Acquisition and Expression of Avoidance: Computational Modeling and Human Studies

回避的习得和表达：计算模型和人类研究

• 批准号: 8438773
• 负责人: CATHERINE E MYERS
• 金额: --
• 依托单位: VA NEW JERSEY HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-10-01 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8438773
• 关键词: Accounting; Address; Affect; Alcohol abuse; Animal Experiments; Animal Model; Animals; Anxiety; Anxiety Disorders; Automobile Driving; Avoidance Learning; Basic Science; Behavior; Behavioral; Behavioral inhibition; Computer Simulation; Computers; Data; Development; Diagnosis; Disease; Drug abuse; Empirical Research; Employment; Event; Extinction (Psychology); Family; Future; General Population; Goals; Health; Human; Inbred WKY Rats; Inbreeding; Individual; Individual Differences; Knowledge; Laboratories; Learning; Life; Link; Maintenance; Mental disorders; Military Personnel; Modeling; Organism; Patients; Pattern; Personality Traits; Physiological; Population; Post-Traumatic Stress Disorders; Predisposition; Process; Psychological reinforcement; Psychopathology; Rattus; Research Personnel; Resistance; Risk; Safety; Services; Severities; Signal Transduction; Simulate; Societies; Speed; Study models; Symptoms; Testing; Therapeutic Intervention; Time; Translating; Translations; Trauma; Veterans; War; Work; animal data; avoidance behavior; base; computer studies; cost; design; expectation; human data; insight; learning extinction; model development; prevent; programs; public health relevance; stressor

DESCRIPTION (provided by applicant): Project Summary Although military personnel may have vulnerabilities and susceptibilities for anxiety disorders similar to the non-military population, the extreme stressors of deployment and war time service enhance the likelihood of developing anxiety disorders such as post-traumatic stress disorder (PTSD). However, only a subset of individuals exposed to such stressors develops PTSD, leading to the concept of pre-existing vulnerability factors such that individuals with one or more of these vulnerability factors, who are then exposed to extreme stressors, are more likely to develop PTSD than individuals who receive equivalent exposure but have no (or fewer) vulnerability factors. Avoidance is a core symptom of PTSD; avoidance symptoms tend to increase rather than decrease over the course of the disorder, and may be particularly predictive of which trauma-exposed individuals are likely to develop PTSD. Vulnerability to PTSD may therefore partially reflect individual differences in an individual's pre-existing tendency to acquire, express, or maintain avoidant behaviors. Understanding the mechanisms by which such vulnerabilities translate into psychopathology in veterans is key for a better understanding of PTSD and also for designing effective therapeutic interventions that target these mechanisms. There is a rich tradition of studying avoidance learning in animals, including work from our lab and others, but work directly linking animal data to human avoidance has lagged behind. Here, we will employ a parallel program of computational modeling and human avoidance studies to begin to bridge the gap between human and animal studies. First, we will develop a computational model of avoidance learning to address data from animals, including data from a rat model of vulnerability to PTSD and anxiety that shows facilitated learning and persistence of avoidance learning. Second, in parallel with the modeling work, we will conduct studies of avoidance learning in veterans with varying degrees of PTSD avoidance symptoms, to determine whether veterans with severe avoidance symptoms show avoidance behavior in laboratory tasks that parallels the behaviors observed in the rats. These studies will provide valuable empirical data on avoidance learning in veterans, in addition to directly testing how closely the rat behavior mimics that observed in the humans. Third, we will apply the computational model to the veteran avoidance learning data, to determine whether the same computational mechanisms that sufficed to account for the rat data can also account for the human data. If so, this will increase our confidence in the translational potential of the rat model; if not, this will identify important limitations that can be studied in future animal and human work. In either case, the results from the computational modeling will begin to bridge the gap in our understanding of the mechanisms driving avoidance learning in rats and in veterans with and without PTSD avoidance symptoms. The long term goal of this program of work is to use computational modeling to better understand the processes by which vulnerability to avoidance translates into psychopathology in anxiety disorders including PTSD. Knowledge of these processes and their underlying mechanisms may guide future development of targeted therapies that modulate these mechanisms to affect the development and maintenance of aberrant avoidance, providing strategies to treat or prevent development of avoidance symptoms in PTSD.

描述(由申请人提供)： 项目摘要虽然军事人员可能与非军事人员一样易患焦虑症，但部署和战时服役的极端应激源增加了患上诸如创伤后应激障碍(PTSD)等焦虑症的可能性。然而，只有一部分暴露在这种应激源下的人会患上创伤后应激障碍，这导致了先前存在的脆弱性因素的概念，即具有一个或多个这些脆弱性因素的个人，然后暴露在极端应激源下，比接受同等暴露但没有(或更少)脆弱性因素的个人更有可能患上创伤后应激障碍。回避是创伤后应激障碍的核心症状；回避症状在疾病的过程中往往会增加而不是减少，并且可能特别预测哪些创伤暴露者可能会患上创伤后应激障碍。因此，创伤后应激障碍的易感性可能在一定程度上反映了个体在获得、表达或维持回避行为的预先存在的倾向上的个体差异。了解这些脆弱性转化为退伍军人精神病理学的机制，对于更好地理解创伤后应激障碍，以及设计针对这些机制的有效治疗干预措施至关重要。在动物身上研究回避学习有着丰富的传统，包括我们实验室和其他实验室的工作，但将动物数据与人类回避直接联系起来的工作一直滞后。在这里，我们将使用计算建模和人类回避研究的并行程序来开始弥合人类和动物研究之间的差距。首先，我们将开发一个回避学习的计算模型来处理来自动物的数据，包括来自易受创伤后应激障碍和焦虑的大鼠模型的数据，该模型显示了促进学习和回避学习的持久性。其次，在建模工作的同时，我们将对患有不同程度创伤后应激障碍回避症状的退伍军人进行回避学习研究，以确定具有严重回避症状的退伍军人在实验室任务中是否表现出与在老鼠身上观察到的行为相似的回避行为。除了直接测试老鼠的行为与在人类中观察到的行为有多相似之外，这些研究还将为退伍军人的回避学习提供有价值的实证数据。第三，我们将把计算模型应用于老兵回避学习数据，以确定足以解释RAT数据的相同计算机制是否也能解释人类数据。如果是，这将增加我们对大鼠模型翻译潜力的信心；如果不是，这将确定可以在未来的动物和人类工作中研究的重要限制。无论在哪种情况下，计算模型的结果都将开始弥合我们对大鼠和有或没有创伤后应激障碍回避症状的退伍军人回避学习机制的理解上的差距。这项工作计划的长期目标是使用计算模型来更好地理解回避易感性转化为包括创伤后应激障碍在内的焦虑症的精神病理学的过程。对这些过程及其潜在机制的了解可能会指导未来靶向治疗的发展，通过调节这些机制来影响异常回避的发展和维持，提供治疗或预防创伤后应激障碍回避症状发展的策略。