Neuroimaging in the Oklahoma Family Health Patterns Project

描述(由申请人提供)：我们的目标是更好地了解酗酒高危人群的中枢神经系统特征。尽管有大量关于酒精中毒的临床文献，但人们对这种疾病最高风险人群的临床前特征知之甚少。俄克拉荷马州家庭健康模式项目研究了有和没有酗酒家族史的健康年轻人。有阳性家族史的人患酒精使用障碍的可能性是没有家族史的人的四倍，而且这种风险在也有反社会和抑制特征的人中加倍。这两种倾向是共同继承的。因此，既有阳性家族史又有个人行为去抑制证据的人被认为是未来酗酒的高风险者，而那些缺乏这些因素的人被认为是低风险者。我们的主要假设是，高危人群已经改变了大脑机制，这些机制服务于对环境产生正常的情绪反应，并且对公开行为的调节不足。虽然有证据表明边缘系统和前额叶皮质之间的通讯发生了变化，但缺乏确凿的神经成像。这项修订后的申请延续了我们最近的发现，即与没有酒精家族史的人相比，有酗酒家族史的人在休息状态下的局部大脑葡萄糖代谢存在差异。初步发现，FH比FH-in结构具有更大的FDG摄取，这些结构涉及获得视觉信息(Rt.Mid.&Sup.临时工。获得奖赏或评估奖赏价值以做出相关决定(左侧扣带回和尾状回)。这套结构和功能与下丘脑中看到的更大的激活是相容的，这可能在为获得这种奖励做准备方面发挥了相关作用。相反，FH-在涉及前额叶调节控制的功能上比FH有更大的FDG摄取：右额下回参与情绪和自主表达的调节。这一区域与涉及有意识的自主神经调节的功能密切相关，该功能与眼眶额叶皮质有关，该皮质具有下丘脑和脑干的输入。右侧额中回通过与背外侧前额叶皮质的广泛联系参与执行功能。这项研究将扩展静息数据库，以便对与高危人群静息代谢差异有关的大脑区域网络的静息代谢活动进行网络分析。本研究将对我们两个风险组的违约模式和反违约模式功能进行基于种子的相关性分析。这项计划中的研究有望获得有关大脑区域功能变化的新信息，这些区域涉及未来酗酒高危年轻人的认知、决策和行为调节。 公共卫生相关性：酗酒和依赖是行为障碍，是社会的负担。尽管有大量关于酒精依赖者的文献，但人们对这种疾病最高风险人群的临床前特征知之甚少，特别是那些具有遗传风险因素的人。本研究检查了有酗酒家族史的人的静息脑代谢，这些人也有不守规矩和反社会的倾向，这使他们未来酗酒的风险很高。对高危个体的研究对于刻画那些易受酒精中毒影响的人的行为特征是有价值的，这些人没有因酗酒而继发的中枢神经系统影响。拟议的正电子发射断层扫描研究将提供有关这些高危个体潜在脑功能特征的新的有用信息。

DESCRIPTION (provided by applicant): Our goal is to develop a better understanding of central nervous system characteristics of persons at risk for alcoholism. Despite a large clinical literature on alcoholism, far less is known about the preclinical characteristics of persons at greatest risk for the disorder. The Oklahoma Family Health Patterns Project studies healthy young adults with and without a family history of alcoholism. Persons with a positive family history are four times as likely to develop alcohol use disorders as those with no such history, and this risk doubles in persons who also have antisocial and disinhibitory characteristics. The two tendencies are coinherited. Persons with both a positive family history and personal evidence of behavioral disinhibition are accordingly considered to be at High Risk of future alcoholism, and those lacking these factors are considered at Low Risk. Our major hypothesis is that High Risk persons have altered brain mechanisms that serve to produce normal emotional responses to the environment and have deficient regulation of overt behavior. While evidence points to altered communication between the limbic system and prefrontal cortex, confirmatory neuroimaging is lacking. This revised application pursues our recent finding that persons with a family history of alcoholism have differences in regional brain glucose metabolism in the resting state as compared to their counterparts with no such history. Preliminary findings are that FH+ have greater FDG uptake than FH- in structures involved in obtaining visual information (Rt. Middle & Sup. temp. gyrus) and obtaining rewards or assessing reward value to make relevant decisions (Left Cingulate and Caudate). This set of structures and functions is compatible with the greater activation seen in the hypothalamus, which may play a related role in preparation for obtaining such rewards. In contrast FH- have greater FDG uptake than FH+ in functions involving prefrontal regulatory controls: The right inferior frontal gyrus is involved in regulation of emotional and autonomic expression. This region is closely associated with functions involving conscious autonomic regulation in conjunction with the orbital frontal cortex having inputs to the hypothalamus and brainstem. The right middle frontal gyrus is involved in executive functions via extensive connections to the dorsolateral prefrontal cortex. This study will expand the resting database to allow a network analysis of resting metabolic activity of a network of brain areas concerned with resting metabolic differences in High-Risk persons. The present study will carry out a seed- based correlational analysis of default-mode and anti-default-mode function in our two risk groups. The planned studies are expected to yield new information concerning altered functioning in brain regions involved with cognition, decision-making, and behavioral regulation in young adults at high risk for future alcoholism. PUBLIC HEALTH RELEVANCE: Alcohol abuse and dependence are behavioral disorders that are a burden to society. Despite a large literature on persons with alcohol dependence, much less is known about the preclinical characteristics of persons at greatest risk for the disorder, especially those with inherited risk factors. The present study examines resting brain metabolism in persons with a positive family history of alcoholism who also have disinhibited and antisocial tendencies that place them at High Risk of future alcoholism. Studies of High Risk individuals are valuable in characterizing behavioral characteristics of those who are vulnerable to alcoholism free of central nervous system effects secondary to heavy drinking. The proposed positron emission tomography study will provide new and useful information on the underlying brain functional characteristics of these High Risk individuals.