Alcohol, Approach-Avoidance, and Neurocircuitry Interactions in PTSD

PTSD 中的酒精、回避接近和神经回路相互作用

• 批准号: 10628057
• 负责人: Joshua M Cisler
• 金额: $ 65.71万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10628057
• 关键词: Acute; Address; Adult; Affect; Alcohol abuse; Alcohol consumption; Alcoholic Intoxication; Alcohols; Behavioral; Behavioral Mechanisms; Beverages; Biological; Brain; Clinical; Clinical Research; Cognitive deficits; Computer Models; Corpus striatum structure; Data; Decision Making; Development; Diagnosis; Disease; Extinction; Fright; Functional disorder; General Population; Goals; Heavy Drinking; Human; Individual; Interpersonal Violence; Intervention; Intoxication; Learning; Longitudinal Studies; Mediating; Methods; Modeling; Outcome; Participant; Pattern; Placebo Control; Placebos; Post-Traumatic Stress Disorders; Predictive Factor; Prevalence; Prevention; Procedures; Psychophysiology; Relapse; Research; Research Personnel; Rewards; Risk; Risk Behaviors; Risk Factors; Risk Marker; Role; Self Medication; Severities; Symptoms; Testing; Time; Trauma; Woman; Work; alcohol comorbidity; alcohol cue; alcohol effect; alcohol exposure; alcohol misuse; alcohol risk; alcohol use disorder; approach avoidance behavior; clinical prognosis; comorbidity; comparison group; computational neuroscience; expectation; follow-up; high risk; improved; improved outcome; neural; neural circuit; neural network; neuroimaging; neurophysiology; novel; pharmacologic; predictive modeling; programs; reward processing; social; suicidal risk; therapy development; violence exposure

Individuals with posttraumatic stress disorder (PTSD) have greater prevalence of alcohol use disorders (AUDs), with this comorbidity associated with worse illness outcomes, yet there remains limited mechanistic understanding of how PTSD confers risk for AUD. Understanding risk factors that associate with and predict the development of AUDs in PTSD could inform interventions and prevention efforts to reduce the rate of this comorbidity and improve outcomes of both disorders. Identifying predictors of risk requires longitudinal studies in PTSD aimed at capturing the mechanisms leading to the emergence of AUDs. There is growing evidence PTSD is related to biased decision-making during approach-avoidance conflict. Alcohol is also suggested to alter approach-avoidance decision-making. AUDs and acute alcohol intoxication is associated with a bias to seek out reward despite the possibility of threat (e.g., contributing to relapse following alcohol cue exposure and risky behavior during intoxication respectively). Alcohol-induced changes in approach-avoidance decision-making have not been investigated in the context of PTSD, but emerging data support our hypothesis that an interaction between alcohol and approach-avoidance conflict in PTSD may occur and contribute to risk for alcohol misuse and development of alcohol problems. No current data, cross-sectional or longitudinal, have tested the role of alcohol-induced changes in approach-avoidance conflict as a mechanism of risk for AUD among individuals with PTSD. To address this gap, we propose to leverage our group's expertise in placebo-controlled alcohol administration procedures, longitudinal modeling, functional neuroimaging, and computational neuroscience approaches to investigate the effects of acute alcohol on approach-avoidance decision-making and mediating changes in multivariate neurocircuitry patterns in limbic, striatal, and salience networks. The proposed study will test our conceptual model positing that acute alcohol alters the relative bias in computational mechanisms for threat vs reward, thereby decreasing avoidance to threat and increasing approach to reward in adults with PTSD, and through this mechanism increases risk for heavier alcohol use over time. Research aims are to identify alcohol-induced changes in approach-avoidance decision-making and mediating neural networks that predict alcohol use and symptoms of AUDs over a one-year follow-up period in adults with PTSD, compared to adults with interpersonal violence exposure but no PTSD and healthy comparison adults. Essential to successfully improving clinical prognosis in PTSD are research results that enable better prediction, diagnosis, and treatment based on the individual. There is a paucity of human clinical research investigating interactions between acute alcohol exposure and PTSD that may drive risk for development of AUDs following trauma. Data could identify brain and behavioral mechanisms explaining how alcohol alters an important domain of PTSD contributing to risk for alcohol misuse and development of alcohol problems. Results could pave way for development of novel behavioral and pharmacological methods to treat PTSD and decrease risk for developing comorbid AUDs.

患有创伤后应激障碍(PTSD)的人酒精使用障碍(AUD)的患病率更高， 这种共病与更糟糕的疾病结局相关，但机制仍然有限。 了解创伤后应激障碍是如何增加澳门氏症风险的。了解与疾病相关的风险因素，并预测 创伤后应激障碍中AUDS的发展可以为干预和预防工作提供信息，以降低这种情况的发生率 共病并改善两种疾病的结果。确定风险的预测因素需要进行纵向研究 关于创伤后应激障碍的研究，旨在了解导致急性尿毒症出现的机制。有越来越多的证据表明 创伤后应激障碍与接近-回避冲突中的偏向决策有关。酒精也被建议改变 接近--回避决策。急性尿毒症和急性酒精中毒与偏向寻找 尽管存在威胁的可能性(例如，在接触酒精线索后导致复发和危险)，但仍可获得奖励 在醉酒期间的行为)。酒精引起的接近回避决策的改变 没有在创伤后应激障碍的背景下进行调查，但新出现的数据支持我们的假设，即 在创伤后应激障碍中，酒精和接近-回避冲突可能会发生，并增加酒精滥用的风险 以及酒精问题的发展。目前还没有数据，无论是横截面还是纵向数据，都测试了 酒精诱导的接近-回避冲突的变化是AUD的一种风险机制 创伤后应激障碍。为了解决这一差距，我们建议利用我们小组在安慰剂控制酒精方面的专业知识 管理程序、纵向建模、功能神经成像和计算神经科学 研究急性酒精对接近回避决策和调解的影响的方法 边缘、纹状体和突起网络中多变量神经回路模式的变化。拟议的研究将 测试我们的概念模型，假设急性酒精改变了计算机制中的相对偏差 威胁与奖励，从而减少了对威胁的回避，增加了成年创伤后应激障碍患者的奖励方式， 通过这种机制，随着时间的推移，大量饮酒的风险会增加。研究的目的是确定 酒精引起的接近回避决策的改变和预测的中介神经网络 与成人相比，成年创伤后应激障碍患者一年随访期间的酒精使用和AUDS症状 有人际暴力暴露，但没有创伤后应激障碍和健康对照的成年人。成功的关键 改善创伤后应激障碍的临床预后是能够更好地预测、诊断和治疗的研究结果。 以个人为基础。很少有人类临床研究调查急性呼吸道感染之间的相互作用 酒精暴露和创伤后应激障碍可能会增加创伤后发生AUDS的风险。数据可以识别 解释酒精如何改变创伤后应激障碍的一个重要领域的大脑和行为机制 酒精滥用的风险和酒精问题的发展。结果可能为小说的发展铺平道路 行为和药理学方法治疗创伤后应激障碍，降低并发AUDS的风险。