Pathways from Normal and Disordered Personality to Substance Use Disorders

描述(由申请人提供)：慢性物质使用(SU)以及合法和非法物质使用障碍(SODS)使人虚弱，并在很大程度上导致全球发病率和死亡率。人格和人格障碍强烈影响SU和SUDS的风险，但我们对其中涉及的病因知之甚少。该项目利用一种独特的资源来解决一些关于SU和SUDS的新的研究问题。我们将使用最先进的遗传流行病学方法，通过基于挪威人口的纵向、表型丰富和遗传信息丰富的双胞胎注册表(NTR)，识别从正常、异常和病理性人格到合法和非法SU和SUD的因果和非因果路径。我们将把NTR数据与国家、人口和临床登记联系起来，使用挪威唯一的个人识别码来研究合法和非法SU和SUV的风险因素、原因和发病机制以及后果。这将使验证和识别未报告的严重急性呼吸综合征病例成为可能。登记数据还将提供以病假、残疾和疾病衡量的人口统计、社会经济状况和心理社会功能障碍的客观信息，从而使我们能够确定从SU和SUD到心理社会功能障碍的因果和非因果路径。我们的项目有6个科学目标和1个可操作目标。我们将使用横断面和纵向数据来评估去抑制性正常、异常和病理性人格类型、SU和SUD以及相关的I轴障碍之间的表型关联的性质，然后将关联分解为遗传和环境路径。使用互补的方法，我们将模拟我们的关键变量之间的因果关系的方向，同时测试冥想模型以阐明SU作为通往SUDS和相关的外部性谱系障碍的门户的作用。利用遗传信息的纵向模型，我们将探索酒精使用障碍和严重抑郁症之间的因果关系。我们还将将NTR TWINE数据与挪威统计局的数据合并，以检查从SU和SUDS到客观心理社会功能障碍的表型和遗传路径，并以全国病假、残疾和疾病为索引。我们的操作目标是确定新的、第四波关于NTR双胞胎的终身SU和SUD的问卷数据。这将为检验与之竞争的纵向模型提供统计力量。合作小组的建模专门知识将确保对这些资源的最佳利用。本申请是根据国家卫生研究院和挪威研究委员会建立并共同创立的特别资助机制“挪威与美国研究小组的合作项目”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，并通过将NTR的新数据和现有数据与国家、基于人口的人口和临床登记联系起来，预测SU和SUDS的风险。同样的数据将提供关于SU和SUDS如何与病假、疾病和残疾相关的客观信息。

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.