Fibroblast Growth Factor 2's role in Fear and Approach Motivation in Anxious and Depressed Children and their Mothers

成纤维细胞生长因子 2 在焦虑和抑郁儿童及其母亲的恐惧和接近动机中的作用

• 批准号: 9373452
• 负责人: Eli Lebowitz
• 金额: $ 25.13万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-12 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9373452
• 关键词: Acute; Adult; Anhedonia; Animals; Anxiety; Anxiety Disorders; Astrocytes; Autopsy; Behavior; Behavioral; Behavioral Research; Biological; Brain; Child; Childhood; Clinical; Clinical Research; Data; Data Reporting; Depressed mood; Depressive disorder; Development; Dimensions; Disease; Emotions; Environment; FGF2 gene; Factor Analysis; Family; Foundations; Fright; Funding; Growth Factor; Hippocampus (Brain); Human; Image; Immunoassay; Impairment; Lead; Life; Limbic System; Link; Longevity; Measurement; Measures; Mental Depression; Modeling; Mothers; Motivation; National Institute of Mental Health; Negative Valence; Neurons; Organism; Patient Self-Report; Pilot Projects; Play; Positive Valence; Research; Research Domain Criteria; Research Project Grants; Research Proposals; Rewards; Role; Sampling; Sampling Studies; Serum; Shapes; Stimulus; System; Time; anxious; base; brain tissue; depressive symptoms; neurodevelopment; neuroregulation; postnatal; progenitor; psychiatric disability; response; self reported behavior; willingness

Project Summary This is an exploratory/developmental research proposal which seeks to build on and to enlarge our data into the role of fibroblast growth factor 2 (FGF2) in Fear (Acute Threat) and Approach Motivation, two constructs within the Negative Valence System and Positive Valence System, respectively, in the NIMH Research Domain Criteria (RDoC) project. FGF2 is one of a family of growth factors that impact neural development and that play neuromodulatory roles throughout life, shaping the organism's response to the environment. Disruptions in the Negative Valence and Positive Valence Systems characterize anxiety and depressive disorders, which account for the majority of psychiatric disability over the lifespan. The animal and sparse adult human studies implicating FGF2 in models of anxiety and depression led to FGF2's inclusion in RDoC as a target biological unit of analysis of the Fear construct. We know of no study that has examined FGF2 in humans with anxiety and its disorders, nor do we know of a study that examined FGF2 in clinical and nonclinical pediatric samples, anxious and/or depressed. Our team collected pilot data of FGF2 levels in a clinical sample of 50 anxious and depressed children and their mothers in addition to self-report and behavior data that corresponded with Fear, and Approach Motivation, respectively. We examined the associations between FGF2 levels, self-reports, and behavior in the children and mothers and found significant associations between the measurement units, and in the expected directions. These data, consistent with the animal and human studies, suggest FGF2 may play a role in modulating Fear, and Approach Motivation, which can lead to exciting, new research directions. We have since accumulated serum samples in 150 anxious and/or depressed children and mothers, and self-report and behavior data. We request R21 funds to conduct immunoassay analysis to measure FGF2 concentrations in this sample data. We also propose to broaden our sampling frame by collecting FGF2, self-report, and behavior data on 100 additional children who represent “normal” controls, and subclinical or subthreshold anxiety and/or depression, and mothers. With these cumulative, dimensional data, we will study these measurement units' associations with Fear, and Approach Motivation in a measurement model using confirmatory factor analysis. Our final, exploratory aim is on the question of stability of FGF2, in relation to self-reports and behavior.

项目摘要 这是一项探索性/发展性研究提案，旨在建立和扩大 我们的数据显示成纤维细胞生长因子2(FGF2)在恐惧(急性威胁)和接近中的作用 动机，负价系统和正价系统中的两个结构， 分别在NIMH研究领域标准(RDoC)项目中。FGF2是一家 影响神经发育并自始至终发挥神经调节作用的生长因子 生命，塑造有机体对环境的反应。负价中的破坏 正向配价系统表征焦虑和抑郁障碍，这解释了 大多数精神残疾的人都是终生的。动物和稀疏的成年人类 在焦虑和抑郁模型中涉及成纤维细胞生长因子2的研究导致成纤维细胞生长因子2的S被纳入RDoC 作为分析恐惧结构的目标生物单位。据我们所知，没有一项研究 检查了患有焦虑及其障碍的人类的FGF2，我们也不知道有一项研究 在焦虑和/或抑郁的临床和非临床儿科样本中检测FGF2。我们的 研究小组收集了50名焦虑和抑郁患者的临床样本中FGF2水平的试点数据 儿童和他们的母亲除了自我报告和行为数据外 分别是恐惧和接近动机。我们研究了成纤维细胞生长因子2与 儿童和母亲的水平、自我报告和行为，并发现显著的相关性 在测量单位之间，在预期的方向上。这些数据，与 动物和人类的研究表明，FGF2可能在调节恐惧和接近 动机，这可以导致令人兴奋的新的研究方向。自那以后，我们积累了 150名焦虑和/或抑郁的儿童和母亲的血清样本，以及自我报告和 行为数据。我们要求R21基金进行免疫分析以测量FGF2 此样本数据中的浓度。我们还建议扩大我们的抽样范围： 收集另外100名儿童的FGF2、自我报告和行为数据 “正常”对照，亚临床或亚阈值焦虑和/或抑郁，以及母亲。使用 这些累积的维度数据，我们将研究这些度量单位与 使用验证性因素分析的测量模型中的恐惧和接近动机。我们的 最后，探索性目标是关于FGF2的稳定性问题，与自我报告和 行为。