性状相关冲动的背景下。双相情感障碍为状态依赖性变化提供了模型，因为增加的冲动性与躁狂状态密切相关。反社会个性提供了一个比较组，冲动是 与情感状态相关。去甲肾上腺素及其神经生理学作用在躁狂症中也有所增加。对事件相关电位的影响提供了与CNS直接相关的客观且随时可用的措施。基于此模型，我们将研究冲动性的短期变化是否与去甲肾上腺素能活性及其神经生理学后果的变化有关。使用我们小组开发的行为实验室方法来测量与国家相关的冲动性变化。 具体目的是1）比较躁动和躁狂受试者的冲动性，去肾上腺素功能功能以及与事件相关的潜力（感觉滑雪）的状态和特征度量，具有双相情感障碍，具有抗性性人格障碍的受试者以及健康控制受试者，2）研究与甲肾上腺疾病中的甲酸盐功能相关的作用，以研究与甲苯丙诺拉氏症相关的作用，以降低甲酸盐的效果。人格障碍，假设血浆MHPG，与状态相关的冲动性和感觉门控障碍将平行降低，3）研究Yohimbine在具有抗社会人格障碍和健康健康的受试者的药理学上增加的去甲肾上腺素活性的影响 对照组的假设是，在AIM 2中，可乐定在躁狂受试者中，相同的参数将平行增加，而在AIM 2和3中，我们将研究基线性状样的冲动性与冲动性对甲肾上腺素能功能变化的敏感性之间的关系。这些实验的结果可能表明，用于监测冲动行为的风险以及对冲动性的合理治疗模式的手段。