Psychiatric outcomes of children at high- and low-risk for depression: follow up

描述（由申请人提供）：在我们对家族性抑郁症风险儿童（和对照组）的研究的修订后的重新提交中，我们回应了IRG的关注，并相应地修改了我们的方案。正如我们所解释的，认知灵活性被认为是执行功能的一个组成部分，它可以被索引为响应环境需求而重新集中/转移注意力和快速改变认知集的能力。现在，我们将认知（in）灵活性指数与抑郁症的传统认知风险因素联系起来，并纳入生理灵活性指数，即心脏迷走神经控制（CVC）。父母抑郁是青少年重度抑郁障碍（MDD）的重要危险因素，也增加了共病非情感性障碍的几率。在精神病学高危家庭研究的传统中，我们建议在具有抑郁症家族风险的青少年中，检查选定的个人特征组合作为重度抑郁症和行为和/或物质使用相关障碍的预测因子。个人特征包括父母的临床（如情绪障碍史的严重程度）和儿童的神经认知属性（认知灵活性受损）。作为执行功能的认知灵活性将通过传统的神经心理学测试和他们的新修改来评估，其中包括情绪分散的特征。作为我们的主要目的，我们将检验关于儿童和父母因素如何影响后代患重度抑郁症和非情感性障碍的风险的假设。我们的样本将由n= 250名青少年组成，包括先证者父母的后代（他们自己也有童年发作的情绪障碍）和对照组父母没有重大精神疾病史的后代。作为我们的次要目标，我们将探讨两个传统的认知风险因素（反思性反应风格和消极归因风格）与认知不灵活性的关系，以及生理不灵活性（反映在功能失调的CVC中）在多大程度上为我们的涉及神经认知临床变量的预测模型增加了增量信息。初步评估时的子女年龄为8至16岁，随访时为10至18岁；这一年龄范围涵盖了过渡到青春期和整个青春期，这是重度抑郁症事件（新发）病例和行为/物质使用相关疾病的高风险时期。这项研究的可行性强调了这样一个事实，即我们有机会接触到一个独特的、维护良好的家庭样本，这些家庭样本已被确定为先前抑郁症项目的一部分。我们的研究:A)是创新的，因为它在高风险家庭设计的背景下整合了发育和神经认知的观点，并针对可能构成抑郁症一系列信息处理偏见的认知过程；b)具有重大的公共卫生意义，因为抑郁症既是一种个人毁灭性的疾病，也是世界范围内致残的主要原因。基于对个人特定风险因素/机制的更好理解，这可能会被预防或预先阻止，并且c)是及时的，因为它反映了NIMH关于精神障碍研究的战略目标的几个组成部分。

DESCRIPTION (provided by applicant): In this revised re-submission of our study of children at familial risk for depression (and controls), we have responded to the concerns of the IRG and revised our protocol accordingly. As we explicate, cognitive flexibility has been regarded as one component of executive function, which can be indexed as the ability to re- focus/shift attention and rapidly change cognitive sets in response to environmental demands. We now link our index of cognitive (in)flexibility to traditional cognitive risk factors for depression, and also incorporate an index of physiological flexibility, namely cardiac vagal control (CVC). Parental depression is a significant risk factor for major depressive disorder (MDD) in juveniles and also increases the odds of comorbid non-affective disorders. In the tradition of psychiatric high-risk family studies, we propose to examine combinations of selected personal characteristics as predictors of MDD and conduct and/or substance use-related disorders in juveniles at familial risk for depression. The personal characteristics include parental clinical (e.g., severity of mood disorder history) and child neurocognitive attributes (impaired cognitive flexibility). Cognitive flexibility as an executive function will be assessed both by traditional neuropsychological tests and their novel modifications which incorporate emotionally distracting features. As our Primary Aims, we will test hypotheses about the how the confluence of child and parent factors affect risk of MDD and non-affective disorders in offspring. Our sample will consist of n= 250 youths, including offspring of proband parents (who themselves had childhood-onset mood disorder) and offspring of control parents with no history of major psychiatric disorders. As our Secondary Aims, we will explore the relations of 2 traditional cognitive risk factors (ruminative response style and negative attributional style) to cognitive inflexibility, and the extent to which physiologic inflexibility (reflected in dysfunctional CVC) adds incremental information to our predictive model involving neurocognitive-clinical variables. Offspring will be 8-to-16-years old at initial assessment and 10-to- 18-years old at follow-up; this age range covers the transition into and across adolescence, which is the high risk period for MDD incident (new onset) cases and conduct/substance use related disorders. The feasibility of this study is underscored by the fact that we have access to a unique and well-maintained sample of families that had been ascertained as part of a prior Program Project on depression. Our study: a) is innovative because it integrates developmental and neurocognitive perspectives in the context of a high-risk family design and targets a cognitive process that may underlie a range of information processing biases in depression, b) has great public health significance because depression is both a personally devastating condition and a leading cause of disability worldwide, which may possibly be prevented or forestalled based on a better understanding of person-specific risk factors/mechanisms, and c) is timely because it reflects several components of NIMH's Strategic Objectives for research on mental disorders.