BRAIN SUBSTRATES OF SELF-CONTROL IN ADDICTION

成瘾时自我控制的大脑基质

• 批准号: 6682493
• 负责人: John R Monterosso
• 金额: $ 9.68万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6682493
• 关键词: behavioral /social science research tag; clinical research; cocaine; craving; cues; drug addiction; frontal lobe /cortex; functional magnetic resonance imaging; human subject; locus of control; neuropsychological tests; outcomes research; positron emission tomography; postdoctoral investigator; relapse /recurrence; behavioral /social science research tag; clinical research; cocaine; craving; cues; drug addiction; frontal lobe /cortex; functional magnetic resonance imaging; human subject; locus of control; neuropsychological tests; outcomes research; positron emission tomography; postdoctoral investigator; relapse /recurrence

DESCRIPTION: (Provided by Applicant) The goal of this K01 proposal is to provide John Monterosso, Ph.D., with the training and support to become an independent investigator in the field of clinical substance abuse research. The research plan builds on the candidate's expertise in animal models of impulsivity; its basic aim is to measure analogous constructs in cocaine dependent patients and to use these measurements in conjunction with cue reactivity to better characterize patients and to better predict treatment outcomes. The training plan provides extensive clinical exposure, individual mentoring in areas related to the research, and structured didactics. Both the research and training plans are opportunistic, utilizing readily-available patient populations from ongoing research, and seasoned investigators in the University of Pennsylvania research community. Dr. Anna Rose Childress will provide primary mentorship and daily supervision in the proposed research; her expertise lies in the phenomenology of cocaine dependence, cue-induced craving, and its brain substrates. Dr. Ronald Ehrman will provide expertise in the laboratory measurement of cue reactivity, and in statistical modeling. Dr. Charles O'Brien will provide expertise on the neurobiology of addiction, will ensure support for successful execution of the project, and will chair an Advisory Board of selected investigators who will be a resource to the candidate and monitor his development. Relapse is a cardinal feature of the addictions, and the one which exacts the greatest human and economic costs. Understanding its mechanisms is critical to reducing these costs. Though cue-induced craving and arousal have been offered by us, and by others, as one possible mechanism, craving has been an imperfect predictor of drug use: not every craving episode eventuates in relapse, and patients vary in their ability to manage these episodes. Host variables may help explain this variability. Since the reward of drug is immediate and the benefits of abstinence are delayed, individual differences in sensitivity to future consequences may be an important variable. Tasks have recently been developed for assessing this dimension: one derived from an animal model of impulsivity, and two others from neuropsychological research with orbitofrontal patients, who show extreme behavioral "myopia" (Damasio, 1994). We have combined these methods into a "Myopia Battery (MB)" for use in the proposed studies. We have conducted a large pilot study with encouraging results. Differences in myopia may be particularly useful for understanding the disconnect between reported craving and drug use/relapse. In Study 1, cocaine-dependent patients participating in a large-scale treatment outcome study (n= 120) will be assessed on cue reactivity/craving, ASP, Impulsivity, I.Q. and will be administered the MB. The MB will also be administered to a group of matched controls (n=80). In Study 2, the MB will be administered to cocaine patients (n=60) participating in ongoing PET studies that directly assess orbitofrontal activity. Our primary hypotheses are: 1) cocaine-dependent patients will perform worse on the MB than controls; 2) performance on the MB will be especially poor in cocaine-dependent patients with ASP; 3) performance on the MB will be related to the variability of patients' ability to manage craving states without relapsing, and 4) MB performance will be correlated with orbitofrontal functioning. The link between severe myopia and orbitofrontal impairment is particularly exciting given emerging evidence (including that collected recently in our own lab) of orbitofrontal deficits in cocaine addicts relative to controls. Whether the dysfunction is a predisposing factor for, or a consequence of, stimulant use - or both - it could undermine an important psychological resource for recovery.

描述：（申请人提供） 该K01提案的目标是向约翰·蒙特罗索（John Monterosso）博士提供 培训和支持成为该领域的独立调查员 临床药物滥用研究。研究计划建立在候选人的基础上 动物模型的专业知识；它的基本目的是衡量 可卡因依赖性患者的类似结构，并使用这些 结合提示反应性以更好地表征患者的测量 并更好地预测治疗结果。培训计划提供了广泛的 临床暴露，与研究相关领域的个人指导以及 结构性教学。研究和培训计划都是机会主义的， 利用正在进行的研究和 宾夕法尼亚大学研究界经验丰富的调查人员。 Anna Rose Childress博士将提供主要指导和日常监督 在拟议的研究中；她的专业知识在于可卡因的现象学 依赖性，提示引起的渴望及其大脑底物。罗纳德·埃尔曼（Ronald Ehrman）博士 将在实验室测量提示反应性方面提供专业知识，并在 统计建模。查尔斯·奥布赖恩（Charles O'Brien）博士将提供有关 成瘾的神经生物学将确保成功执行成功 项目，并将主席选定调查人员的顾问委员会 候选人的资源并监控他的发展。 复发是成瘾的基本特征，而精确 最大的人类和经济成本。了解其机制对 降低这些成本。尽管提出了提示引起的渴望和唤醒 由我们和其他人作为一种可能的机制，渴望是不完美的 毒品使用的预测因素：并非每一个渴望发作都会发生复发，并且 患者管理这些发作的能力各不相同。主机变量可能 帮助解释这种变异性。由于药物的奖励是立即的， 禁欲的益处被延迟，对敏感性的个体差异 未来后果可能是一个重要的变量。最近的任务是 开发用于评估这一维度的开发：一个来自的动物模型 冲动性，另外两个来自神经心理学研究 表现出极端行为“近视”的患者（Damasio，1994年）。我们有 将这些方法合并为“近视电池（MB）”，以便在拟议中使用 研究。我们进行了一项大型试点研究，结果令人鼓舞。 近视的差异可能对于理解 报道的渴望和药物使用/复发之间的连接。 在研究1中，可卡因依赖性患者参加了大规模治疗 结果研究（n = 120）将在提示反应性/渴望，ASP， 冲动性，I.Q。并将管理MB。 MB也将 用于一组匹配的对照组（n = 80）。在研究2中，MB将是 对正在进行的PET研究的可卡因患者（n = 60）管理 直接评估眶额活动。我们的主要假设是：1） 可卡因依赖性患者在MB上的表现将比对照组差。 2） 在可卡因依赖性患者中，在MB上的表现尤其较差 使用ASP; 3）MB的性能将与 患者在不复发的情况下管理渴望状态的能力，4）MB 性能将与轨道额的功能相关。之间的链接 考虑到严重的近视和轨道额外损害特别令人兴奋 新兴证据（包括最近在我们自己的实验室收集的证据） 可卡因成瘾者的轨道额缺陷相对于对照。是否 功能障碍是刺激性使用或结果的诱发因素 - 或两者兼而有之 - 它可能破坏恢复的重要心理资源。