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

• 批准号: 10739677
• 负责人: Severine Patricia Lannoy
• 金额: $ 15.06万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-06 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739677
• 关键词: Adolescence; Adolescent; Adult; Affective; Alcohol abuse; Alcohol consumption; Alcohols; Behavior Control; Behavioral Genetics; Characteristics; Clinical; Cognitive; Data; Decision Making; Development; Dimensions; Discipline; Disinhibition; Emotional; Environment; Environmental Risk Factor; Equation; Etiology; Evaluation; Feeling suicidal; Foundations; Funding; General Population; Genes; Genetic; Genetic Models; Genetic Risk; Goals; Health; Heritability; Human; Impairment; Impulsivity; Individual; Intervention; Investigation; Knowledge; Lead; Leadership; Measures; Mediating; Medical; Mentorship; Methods; Mission; Modeling; National Institute on Alcohol Abuse and Alcoholism; Neurocognitive; Neurocognitive Deficit; Neuropsychology; Other Genetics; Pathway interactions; Patient Self-Report; Phenotype; Play; Population; Prevalence; Prevention; Principal Investigator; Problem behavior; Process; Public Health; Reporting; Research; Rewards; Risk Behaviors; Role; Sampling; Series; Severities; Specific qualifier value; Statistical Methods; Stressful Event; Suicide; Suicide attempt; System; Testing; Training; Treatment outcome; Virginia; adverse outcome; alcohol use disorder; career; cognitive control; cognitive system; comorbidity; disability; drinking behavior; drinking onset; early adolescence; early life adversity; economic cost; genetic information; hedonic; high reward; improved; insight; interest; neural circuit; programs; promote resilience; psychogenetics; psychologic; suicidal; suicidal behavior; suicidal morbidity; suicidal risk; underage drinking

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.

项目概要/摘要 K99/R00 提案的总体目标是探索总体遗传责任和神经认知 酒精使用/问题与自杀想法和行为（STB）同时发生的机制。 饮酒在全世界都很普遍，对人类健康造成重大负担； STB 等医疗和精神病理问题是一个重要的公共卫生问题。 在美国，自杀企图和死亡人数每年持续增加，STB 的患病率尤其严重。 有酗酒问题的人中这一比例很高，研究从不同的角度解决了这个问题。 研究表明，酒精问题可能会影响 STB 的风险；也有实证支持； 酗酒/问题与 STB 之间存在共同的遗传倾向，这种共同的遗传倾向强调了这一点。 是否存在涉及酒精使用/问题和 STB 的可能共同机制。 据观察，决策（DM）与青少年饮酒行为和酒精使用障碍有关， 虽然两者都与 STB 有关，但在 STB 研究中，已经描述了 DM 困难，并且可能是这样。 冲动自杀的特征，但目前的研究结果很大程度上依赖于自我报告，缺乏客观性 通过依赖 DM 的理论概念可以获得更多知识。 系统评估其潜在的神经认知机制，并考虑遗传的作用 利用遗传学和神经心理学，我们将探讨哪些 DM 机制在其中发挥作用。 酒精使用/问题和 STB 共存，遗传责任如何参与这种关联，以及是否 环境因素可能会影响 DM 的发展及其与饮酒/问题和 STB 的关系。 加深对这些过程的了解将有助于通过推进预防和干预工作 我们有能力根据基因和环境的影响来瞄准潜在的可改变机制。 该提案描绘了一系列旨在增进我们对共现的理解的培训 酒精使用/问题与 STB 之间的关系：1) 候选人将建立评估总体的专业知识 遗传风险和其他遗传模型，以及先进的统计方法将为她奠定基础 独立的职业；2）将根据其关联来使用和区分不同的自杀表型 与酒精使用、神经认知和遗传特征有关；3) K99/R00 提案聚集了以下领域的专家： 遗传学和神经心理学学科将支持科学项目的发展和 弗吉尼亚精神病学和行为遗传学研究所的环境是独立的。 非常适合候选人开发遗传学、酒精和 STB 研究综合项目的目标， 拟议的项目对增进对酒精的理解做出了重要贡献 通过结合遗传学和神经心理学方法来解决使用/问题和 STB，与 NIAAA 的使命。