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.

创伤后应激障碍（PTSD）的患者的酒精使用障碍患病率更高（AUDS）， 由于这种合并症与疾病结果较差有关，但机理仍然有限 了解PTSD如何赋予AUD风险。了解与之关联并预测的风险因素 PTSD中AUDS的开发可以为降低这一比率的干预措施和预防措施提供信息 合并症和改善两种疾病的结果。确定风险的预测因素需要纵向研究 在PTSD中，旨在捕获导致AUD出现的机制。越来越多的证据 PTSD与避免进路冲突期间的偏见决策有关。还建议酒精改变 避免进近决策。 auds和急性酒精中毒与寻找的偏见有关 奖励尽管有可能威胁（例如，在酒精提示暴露和风险之后导致复发 中毒期间的行为）。酒精引起的避免进近决策的变化 尚未在PTSD的背景下进行研究，但新兴数据支持我们的假设，即相互作用 在PTSD中酒精和避免进近冲突之间可能发生，并导致滥用酒精的风险 和酒精问题的发展。目前没有横截面或纵向的数据测试了 酒精引起的避免进口冲突的变化是在患有AUD的风险机制 PTSD。为了解决这一差距，我们建议在安慰剂控制的酒精中利用小组的专业知识 给药程序，纵向建模，功能性神经影像学和计算神经科学 研究急性酒精对避免进近决策和调解的影响的方法 边缘，纹状体和显着性网络中多元神经记录模式的变化。拟议的研究将 测试我们的概念模型，认为急性酒精会改变计算机制的相对偏见 威胁与奖励，从而减少了对PTSD成年人的威胁和奖励的不断增加的避免， 通过这种机制，随着时间的推移，增加了饮酒较重的风险。研究目的是确定 酒精引起的避免进近决策的变化和介导的神经网络预测 与成年人相比 人际关系暴力暴露，但没有PTSD和健康的比较成年人。成功的至关重要 改善PTSD的临床预后是研究结果，可以更好地预测，诊断和治疗 基于个人。人类临床研究很少研究急性之间的相互作用 酗酒和PTSD可能会导致创伤后auds发展的风险。数据可以识别 大脑和行为机制解释了酒精如何改变PTSD的重要领域 滥用酒精和饮酒问题的风险。结果可以为开发新颖的方式铺平道路 治疗PTSD并降低开发合并AUD的风险的行为和药理方法。