Does amphetamine use impair brain systems in OEF/OIF veterans with PTSD?

使用安非他明是否会损害患有 PTSD 的 OEF/OIF 退伍军人的大脑系统？

• 批准号: 8142267
• 负责人: MARTIN P. PAULUS
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-10-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8142267
• 关键词: Accounting; Acute; Addictive Behavior; Address; Affect; Alcohols; Amphetamine Abuse; Amphetamines; Amygdaloid structure; Anterior; Attenuated; Behavior; Behavior assessment; Behavioral; Brain; Brain imaging; Breathing; C Fiber; Cessation of life; Characteristics; Choice Behavior; Clinical; Cocaine; Complex; Corpus striatum structure; Decision Making; Disease; Drug usage; Emotional; Emotions; Esthesia; Event; Exhibits; Feeling; Freedom; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Heating; Hospitalization; Illicit Drugs; Individual; Institutes; Insula of Reil; Intervention; Lesion; Life; Marijuana; Measures; Methamphetamine; Methamphetamine dependence; Modeling; Myocardial Infarction; Nature; Neurobiology; Outcome; Paralysed; Patients; Pharmaceutical Preparations; Play; Post-Traumatic Stress Disorders; Prevention; Principal Investigator; Process; Relapse; Relative (related person); Reporting; Research; Research Personnel; Risk; Role; Severities; Smoke; Soldier; Stimulus; Stroke; Structure; Sudden Death; Suicide; Symptoms; System; Techniques; Testing; Time; Veterans; addiction; base; clinical care; comparison group; cost; daily functioning; experience; flexibility; follow-up; heuristics; high risk; operation; programs; relating to nervous system; research clinical testing; response; smoking cessation; statistics; tool; young man

DESCRIPTION (provided by applicant): Amphetamines are among the most widely used illicit drugs worldwide and in the U.S. The Department of Veterans Affairs spends annually $15 million for treatment of acute hospitalization for methamphetamine dependence alone and approximately 11% of Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) veterans are estimated to have used methamphetamine over the past year. Amphetamine use disorder (AUD) is an emerging problem among OEF/OIF veterans that may have significant impact on long-term functioning. Decision-making is an important function of daily life and is among the central dysfunctional behaviors in individuals with drug use problems. However, many decisions in general and decisions involving drug taking occur in a particular feeling state. Interoception comprises the neural process that underlies "how we feel" and "how we relate to others" and plays a critical role in drug-taking behavior. The insula cortex, the brain structure underlying interoceptive processing, has recently been implicated in ones ability to abstain from using drugs. A central characteristic of addictive behaviors is their relapsing nature. Several investigators have proposed that triggering aversive internal states in response to conditioned stimuli is part of the relapse process. We have some evidence that brain imaging can predict who among treatment seeking AUD individuals will relapse. Thus, by studying the behavioral and brain processes underlying decision-making and interoception in AUD individuals we can understand the neural processes underlying an individual's ability to abstain. In this proposal, two experimental approaches: (1) behavioral assessment of interoception and decision-making and (2) functional magnetic resonance imaging (fMRI) will be used to examine how amphetamine use alters behavioral and brain functioning in OEF/OIF veterans and whether these results can be used practically to predict relapse. We test the basic hypothesis that amphetamine abuse sensitizes brain structures that process the anticipation or experience of aversive emotional events and reduces the brain's ability to modulate decision-making behavior. We propose to study n=100 AUD OEF/OIF veterans and n=50 alcohol and PTSD-symptom severity matched comparison group using pleasant/aversive interoceptive stimulation to examine the reactivity of the interoceptive system and to determine the interaction between interoception and the degree to which decision-making changes as a function of errors ("how we choose after making a mistake"). The study will be focused on three specific aims: (1) to determine the subjective and behavioral effects of anticipating or experiencing an aversive or pleasant interoceptive stimulus and its impact on decision making in OEF/OIF veterans with and without AUD; (2) to determine brain activation differences during anticipating and experiencing an aversive or pleasant interoceptive stimulus and the impact on brain activation during decision making in OEF/OIF veterans with and without AUD; and (3) to determine whether behavioral or brain activation differences in OEF/OIF veterans with AUD can be used to predict severity of use - including relapse - at 1 year follow-up. The combined approach of behavioral assessment of interoception and decision-making with fMRI will be used to delineate the behavioral and neural processes in AUD individuals, which is the basis for understanding the pathophysiology of this complex disorder. The behavioral and brain imaging results will be examined for their utility as clinical tests, e.g. positive and negative likelihood ratio will be computed to determine their potential as a clinical tool to predict relapse of drug use. Ultimately, we aim to obtain a measure that can be used to predict outcomes and to use this measure in OEF/OIF veterans with AUD to develop specific interventions for high-risk patients. PUBLIC HEALTH RELEVANCE: Amphetamine use occurs in about 11% of Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) veterans. However, the effects of this use on the brain are not well understood and it is not clear who will develop a prolonged course of addiction. This application utilizes two behavioral techniques, measuring decision-making and interoception (sensation originating from the body), and functional brain imaging to address the basic question "does amphetamine use contribute to poor functioning in OEF/OIF veterans by sensitizing individuals to negative emotions and paralyzing the individual's ability to adjust to aversive events?" The goal of this proposal is twofold: (1) to better understand the neurobiology of how amphetamine affects the brain and (2) to determine whether one can use functional brain imaging as a tool to predict who is at greatest risk for relapse in order to provide better prevention tools.

