Psychobiological Mechanisms Underlying the Association Between Early Life Stress and Depression Across Adolescence

早期生活压力与青春期抑郁之间关联的心理生物学机制

• 批准号: 10540533
• 负责人: IAN H GOTLIB
• 金额: $ 22.79万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10540533
• 关键词: 17 year old; 19 year old; Administrative Supplement; Adolescence; Adolescent; Affect; Age; Anisotropy; Behavioral; Biological Assay; Blood; Blood specimen; Brain; C-reactive protein; Characteristics; Clinical; Cognitive; Data; Data Set; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Dimensions; Endocrine; Ensure; Exposure to; Family; Funding; Goals; Hormonal; Immune system; Inflammation; Infrastructure; Interleukin-6; Interview; Link; Longitudinal Studies; Major Depressive Disorder; Measures; Mediating; Mediation; Mental Depression; Modeling; Neighborhoods; Neuroimmune; Participant; Peripheral; Play; Positioning Attribute; Research; Research Domain Criteria; Rewards; Risk; Risk Factors; Sampling; Secure; Socioeconomic Status; Structure; TNF gene; Testing; Ventral Striatum; Work; boys; child depression; depressive symptoms; deprivation; early childhood; early life stress; experience; girls; indexing; inflammatory marker; insight; neural circuit; neurodevelopment; neuroimaging; parent grant; parent project; psychobiologic; recruit; relating to nervous system; response; reward circuitry; reward processing; stress symptom; white matter; 17 year old; 19 year old; Administrative Supplement; Adolescence; Adolescent; Affect; Age; Anisotropy; Behavioral; Biological Assay; Blood; Blood specimen; Brain; C-reactive protein; Characteristics; Clinical; Cognitive; Data; Data Set; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Dimensions; Endocrine; Ensure; Exposure to; Family; Funding; Goals; Hormonal; Immune system; Inflammation; Infrastructure; Interleukin-6; Interview; Link; Longitudinal Studies; Major Depressive Disorder; Measures; Mediating; Mediation; Mental Depression; Modeling; Neighborhoods; Neuroimmune; Participant; Peripheral; Play; Positioning Attribute; Research; Research Domain Criteria; Rewards; Risk; Risk Factors; Sampling; Secure; Socioeconomic Status; Structure; TNF gene; Testing; Ventral Striatum; Work; boys; child depression; depressive symptoms; deprivation; early childhood; early life stress; experience; girls; indexing; inflammatory marker; insight; neural circuit; neurodevelopment; neuroimaging; parent grant; parent project; psychobiologic; recruit; relating to nervous system; response; reward circuitry; reward processing; stress symptom; white matter

PROJECT SUMMARY/ABSTRACT Early life stress (ELS) is a significant risk factor for the development of depressive symptoms and of Major Depressive Disorder (MDD) in adolescence. The mechanisms through which ELS confers this risk, however, are poorly understood. Recent research implicates high levels of inflammation as a mechanism that may link ELS with depression. Elevated peripheral markers of inflammation, such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), have been associated with depressive symptoms and the onset of MDD in adolescents, potentially by altering functional and structural circuits in the brain that underlie reward processing. To date, however, research has been limited by a conceptualization of ELS as a unitary construct, despite growing evidence that experiences of threat, deprivation, and unpredictability have different neural consequences. Therefore, in this administrative supplement, we are proposing to leverage the infrastructure of the parent project (R37MH101495) to examine longitudinal associations among different dimensions of ELS, inflammation, reward neurocircuitry, and depressive symptoms in adolescence. In the parent grant, we recruited over 200 boys and girls ages 9–13 years and obtained data at two-year intervals to examine the effects of ELS on neural trajectories across adolescence and their relation to depression. At the third timepoint (T3), when the participants were 14–17 years of age, we secured internal funding to collect blood samples and to assay a portion of these samples to measure levels of CRP, IL-6, and TNF-α; we are continuing to collect blood samples as we complete the fourth timepoint (T4), when participants are 16–19 years of age. By leveraging our existing data set that includes comprehensive assessments of ELS and rich measures of reward processing across multiple units of analysis (behavioral, cognitive, neural), we are well positioned to examine the extent to which inflammation plays a key role in linking ELS with depression symptoms and diagnosis in adolescence by altering the development of reward neurocircuitry. Specifically, we will be able to test whether: 1) different dimensions of ELS (i.e., experiences of deprivation, threat, and unpredictability) are associated with levels of and changes in inflammation in later adolescence; 2) changes in inflammation are associated with changes in the function and structure of reward neurocircuitry; and 3) inflammation-related changes in functional and structural reward circuitry that may underlie altered reward processing mediate the association between dimensions of ELS and depression symptoms and diagnosis in later adolescence. By leveraging our existing data, planned assessments, and analyses of trajectories of neurodevelopment and depression, we will be able to elucidate neuroimmune characteristics that may underlie the emergence of adolescent depression.

项目摘要/摘要 早期生活压力（EL）是发展抑郁症状和主要症状的重要危险因素 青春期抑郁症（MDD）。但是，ELS承认这种风险的机制，但是 知之甚少。最近的研究将高水平的炎症作为一种可能联系的机制 Els患有抑郁症。炎症的外围标记升高，例如C反应蛋白（CRP）， 白介素6（IL-6）和肿瘤坏死因子-Alpha（TNF-α）与抑郁症状有关 以及青少年中MDD的发作，可能是通过改变大脑中的功能和结构回路 基础奖励处理。然而，迄今为止，研究受到ELS概念化的限制 统一的建构，目的地日益增长的证据，证明威胁，剥夺和不可预测性的经历已有 不同的神经元后果。因此，在这种行政补充中，我们提议利用 父项目的基础设施（R37MH101495）检查不同的纵向关联 EL的尺寸，创新，奖励神经记录和青少年症状的抑郁症状。在 父母赠款，我们招募了200多名9-13岁的男孩和女孩，并以两年的间隔获得了数据 检查EL对青少年神经轨迹的影响及其与抑郁症的关系。在 第三时间点（T3），当参与者年满14-17岁时，我们获得了内部资金来收集 血液样本并主张部分样品以测量CRP，IL-6和TNF-α的水平；我们是 当我们完成第四时间点（T4）时，继续收集血液样本，当时参与者为16-19 年龄。通过利用我们现有的数据集，包括对EL和RICH的全面评估 跨多个分析单位（行为，认知，神经）的奖励处理度量，我们很好 定位以检查炎症在将EL与抑郁症联系起来的关键角色程度 通过改变奖励神经记录的发展，青少年的症状和诊断。具体来说，我们 将能够测试：1）EL的不同维度（即剥夺，威胁和 不可预测性）与后来青少年的炎症水平和变化有关； 2）更改 炎症与奖励神经循环的功能和结构的变化有关； 3） 与炎症相关的功能和结构奖励电路的变化，这可能是奖励改变的基础 处理介导EL的维度与抑郁症状和诊断的尺寸之间的关联 后来的青少年。通过利用我们的现有数据，计划的评估和分析 神经发育和抑郁症，我们将能够阐明可能是基础的神经免疫性特征 青春期抑郁症的出现。