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

描述(由申请人提供)： 安非他明是全世界和美国使用最广泛的非法药物之一。退伍军人事务部每年花费1500万美元治疗仅甲基苯丙胺依赖的急性住院治疗，据估计，在过去一年中，大约11%的伊拉克自由行动(OIF)和持久自由行动(OEF)退伍军人使用过甲基苯丙胺。苯丙胺使用障碍(AUD)是OEF/OIF退伍军人中出现的一个新问题，可能会对长期功能产生重大影响。决策是日常生活中的一项重要功能，也是有药物使用问题的个体的中心功能障碍行为之一。然而，许多一般的决定和涉及吸毒的决定发生在一种特定的感觉状态中。内感包括构成“我们的感觉”和“我们与他人的关系”的神经过程，并在吸毒行为中发挥关键作用。岛叶皮质是进行内感处理的大脑结构，最近被认为与戒毒的能力有关。上瘾行为的一个主要特征是其反复发作的性质。一些研究人员提出，对条件性刺激的反应触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，脑成像可以预测寻求治疗的AUD患者中谁会复发。因此，通过研究AUD个体潜在的决策和内感的行为和大脑过程，我们可以理解个体戒酒能力的神经过程。在这项建议中，将使用两种实验方法：(1)内感觉和决策的行为评估和(2)功能磁共振成像(FMRI)，以检查苯丙胺的使用如何改变OEF/OIF退伍军人的行为和脑功能，以及这些结果是否可以用于预测复发。我们测试了基本假设，即苯丙胺滥用会使大脑结构变得敏感，这些结构处理对令人厌恶的情绪事件的预期或体验，并降低大脑调节决策行为的能力。我们建议对100名退伍军人和50名酒精和创伤后应激障碍症状严重程度匹配的对照组进行研究，使用愉快/厌恶的内感觉刺激来检查内感觉系统的反应性，并确定内感觉之间的交互作用和作为错误函数的决策变化的程度(“我们在犯错误后如何选择”)。这项研究将集中于三个具体目标：(1)确定患有和不患有AUD的OEF/OIF退伍军人在预期或经历厌恶或愉快的内感觉刺激时的主观和行为影响及其对决策的影响；(2)确定患有和不患有AUD的OEF/OIF退伍军人在预期和经历厌恶或愉快的内感觉刺激时的脑激活差异，以及在决策过程中对大脑激活的影响；以及(3)确定患有AUD的OEF/OIF退伍军人的行为或脑激活差异是否可用于预测1年后使用的严重程度-包括复发。将内感和决策的行为评估与功能磁共振相结合的方法用于描绘AUD个体的行为和神经过程，这是理解这种复杂疾病的病理生理学的基础。行为和脑成像结果将作为临床测试的效用进行检查，例如将计算阳性和阴性似然比，以确定其作为预测药物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果的测量方法，并在患有AUD的OEF/OIF退伍军人中使用这一测量方法，为高危患者开发特定的干预措施。

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.