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

描述（由申请人提供）：在我们对有抑郁症家族风险的儿童（和对照组）研究的修订后重新提交中，我们对IRG的担忧做出了回应，并相应地修订了我们的方案。正如我们所阐述的，认知灵活性已被视为执行功能的一个组成部分，其可以被索引为响应环境需求而重新聚焦/转移注意力和快速改变认知集合的能力。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症（MDD）的一个重要危险因素，也增加了共病非情感性精神障碍的几率。在传统的精神病高风险的家庭研究，我们建议检查组合选定的个人特征作为预测因子的抑郁症和行为和/或物质使用相关的障碍，在青少年的抑郁症的家庭风险。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他们的新修改，其中包括情绪分散功能进行评估。作为我们的主要目的，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和非情感性精神障碍的风险的假设。我们的样本将由n= 250名青少年组成，包括先证者父母（他们自己也患有儿童期发作的情绪障碍）的后代和没有重大精神疾病史的对照父母的后代。作为我们的次要目标，我们将探讨2个传统的认知风险因素（沉思反应风格和消极归因风格）与认知能力的关系，以及生理能力（反映在功能障碍的CVC）在多大程度上增加了我们的预测模型涉及神经认知-临床变量的增量信息。后代在初始评估时为8-16岁，随访时为10- 18岁;该年龄范围涵盖进入和跨越青春期的过渡期，这是MDD事件（新发）病例和行为/物质使用相关疾病的高风险期。这项研究的可行性是强调了一个事实，即我们有机会获得一个独特的和维护良好的家庭样本，已被确定为一个先前的计划项目的一部分抑郁症。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的观点，并针对可能构成抑郁症中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，也是全球残疾的主要原因，这可能是预防或预防的基础上，更好地了解个人的具体风险因素/机制，c）是及时的，因为它反映了NIMH的战略目标对精神障碍的研究的几个组成部分。 公共卫生相关性：虽然父母抑郁会增加年轻后代患抑郁症和其他（非情绪）精神疾病的几率，但并非所有有这种家族风险的孩子都会受到影响。因此，我们将调查是否某些父母的临床特征和儿童神经心理学特征（认知灵活性受损）预测重性抑郁症（MDD）和行为/物质使用相关的障碍在10-18岁的后代在抑郁症的家族风险。在这项研究中，认知灵活性是指重新集中/转换注意力和快速改变认知集以应对环境需求的能力;它将通过传统的神经心理学测试和新的修改这些测试，其中包括情绪分散功能进行评估。我们还将研究认知（不）灵活性如何与抑郁症的更传统的认知风险因素相关，以及包括生理（不）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，并针对可能构成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，这对个人来说是毁灭性的，也是世界范围内残疾的主要原因，c）是及时的，因为它反映了NIMH对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.