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

剖析饮酒/问题与自杀行为的共存:遗传倾向和神经认知机制的作用

基本信息

项目摘要

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.
项目摘要/摘要 这项K99/R00提案的首要目标是探索总体遗传风险和神经认知 酒精使用/问题与自杀想法和行为(STB)共存的机制。过份 酒精的使用在世界范围内很普遍,对人类健康是一个重大的负担;它与 医疗和精神病理问题,如性传播疾病。STB是一个严重的公共卫生问题,具有 在美国,自杀未遂和死亡人数每年都在持续增加。STB的流行情况尤其严重 在有酒精问题的人中很高,研究从不同的角度解决了这个问题。 研究表明,酒精问题可能会对性传播疾病的风险产生因果影响;也有经验支持 酒精使用/问题和性传播疾病之间的共同遗传责任。这种共同的遗传责任突显了 存在可能涉及酒精使用/问题和性传播疾病的共同机制。 已经观察到决策(DM)与青少年饮酒行为和酒精使用障碍的关系, 而两者都与STB有关。在STB研究中,DM的困难已经被描述并且可能是 以冲动自杀企图为特征,但目前的发现主要依赖于自我报告,缺乏客观性 评估。通过依赖于DM的理论概念化,可以获得额外的知识 系统评估其潜在的神经认知机制,并考虑基因的作用 各种因素。利用遗传学和神经心理学,我们将探索DM在哪些机制中发挥作用 酒精使用/问题和性传播疾病的共同发生,遗传责任如何参与这种关联,以及是否 环境因素可能影响糖尿病的发展及其与酒精使用/问题和STB的关系。 对这些过程的更好的理解将有助于通过推动 根据基因和环境的影响,我们有能力针对潜在的可修改机制。 这项建议勾勒出了一系列旨在增进我们对共同发生的理解的培训 在酒精使用/问题和STB之间:1)应聘者将在总体评估方面建立专业知识 遗传风险和其他遗传模型,以及将为HER奠定基础的高级统计方法 独立职业;2)使用不同的自杀表型,并根据其关联性进行区分 与酒精使用、神经认知和遗传特征有关;3)K99/R00提案汇集了 遗传学和神经心理学的学科将支持科学项目的发展和 通向独立的道路。弗吉尼亚精神病学和行为遗传学研究所的环境是 非常适合候选人的目标,即在遗传学、酒精和STB研究方面开发一个全面的项目, 这项拟议的项目对促进人们对酒精的理解做出了重要贡献 通过遗传学和神经心理学方法的结合使用/问题和性传播障碍,符合 国家航空航天局的任务。

项目成果

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