Neural, endocrine, and behavioral markers of psychosocial stress predicting drug use outcomes in human opioid addiction

心理社会压力的神经、内分泌和行为标志物预测人类阿片类药物成瘾的药物使用结果

• 批准号: 10551319
• 负责人: Scott J Moeller
• 金额: $ 52.84万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10551319
• 关键词: Abstinence; Acute; Addictive Behavior; Address; Adherence; Adrenal Glands; Affect; Amygdaloid structure; Area; Aversive Stimulus; Behavioral; Biological; Biology; Chronic; Chronic stress; Clinical; Cognitive; Data; Decision Making; Development; Diagnosis; Disease; Dose; Drug usage; Emotions; Endocrine; Ensure; Environmental Risk Factor; Evidence based treatment; Exposure to; Food; Frequencies; Functional Magnetic Resonance Imaging; Gender; Heroin; Human; Hydrocortisone; Hypersensitivity; Hypothalamic structure; Image; Imagery; Impairment; Individual; Individual Differences; Intervention; Interview; Investigation; Knowledge; Laboratories; Longitudinal Studies; Magnetic Resonance Imaging; Matched Group; Measures; Medial; Methadone; Morphology; Neurobiology; Opiate Addiction; Opioid; Outcome; Participant; Patient Noncompliance; Patients; Pattern; Peripheral; Persons; Pharmaceutical Preparations; Phenotype; Pituitary Gland; Pre-Clinical Model; Prefrontal Cortex; Psychosocial Stress; Public Health; Reaction Time; Relapse; Research; Resources; Salivary; Services; Severities; Stress; Structure; System; Testing; Time; Translating; acute stress; addiction; alpha-amylase; biological adaptation to stress; brain circuitry; cognitive function; combat; craving; design; experience; fortification; gray matter; heroin use; hypothalamic-pituitary-adrenal axis; improved; insight; medication-assisted treatment; morphometry; multimodality; neural; new therapeutic target; novel; novel marker; opioid epidemic; opioid use; opioid use disorder; pre-clinical; preclinical study; prospective; psychosocial; response; social; social cognition; stress reactivity; stressor; trait

PROJECT SUMMARY/ABSTRACT Opioid use disorder (OUD) is a public health crisis in America. Even among those in treatment, long-term adherence to medication is low, and relapse is the norm. A core trigger for relapse is the experience of stress, often involving psychosocial or interpersonal challenges. Preclinical models of OUD show that stress impacts neural, endocrine, and behavioral functioning, increasing one’s vulnerability for initiating and sustaining the addictive behavior. Here, we aim to translate these preclinical findings to human OUD patients on medication- assisted treatment (primary drug: heroin; stabilized on the same medication dose for 1-6 months). We will employ two broad approaches for examining psychosocial stress in patients, one utilizing chronic markers (i.e., trait-like behavioral and imaging phenotypes) and one utilizing acute markers (i.e., state-like reactivity to a laboratory induction paradigm which tests the adaptive capacity of the stress system). These approaches are fully complementary (orthogonal), in that the chronic markers depend on between-person differences while the acute markers depend on within-person fluctuations from each participant’s baseline. The chronic psychosocial stress markers, to be acquired on Day 1 of the study, include: (1) social-cognitive functioning (emotion recognition task), (2) fMRI activation during a decision-making task that involves exposure to threatening and drug-related images, and (3) gray matter volume assessed with structural MRI and voxel-based morphometry. The acute psychosocial stress markers will be acquired on Day 2 of the study (two weeks after Day 1), during which participants undergo an experimental stress induction via personalized imagery. The acute stress markers include: experimentally- induced changes in craving, salivary cortisol (marker of HPA functioning), and salivary alpha amylase (marker of sympathetic activation). For each of these two approaches, we will test for hypothesized differences between OUD participants and matched healthy controls (HC), and then within OUD we will test for hypothesized correlations of the stress variables with scores from the Cumulative Adversity Interview (CAI), a well-validated measure of lifetime cumulative psychosocial stress. Finally, OUD participants will be followed for 8 months to track relapse status and drug use, which we hypothesize will be prospectively predicted by our multimodal stress markers. With this design, we will address our study aims of uncovering whether there are abnormalities in the neural, endocrine, and behavioral correlates of stress in OUD versus HC; whether such abnormalities in OUD are exacerbated by cumulative adversity; and whether stress and its biological mechanisms predict OUD relapse trajectories. Our study will advance basic knowledge of stress biology in OUD, a research area that to date has been profoundly understudied compared with other addictions. Such knowledge may inform new therapeutic targets for medication development and psychosocial intervention to help combat the opioid epidemic.

项目概要/摘要 阿片类药物使用障碍（OUD）是美国的一场公共卫生危机。即使在接受治疗的患者中，长期 药物依从性低，复发是常态。旧病复发的一个核心诱因是压力的经历， 通常涉及心理或人际挑战。 OUD 的临床前模型表明压力会影响 神经、内分泌和行为功能，增加一个人启动和维持 成瘾行为。在这里，我们的目标是将这些临床前发现转化为接受药物治疗的人类 OUD 患者—— 辅助治疗（主要药物：海洛因；以相同药物剂量稳定1-6个月）。我们将聘用 检查患者心理社会压力的两种广泛方法，一种利用慢性标记（即特质样 行为和成像表型）和一种利用急性标记物（即对实验室的状态反应） 测试压力系统适应能力的归纳范式）。这些方法完全 互补（正交），因为慢性标记取决于人与人之间的差异，而急性标记取决于人与人之间的差异。 标记取决于每个参与者基线的人内波动。慢性社会心理压力 在研究第一天获得的标记包括：(1) 社会认知功能（情绪识别任务）， (2) 在涉及暴露威胁性和毒品相关图像的决策任务期间激活功能磁共振成像， (3) 使用结构 MRI 和基于体素的形态测定法评估灰质体积。急性社会心理 压力标记将在研究的第 2 天（第 1 天后两周）获得，在此期间参与者经历 通过个性化图像进行实验性压力诱导。急性应激标记包括：实验上- 诱导渴望、唾液皮质醇（HPA 功能的标记）和唾液 α 淀粉酶（HPA 功能的标记）的变化 交感神经激活）。对于这两种方法中的每一种，我们将测试之间的假设差异 OUD 参与者和匹配的健康对照 (HC)，然后在 OUD 内我们将测试假设 压力变量与累积逆境访谈（CAI）分数的相关性，这是一个经过充分验证的 一生累积心理社会压力的衡量标准。最后，OUD 参与者将被跟踪 8 个月，以 跟踪复发状态和药物使用，我们假设我们的多模式压力可以前瞻性地预测这些情况 标记。通过这种设计，我们将实现我们的研究目标，即揭示大脑中是否存在异常。 OUD 与 HC 中压力的神经、内分泌和行为相关性； OUD 是否存在此类异常 因累积的逆境而加剧；压力及其生物学机制是否可以预测 OUD 复发 轨迹。我们的研究将推进 OUD 中应激生物学的基础知识，迄今为止，这一研究领域已 与其他成瘾相比，它的研究还很深入。这些知识可能会为新的治疗提供信息 药物开发和社会心理干预的目标，以帮助对抗阿片类药物的流行。