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）的个体有更高的酒精使用障碍（AUD）患病率， 这种合并症与更糟糕的疾病结局相关，但仍存在有限的机制， 了解PTSD如何导致AUD风险。了解与糖尿病相关并预测糖尿病的风险因素 在PTSD中AUDs的发展可以为干预和预防工作提供信息，以降低这一比率。 并改善两种疾病的结局。确定风险的预测因子需要纵向研究 旨在捕捉导致AUD出现的机制。越来越多的证据 PTSD与趋避冲突中的决策偏差有关。酒精也被建议改变 接近-回避决策AUDs和急性酒精中毒与寻求 尽管存在威胁的可能性，导致酒精暴露后复发， 中毒时的行为）。酒精引起的接近-回避决策的变化 尚未在创伤后应激障碍的背景下进行研究，但新出现的数据支持我们的假设， 酒精和PTSD中的接近-回避冲突之间可能会发生，并导致酒精滥用的风险 和酒精问题的发展。目前还没有横向或纵向的数据来检验以下因素的作用： 酒精诱导的接近-回避冲突变化是患有糖尿病的个体中AUD的风险机制 创伤后应激障碍为了弥补这一差距，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 探讨急性酒精对接近-回避决策和中介的影响 边缘系统、纹状体和显著性网络中多变量神经回路模式的变化。拟定的研究将 测试我们的概念模型，假设急性酒精改变了计算机制的相对偏差， 威胁与奖励，从而减少了PTSD成年人对威胁的回避，增加了对奖励的接近， 通过这种机制，随着时间的推移，增加了大量饮酒的风险。研究目的是确定 酒精引起的接近-回避决策和中介神经网络的变化， 与成年人相比，PTSD成年人在一年随访期内的酒精使用和AUDs症状 有人际暴力暴露但没有创伤后应激障碍的健康成年人。成功的关键 改善创伤后应激障碍的临床预后的研究结果，使更好的预测，诊断和治疗 基于个人。缺乏研究急性炎症和慢性炎症之间相互作用的人类临床研究。 酒精暴露和创伤后应激障碍可能会导致创伤后AUD的发展风险。数据可以识别 大脑和行为机制解释了酒精如何改变PTSD的一个重要领域， 酒精滥用和酒精问题发展的风险。结果可以为小说的发展铺平道路 行为和药理学方法来治疗PTSD和降低发展共病AUDs的风险。