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

酒精和吸烟引起的脑损伤的生物学基础

• 批准号: 8538870
• 负责人: DIETER J MEYERHOFF
• 金额: $ 43.94万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8538870
• 关键词: AODR mortality; Abstinence; Aftercare; Alcohol consumption; Alcohol dependence; Alcohols; Anterior; Behavioral; Biological; Blood flow; Brain; Brain Injuries; Brain region; Brain-Derived Neurotrophic Factor; Chronic; Clinical; Complex; DNA Library; Decision Making; Development; Diffusion; Functional disorder; Future; Genes; Genetic; Genetic Polymorphism; Genotype; Goals; Grant; Impulsivity; Individual; Intervention; Knowledge; Light; Magnetic Resonance; Maintenance; Measurement; Measures; Mediating; Methods; Morphology; Neurobiology; Neurocognition; Neurocognitive; Neurocognitive Deficit; Neurons; Outcome Measure; Perfusion; Phenotype; Psychosocial Factor; Recovery; Relapse; Remittance; Research; Resources; Rewards; Risk; Risk Factors; Risk-Taking; Sensitivity and Specificity; Severities; Smoking; Structure; Subgroup; Surrogate Markers; System; Systems Biology; Thinking; Time; Treatment Efficacy; addiction; alcohol abstinence; alcohol use disorder; base; biopsychosocial; brain morphology; cigarette smoking; clinically significant; cost effective; design; drinking; follow-up; hazardous drinking; indexing; mortality; multimodality; neocortical; neuropsychological; novel; problem drinker; processing speed; psychologic; psychosocial; skills; sobriety; substance abuse treatment; treatment strategy

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.

描述（由申请人提供）：超过60%的酒精使用障碍（AUD）患者在治疗后6个月内复发。这种竞争性更新的主要目标是确定预测接受AUD治疗的个体复发危险酒精消费的显著神经生物学和神经心理学因素。确定这些复发风险因素对于更好地了解复发和持续戒断的机制至关重要，并将有助于确定最容易复发的个人。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治疗的疗效并降低酒精相关死亡率。 在目前的资助期内，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，寻求治疗的酗酒者（ALC）同时慢性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，长期吸烟会阻碍戒酒期间神经生物学和神经认知的恢复。此外，初步的回顾性分析显示，大脑形态，神经元的完整性和血流量以及清醒早期的处理速度的区域措施区分保持清醒的人（戒酒者）和那些在治疗后12个月内恢复危险饮酒的人（复发者）。其中一些措施也显着预测复发，和MR为基础的神经生物学措施的组成部分，大脑奖励系统（BRS）的治疗后酒精消费的复发者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BRS的“自上而下”成分以及执行技能、奖励相关决策、冒险、冲动控制和处理速度方面的相关神经认知缺陷，可预测AUD治疗后1年内的复发。我们建议通过最先进的高场MR方法（代谢物浓度，形态学，灌注，扩散），测量奖励相关决策，风险承担，冲动控制和其他神经认知领域，在治疗后12个月内定量饮酒，并收集DNA用于银行和选择基因分型以探索复发表型，对100例ALC进行纵向研究。然后，我们将确定基线和3个月随访时的横断面测量以及区分未来复发者和未来戒烟者的纵向变化测量，并确定这些因素中的哪些或其组合准确预测复发与戒断。这项研究将为AUD个体和亚组建立一个更全面和综合的生物心理社会复发风险特征。该研究在AUD治疗中具有高度的临床意义，因为它将提供关键的新信息，将有限的治疗资源集中在最容易复发的患者身上，从而提高AUD的整体治疗疗效并降低AUD的死亡率。