Dissecting the co-occurrence of alcohol use/problems and suicidal behaviors: the roles of genetic liability and neurocognitive mechanisms

项目概要/摘要 这项K99/R 00提案的总体目标是探索总体遗传易感性和神经认知功能。 酒精使用/问题与自杀想法和行为（STB）共同发生的机制。过度 酒精使用在世界范围内普遍存在，对人类健康造成重大负担;它与 医学和精神病理学问题，如STB。STB是一个严重的公共卫生问题， 在美国，自杀未遂和死亡人数每年都在增加。STB的患病率尤其 在有酒精问题的人中，酒精浓度很高，研究从不同的角度解决了这个问题。 研究表明，酒精问题可能会对STB的风险产生因果影响;也有实证支持， 酒精使用/问题和STB之间的共同遗传责任。这种共同的遗传责任强调了 存在可能涉及酒精使用/问题和STB的共同机制。 决策（DM）与青少年饮酒行为和酒精使用障碍有关， 而两者都与机顶盒有关。在STB研究中，DM困难已经被描述，并且可能是 这是冲动性自杀企图的特征，但目前的研究结果主要依赖于自我报告，缺乏客观性 评价。通过依赖DM的理论概念化可以获得额外的知识， 系统评价其潜在的神经认知机制，并考虑遗传因素的作用， 因素利用遗传学和神经心理学，我们将探讨哪些DM机制在糖尿病发病中起作用。 酒精使用/问题和STB共同发生，遗传责任如何参与这种关联，以及是否 环境因素可能影响DM的发展及其与酒精使用/问题和STB的关系。 更好地了解这些过程将有助于预防和干预工作， 根据基因和环境的影响，我们有能力瞄准潜在的可修改机制。 这份建议书描述了一系列的培训，旨在促进我们对共现现象的理解 酒精使用/问题和STB之间的关系：1）候选人将建立在综合评估方面的专业知识 遗传风险和其他遗传模型，并在先进的统计方法，将奠定基础，她 独立的职业生涯; 2）不同的自杀表型将被使用，并根据它们的关联进行区分 酒精使用，神经认知和遗传特征; 3）K99/R 00提案聚集了 遗传学和神经心理学的学科，将支持科学项目的发展， 通往独立的道路。弗吉尼亚精神病和行为遗传学研究所的环境是 非常适合候选人在遗传学，酒精和STB研究方面发展综合计划的目标， 而这个项目的提出代表了对酒精理解的重要贡献 使用/问题和STB通过遗传学和神经心理学方法相结合，符合 NIAA的使命

Project summary/ Abstract The overarching goal of this K99/R00 proposal is to explore aggregate genetic liability and neurocognitive mechanisms in the co-occurrence of alcohol use/problems and suicidal thoughts and behaviors (STB). Excessive alcohol use is prevalent worldwide and represents a significant burden to human health; it is associated with medical and psychopathological problems such as STB. STB are a critical public health concern, with a continuing increase in suicide attempts and deaths every year in the US. The prevalence of STB is particularly high among individuals with alcohol problems and studies have tackled this question from different perspectives. Research indicates that alcohol problems could causally impact risk of STB; there is also empirical support for a shared genetic liability between alcohol use/problems and STB. This shared genetic liability underscores the existence of possible common mechanisms that would be involved in both alcohol use/problems and STB. Decision-making (DM) has been observed in relation with adolescent drinking behavior and alcohol use disorder, while both have been associated with STB. In STB research, DM difficulties have been described and may be characteristic of impulsive suicide attempts, but current findings largely rely on self-reports and lack objective evaluations. Additional knowledge could be gained by relying on a theoretical conceptualization of DM, a systematic evaluation of its underlying neurocognitive mechanisms, and a consideration of the role of genetic factors. Capitalizing on genetics and neuropsychology, we will explore which DM mechanisms play a role in alcohol use/problems and STB co-occurrence, how genetic liability is involved in this association, and whether environmental factors may influence the development of DM and its relation with alcohol use/problems and STB. An improved understanding of these processes will contribute to prevention and intervention efforts by advancing our ability to target potentially modifiable mechanisms according to the influence of genes and environment. This proposal delineates a series of training aims to advance our understanding of the co-occurrence between alcohol use/problems and STB: 1) the candidate will establish expertise in the assessment of aggregate genetic risks and other genetic models, and in advanced statistical methods that will lay the foundation of her independent career; 2) different suicide phenotypes will be used and distinguished according to their association with alcohol use, neurocognitive, and genetic characteristics; 3) the K99/R00 proposal gathers experts in the disciplines of genetics and neuropsychology that will support the development of the scientific project and the pathway to independence. The environment at the Virginia Institute for Psychiatric and Behavioral Genetics is ideal for the candidate’s goal of developing a comprehensive program in genetics, alcohol, and STB research, and the proposed project represents an important contribution toward advancing the understanding of alcohol use/problems and STB through a combination of genetics and neuropsychological methods, consistent with NIAAA’s missions.