Computational psychiatry investigation of the role of unrealistic optimism in opioid use disorder and relapse

计算精神病学研究不切实际的乐观情绪在阿片类药物使用障碍和复发中的作用

• 批准号: 10542386
• 负责人: Anna Borisova Konova
• 金额: $ 51.8万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10542386
• 关键词: Automobile Driving; Behavioral; Belief; Brain region; Cessation of life; Chronic; Clinical; Clinical assessments; Cognitive; Complex; Computing Methodologies; Corpus striatum structure; Data; Data Collection; Decision Making; Decision Theory; Diagnosis; Dimensions; Drug usage; Evaluation; Event; Exhibits; Feeling; Functional Magnetic Resonance Imaging; General Population; Goals; Health; Human; Imaging Device; Individual; Inferior frontal gyrus; Intervention; Investigation; Judgment; Laboratories; Life Expectancy; Longitudinal Studies; Measures; Mediating; Mediation; Mediator; Modeling; Monitor; Nature; Neurobiology; Neurocognitive; Opioid; Opioid replacement therapy; Outcome; Overdose; Patient-Focused Outcomes; Patients; Pattern; Persons; Pharmaceutical Preparations; Population; Prefrontal Cortex; Probability; Process; Process Measure; Psychiatry; Psychopathology; Recovery; Relapse; Resolution; Risk; Role; Safety; Sampling; Testing; Therapeutic Intervention; Translating; Uncertainty; Work; behavioral study; behavioral tolerance; clinically relevant; cognitive task; cohort; computerized tools; cost; design; disorder risk; driving behavior; evidence base; follow-up; high risk; improved; individual patient; longitudinal design; medication for opioid use disorder; mortality; neural; neural circuit; neural patterning; novel; novel therapeutic intervention; opioid epidemic; opioid use; opioid use disorder; optimism; patient engagement; patient subsets; prospective; relapse risk; targeted treatment; theories; time use; tool

Project Summary/Abstract The current opioid epidemic is a major health crisis that has contributed to decreased life expectancy in the U.S. A main cause of morbidly and mortality is opioid reuse and relapse in chronic cases. Understanding the neurocognitive mechanisms and factors underlying reuse vulnerability is thus a pressing need. Leveraging a novel combination of neurocognitive tools and a multi-session longitudinal design, our recent work in opioid use disorder (OUD) has begun to delineate a precise decision making mechanism for opioid reuse by showing that treatment-engaged patients are at higher risk for reuse when they exhibit increased tolerance of unknown probabilistic outcomes (ambiguity tolerance) in a financial choice task (Konova et al., 2019 JAMA Psychiatry). But why patients become more tolerant of ambiguous uncertainty in periods preceding reuse remains unknown. One potential explanation consistent with decision theory is that, in these periods, they become overoptimistic about ambiguous outcomes, which leads them to overestimate the probability of good outcomes (or underestimate bad outcomes) when faced with a decision to reuse, and therefore more likely to do so. Here, we propose a multi-level, convergent test of this framework by using well-defined, quantitative measures of this presumed “optimism bias”, alongside quantitative measures of uncertainty tolerance, which we propose to collect with concurrent high-resolution fMRI recordings, and yoked to longitudinal clinical assessments. In Aim 1, we aim to establish the relationship between uncertainty tolerance and optimism bias in patients with OUD and matched controls by studying these behaviors across a set of choice and estimation tasks (the latter designed to capture optimism about simple financial and more complex outcomes, tapping into drug-choice-relevant domains such as health outcomes). We also examine for potential moderation by various psychopathological dimensions in a large, unselected population of online (MTurk) subjects. In Aim 2, we collect fMRI data during the same choice and estimation tasks to delineate the mechanism by which optimistic neural representations of uncertainty might drive behavioral tolerance of this uncertainty, and reuse, in OUD. In Aim 3, we use a multi- session longitudinal design to understand the interaction between optimism bias and uncertainty tolerance as they relate to opioid reuse, session-to-session, allowing us to elucidate the specific timescale and nature of this interaction. With this project we aim to provide an answer to why patients become more uncertainty tolerant in periods preceding reuse and, in doing so, hope to uncover an upstream mechanism (centered on optimism bias) of this vulnerability, including its neural implementation. In addition to this conceptual advance, this work will provide a novel set of cognitive tools to precisely and objectively measure these processes with potential to predict poor outcomes such as reuse, in a way that can be easily implemented in clinical settings. Finally, the findings from this work will inform novel therapeutic interventions by providing precise neurocognitive targets, as well as their ideal timing, with the goal of mitigating reuse risk and improving long-term patient outcome.

项目摘要/摘要 当前的阿片类流行是一种重大的健康危机，导致美国预期寿命降低 病态和死亡率的主要原因是阿片类药物的再利用和缓解。了解 因此，神经认知机制和重复使用脆弱性的因素是紧迫的需求。利用 神经认知工具和多课程纵向设计的新型组合，我们最近在阿片类药物中的工作 疾病（OUD）已开始通过证明阿片类药物再利用的精确决策机制来描述 当治疗的患者暴露于未知的容忍度时，重复使用的风险较高 财务选择任务中的概率结果（歧义公差）（Konova等人，2019 JAMA Psychiatry）。 但是，为什么患者在再利用之前的时期中更容易宽容不确定性。 与决策理论一致的一种潜在解释是，在这些时期，它们变得过于充实 关于模棱两可的结果，这导致他们高估了良好结果的可能性（或 低估了不良结果）面对重复使用的决定，因此更有可能这样做。在这里，我们 通过使用明确的定量衡量标准，对该框架进行多层收敛测试 假定的“乐观偏见”，以及不确定性耐受性的定量度量，我们建议收集 同时使用的高分辨率fMRI记录，并进行纵向临床评估。在AIM 1中，我们 旨在建立OUD患者的不确定性耐受性与乐观偏见之间的关系 通过在一组选择和估计任务中研究这些行为来匹配控制（后者设计的 为了捕捉对简单财务和更复杂结果的乐观情绪，请利用与药物选择相关的 诸如健康结果之类的领域）。我们还检查了各种心理病理学的潜在节制 大量未选择的在线（MTURK）受试者中的维度。在AIM 2中，我们收集fMRI数据 相同的选择和估计任务来描述乐观的神经表示的机制 不确定性可能会在OUD中推动这种不确定性和重复使用的行为容忍度。在AIM 3中，我们使用了 会话纵向设计，以了解乐观偏见和不确定性耐受性之间的相互作用 它们与阿片类药物的再利用，会议之间有关，使我们能够阐明特定的时间表和性质 相互作用。在这个项目中，我们旨在提供一个答案，说明为什么患者变得更加不确定性。 在重用之前的时期，并希望发现上游机制（以乐观偏见为中心） 这种脆弱性，包括其神经实施。除了这项概念上的进步之外，这项工作还将 提供一组新颖的认知工具，以精确和客观地衡量这些过程，并有潜力 以一种可以在临床环境中轻松实施的方式预测不良结果，例如重复使用。最后， 这项工作的发现将通过提供精确的神经认知靶标的新型热干预措施，作为 以及他们理想的时机，目的是减轻再利用风险并改善长期患者的结果。