Children at Risk for Anxiety Disorders: A Follow up Stu*

描述（由申请人提供）：拟议的研究是对一个大队列（N=446）的有惊恐障碍（PD）风险的后代进行12年随访，并比较有重度抑郁症（MD）风险或没有易感性的后代情绪或焦虑障碍。这些儿童最初是在幼儿期和幼儿期招募的，在儿童中期（6年级）重新评估，并将在下一波中进入青春期。该样本的独特之处在于：a）在儿童进入儿童期焦虑障碍的风险期之前，使用行为抑制（BI）的实验室测量和新生神经病理学评估，在基线时对儿童进行了广泛的表征; B）先证者父母对其成年和儿童期精神病理学进行了全面的评估，并仔细注意描绘后代可能暴露的事件; c）据我们所知，这是迄今为止纵向跟踪的最大样本的焦虑风险儿童。我们的研究也是独一无二的，因为它在几个有希望的方向上产生了分支，包括BI遗传基础的研究和对有焦虑风险的幼儿的早期干预。 我们正在进行的目标是研究是否有可能预测父母患有PD的儿童中焦虑症的发展和顺序，以及确定儿童精神病理学的风险因素，包括气质（行为抑制或去抑制[BD]），父母的共病和可能影响或中度风险的心理社会逆境因素。我们已经发现，PD父母的后代在儿童中期患PD、广场恐怖症和多种焦虑症的风险增加，MD父母的后代患一系列焦虑、情绪和破坏性行为障碍的风险增加，BI青少年患社交焦虑的风险增加，BD儿童患破坏性行为障碍的风险增加。我们还注意到焦虑症风险与围产期和心理社会风险因素之间的关联。现在，随着儿童进入青春期，这是社交恐惧症，PD和MD发病风险增加的时期，以及酒精和药物滥用，同伴困难和其他心理问题，我们处于令人兴奋和独特的位置，可以回答有关父母PD，父母MD，BI或BD以及预先存在的儿童疾病所赋予的特定脆弱性的问题。我们也能够开始询问，我们在童年早期发现的风险因素为什么会影响青春期的精神病理学或心理弹性，以及它们是如何与保护因素联合收割机结合来预测结果的。 这些研究问题很简单，但它们具有广泛的影响。对高危儿童和青少年的研究具有极其重要的公共卫生意义，因为确定精神病理学和物质使用障碍的预测因子可以为有针对性的初级或二级预防方案奠定基础。如果我们要理解为什么一些具有生物或心理社会风险因素的儿童在青春期保持健康，并成功地完成这一时期的发展任务，而另一些儿童则发展出精神病理学或功能出轨，那么识别这些预测因素（无论是宪法还是环境）是至关重要的。仔细阐明这些因素的运作机制，将使具体的，有效的，具有成本效益的干预措施，以防止在青春期的不良后果的设计，并将允许针对稀缺的社会资源的人口最有可能受益于这些方案。

DESCRIPTION (provided by applicant): The proposed study is a 12-year follow-up of a large cohort (N=446) of offspring at risk for panic disorder (PD), and comparison offspring at risk for major depression (MD) or without vulnerability for mood or anxiety disorders. The children were originally recruited in toddler hood and early childhood, were reassessed in middle childhood (at Year 6), and will enter adolescence during the next wave. This sample is unique in that a) children were characterized extensively at Baseline, using laboratory measures of behavioral inhibition (BI) and assessments of nascent symptomatology well before they entered the period of risk for childhood anxiety disorders; b) proband parents underwent comprehensive assessments of their adult and childhood psychopathology, with careful attention to delineating episodes to which offspring might have been exposed; and c) to our knowledge, it represents the largest sample of children at risk for anxiety followed longitudinally to date. Our study is also unique in that it has spawned offshoots in several promising directions, including studies of the genetic bases of BI and of an early intervention for young children at risk for anxiety. Our ongoing goals have been to study whether it is possible to predict the development and sequence of anxiety disorders among children of parents with PD, as well as to identify risk factors for childhood psychopathology, including temperamental (behavioral inhibition or disinhibition [BD]), parental comorbidity, and psychosocial adversity factors which might influence or moderate risk. We have already identified increased risks in middle childhood for PD, agoraphobia, and multiple anxiety disorders in offspring of PD parents, for a range of anxiety, mood and disruptive behavior disorders in offspring of MD parents, for social anxiety in BI youngsters, and for disruptive behavior disorders in children with BD. We have also noted associations between risk for anxiety disorders and perinatal and psychosocial risk factors. Now, as the children enter adolescence, a period of heightened risk for onset of social phobia, PD, and MD, as well as alcohol and substance abuse, peer difficulties, and other psychosocial problems, we are in the exciting and unique position to answer questions about the specific vulnerabilities conferred by parental PD, parental MD, BI or BD, and pre-existing childhood disorders. We are also able to begin to ask why and how the risk factors we have identified early in childhood influence psychopathology or resiliency in adolescence, and in what ways they combine with protective factors in predicting outcome. These research questions are straightforward, yet they carry broad implications. Studies of high-risk children and adolescents are of the utmost major public health relevance, since the identification of predictors of psychopathology and substance use disorders can set the stage for targeted primary or secondary prevention programs. The identification of such predictors, whether constitutional or environmental, is essential if we are to understand why some children with biological or psychosocial risk factors remain healthy during adolescence and successfully negotiate developmental tasks of this period while others develop psychopathology or derailments in functioning. Careful articulation of the mechanisms by which such factors operate would enable the design of specific, efficient, and cost-effective interventions to prevent poor outcomes in adolescence, and would permit the targeting of scarce societal resources for populations most likely to benefit from such programs.