Oklahoma Family Health Patterns: A Study Across Generations

描述（由申请人提供）：我们的长期目标是更好地了解有酗酒风险的人的诱发动机特征。酒精成瘾是一种遗传和环境因素共同作用的行为障碍。有阳性家族史的人酗酒的风险增加是更基本的遗传特征的表现。这些特征被认为来自于调节情绪体验和表达的大脑区域的活动改变。本项目将检查有酗酒家族史的人，并根据他们对阿片受体阻断剂纳洛酮的皮质醇反应将他们分类。皮质醇对纳洛酮的反应幅度是中枢阿片调节异常升高的有用指标。阿片功能的这种提升也是其他大脑调节系统功能差异的指标。这些系统对边缘系统和前额叶皮层的功能有影响，反过来可能会为酗酒高危人群的动机相关行为的潜在变化提供见解。我们计划测试200名健康志愿者，其中100名有酗酒家族史，100名没有。我们预测，高风险个体的中枢阿片类激活升高将在四个功能领域中观察到：1）行为控制不足：人的积极情绪与消极情绪的气质平衡应该不太稳定，并倾向于烦躁不安。2)认知处理在测试或工作记忆中会受损。3)在激励条件下，选择行为会表现出对冒险和冲动的偏好。行为经济学（延迟贴现）的测试将显示一个短的时间范围。4)内脏对心理压力的反应会变迟钝，压力激素、皮质醇和控制心脏的自主神经的反应会减少。我们的长期目标是对参与研究的受试者进行年度随访，以寻找决定长期饮酒模式的因素。该项目旨在了解酗酒者子女的心理和行为特征，以确定那些使他们未来酗酒风险高的个人特征。预防酒精中毒等复杂疾病需要及早查明风险最大的人，该项目力求提供有关这种风险的新信息。

DESCRIPTION (provided by applicant): Our long-term goal is to develop a better understanding of predisposing motivational characteristics of persons at risk for alcoholism. Alcohol addiction is a behavioral disorder with genetic and environmental contributions. Increased risk for alcoholism in persons with a positive family history is an expression of more basic inherited traits. These traits are thought to derive from altered activity of brain regions regulating emotional experience and expression. The present project will examine persons with a family history of alcoholism and classify them according to their cortisol response to naltrexone, an opiate receptor blocker. The magnitude of cortisol response to naltrexone is a useful indicator of an abnormally elevated central opioid regulation. This elevation in opioid function is also an indicator of differential functioning of other brain regulatory systems. These systems have an impact on functioning of the limbic system and prefrontal cortex, and in turn may provide insights into underlying alterations in motivation-related behavior in persons who are at high risk for alcoholism. We plan to test 200 healthy volunteers, 100 with a family history of alcoholism, 100 without. We predict that elevated central opioid activation in high-risk individuals will be observable in four domains of function: 1) Behavioral undercontrol: the person's temperamental balance of positive to negative affect should be less stable and weighted toward dysphoria. 2) Cognitive processing will be impaired on tests or working memory. 3) Choice behaviors will show biases toward risk-taking and impulsivity under motivational conditions. Tests of behavioral economics (delay-discounting) will show a short time horizon. 4) Visceral responses to psychological stress will be blunted, with reduced responses in the stress hormone, cortisol, and autonomic measures controlling the heart. Our longer-term goal is to perform annual follow-ups of subjects who have taken part in the study to seek factors that determine long-term drinking patterns. This project seeks to understand psychological and behavioral characteristics of young adults who are children of alcoholics to identify those personal characteristics that put them at high risk for future alcoholism. Prevention of complex disorders such as alcoholism requires early identification of those persons who are most at risk, and this project seeks to provide new information about such risk.