Using event-related potentials to longitudinally track cue-induced craving incubation in cocaine addicted individuals

 描述（由申请人提供）：在许多成瘾中，可卡因成瘾特别难治，估计复发率大于45%。虽然大多数患有可卡因使用障碍（iCUD）的戒断个体在戒断的最初几周内复发，但在急性戒断症状减轻后很长时间内复发仍会继续发生。重新接触到以前与吸毒有关的线索，唤起渴望是吸毒复发的一个主要因素。使用几种药物成瘾动物模型（包括可卡因、海洛因、酒精、尼古丁和甲基苯丙胺成瘾模型）的临床前研究表明，与对戒断减少渴望和药物寻求的普遍预期相反，线索诱导的药物渴望逐渐增加（即，在禁欲的最初几个月里。首先，使用横断面研究设计和在不同戒断期（从戒断后7天到戒断24个月）评估的主观渴望指标，几项人体研究显示了尼古丁、甲基苯丙胺和海洛因使用障碍的类似影响。总之，这些研究表明，在戒断3至6个月时，线索诱导的渴望最高，这表明这种渴望的潜伏使戒断药物成瘾者容易复发。然而，缺乏使用客观标记物和受试者内方法来量化和纵向跟踪线索诱导的渴望的轨迹及其用于复发监测和预测的孵化的系统研究。脑电图的晚正电位（LPP）成分已被证明可以客观地跟踪对包括药物线索在内的显著刺激的动机性注意，与线索诱导的渴望相关，并预测可卡因和尼古丁成瘾个体的复发。使用LPP，我们的初步数据表明，与最初禁欲的iCUD的治疗寻求基线相比，线索诱导的渴望在6个月时增加，然后在12个月随访时减少。因此，我们的目标是使用LPP来评估在仔细选择的戒断持续时间[在7，14，30天（横截面评估）和3，6，9和12个月（纵向评估）]的线索诱导的渴望，以客观地测量人类可卡因成瘾的渴望孵化的动态。假设的倒U形轨迹将通过LPP振幅的变化来阐明，并将通过模拟药物寻求和自我报告的渴望的测量来补充。我们的第二个目标是使用渴望潜伏期的纵向动态来监测和前瞻性预测复发。研究结果有助于制定对时间敏感的个性化干预措施，以降低寻求治疗的物质使用障碍患者复发的风险。

 DESCRIPTION (provided by applicant): Among the many addictions, cocaine addiction is particularly treatment-resistant, with estimated relapse rates greater than 45%. While most abstaining individuals with cocaine use disorders (iCUD) relapse within the first few weeks of abstinence, relapse continues to occur long after acute withdrawal has abated. Re-exposure to cues previously associated with drug use that evoke craving is a major contributing factor in relapse to drug use. Pre-clinical studies using several animal models of drug addiction (including in cocaine, heroin, alcohol, nicotine, and methamphetamine addiction models) have shown that, contrary to common expectations for the reduction of craving and drug-seeking with abstinence, cue-induced drug craving increases progressively (i.e., incubates) in the first several months of abstinence. Primarily using a cross-sectional study design and subjective measures of craving assessed at different periods of abstinence (from 7 days post abstinence onset up to 24 months of abstinence), several human studies have shown similar effects in nicotine, methamphetamine and heroin use disorders. Together, these studies show highest cue-induced craving at 3 to 6 months of abstinence, suggesting that such incubation of craving renders abstaining drug addicted individuals vulnerable to relapse. However, a systematic investigation that uses objective markers and a within- subjects approach to quantify and longitudinally track the trajectory of cue-induced craving and its incubation for relapse monitoring and prediction is lacking. The late positive potential (LPP) component of the electroencephalography has been shown to objectively track motivated attention to salient stimuli including drug-cues, correlating with cue-induced craving and predicting relapse in cocaine and nicotine addicted individuals. Using LPP, our preliminary data suggests that cue-induced craving increases at 6-months and then decreases at 12-months follow-up compared to a treatment-seeking baseline in initially abstinent iCUD. Thus, we aim to use LPPs to assess cue-induced craving at carefully selected abstinence durations [at 7, 14, 30 days (assessed cross-sectionally) and at 3, 6, 9, and 12 months (assessed longitudinally)] to objectively measure the dynamics of craving incubation in human cocaine addiction. The hypothesized inverted-U shaped trajectory will be elucidated via changes in LPP amplitude, and will be supplemented by measures of simulated drug-seeking and self-reported craving. Our second aim is to use the longitudinal dynamics of craving incubation to monitor and prospectively predict relapse. Results could aid in developing time-sensitive personalized interventions to reduce risk of relapse in treatment-seeking individuals with substance use disorders.