BRAIN SUBSTRATES OF SELF-CONTROL IN ADDICTION

成瘾时自我控制的大脑基质

• 批准号: 6746979
• 负责人: John R Monterosso
• 金额: $ 11.77万
• 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/6746979
• 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） 本K 01提案的目标是为John Monterosso博士提供与 培训和支持，使其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 冲动的动物模型的专业知识;其基本目的是测量 在可卡因依赖患者中的类似构建体，并使用这些 结合提示反应性的测量，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 临床接触，与研究相关领域的个人指导，以及 结构化教学法研究和培训计划都是机会主义的， 利用正在进行的研究中现成的患者人群，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的指导和日常监督 她的专长在于可卡因的现象学 依赖、线索诱发的渴望及其大脑基质。罗纳德·埃尔曼博士 将提供实验室测量线索反应性的专业知识， 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，将确保成功执行的支持， 项目，并将主持一个咨询委员会的选定调查人员， 为候选人提供资源，并监督他的发展。 复吸是成瘾的一个主要特征，而这一特征要求人们 最大的人力和经济成本。了解其机制对于 降低这些成本。虽然暗示诱导的渴望和唤醒已经提供了 对我们和其他人来说，作为一种可能的机制，渴望一直是一种不完美的机制。 药物用途：并非每一次渴望发作都会复发， 患者控制这些发作的能力各不相同。主机变量可能 有助于解释这种变化。由于药物的回报是即时的， 禁欲的好处是延迟的，个体差异的敏感性， 未来的后果可能是一个重要的变数。最近的任务是 开发用于评估这方面：一个来自动物模型， 冲动，和其他两个来自神经心理学研究与眶额 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“近视电池（MB）”，用于拟议的 问题研究我们进行了一项大规模的试验性研究，取得了令人鼓舞的结果。 近视的差异可能对理解近视眼特别有用。 报告的渴望和药物使用/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/渴望，ASP， 冲动，智商。并将被给予MB。MB也将 给药至一组匹配的对照（n = 80）。在研究2中，MB将 给予参与正在进行的PET研究的可卡因患者（n = 60） 可以直接评估眶额活动我们的主要假设是：1） 可卡因依赖患者在MB上的表现比对照组差; 2） 在可卡因依赖患者中，MB的性能尤其差 3）MB的性能将与以下变量相关： 患者控制渴望状态而不复发的能力，以及4）MB 表现将与眶额功能相关。之间的联系 严重的近视和眶额损伤是特别令人兴奋的， 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眶额缺损。是否 功能障碍是使用兴奋剂的诱发因素或后果- 或者两者都有，这可能会破坏恢复的重要心理资源。