Integrating genetic and ecological momentary assessment technologies to advance models of PTSD-AUD comorbidity

整合遗传和生态瞬时评估技术来推进 PTSD-AUD 共病模型

基本信息

批准号：
10735391
负责人：
ANANDA B AMSTADTER
金额：
$ 72.67万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10735391
关键词：
Accounting Acute Address Affect Alcohol Phenotype Alcohol consumption Area Black Populations COVID-19 pandemic Clinical Consumption Data Development Diagnostic Disease Disparity Dropout Ecological momentary assessment Economics Enrollment Equation Equity Etiology Financial Hardship Genetic Genetic Research Genetic Risk Genetic study Genomics Goals Health Heritability Individual Intervention Interview Investigation Knowledge Lead Light Measurement Measures Mental Health Methodology Methods Modeling Molecular Genetics Participant Pathway interactions Patient Recruitments Patient Self-Report Persons Phenotype Population Populations at Risk Post-Traumatic Stress Disorders Predisposition Prevalence Prevention Prevention program Prognosis Protocols documentation Public Health Recording of previous events Reduce health disparities Research Resources Risk Risk Behaviors Risk Factors Sampling Self Medication Series Severities Social support Specificity Symptoms Technology Assessment Testing Time Trauma Underrepresented Populations Urban Community Urban Population Variant Woman Work alcohol risk alcohol use disorder binge drinking comorbidity craving design disparity gap follow up assessment follow-up genome wide association study genome-wide analysis high risk indexing inner city knowledge base longitudinal design low socioeconomic status men novel pandemic disease people of color polygenic risk score prospective protective factors racial discrimination racial minority racial minority population relapse risk risk sharing saliva sample sex social social health determinants trauma exposure treatment program

项目摘要

Project Summary Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) commonly co-occur, and this comorbidity is associated with higher consumption, treatment dropout, and risk for relapse. Urban populations of low socioeconomic status are particularly at risk for AUD and PTSD. Research on the etiology of co-occurring AUD and PTSD is needed in these understudied and low resourced populations to help address a disparity in the knowledge base. Directional models of comorbidity exist, self-medication and susceptibility, although there are major gaps (e.g., few studies testing direction of causation and or bidirectionality effects, lack of specificity of assessment, lack of test of sex effects). Additionally, comorbidity could be influenced by genetic risk as both AUD and PTSD are moderately heritable, overlap in latent genetic risk, and are genetically correlated in large genome wide association studies (GWAS; rG=0.35). Black persons are underrepresented in genetics research, and thus, genetically informed studies in this population are critically needed for equity in knowledge gained in this area. The current multi-method study will fill these gaps by conducting a genetically informative ecological momentary assessment (EMA) study using a longitudinal measurement burst design. Participants recruited through the Grady Trauma Project (GTP), which consists of high-risk inner-city residents. We will enroll a sample of 400 individuals and they will be asked to provide: clinical interview diagnostic data on PTSD, AUD, and comorbidities, detailed self-report measures including trauma history, social determinants of health, other risk and protective factors, and a saliva sample for GWAS. The EMA protocol will capture the temporal relations between PTSD and alcohol use phenotypes (e.g., consumption, binge, AUD symptoms, craving) and clarify not only who is at risk, but when the risk behaviors occur. Analyses will simultaneously test all three models of comorbidity (i.e., self-medication, susceptibility, shared risk) and will test for sex specific pathways. Following this initial period of EMA, a measurement burst design consisting of three EMA bursts, each spaced two months apart, will occur to examine the impact of time varying social determinants of health (e.g., new trauma, financial stress, racial discrimination) on the functional relationships found in the first aim. Lastly, the exploratory aim will conduct genome wide analyses with a focus on a novel multivariate genetic method, genomic Structural Equation Modeling (gSEM), which will be used to produce polygenetic risk scores (PRS) that index genetic risk for comorbidity of PTSD and AUD, and unique risk for each condition. PRS indexing shared risk between AUD- PTSD, unique to AUD, and unique to PTSD, will be incorporated into the best fitting models from the EMA analyses to determine if the phenotypic relations found are influenced by genetic risk. This study will advance our understanding of risk underlying co-occurring AUD and PTSD, which is imperative to the development of effective prevention and treatment programs, particularly among racially minoritized inner-city residents who are at increased risk for trauma exposure and subsequent AUD and PTSD.

项目概要酒精使用障碍 (AUD) 和创伤后应激障碍 (PTSD) 通常同时发生，并且这种合并症与较高的消耗量、治疗中断和复发风险相关。城市人口低社会经济地位对 AUD 和 PTSD 的影响尤其大。并发AUD的病因学研究这些未得到充分研究和资源匮乏的人群需要创伤后应激障碍 (PTSD)，以帮助解决性别差异问题知识库。存在共病的定向模型、自我药疗和易感性，尽管有主要差距（例如，很少有研究测试因果关系和/或双向效应的方向，缺乏特异性评估，缺乏性别影响测试）。此外，合并症可能受到遗传风险的影响，因为 AUD 和 PTSD 具有中等遗传性，潜在遗传风险重叠，并且在很大程度上具有遗传相关性。全基因组关联研究（GWAS；rG=0.35）。黑人在遗传学研究中的代表性不足，因此，为了公平地获得知识，迫切需要在这一人群中进行遗传信息研究。这个区域。目前的多方法研究将通过进行遗传信息生态学研究来填补这些空白使用纵向测量突发设计的瞬时评估（EMA）研究。招募参与者通过格雷迪创伤项目 (GTP)，该项目由高风险的内城区居民组成。我们将登记样品 400 个人，他们将被要求提供： PTSD、AUD 和的临床访谈诊断数据合并症、详细的自我报告措施，包括创伤史、健康的社会决定因素、其他风险和保护因素，以及 GWAS 的唾液样本。 EMA 协议将捕获时间关系 PTSD 和饮酒表型（例如，饮酒、暴饮暴食、AUD 症状、渴望）之间的关系，并澄清不只有谁处于危险之中，以及何时发生危险行为。分析将同时测试所有三个模型合并症（即自我药疗、易感性、共同风险）并将测试性别特异性途径。下列的 EMA 的初始阶段，由三个 EMA 突发组成的测量突发设计，每次间隔两个月除此之外，还将研究随时间变化的健康社会决定因素的影响（例如，新的创伤、财务压力、种族歧视）对第一个目标中发现的功能关系的影响。最后，探索性目标将进行全基因组分析，重点是一种新颖的多变量遗传方法，即基因组结构方程建模 (gSEM)，将用于生成多遗传风险评分 (PRS)，以反映遗传风险 PTSD 和 AUD 的共病，以及每种情况的独特风险。 PRS 指数在澳元-之间分担风险 AUD 独有的 PTSD 以及 PTSD 独有的 PTSD 将被纳入 EMA 的最佳拟合模型中分析以确定发现的表型关系是否受到遗传风险的影响。这项研究将推进我们对同时发生的 AUD 和 PTSD 潜在风险的理解，这对于开发有效的预防和治疗计划，特别是针对少数族裔的内城居民遭受创伤暴露以及随后的 AUD 和 PTSD 的风险增加。