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

描述(由申请人提供)：在我们重新提交的这项关于患有抑郁症(和对照)的家庭风险儿童的研究的修订中，我们已经回应了IRG的关切，并相应地修改了我们的方案。正如我们所解释的，认知灵活性一直被认为是执行功能的一个组成部分，它可以被标示为重新聚焦/转移注意力并迅速改变认知集以响应环境要求的能力。我们现在将我们的认知灵活性指数与抑郁症的传统认知风险因素联系起来，并纳入了一个生理灵活性指数，即心脏迷走神经控制(CVC)。父母抑郁是青少年严重抑郁障碍(MDD)的重要危险因素，也增加了并发非情感性障碍的几率。在精神病学高危家庭研究的传统中，我们建议检查选定的个人特征的组合作为MDD和行为和/或物质使用相关障碍的预测因子，这些青少年有抑郁的家庭风险。个人特征包括父母临床(例如，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)。认知灵活性作为一种执行功能，将通过传统的神经心理学测试和结合了情绪分散特征的新修改进行评估。作为我们的主要目标，我们将测试关于儿童和父母因素的汇合如何影响后代患MDD和非情感性障碍风险的假设。我们的样本将包括250名年轻人，包括先证者父母的子女(他们自己也有儿童期起病的情绪障碍)和没有严重精神障碍病史的对照父母的子女。作为我们的次要目标，我们将探索两个传统的认知风险因素(沉思反应风格和消极归因风格)与认知不灵活的关系，以及生理性不灵活(反映在功能障碍的CVC中)在多大程度上增加了涉及神经认知-临床变量的预测模型的信息。子女初次评估将为8至16岁，后续为10至18岁；这一年龄范围涵盖过渡到青春期和跨越青春期，青春期是MDD事件(新发病)病例和与行为/药物使用相关的障碍的高危时期。这项研究的可行性是因为我们可以获得一个独特的、维护良好的家庭样本，这些家庭是作为先前关于抑郁症的计划项目的一部分确定的。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展和神经认知观点，并针对可能导致抑郁症的一系列信息处理偏差的认知过程；b)具有重大的公共卫生意义，因为抑郁症既是个人的毁灭性疾病，也是全球残疾的主要原因，基于对个人特定风险因素/机制的更好理解，它可能被预防或预防；以及c)是及时的，因为它反映了NIMH精神障碍研究战略目标的几个组成部分。 公共卫生相关性：尽管父母抑郁会增加年轻子女患抑郁症和其他(非情绪)精神疾病的几率，但并不是所有处于这种家庭风险中的儿童都会受到影响。因此，我们将调查某些父母的临床特征和儿童的神经心理特征(认知灵活性受损)是否可以预测10-18岁的有抑郁家族风险的子女患上严重抑郁障碍(MDD)和与行为/物质使用相关的障碍。在这项研究中，认知灵活性指的是重新聚焦/切换注意力并根据环境要求快速改变认知集的能力；它将通过传统的神经心理测试和包含情绪分散特征的新的此类测试的修改来评估。我们还将研究认知(In)灵活性如何与更传统的抑郁症认知风险因素相关，以及包括生理(In)灵活性指数是否会改善我们的预测模型。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展精神病理学和神经认知观点，并针对可能导致抑郁症信息处理偏差的认知过程；b)具有相当大的公共卫生意义，因为更好地了解个人特定的风险因素/机制可能为有针对性地预防抑郁症铺平道路，抑郁症对个人来说是毁灭性的，也是全球残疾的主要原因；c)是及时的，因为它反映了NIMH精神障碍研究的战略目标。

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. PUBLIC HEALTH RELEVANCE: Although parental depression increases the odds of depression and other (non-mood) psychiatric disorders in young offspring, not all children who are at such familial risk become affected. We will therefore investigate whether certain parental clinical characteristics and child neuropsychological characteristics (impaired cognitive flexibility) predict major depressive disorder (MDD) and conduct/substance use-related disorders in 10-18 year-old offspring at familial risk for depression. In this study, cognitive flexibility refers to the ability to re-focus/switch attention and to rapidly change cognitive sets in response to environmental demands; it will be assessed both by traditional neuropsychological tests and novel modifications of such tests which incorporate emotionally distracting features. We also will examine how cognitive (in)flexibility relates to more traditional cognitive risk factors for depression and whether including an index of physiologic (in)flexibility will improve our predictive models. Our study: a) is innovative because it integrates developmental psychopathology and neurocognitive perspectives in the context of a high-risk family design and targets a cognitive process that may underlie information processing biases in depression, b) has considerable public health significance because a better understanding of person-specific risk factors/mechanisms may pave the way for targeted prevention of depression, which is both personally devastating and a leading cause of disability worldwide, and c) is timely because it reflects NIMH's Strategic Objectives for research on mental disorders.