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: 8261653
• 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/8261653
• 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.

描述（由申请人提供）： 安非他明是世界上使用最广泛的非法药物之一，在美国，退伍军人事务部每年花费1500万美元用于治疗仅因甲基安非他明依赖而急性住院治疗，估计大约11%的伊拉克自由行动（OIF）和持久自由行动（OEF）退伍军人在过去一年中使用过甲基安非他明。安非他明使用障碍是持久自由行动/伊法组织退伍军人中一个新出现的问题，可能对长期功能产生重大影响。决策是日常生活的一项重要功能，也是有药物使用问题的个体的核心功能失调行为之一。然而，许多一般的决定和涉及药物服用的决定都是在一种特殊的感觉状态下发生的。内感受包括构成“我们感觉如何”和“我们如何与他人联系”的神经过程，并在吸毒行为中起着关键作用。内感受性处理的大脑结构--大脑皮层，最近被认为与一个人戒除毒品的能力有关。成瘾行为的一个核心特征是复发性。一些研究者提出，对条件刺激的反应引发厌恶的内部状态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治疗的AUD个体中谁会复发。因此，通过研究AUD个体决策和内感受的行为和大脑过程，我们可以了解个体弃权能力的神经过程。在这项提议中，两种实验方法：（1）内感受和决策的行为评估和（2）功能性磁共振成像（fMRI）将用于研究安非他明的使用如何改变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用于预测复发。我们测试的基本假设，安非他明滥用敏感的大脑结构，处理预期或经验的厌恶情绪事件，并降低大脑的能力，以调节决策行为。我们建议研究n=100 AUD OEF/OIF退伍军人和n=50酒精和PTSD症状严重程度匹配的对照组，使用愉快/厌恶的内感受性刺激，以检查内感受系统的反应性，并确定内感受和决策变化程度之间的相互作用作为错误的函数（“我们如何选择后，犯了一个错误”）。本研究将集中于三个具体目标：（1）确定预期或经历厌恶或愉快的内感受性刺激的主观和行为效应及其对有和无AUD的OEF/OIF退伍军人决策的影响;（二）为了确定在预期和经历厌恶或愉快的内感受性刺激期间的大脑激活差异以及在决策过程中对大脑激活的影响，OEF/OIF退伍军人与非AUD;和（3）确定OEF/OIF退伍军人与AUD的行为或大脑激活差异是否可用于预测使用的严重程度-包括复发-在1年随访。内感受和决策的行为评估与功能磁共振成像相结合的方法将被用来描绘在AUD个体的行为和神经过程，这是理解这种复杂的疾病的病理生理学的基础。将检查行为和脑成像结果作为临床试验的效用，例如，将计算阳性和阴性似然比，以确定其作为预测药物使用复发的临床工具的潜力。最终，我们的目标是获得一种可用于预测结局的指标，并在患有AUD的OEF/OIF退伍军人中使用该指标，为高危患者制定特定的干预措施。