Neurocircuitry of clinical insight predicting relapse outcomes in opioid addiction

项目摘要 对疾病严重程度的自我意识（洞察力）受损与发病率增加和不良反应有关。 多种神经精神疾病的治疗结果。尽管传统上对洞察力的研究 仅限于精神障碍（例如，精神分裂症，躁狂症），新兴的理论和证据表明， 该构建体也可能与药物成瘾高度相关。例如，吸毒成瘾的人往往 高估了他们与成瘾有关的自我控制能力，低估了他们的神经认知障碍，并且经常这样做。 尽管吸毒造成了广泛的后果，但他们并不认为需要治疗。为 尤其是阿片类药物使用障碍（OUD）患者，因为一线治疗通常涉及药物治疗- 辅助治疗，必须采取长期和无限期的时间，一个强大的和持续的个人 需要参与治疗，以防止复发（这是常态，而不是例外）。在此R 01 应用，我们进行了第一次系统的调查洞察力及其潜在的神经回路， OUD患者复发和治疗依从性的生物标志物和纵向预测因子。最近- 脱毒和药物维持的OUD参与者（主要药物：海洛因）和匹配的健康对照组 (HC)将完成一项新的功能性磁共振成像（fMRI）“洞察力”任务，在此期间， 对有关其药物使用严重程度和行为改变需求的陈述做出反应。具体 目的包括揭示OUD中药物相关洞察力的行为和神经相关性，并检查 该回路（A）预测未来阿片类药物使用的能力和（B）随着时间的推移恢复功能的能力， 禁欲我们假设，较低的阿片类药物使用和更好的治疗依从性（避免复发）将是 与更完整的基线功能和从基线到6个月的更多功能改善相关 随访，喙侧前扣带回皮质延伸到腹内侧前额叶皮质 (rACC/vmPFC）。这个rACC/vmPFC区域，就其在健康中调节个人相关性而言， 在药物成瘾（和其他精神病理学），提供了一个合理的和先验的候选区域，用于研究 洞察力回路如果观察到预期的关系，我们的结果将揭示一个关键的结构， OUD -以及更普遍的药物成瘾-有可能使药物使用永久化，但迄今为止， 有一个非常精益的经验研究传统，特别是关于潜在的大脑机制。更好的 对该回路的理解可以提出用于增加OUD中的治疗依从性的新的治疗靶点， 这反过来又有利于解决目前的阿片类药物流行病。

PROJECT SUMMARY Impaired self-awareness of illness severity (insight) is associated with increased morbidity and poorer treatment outcome across multiple neuropsychiatric diseases. Although the study of insight has traditionally been limited to psychotic disorders (e.g., schizophrenia, mania), emerging theory and evidence suggest that this construct may also be highly relevant to drug addiction. For example, drug-addicted individuals often overestimate their addiction-related self-control, underestimate their neurocognitive impairments, and often do not perceive a need for treatment despite the pervasive consequences precipitated by their drug use. For individuals with opioid use disorder (OUD) especially, because first-line treatment often involves medication- assisted therapy that must be taken for long and indefinite periods of time, a strong and sustained personal engagement with treatment is required to prevent relapse (which is the norm, not the exception). In this R01 application, we undertake the first systematic investigation of insight and its underlying neural circuitry as biomarkers and longitudinal predictors of relapse and treatment adherence in individuals with OUD. Recently- detoxified and medication-maintained OUD participants (primary drug: heroin) and matched healthy controls (HC) will complete a novel functional magnetic resonance imaging (fMRI) ‘insight’ task, during which they respond to statements about the severity of their drug use and perceived need for behavior change. Specific Aims include uncovering the behavioral and neural correlates of drug-related insight in OUD, and examining the ability of this circuitry (A) to predict future opioid use and (B) to recover functioning over time with abstinence. We hypothesize that lower opioid use and better treatment adherence (avoiding relapse) will be linked with more intact baseline functioning, and more improvements in functioning from baseline to 6-month follow-up, of the rostral anterior cingulate cortex extending into the ventromedial prefrontal cortex (rACC/vmPFC). This rACC/vmPFC region, insofar as it mediates personal relevance in health and is disrupted in drug addiction (and other psychopathologies), provides a plausible and a priori candidate region for studying insight circuitry. If the anticipated relationships are observed, our results will shed light on a critical construct in OUD – and in drug addiction, more generally – that has the potential to perpetuate drug use, but that to date has a very lean tradition of empirical study, especially with regard to underlying brain mechanisms. A better understanding of this circuitry can suggest novel treatment targets for increasing treatment adherence in OUD, which in turn can be beneficial for addressing the current opioid epidemic.