The Biological Basis of Alcohol-and Smoking-Induced Brain Injury

描述(由申请人提供)：接受酒精使用障碍(AUD)治疗的患者中，超过60%的人在治疗后6个月内复发。这次竞争性更新的主要目标是确定显著的神经生物学和神经心理学因素，这些因素预测接受AUD治疗的个人复发到危险的酒精消费。查明这种复发风险因素对于更好地了解复发和持续戒除的机制至关重要，并将有助于查明最易复发的个人。SCH知识最终将为开发更个性化的干预措施提供信息，以提高AUD治疗的效率并降低与酒精相关的死亡率。在目前的赠款期间，通过最先进的磁共振(MR)方法和神经认知评估，我们已经证明，在寻求酒精治疗的患者(ALC)中同时长期吸烟与复合神经生物学和神经认知功能障碍有关。我们进一步表明，长期吸烟阻碍了戒酒期间神经生物学和神经认知的恢复。此外，初步的回顾分析显示，在戒酒早期对大脑形态、神经元完整性和血流以及处理速度的区域性测量将保持清醒的人(戒酒者)与那些在治疗后12个月内恢复危险饮酒的人(复吸者)区分开来。其中一些指标也显著地预测了复发，基于MR的脑奖励系统(BRS)组成部分的神经生物学指标与复发者治疗后饮酒的严重程度密切相关。在这次修订的更新中，我们假设大脑区域的神经生物学异常，包括自上而下的BRS组成部分，以及在执行技能、与奖励相关的决策、冒险、冲动控制和处理速度方面的相关神经认知缺陷，可以预测AUD治疗后1年内复发。我们建议通过最先进的高场磁共振方法(代谢物浓度、形态、灌注、扩散)对100例ALC进行纵向研究，测量与奖励相关的决策、冒险、冲动控制和其他神经认知领域，量化治疗后12个月的酒精消耗量，并收集DNA用于银行和选择基因分型以探索复发表型。然后，我们将确定基线和3个月随访时的哪些横断面指标，以及哪些纵向变化指标将未来的复吸者与未来的戒戒者区分开来，并确定这些因素中的哪些或其组合准确地预测复发与戒断。这项研究将为AUD个人和亚组建立一个更全面和更完整的生物心理社会复发风险概况。这项研究在AUD治疗中具有很高的临床意义，因为它将提供关键的新信息，将有限的治疗资源集中在那些最容易复发的人身上，从而提高AUD的整体治疗效率，降低AUD的死亡率。

DESCRIPTION (provided by applicant): More than 60% of individuals treated for alcohol use disorders (AUD) relapse within 6 months of treatment. The primary goal of this competitive renewal is to determine salient neurobiological and neuropsychological factors that predict relapse to hazardous alcohol consumption in individuals treated for AUD. Identification of such relapse risk factors is pivotal for a better understanding of mechanisms of relapse and sustained abstinence and will facilitate identification of individuals with greatest relapse vulnerability. Sch knowledge will ultimately inform the development of more personalized interventions to increase the efficacy of AUD treatment and reduce alcohol-related mortality. In the current grant period, via state-of-the-art magnetic resonance (MR) methods and neurocognitive assessments, we have demonstrated that concurrent chronic cigarette smoking in treatment seeking alcoholics (ALC) is associated with compounded neurobiological and neurocognitive dysfunction. We have further shown that neurobiological and neurocognitive recovery during abstinence from alcohol is hampered by chronic cigarette smoking. In addition, preliminary retrospective analyses revealed that regional measures of brain morphology, neuronal integrity and blood flow as well as processing speed early in sobriety discriminated individuals who maintained sobriety (abstainers) from those who resumed hazardous drinking within 12 months following treatment (relapsers). Some of these measures also significantly predicted relapse, and MR-based neurobiological measures of components of the brain reward system (BRS) were strongly related to the severity of post-treatment alcohol consumption in relapsers. In this revised renewal, we postulate that neurobiological abnormalities in brain regions that include the 'top-down' components of the BRS and related neurocognitive deficits in executive skills, reward-related decision-making, risk taking, impulse control, and processing speed predict relapse within 1 year following treatment for AUD. We propose to study longitudinally over three months 100 ALC by state-of-the-art high-field MR methods (metabolite concentrations, morphology, perfusion, diffusion), measurements of reward-related decision-making, risk taking, impulse control and other neurocognitive domains, to quantitate alcohol consumption over 12 months following treatment, and to collect DNA for banking and select genotyping to explore the relapse phenotype. We will then determine what cross-sectional measures at baseline and 3-month-follow-up and what longitudinal change measures distinguish future relapsers from future abstainers, and determine which of these factors or combinations thereof accurately predict relapse vs. abstinence. This research will establish a more comprehensive and integrated biopsychosocial relapse risk profile for AUD individuals and subgroups. The research is of high clinical significance in AUD treatment, as it will provide critical new information for focusing limited treatment resources on those with greatest relapse vulnerability, thereby increasing overall AUD treatment efficacy and reducing mortality in AUD.