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

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) 这项K01提案的目标是为约翰·蒙特罗索博士提供 培训和支持，以成为一名独立的调查员 临床药物滥用研究。这项研究计划建立在候选人的基础上 动物冲动模型方面的专业知识；它的基本目标是测量 在可卡因依赖患者中的类似结构并使用这些 结合线索反应性进行测量以更好地表征患者 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 结构化的教学论。研究和培训计划都是机会主义的， 利用正在进行的研究中容易获得的患者群体，以及 宾夕法尼亚大学研究界经验丰富的研究人员。 安娜·罗斯·奇尔德里斯博士将提供主要指导和日常监督 她的专长在于可卡因的现象学。 依赖、线索诱导的渴望及其大脑底物。罗纳德·埃尔曼博士 将提供线索反应性的实验室测量方面的专业知识，以及 统计建模。查尔斯·奥布莱恩博士将提供有关 成瘾的神经生物学，将确保支持成功执行 项目，并将主持一个由选定的调查人员组成的咨询委员会，该委员会将 为候选人提供资源，并监督他的发展。 复发是上瘾的主要特征，而上瘾的主要特征是 最大的人力和经济代价。了解它的机制对于 降低这些成本。尽管已经提供了线索诱导的渴望和唤醒 无论是我们，还是其他人，作为一种可能的机制，渴望一直是一种不完美的 毒品使用的预测因素：并不是每一次渴望发作都会导致复发，而且 患者处理这些发作的能力各不相同。主机变量可以 帮助解释这种可变性。因为毒品的回报是立竿见影的 节欲的好处是延迟的，个体对 未来的后果可能是一个重要的变量。最近的任务是 为评估这一维度而开发的：源自动物模型的维度 冲动，以及其他两个来自orbitofrontal的神经心理学研究 表现出极端行为“近视”的患者(Damasio，1994)。我们有 将这些方法组合成一种“近视电池(MB)”，用于建议的 学习。我们进行了一项大规模的试点研究，取得了令人鼓舞的结果。 近视的差异可能特别有助于理解 报告的渴求与吸毒/复发之间的脱节。 在研究1中，参与大规模治疗的可卡因依赖患者 结果研究(n=120)将评估线索反应性/渴求、ASP、 冲动，智商，并将被给予MB。MB也将是 给一组匹配的对照组(n=80)。在研究2中，甲基溴将是 注射给参与正在进行的PET研究的可卡因患者(n=60) 直接评估眼眶前额的活动。我们的主要假设是：1) 可卡因依赖者在MB上的表现会比对照组差；2) 在可卡因依赖患者中，MB的表现将特别差 使用ASP；3)MB上的性能与以下各项的可变性有关 患者管理渴望状态的能力而不会复发，以及4)MB 表现将与眼眶额叶功能相关。两者之间的联系 严重近视和眼眶前额损伤尤其令人兴奋 新出现的证据(包括最近在我们自己的实验室收集的证据) 可卡因成瘾者相对于对照组的眼眶前额叶缺陷。无论是 功能障碍是兴奋剂使用的诱因或后果- 或者两者兼而有之--这可能会破坏恢复的重要心理资源。