描述（由申请人提供）： 苯丙胺是全球使用最广泛的非法药物之一，在美国，退伍军人事务部每年仅花费1500万美元用于治疗甲基苯丙胺依赖性的急性住院治疗，估计伊拉克自由（OIF）行动（OIF）和持久自由（OEF）的大约11％的退伍军人（OEF）的退伍军人被估计已估计甲基苯丙胺超过了一年。苯丙胺使用障碍（AUD）是OEF/OIF退伍军人的新兴问题，可能会对长期运作产生重大影响。决策是日常生活的重要功能，并且是有药物使用问题的人的中心功能失调行为之一。但是，一般的许多决定和涉及吸毒的决定以特定的感觉状态发生。 Interception包括基于“我们的感觉”和“我们如何与他人联系”的神经过程，并在吸毒行为中起着至关重要的作用。岛状皮质是互感性加工的大脑结构，最近与戒烟的能力有关。成瘾行为的主要特征是它们的复发性质。一些研究人员提出，触发厌恶性内部状态以响应条件刺激是复发过程的一部分。我们有一些证据表明，大脑成像可以预测寻求AUD个体的治疗中的谁会复发。因此，通过研究AUD个体的决策和际观察的行为和大脑过程，我们可以理解个人弃权能力的神经过程。在此提案中，两种实验方法：（1）对互感和决策制定的行为评估以及（2）功能磁共振成像（fMRI）将用于检查苯丙胺使用的使用如何改变OEF/OIF退伍军人的行为和大脑功能，以及这些结果是否可以实际使用以预测复发。我们检验了基本假设，即苯丙胺滥用使大脑结构敏感，这些结构可以处理厌恶情绪事件的预期或经验，并降低大脑调节决策行为的能力。我们建议使用令人愉悦/厌恶的感受性刺激研究N = 100 Aud Oef/OIF退伍军人，并使用愉快/厌恶的互感刺激匹配50次酒精和PTSD-Symptom严重性匹配组，以检查感受性的系统的反应性，并确定际交往和确定对决定错误的决策变化的程度与我们选择错误的决定的程度之间的相互作用。”该研究将集中在三个具体目标上：（1）确定预期或经历厌恶或愉快的互感刺激的主观和行为影响及其对具有和没有AUD的OEF/OIF退伍军人的决策的影响； （2）确定在预测和经历厌恶或愉快的互认为互感刺激和对脑部激活的影响期间，在有或没有AUD的OEF/OIF退伍军人中对大脑激活的影响； （3）确定具有AUD的OEF/OIF退伍军人的行为或大脑激活差异是否可以用于预测1年随访时使用的严重程度（包括复发）。与fMRI的互相评估和决策制定的行为评估的综合方法将用于描述AUD个体中的行为和神经过程，这是理解这种复杂疾病的病理生理学的基础。将检查其用作临床测试的行为和大脑成像结果，例如将计算阳性和负的可能性比率，以确定其作为预测药物使用复发的临床工具的潜力。最终，我们旨在获得一项可用于预测结果的措施，并在具有AUD的OEF/OIF退伍军人中使用此措施来为高危患者开发特定的干预措施。 公共卫生相关性： 苯丙胺的使用发生在大约11％的伊拉克自由行动（OIF）和持久自由（OEF）退伍军人行动中。但是，这种用途对大脑的影响尚不清楚，尚不清楚谁会长期成瘾。该应用利用两种行为技术，测量决策和互认为（源自身体的感觉），而功能性的大脑成像来解决基本问题：“苯丙胺的使用是否有助于通过使个体对负面情绪和瘫痪的人对厌恶事件的能力敏感，从而使OEF/OIF退伍军人的功能不佳？”该提议的目标是双重的：（1）更好地了解苯丙胺如何影响大脑的神经生物学，以及（2）确定是否可以使用功能性脑成像作为预测谁具有最大风险的工具，以提供更好的预防工具。