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: 8901828
• 负责人: DIETER J MEYERHOFF
• 金额: $ 43.41万
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8901828
• 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; clinical predictors; clinically significant; cost effective; design; drinking; follow-up; hazardous drinking; indexing; mortality; multimodality; neocortical; neuropsychological; novel; personalized intervention; 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％的接受酒精使用障碍的人（AUD）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明显的神经生物学和神经心理学因素，这些因素预测了接受AUD处理的个体的危险饮酒复发。确定这种复发危险因素是至关重要的，可以更好地理解复发机制和持续的戒酒机制，并将促进识别具有最大复发脆弱性的个体。 SCH知识最终将为更个性化的干预措施的发展提供信息，以提高AUD治疗的功效并降低与酒精有关的死亡率。 在当前的赠款期间，通过最新的磁共振（MR）方法和神经认知评估，我们已经证明，在寻求酗酒者（ALC）中同时慢性吸烟与复合的神经生物学和神经认知功能障碍有关。我们进一步表明，在戒酒期间，神经生物学和神经认知恢复受到慢性吸烟的阻碍。此外，初步回顾性分析表明，在清醒歧视的个体中，脑形态，神经元完整性和血流以及处理速度的区域测量，这些人在治疗后12个月内恢复了危险饮酒的人（弃权）。其中一些措施还显着预测了复发，基于MR的脑奖励系统组成部分（BRS）的神经生物学测量与复发剂的治疗后酒精消耗的严重程度密切相关。在此修订后的续约中，我们假设大脑区域的神经生物学异常包括BRS的“自上而下”组件以及执行技能中相关的神经认知缺陷，与奖励相关的决策，风险采取，冲动控制和处理速度在1年之内进行了AUD频率的复发。我们建议通过最先进的高场MR方法（代谢产物浓度，形态，灌注，扩散），奖励相关决策，冒险，脉冲控制和其他神经认知领域的测量，以在12个月的时间内量化dna for Bansote for Bankyotation，在12个月内定量酒精消耗，以供奖励，并选择了基因研究。然后，我们将确定基线和3个月遵循的横截面测量方法，以及哪些纵向变化措施将未来的复发者与未来的弃权者区分开来，并确定这些因素或组合中的哪些因素准确地预测了复发与戒酒。这项研究将为AUD个人和亚组建立更全面和综合的生物心理复发风险概况。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，以将有限的治疗资源集中在具有最大复发脆弱性的患者上，从而提高了整体AUD治疗效果并降低AUD的死亡率。