Pathways from Normal and Disordered Personality to Substance Use Disorders

从正常和紊乱人格到药物使用障碍的途径

• 批准号: 8926378
• 负责人: Nathan Alexander Gillespie
• 金额: $ 37.6万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8926378
• 关键词: Address; Adult; Alcohol or Other Drugs use; Cannabis; Chronic; Clinical; Cocaine; Codeine; Data; Databases; Dental crowns; Diagnostic; Disease; Drug Prescriptions; Drug usage; Ensure; Environmental Risk Factor; Epidemiologic Methods; Ethanol; Etiology; Functional disorder; Funding; Funding Mechanisms; Genetic; Genetic Risk; Hallucinogens; Health; Interview; Intoxication; Legal; Level of Evidence; Link; Major Depressive Disorder; Maps; Measures; Mediating; Mental disorders; Modeling; Morbidity - disease rate; Nature; Nicotine; Normal Range; Norway; Outcome; Pathway interactions; Personality; Personality Disorders; Pharmaceutical Preparations; Physiological; Prevention program; Psychopathology; Questionnaires; Registries; Research; Resources; Risk; Risk Factors; Role; Sampling; Sick Leave; Socioeconomic Status; Substance Use Disorder; Symptoms; Testing; Time; Twin Multiple Birth; Twin Studies; United States; United States National Institutes of Health; Validation; Withdrawal; alcohol use disorder; base; cost; data registry; demographics; design; disability; disorder prevention; evidence base; indexing; intervention program; longitudinal design; mortality; novel; patient registry; population based; prospective; psychosocial; statistics; trait

DESCRIPTION (provided by applicant): Chronic substance use (SU) and licit and illicit substance use disorders (SUDs) are debilitating and contribute substantially to global morbidity and mortality. Personality and personality disorders strongly influence risk of SU and SUDs, but we know little about the etiologic pathways involved. This project utilizes a unique resource to address a number of novel research questions concerning SU and SUDs. We will use state-of-the-art genetic epidemiological methods to identify causal and non-causal pathways from normal, abnormal and pathological personality to licit and illicit SU and SUDs using the longitudinal, phenotypically rich, and genetically informative population-based Norwegian Twin Registry (NTR). We will link the NTR data to national, population-based and clinical registries, using Norway's unique personal identification number to study the risk factors, causes and disease mechanism as well as consequences of licit and illicit SU and SUDs. This will enable validation and identification of unreported SUD cases. The registry data will also provide objective information on demographics, socioeconomic status and psychosocial dysfunction as measured by sick leave, disability, and illness thereby enabling us to determine the causal and non-causal pathways from SU and SUD to psychosocial dysfunction. Our project has 6 scientific and one operational aim. We will use cross-sectional and longitudinal data to estimate the nature of the phenotypic associations between disinhibitory normal, abnormal and pathological personality types, SU and SUD, and correlated Axis I disorders before decomposing the associations into genetic and environmental pathways. Using complementary approaches we will model direction of causation between our key variables, while testing meditational models to clarify the role of SU as a gateway to SUDs and correlated externalizing spectrum disorders. Using genetically informative longitudinal models we will explore the causal relationship between alcohol use disorders and major depression. We will also merge NTR twin data with data from Statistics Norway to examine the phenotypic and genetic pathways from SU and SUDs to objective psychosocial dysfunction as indexed by nationwide sick leave, disability and illness. Our operational aim is to ascertain a new, fourth wave of questionnaire data on lifetime SU and SUDs from the NTR twins. This will provide statistical power to test competing longitudinal models. The modelling expertise of the collaborative group will ensure optimal exploitation of these resources. This application is submitted under a special funding mechanism "Norwegian Collaborative Projects with Research Groups in the United States" established and cofounded by the NIH and the Research Council of Norway. We propose to study how genetic and environmental risk factors in normal, abnormal and pathological personality impact and predict the risk of SU and SUDs by linking new and existing data from the NTR to national, population-based demographic and clinical registries. The same data will provide objective information on how SU and SUDs are related to sick leave, illness and disability.

描述（由申请方提供）：慢性物质使用（SU）以及合法和非法物质使用障碍（SUD）使人衰弱，并对全球发病率和死亡率有很大影响。人格和人格障碍强烈影响SU和SUD的风险，但我们对所涉及的病因学途径知之甚少。该项目利用独特的资源来解决一些关于SU和SUD的新研究问题。我们将使用最先进的遗传流行病学方法，以确定从正常，异常和病理性人格合法和非法SU和SUD的因果和非因果途径，使用纵向，表型丰富，遗传信息丰富的人口为基础的挪威双胞胎登记处（NTR）。我们将把NTR数据与国家、基于人群和临床登记处联系起来，使用挪威唯一的个人识别号码来研究合法和非法SU和SUD的风险因素、原因和疾病机制以及后果。这将有助于验证和识别未报告的SUD病例。登记数据还将提供有关人口统计学、社会经济状况和心理社会功能障碍（通过病假、残疾和疾病衡量）的客观信息，从而使我们能够确定SU和SUD至心理社会功能障碍的因果和非因果途径。我们的项目有6个科学目标和1个操作目标。我们将使用横截面和纵向数据来估计去抑制正常，异常和病理性人格类型，SU和SUD之间的表型关联的性质，以及相关的轴I障碍，然后将关联分解为遗传和环境途径。使用互补的方法，我们将模型的方向之间的因果关系，我们的关键变量，同时测试冥想模型，以澄清SU的作用作为一个网关SUD和相关的外化频谱障碍。使用遗传信息纵向模型，我们将探讨酒精使用障碍和重性抑郁症之间的因果关系。我们还将把NTR双胞胎数据与挪威统计局的数据合并，以检查从SU和SUD到客观心理社会功能障碍的表型和遗传途径，如全国范围内的病假，残疾和疾病所示。我们的操作目标是确定一个新的，第四波的问卷调查数据的一生SU和SUD的NTR双胞胎。这将为检验竞争性纵向模型提供统计功效。协作小组的建模专门知识将确保最佳利用这些资源。本申请是根据由NIH和挪威研究理事会建立和共同创立的“挪威与美国研究小组合作项目”特别资助机制提交的。我们建议研究正常，异常和病理性人格中的遗传和环境风险因素如何影响和预测SU和SUD的风险，方法是将NTR的新数据和现有数据与国家，基于人口的人口统计学和临床登记联系起来。同样的数据将提供关于SU和SUD如何与病假、疾病和残疾相关的客观信息。