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

抑郁症高风险和低风险儿童的精神结局：随访

• 批准号: 8033810
• 负责人: MARIA KOVACS
• 金额: $ 65.76万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8033810
• 关键词: 16 year old; 18 year old; Accounting; Adolescence; Adolescent; Adult; Affect; Affective; Age; Alcohol or Other Drugs use; Area; Attention; Biological; Bipolar Disorder; Cardiac; Characteristics; Child; Childhood; Chronic; Clinical; Cognitive; Cognitive Science; Conduct Disorder; Depressive disorder; Development; Disease; Documentation; Early Diagnosis; Elements; Endogenous depression; Enrollment; Environment; Evaluation; Family; Family Characteristics; Family Study; Feasibility Studies; Functional disorder; Generations; Grouping; Heterogeneity; Hospitalization; Impaired cognition; Incidence; Individual Differences; Inpatients; Intake; Intervention; Laboratories; Life; Link; Literature; Major Depressive Disorder; Measures; Mediating; Mental Depression; Mental disorders; Methodology; Modeling; Modification; Mood Disorders; National Institute of Mental Health; Neurocognitive; Neuropsychological Tests; Neuropsychology; Onset of illness; Outcome; Parents; Performance; Persons; Phenotype; Physiological; Predictive Value; Prevalence; Prevention; Probability; Process; Protocols documentation; Psychopathology; Public Health; Questionnaires; Recording of previous events; Recurrence; Relative (related person); Research; Research Design; Rest; Risk; Risk Factors; Sampling; Severities; Source; Staging; Statistical Models; Strategic Planning; Suicide attempt; System; Task Performances; Techniques; Testing; Time; Youth; aged; base; childhood onset depression; cognitive change; cognitive neuroscience; cost; data reduction; depressive symptoms; design; disability; disorder control; disorder risk; early onset; executive function; flexibility; follow-up; high risk; improved; indexing; information processing; innovation; neurocognitive test; neuropsychological; novel; offspring; predictive modeling; prevent; proband; programs; prospective; psychologic; psychosocial; public health relevance; response; sex; successful intervention; transmission process; trend

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.

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）的研究的重新提交修订版中，我们回应了 IRG 的担忧，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，它可以被索引为重新聚焦/转移注意力和快速改变认知设置以响应环境需求的能力。现在，我们将认知灵活性指数与抑郁症的传统认知风险因素联系起来，并且还纳入了生理灵活性指数，即心脏迷走神经控制（CVC）。父母抑郁是青少年患重度抑郁症（MDD）的一个重要危险因素，也会增加共病非情感障碍的几率。按照精神科高风险家庭研究的传统，我们建议检查选定的个人特征的组合作为MDD的预测因素以及有抑郁症家族风险的青少年的行为和/或物质使用相关疾病。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）。作为一种执行功能的认知灵活性将通过传统的神经心理学测试及其包含情绪分散特征的新颖修改来评估。作为我们的主要目标，我们将测试关于儿童和父母因素的融合如何影响后代患 MDD 和非情感障碍风险的假设。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（他们本身患有童年期发病的情绪障碍）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预测模型添加了增量信息，包括神经认知临床变量。后代在初次评估时年龄为8至16岁，在随访时年龄为10至18岁；这个年龄范围涵盖了进入青春期和跨越青春期的过渡期，这是MDD事件（新发）病例和行为/药物使用相关疾病的高风险期。我们获得了一个独特且维护良好的家庭样本，这些样本是之前抑郁症计划项目的一部分，这一事实强调了这项研究的可行性。我们的研究：a）具有创新性，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，因为抑郁症它既是一种对个人具有毁灭性的疾病，也是全世界范围内残疾的主要原因，基于对个人特定风险因素/机制的更好了解，这种情况可能是可以预防或预防的，并且 c) 是及时的，因为它反映了 NIMH 的战略目标的几个组成部分精神障碍研究。 公共卫生相关性：尽管父母抑郁会增加年幼后代患抑郁症和其他（非情绪）精神疾病的几率，但并非所有处于此类家族风险的儿童都会受到影响。因此，我们将研究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）是否可以预测有抑郁症家族风险的 10-18 岁后代患重度抑郁症 (MDD) 和行为/物质使用相关疾病。在本研究中，认知灵活性是指重新集中/切换注意力并快速改变认知设置以响应环境需求的能力；它将通过传统的神经心理学测试和此类测试的新颖修改（其中包含情绪分散特征）进行评估。我们还将研究认知（不）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（不）灵活性指数是否会改善我们的预测模型。我们的研究：a）具有创新性，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，因为更好地理解对个人特定风险因素/机制的研究可能为有针对性地预防抑郁症铺平道路，抑郁症不仅对个人具有毁灭性，而且是全世界残疾的主要原因，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。