Neural Basis of alcohol/substance use disorders and suicide in American Indians

项目摘要 自杀是一个重要的心理健康问题，但没有任何地方比这个问题更引人注目和极端，因为它是 美国印第安人/阿拉斯加原住民（AI/AN）和第一民族（FN）。虽然AI/AN的自杀率各不相同， 在一些社区，死亡率几乎是全国平均水平的10倍。此外，美国流行病学 研究表明，与美国其他族裔群体相比，AI/AN青少年和成年人的饮酒率最高 使用障碍（AUD），与显著残疾和死亡率相关。因此，确定风险的研究 AI/AN青少年和成人自杀风险和物质使用障碍的因素和精神病理学机制是 需要解决AI/AN所经历的巨大健康差异。然而，全面的循证研究表明， AI/AN和FN完全缺乏自杀风险和AUDs，特别是那些包括生物措施的AUDs 人这项研究计划的总体目标是确定神经机制，以及个人和社区 美国社区样本中酒精和其他物质使用障碍及自杀行为（SB）的危险因素 居住在农村保留地的印第安人（大赦国际）。我们以前的研究记录了中度肥胖的高终生患病率。 和严重的酒精使用障碍（AUD）（45%）在这一组，并在最近确定了过量的自杀行为 （>15%）在成人AI中。我们的数据集是独一无二的，因为它包括广泛的临床数据，心理社会措施， 睡眠、电生理和全基因组测序数据。利用这一丰富的数据集，我们建议确定是否 这组AI具有远端和近端风险因素和生物标志物（电生理学和遗传学），与 一般人口样本中描述的文献，或有独特的决定因素SB。 可能会为人工智能中的SB增加特别独特的风险因素，我们还建议使用最先进的地理编码方法， 获得新的基于社区的SB风险因素数据。我们方法的独特之处在于我们强调高风险因素的作用， 酒精使用水平和AUDs在诱导抑郁性精神病学中发挥作用，结合独特的环境因素， 我们还建议收集新的纵向数据， 在生命周期内跟踪SB。最后，我们将使用现有和扩展的横断面队列研究的数据 青少年和成人以及新的纵向回顾性多队列研究，以开发全面的生物 AUD和SB的心理社会模型。拟议的分析有可能揭示重要的风险， 在这个独特的AI高危人群中SB的保护因素，以及确定发育相关点 预防和干预，以减少青少年和成年期AUD和SB的负面影响。

PROJECT SUMMARY Suicide is an important mental health problem but nowhere is this problem more striking and extreme as it is in American Indian/Alaska Native (AI/AN) and First Nations (FN) people. Although suicide rates vary among AI/AN communities, rates in some communities are almost 10 times the national average. Additionally, U.S. epidemiological studies demonstrate that compared with other U.S. ethnic groups, AI/AN teens and adults have the highest rates of alcohol use disorders (AUDs), that are associated with significant disability and mortality. Thus, studies identifying the risk factors and psychopathological mechanisms for suicide risk and substance use disorders in AI/AN teens and adults are needed to address the substantial health disparities experienced by AI/AN. Yet comprehensive evidence-based studies of suicide risk and AUDs, especially those that include biological measures, are completely lacking in AI/AN and FN people. The overall objective of this research plan is to identify neural mechanisms, as well as individual and community risk factors for alcohol and other substance use disorders and suicidal behaviors (SB) in a community sample of American Indians (AI) residing on rural reservations. Our previous studies have documented a high lifetime prevalence of moderate and severe alcohol use disorders (AUD) (45%) in this group, and have recently identified an excess of suicidal behaviors (>15% attempted) in AI adults. Our data set is unique in that it includes extensive clinical data, psychosocial measures, sleep, electrophysiology and whole genome sequencing data. Using this rich data set we propose to determine whether this group of AI have distal and proximal risk factors and biomarkers (electrophysiological and genetic), that are similar to general population samples described in the literature, or have unique determinants for SB. Since living on a reservation may add particularly unique risk factors for SB in AI we also propose to use state of the art geocoding methodology to obtain new community based data on risk factors for SB. Unique to our approach is our emphasis on the role that high levels of alcohol use and AUDs play in inducing depressive symptomatology, combined with unique environmental conditions on reservations, as critical factors in driving SB. We additionally propose to collect new longitudinal data to follow up on SB over the life span. Finally, we will use data from the existing and expanded cross-sectional cohort studies of teens and adults as well as the new longitudinal retrospective multi-cohort studies to develop comprehensive bio- psychosocial models of AUD and SB. The proposed analyses have the possibility of uncovering important risk and protective factors for SB in this unique high-risk population of AI, as well as identifying developmentally-relevant points of prevention and intervention to reduce the negative impacts of AUD and SB in adolescence and adulthood.