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

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

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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.

项目摘要酒精使用障碍（AUD）和创伤后应激障碍（PTSD）通常是共同发生的，并且这种合并症与更高的消费，治疗辍学和复发风险有关。低点的城市人口社会经济地位尤其面临AUD和PTSD的风险。关于同时发生AUD的病因的研究在这些经过研究且资源低的人群中需要PTSD，以帮助解决差异知识库。存在定向合并症的定向模型，尽管存在主要差距（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，缺乏性影响测试）。此外，合并症可能会受到遗传风险的影响 AUD和PTSD是适中的遗传性，在潜在遗传风险中重叠，并且在遗传上相关性很大基因组广泛的关联研究（GWAS； RG = 0.35）。黑人在遗传学研究中的人数不足，因此，对该人群的基因知识研究至关重要这个区域。当前的多方法研究将通过进行遗传信息的生态学来填补这些空白瞬时评估（EMA）研究使用纵向测量爆发设计。参与者招募通过Grady创伤项目（GTP），该项目由高危市中心居民组成。我们将注册样本在400个人中，他们将被要求提供：PTSD，AUD和合并症，详细的自我报告措施，包括创伤历史，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和酒精使用表型之间（例如消费，暴饮暴食，AUD症状，渴望），而不是澄清只有谁处于危险之中，但是当风险行为发生时。分析将同时测试所有三个模型合并症（即自我药物，易感性，共享风险），并将测试特定性途径。下列的 EMA的最初时期是一个由三个EMA爆发组成的测量爆发设计，每个爆发都有两个月的间隔除了，将发生时间变化的健康决定因素的影响（例如，新创伤，财务状况）压力，种族歧视）在第一个目标中发现的功能关系。最后，探索性目标进行基因组广泛的分析，重点是一种新型的多元遗传方法，基因组结构方程建模（GSEM），该模型将用于产生索引遗传风险的多基因风险评分（PR） PTSD和AUD的合并症，以及每种情况的独特风险。 PRS对AUD的共同风险索引 PTSD，AUD独有的，PTSD独有的PTSD将纳入EMA的最佳拟合模型中分析以确定发现的表型关系是否受遗传风险的影响。这项研究将进步我们对同时发生的AUD和PTSD的风险的理解，这对于发展至关重要有效的预防和治疗计划，尤其是在种族少数城市居民中增加创伤暴露的风险以及随后的AUD和PTSD。