Sex differences in the neural mechanisms of brief interventions for binge drinking

 描述(申请人提供)：这个K01指导研究科学家奖将支持我建立一个独立的研究生涯，使用神经成像来调查个体差异在酒精使用障碍风险和治疗结果中的作用。这个应用程序的培训部分建立在我的神经科学和神经成像背景之上，这表明我具有很强的技术天赋，并为研究物质风险的精神病理学提供了坚实的基本科学基础。为了实现完全的研究独立性，我确定了四个关键的培训目标：1)获得临床环境的经验，以便了解酒精使用障碍的所有方面及其治疗；2)获得性别差异和成瘾领域的专业知识；3)获得统计方法方面的高级培训；4)增加关于简短干预和激励性访谈技巧的知识。通过这个过程，我将得到密歇根大学精神病学系副教授莫琳·沃尔顿博士和密歇根大学精神病学系助理教授玛丽·海策格博士的指导。由精心挑选的顾问组成的团队将提供额外的指导和培训。拟议的K01项目将在密歇根大学精神病学系的成瘾研究中心(UMARC)内进行，这是一个由NIAAA、NIDA、NIMH和其他一些外部资金来源资助的多学科研究中心，以解决成瘾问题、其原因和补救措施。密歇根大学校园里活跃着80个其他药物滥用研究项目，UMARC的教职员工与这些其他科学家互动合作。该大学的功能磁共振实验室也是一个协作的、跨学科的设施，由许多部门的许多研究人员使用，包括精神病学、心理学、生物医学工程和放射学，仅举几例。密歇根大学活跃的研究环境培养了越来越多的神经成像研究人员，其中包括海策格博士，她担任密歇根纵向研究神经成像部门的负责人已有8年，并因在发育性神经成像和成瘾方面的工作而获得NIDA早期职业调查者奖。研究部分的重点是确定男性和女性大学生酗酒者在与酒精使用障碍风险相关的神经区域--冲动控制、情绪处理和酒精提示反应性--是否存在差异，以及这些区域在短暂干预后如何变化。有大量的行为证据表明，风险轨迹存在差异，女性在负面情绪方面的得分往往较高，而男性在冲动方面的得分往往较高。当酗酒和这种行为产生的负面后果变得有问题时，这种情况可能会延伸到年轻的成年期。此外，简单的干预措施已被证明对大学酗酒者有效，在男性和女性的成功率方面，结果喜忧参半。性别差异如何缓和成瘾的神经生物学还没有得到充分的研究；对这些差异进行更仔细的检查将有助于制定有针对性的预防和干预计划。本文将对两组18-20岁的酗酒大学生进行功能磁共振成像(FMRI)检查，每组男女人数相等(n=100)。其中一组(BI组)将从密歇根大学健康服务基础计划(一项针对大学生的简短酒精干预计划)中招募，并将在计划开始前参加基线fMRI扫描，并在计划结束后立即进行后续扫描。另一组(控制组)将从校园招募，只接受有关饮酒的教育信息。他们将参加基线和后续fMRI扫描，时间安排与BI组相同。在每次扫描以及扫描后3个月和6个月时，将测量情绪功能、饮酒动机、饮酒和酒精相关问题的指标。研究的具体目标是：1)在基线水平上检验大学生酗酒风险因素、动机和潜在神经相关因素的性别差异；2)表征短暂干预狂饮背后的神经变化机制的性别差异；3)表征短暂干预狂饮背后的神经变化机制的性别差异。我将通过一个在这些内容领域拥有专业知识的团队的密切指导、教学课程和定向阅读来实现这些研究和培训目标。

 DESCRIPTION (provided by applicant): This K01 Mentored Research Scientist Award will support me in establishing an independent research career using neuroimaging to investigate the role of individual differences in alcohol use disorder risk and treatment outcomes. The training component of this application builds on my neuroscience and neuroimaging background, which demonstrates a strong technical aptitude and provides a robust basic scientific foundation from which to study the psychopathology of substance risk. To achieve full research independence, I have identified four key training objectives: 1) obtain experience in a clinical setting in order to understand all aspects of alcohol use disorders and their treatment; 2 gain expertise in the area of sex differences and addiction; 3) acquire advanced training in statistical methodologies; and 4) increase knowledge about brief interventions and motivational interviewing techniques. I will be mentored through this process by Dr. Maureen Walton, Associate Professor, Department of Psychiatry at the University of Michigan, and Dr. Mary Heitzeg, Assistant Professor, Department of Psychiatry, University of Michigan. A team of carefully selected consultants will provide additional guidance and training. The proposed K01 project will take place within the University of Michigan Addiction Research Center (UMARC), Department of Psychiatry, a multidisciplinary research center that has been funded by NIAAA, NIDA, NIMH, and a number of other external funding sources to address addiction problems, their causes, and their remediation. Eighty other substance abuse research projects are active on the University of Michigan campus, and UMARC faculty interact and collaborate with these other scientists. The University's Functional MRI Laboratory is also a collaborative, interdisciplinary facility used by a number of researchers across many departments, including Psychiatry, Psychology, Biomedical Engineering, and Radiology, just to name a few. The University of Michigan's vigorous research environment nurtures an expanding group of neuroimaging researchers, including Dr. Heitzeg, who has been the lead of the neuroimaging arm of the Michigan Longitudinal Study for 8 years and was the recipient of a NIDA Early Career Investigator Award for her work in developmental neuroimaging and addiction. The research component focuses on identifying whether there are differences between male and female collegiate binge drinkers in neural regions associated with risk for alcohol use disorders--impulse control, emotion processing, and alcohol cue reactivity--and how these regions change after a brief intervention. There is substantial behavioral evidence for disparities in risk trajectories such that females tend to score higher of measures of negative affect and males tend to score higher on measures of impulsivity. This can extend into young adulthood when binge drinking and negative consequences stemming from this type of behavior becomes problematic. Additionally, brief interventions have been shown to be effective for collegiate binge drinkers, with some mixed outcomes regarding male and female success rates. How sex differences moderate the neurobiology of addiction is understudied; a more careful examination of these differences would be beneficial for the development of targeted prevention and intervention programs. Here, functional magnetic resonance imaging (fMRI) will be conducted in two groups of binge drinking college students between the ages of 18-20yrs, with equal numbers of males and females in each group (n=100 total). One group (BI group) will be recruited from the University of Michigan University Health Services BASICS program (a brief alcohol intervention program for college students), and will partake in a baseline fMRI scan prior to beginning the program, and a follow-up scan immediately after the program finishes. The other group (Control group) will be recruited from campus and will only receive educational information about alcohol use. They will partake in a baseline and follow-up fMRI scan on the same time schedule as the BI group. Measures of emotional functioning, drinking motives, alcohol consumption, and alcohol-related problems will be measured at each scan, as well as 3 and 6 months post-scan. The research specific aims are: 1) examine sex differences in binge drinking risk factors, motivations, and underlying neural correlates at baseline in collegiate bing drinkers; 2) characterize sex differences in neural mechanisms of change underlying a brief intervention for binge drinking; and 3) characterize sex differences in neural mechanisms of change underlying a brief intervention for binge drinking. I will accomplish these research and training goals through close mentorship from a team with expertise in these content areas, didactic coursework, and directed readings.