Neural Correlates of Emotion Regulation in Youth at Risk for Alcoholism

有酗酒风险的青少年情绪调节的神经相关性

• 批准号: 10004489
• 负责人: Joshua Leigh Gowin
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10004489
• 关键词: Adolescence; Adolescent; Adult; Affect; Age; Alcohol abuse; Alcohol consumption; Alcoholic beverage heavy drinker; Alcoholism; Algorithms; American; Amygdaloid structure; Anterior; Area; Aversive Stimulus; Behavioral; Biological; Brain; Cessation of life; Clinical; Cognitive; Communication; Communities; Consumption; Control Groups; Corpus striatum structure; Cues; Data; Development; Early Intervention; Early identification; Educational process of instructing; Emotional; Emotions; Ethnic Origin; Evaluation; Event; Exhibits; Extramural Activities; Family; Family history of; Functional Magnetic Resonance Imaging; Gender; Goals; Hearing; Heavy Drinking; Individual; Institution; Insula of Reil; Learning; Letters; Loudness; Matched Group; Measures; Mentors; National Institute of Drug Abuse; National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; Negative Valence; Outcome; Parents; Participant; Patients; Personality; Pharmacotherapy; Phase; Positioning Attribute; Positive Valence; Postdoctoral Fellow; Predictive Value; Process; Public Health; Questionnaires; Recording of previous events; Relapse; Research; Research Personnel; Rest; Review Literature; Rewards; Risk; Risk Factors; Running; Sampling; Scanning; Services; Severities; Signal Transduction; Socioeconomic Status; Stimulus; Substance Use Disorder; System; Targeted Research; Techniques; Testing; Time; Training; Ventral Striatum; Youth; aged; alcohol risk; alcohol use disorder; base; career; cingulate cortex; clinical predictors; cognitive neuroscience; design; disorder prevention; disorder risk; drinking; drinking behavior; emotion regulation; executive function; experience; experimental study; faculty research; financial incentive; follow-up; functional MRI scan; high risk; improved; knowledge base; machine learning algorithm; negative affect; neural correlate; neuroimaging; positive emotional state; predicting response; predictive tools; prevent; programs; recruit; relapse prediction; relating to nervous system; response; skills; sound; success; tenure track; tool; underage drinking

Project Summary/Abstract According to the latest estimates, over 1 in 7 Americans will develop an Alcohol Use Disorder (AUD) over the course of their lifetime, and alcohol consumption is involved in nearly 4% of deaths worldwide. Thus, AUDs represent a significant public health concern. Currently, the best pharmacotherapies for AUDs require the treatment of 10 patients to observe 1 patient reduce drinking to healthy levels. For this reason, one appealing option is to identify at-risk individuals before they become heavy drinkers; for instance a family history of alcoholism is currently among the best predictors of AUD. Adolescence presents an ideal period to study these factors as it precedes the onset of AUDs but is also a time when there is a rapid increase in consumption. We have recently shown that neuroimaging measures can be used to predict clinically meaningful outcomes (e.g. relapse), suggesting it would also be possible to develop neuroimaging as a predictor of onset of heavy drinking in adolescents. Developing predictive tools to identify adolescents likely to progress to heavy drinking would offer the opportunity for early intervention and could potentially reduce the progression to AUD. Substantial evidence suggests that primary motives for problematic drinking are to enhance positive valence and reduce negative valence emotions. Further, substance use disorders are associated with altered activity in the insula, ventral striatum, amygdala, and anterior cingulate cortex when processing potential rewards and aversive outcomes. We hypothesize that individuals at risk for AUDs will show heightened response to aversive stimuli in the anterior insula and amygdala and heightened response to rewarding stimuli in the ventral striatum and anterior cingulate cortex. We further hypothesize that they will exhibit diminished functional connectivity between reward, salience, and executive control networks. To test this, we will recruit 70 adolescents aged 18–20. Half will be have a biological parent with an AUD. The other half will be a control group matched on current drinking levels, age, gender, ethnicity, and socioeconomic status. All participants will undergo a functional MRI scan with a resting state run and a run during a modified version of the monetary incentive delay task that includes the risk of hearing an aversive sound (i.e. a loud scream). All participants will be followed for 6 months after the scan to determine levels of drinking. This study will provide both mechanistic information on risk for AUD as well as a tool to identify adolescents at greatest risk prior to the onset of problem drinking. This information could help provide personalized information about risk that may maximize likelihood of AUD prevention. In addition to the research goals described above, this is a training proposal that is designed to facilitate the transition of the primary investigator, Dr. Joshua Gowin, from mentored post-doctoral research fellow to independent, tenure-track research faculty at an academic institution. The mentored phase of the proposal will use a multifaceted training plan to improve Dr. Gowin’s knowledge base as well as his research and professional skillsets. Specifically, Dr. Gowin will learn new techniques in resting state functional connectivity analysis and in the cognitive neuroscience of emotion regulation. In addition to this scientific training, Dr. Gowin will gain experience management, teaching, and data presentation. To achieve these goals, Dr. Gowin has assembled a team of advisors from the intra- and extramural community with expertise in these areas to guide his training and development. This committee will include Dr. Vijay Ramchandani-NIAAA, Dr. Monique Ernst-NIMH, Dr. Elliot Stein-NIDA, and Dr. Susan Tapert-UCSD (see letters of support). The skills that will be developed during the mentored phase will position Dr. Gowin for success as he applies for an independent position and establishes his own research program.

