Neurocircuitry of clinical insight predicting relapse outcomes in opioid addiction

项目总结 对疾病严重性的自我意识受损(洞察力)与发病率的增加和疾病的恶化有关 多种神经精神疾病的治疗结果。尽管对洞察力的研究传统上 仅限于精神障碍(如精神分裂症、躁狂症)，新兴的理论和证据表明 这一结构也可能与药物成瘾高度相关。例如，吸毒成瘾的人经常 高估了他们与上瘾有关的自我控制能力，低估了他们的神经认知障碍，而且经常这样做 他们不认为有必要接受治疗，尽管他们使用毒品造成了普遍的后果。为 阿片类药物使用障碍(OUD)患者尤其如此，因为一线治疗通常涉及药物治疗- 必须长期和无限期地进行辅助治疗，强烈和持续的个人 需要参与治疗以防止复发(这是常态，而不是例外)。在本R01中 应用，我们对洞察力及其潜在的神经回路进行了第一次系统研究， 黑色素瘤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- 戒毒和药物维持的受试者(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磁共振成像(FMRI)“洞察”任务，在此期间，他们 对有关他们吸毒的严重性和他们认为需要改变行为的说法做出回应。特定的 目的包括在OUD中发现与药物相关的洞察力的行为和神经关联，并检查 这个回路的能力(A)预测未来阿片类药物的使用和(B)随着时间的推移恢复功能 禁欲。我们假设较少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相关联，并在从基线到6个月的功能方面有更多改进 吻侧前扣带回皮质延伸至腹内侧前额叶皮质的随访 (rACC/vmPFC)。这个rACC/vmPFC区域，因为它调节了个人与健康的相关性，并被扰乱了 在毒瘾(和其他精神病理学)中，为研究提供了一个可信的和先验的候选区域 洞察电路。如果观察到预期的关系，我们的结果将阐明 OUD--更广泛地说，在吸毒成瘾中--这有可能使吸毒永久化，但到目前为止 在实证研究方面有非常精湛的传统，特别是关于潜在的大脑机制。更好的 对该回路的理解可以建议用于增加OUD中的治疗依从性的新的治疗目标， 这反过来又有利于解决目前的阿片类药物流行问题。

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.