Adolescents at High Risk for Familial Bipolar Disorder.

描述(申请人提供)双相情感障碍是一种严重的遗传性精神疾病，影响1%的总人口。发病年龄一般在青少年后期或成年期早期。对影响这种疾病的发病率和发病年龄的具体危险因素知之甚少。1988年，NIMH建立了双相情感障碍遗传学倡议，目的是确定易感基因；这一合作已经确定了数百个患有多个双相情感障碍病例的家庭。作为最初的三个合作网站(印第安纳大学、约翰霍普金斯大学和圣路易斯华盛顿大学)，我们现在提议评估和跟踪这些家庭和类似家庭中12-18岁的青少年。这一“危险”群体将被与一组匹配的社区比较对象进行比较。300名研究对象和300名对照将使用为青少年和父母(DIGS)建立的诊断工具(KSADS-PL)进行研究。还将使用其他工具来评估行为、气质、家庭环境和药物使用情况。DNA也将被收集。这些数据将被存储在一个数据库中，该数据库旨在促进临床变量的纵向研究。分析将比较高风险组和对照组中的潜在风险因素。高危人群的后续研究将在研究的第二年开始。假设将确定三组：1)有行为症状或障碍的青少年，将表现为早发性双相情感障碍；2)有焦虑症状或障碍的青少年，将出现较晚起病的b相情感障碍；以及3)有轻微情绪症状或障碍的青少年，将出现较晚起病的单相或双相情感障碍。所有受试者将在行为、焦虑和情绪症状的三个维度上进行表征；中间结果和主要情绪诊断将根据基线维度评级进行评估。这项研究的伦理影响将通过检查参与的影响和由于高危状态对自尊的任何影响，以及收集和潜在使用遗传数据预测家庭内的风险的影响来研究。临床数据和DNA将与科学界共享。

DESCRIPTION (provided by applicant) Bipolar disorder is a severe heritable psychiatric illness affecting 1% of the general population. The age of onset is generally in the late teenage years or early adulthood. Very little is known about specific risk factors that influence the incidence and age of onset of this disorder. In 1988 the NIMH established a Genetics Initiative in bipolar disorder with the goal of identifying susceptibility genes; this collaboration has identified several hundred families with multiple cases of bipolar disorder. As three of the initial collaborating sites (Indiana University, Johns Hopkins University, and Washington University at St Louis) we are now proposing to assess and follow adolescents, ages 12 -18 years, in these and similar families. This "at risk" group will be compared to a matched set of community comparison subjects. Three hundred study subjects and three hundred controls will be studied using established diagnostic instruments (KSADS- PL) for the adolescents and the parents (DIGS). Other instruments to assess behavior, temperament, family environment, and substance use will be employed. DNA will also be collected. The data will be stored in a database developed to facilitate longitudinal studies of clinical variables. Analyses will compare potential risk factors among the high risk group and the controls. Follow-up of the high risk group will begin in the second year of the study. It is hypothesized that three groups will be identified: 1) adolescents with behavioral symptoms or disorders who will manifest early-onset bipolar disorder; 2) adolescents with anxiety symptoms or disorders who will manifest later-onset b polar disorder; and 3) adolescents with minor mood symptoms or disorders who will manifest later-onset unipolar or bipolar disorder. All subjects will be characterized on the three dimensions of behavioral, anxiety, and mood symptoms; intermediate outcomes and major mood diagnoses will be evaluated in relation to baseline dimensional ratings. The ethical implications of this research will be studied by examining the effects of participation and any effect on self-esteem due to high risk status as well as the implications of the collections and potential use of genetic data for prediction of risk within families. Clinical data and DNA will be shared with the scientific community.