项目概要/摘要 根据最新估计，超过七分之一的美国人将患上酒精使用障碍 (AUD) 在他们的一生中，饮酒导致了全球近 4% 的死亡。 目前，AUD 是一个重大的公共卫生问题。 要求治疗10名患者，观察其中1名患者减少饮酒至健康水平。 因此，一个有吸引力的选择是在高危人群成为酗酒者之前识别出他们； 例如，酗酒家族史目前是青春期的最佳预测因素之一。 提供了研究这些因素的理想时期，因为它先于澳元的出现，但也是一个时期 我们最近表明，神经影像学测量可以快速增加。 用于预测有临床意义的结果（例如复发），这表明也有可能 开发神经影像学作为青少年酗酒发生的预测指标。 识别可能发展为酗酒的青少年的工具将为早期饮酒提供机会 大量证据表明，干预可能会减少 AUD 的进展。 有问题的饮酒的主要动机是提高正价和减少负价 此外，物质使用障碍与岛叶、腹侧活动的改变有关。 处理潜在奖励和厌恶时的纹状体、杏仁核和前扣带皮层 我们研究发现，有 AUD 风险的个体会对厌恶情绪表现出胃肠道反应。 前岛叶和杏仁核的刺激以及对腹侧奖励刺激的氧气反应 我们进一步指出，它们将表现出减少的纹状体和前扣带皮层。 为了测试这一点，我们将奖励、显着性和执行控制网络之间的功能连接。 招募 70 名 18-20 岁的青少年，其中一半的亲生父母拥有澳元。 是与当前饮酒水平、年龄、性别、种族和社会经济地位相匹配的对照组。 所有参与者都将接受功能性 MRI 扫描，其中包括静息状态跑步和修改后的跑步过程 货币激励延迟任务的版本，包括听到令人厌恶的声音（即 扫描后将对所有参与者进行 6 个月的跟踪以确定其水平。 这项研究将提供有关 AUD 风险的机制信息以及一个工具。 在出现饮酒问题之前识别出面临最大风险的青少年。 提供有关风险的个性化信息，可以最大限度地提高 AUD 预防的可能性。 除了上述研究目标之外，这是一项培训提案，旨在促进 主要研究者 Joshua Gowin 博士从指导博士后研究的转变 学术机构的独立终身教授研究员。 该提案将使用多方面的培训计划来提高 Gowin 博士的知识基础以及他的能力 具体来说，高文博士将在休息状态下学习新技术。 除了功能连接分析和情绪调节的认知神经科学。 通过这次科学培训，Gowin 博士将获得管理、教学和数据演示方面的经验。 为了实现这些目标，Gowin 博士组建了一支来自校内和校外的顾问团队 该委员会将在这些领域拥有专业知识的社区来指导他的培训和发展。 包括 Vijay Ramchandani-NIAAA 博士、Monique Ernst-NIMH 博士、Elliot Stein-NIDA 博士和 Susan 博士 Tapert-UCSD（参见支持信）将在指导阶段培养技能。 为 Gowin 博士申请独立职位并建立自己的职位奠定了成功的基础 研究计划。