Plasticity of Aversive Salience in Opioid Use Disorder

阿片类药物使用障碍中厌恶显着性的可塑性

• 批准号: 10117745
• 负责人: Jennifer Lorraine Stewart
• 金额: $ 64.89万
• 依托单位: LAUREATE INSTITUTE FOR BRAIN RESEARCH
• 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/10117745
• 关键词: Abstinence; Affect; Age; Anterior; Attention; Automobile Driving; Awareness; Base of the Brain; Behavioral; Biological Process; Brain; Brain region; Cardiac; Categories; Cessation of life; Chronic; Corpus striatum structure; Cues; Data; Data Set; Development; Dimensions; Drug usage; Emotions; Esthesia; Ethics; Event; Functional Magnetic Resonance Imaging; Future; Impairment; Individual; Insula of Reil; Intervention; Knowledge; Life; Link; Measures; National Institute of Drug Abuse; Negative Reinforcements; Opiate Addiction; Opioid; Pain; Pain interference; Participant; Patient Self-Report; Pattern; Pharmaceutical Preparations; Process; Public Health; Punishment; Recording of previous events; Recovery; Relapse; Research; Resources; Rewards; Sampling; Signal Transduction; Stimulus; Stress; System; Testing; Time; United States; Urine; Visit; Withdrawal; Withdrawal Symptom; Woman; addiction; anxiety sensitivity; behavioral phenotyping; biobehavior; biological sex; bodily sensation; brain circuitry; brain dysfunction; cingulate cortex; craving; cue reactivity; depressive symptoms; dimensional analysis; directed attention; disorder later incidence prevention; drug craving; drug withdrawal; early detection biomarkers; follow-up; high risk; improved; individualized medicine; longitudinal design; men; mindfulness-based stress reduction; mortality; negative affect; neurofeedback; neuroimaging; novel; opioid use disorder; opioid user; persistent symptom; precision medicine; prospective; recruit; relapse risk; response; stimulant use disorder; stress reactivity; substance use; substance user

ABSTRACT/PROJECT SUMMARY NOT-DA-20-012 Given that deaths linked to opioid addiction are at an all-time high in the United States, there is a crucial need to understand brain mechanisms impeding versus promoting recovery, a process marked by prolonged abstinence and use of internal/external resources to resolve drug problems. The broad aims of this proposal are to understand how brain circuitry implicated in the salience of aversive internal (bodily signals) and external (stressful, loss) stimuli tracks recovery within and across individuals with opioid addiction to (1) inform future targets for intervention (e.g., brain neurofeedback); and (2) aid the development of individualized treatment to reduce drug-related deaths. Within three months of treatment, 50% of substance users relapse, taking drugs to avoid aversive bodily states linked to craving, withdrawal, and stress. Our preliminary data suggest that opioid users show greater negative affect, higher intensity of internal sensations, and faster pain reactivity than healthy controls, paired with lower salience- relevant brain responses during attention to bodily signals and anticipation of monetary losses However, it is unclear whether aversive salience-related brain circuitry improves and tracks recovery during the vulnerable first three months during treatment. The specific aims of this proposal test how salience-based brain circuitry differs between 200 treatment-seeking individuals with opioid use disorder and 50 healthy individuals at four timepoints during early opioid recovery (2 weeks and 1, 2, and 3 months), identifying what self-report, behavioral, and brain variables can be used to identify opioid users at high risk for relapse versus those who maintain abstinence. Functional magnetic resonance imaging (fMRI) paradigms involving bodily awareness, monetary win/loss, and stress/drug cues, substance use assessments, and NIDA self-report/behavioral phenotyping batteries will be collected at each timepoint. Once the proposed aims are completed, the findings from this dataset will be evaluated to determine whether these prediction metrics can be validated in additional treatment-seeking samples.

摘要/项目摘要 非-DA-20-012 鉴于美国与阿片成瘾有关的死亡人数创历史新高， 迫切需要了解大脑阻碍而不是促进恢复的机制，这是一个过程 以长期禁欲和使用内部/外部资源来解决毒品为特点的 有问题。这项提议的主要目的是了解大脑回路是如何牵连到 令人厌恶的内部(身体信号)和外部(紧张、失落)刺激的显著轨迹 在有阿片成瘾的个人内部和之间进行康复，以(1)告知未来的目标 干预(例如，脑神经反馈)；和(2)帮助发展个体化治疗 以减少与毒品有关的死亡。在治疗后的三个月内，50%的吸毒者 复发，服用药物以避免与渴望、戒断和压力有关的令人厌恶的身体状态。 我们的初步数据显示，阿片类药物使用者表现出更大的负面影响，更高的 内感，以及比健康对照组更快的疼痛反应，伴随着更低的显着性- 注意身体信号和预计金钱损失时的相关大脑反应 然而，目前尚不清楚厌恶的与突显相关的大脑回路是否会改善和跟踪 在治疗期间脆弱的前三个月内恢复。这样做的具体目的是 提案测试基于突显的大脑回路在200名寻求治疗的患者中有何不同 阿片类药物使用障碍的个体和50名健康个体在早期的四个时间点 阿片类药物恢复(2周、1、2和3个月)，确定自我报告、行为和 大脑变量可以用来识别阿片类药物使用者与那些有高复发风险的人 保持节制。身体受累的功能磁共振成像(FMRI)范例 意识、金钱输赢、压力/药物线索、药物使用评估和NIDA 将在每个时间点收集自我报告/行为表型电池。一旦 建议的目标已完成，将对此数据集中的结果进行评估以确定 这些预测指标是否可以在其他寻求治疗的样本中得到验证。