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）的个体更容易出现酒精使用障碍（AUDs），