BRAIN SUBSTRATES OF SELF-CONTROL IN ADDICTION

成瘾时自我控制的大脑基质

• 批准号: 6515332
• 负责人: John R Monterosso
• 金额: $ 1.83万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 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 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6515332
• 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：（由申请人提供） 该 K01 提案的目标是为 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 冲动动物模型方面的专业知识；其基本目的是衡量 可卡因依赖患者的类似结构并使用这些 测量与提示反应相结合，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 结构化的教学法。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。 Anna Rose Childress 博士将提供主要指导和日常监督 在拟议的研究中；她的专长在于可卡因的现象学 依赖性、提示引起的渴望及其大脑基质。罗纳德·埃尔曼博士 将提供提示反应性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以下方面的专业知识 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研究人员组成的咨询委员会，这些研究人员将 为候选人提供资源并监控他的发展。 旧病复发是成瘾的一个主要特征，也是成瘾者必须戒掉的一个特征。 最大的人力和经济成本。了解其机制至关重要 减少这些成本。尽管已经提供了暗示引起的渴望和唤醒 对于我们和其他人来说，渴望作为一种可能的机制，一直是一种不完美的机制。 吸毒的预测因素：并非每次渴望发作都会导致复发，并且 患者处理这些事件的能力各不相同。宿主变量可能 帮助解释这种变异性。由于药物的回报是立竿见影的 禁欲的益处会延迟，个体对禁欲的敏感度存在差异 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：源自动物模型的一个维度 冲动，以及另外两个来自眶额神经心理学研究的 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）”，用于建议的 研究。我们进行了一项大型试点研究，取得了令人鼓舞的结果。 近视的差异对于理解近视的差异可能特别有用 报告的渴望与药物使用/复发之间脱节。 在研究 1 中，可卡因依赖患者参与大规模治疗 结果研究（n = 120）将根据线索反应性/渴望、ASP、 冲动、智商并将被管理MB。 MB 也将 给予一组匹配的对照（n=80）。在研究 2 中，MB 将是 给予参加正在进行的 PET 研究的可卡因患者 (n=60) 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 上的表现会比对照组差； 2） 可卡因依赖患者的 MB 表现尤其差 与 ASP； 3）MB上的性能将与可变性相关 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 鉴于严重近视和眶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） 与对照组相比，可卡因成瘾者的眶额缺陷。无论是 功能障碍是使用兴奋剂的诱发因素或结果 - 或两者兼而有之——它可能会破坏康复的重要心理资源。