Individual differences in estrogen during late adolescence: Impact on functioning of positive and negative valence systems - Resubmission 01

项目摘要 重要性：在青春期，参与情绪调节和高级认知功能的大脑区域的成熟和连接被假设为使这些区域对激素环境的变化敏感。实验动物和人类研究的证据表明，雌激素调节各种大脑区域的神经元功能，包括杏仁核、海马体、纹状体和前额皮质。这些区域也参与处理情绪和享乐刺激。因此，对许多女性来说，卵巢激素可能对正、负效价系统的功能完整性至关重要。 我们建议测试雌激素水平和个体差异的神经和行为反应的奖励和积极的情绪刺激和自我报告的积极情绪（积极效价系统）和损失和消极的情绪刺激和自我报告的消极情绪（消极效价系统）之间的关联。目的：1）测试雌激素与激活正和负效价系统的刺激的神经和行为反应之间的关联; 2）测试早期压力暴露、抑郁史、青春期时间和克里思是否调节雌激素与激活正和负效价系统的刺激的神经和行为反应之间的关联。 正负价体系。方法：尿液样本可用于150晚青春期女孩参加纵向研究谁已经完成了fMRI评估情绪刺激的反应。在扫描前立即采集尿样，然后储存在-40°下。关于暴露于压力源的数据（例如，从儿童期开始并持续到青春期后期，前瞻性地收集负面家庭事件、虐待、创伤）、抑郁症状和青春期发育。本申请的目的是测定尿中的雌激素代谢物，并测试雌激素代谢物与尿中的雌激素代谢物之间的关联。 雌激素水平和个体差异的神经和行为反应的积极/消极面对情绪和奖励/损失，以及模型的适度。研究者：Dr. Kathryn Keenan与合作研究者Dr. C.尼尔·埃普曼（Neill Epperson）和玛丽·简·德索萨（Mary Jane De Souza）都是卵巢激素、情绪和行为界面方面的专家，埃里卡·福布斯（Erika Forbes）博士是使用fMRI探测青少年对情绪刺激的神经反应的专家，以及生物统计学家克里斯汀·沃布莱夫斯基（Kristen Wroblewski）。影响：样本量将是迄今为止最大的样本量之一，并将产生足够的功效来测试适度模型。荷尔蒙水平会 在评估正和负效价系统的功能之前直接和立即进行评估，从而避免了从周期阶段推断水平的重大限制。功能的多模式评估是在每个主题内完成的，提供了一个机会来测试激素如何影响心理过程的更精细的模型。利用从父母赠款中前瞻性收集的数据提供了一个前所未有的机会来确定可能增加神经对卵巢激素敏感性的因素，这将显着扩展该领域的现有文献。拟议研究的结果 通过在两个情绪系统中的每一个中指定临床目标，阐明情绪在生理障碍中的作用，以及识别可能特别容易受到情绪系统中的激素相关功能障碍影响的亚组，具有影响临床实践范例的潜力。

Project Summary Significance: The maturation of and connection among brain regions involved in emotion regulation and higher cognitive functioning during adolescence is hypothesized to render these regions sensitive to changes in the hormonal milieu. There is evidence from experimental animal and human studies that estrogen modulates neuronal function in a variety of brain areas including in the amygdala, hippocampus, striatum, and prefrontal cortex. These regions also are involved in the processing of emotional and hedonic stimuli. Thus, for many women ovarian hormones may be critical to the functional integrity of positive and negative valence systems. We propose to test associations between estrogen levels and individual differences in neural and behavioral response to reward and positive emotional stimuli and self-reported positive mood (positive valence system) and to loss and negative emotional stimuli and self-reported negative mood (negative valence system). Aims: 1) Test associations between estrogen and neural and behavioral response to stimuli that activate positive and negative valence systems; 2) Test whether earlier stress exposure, depression history, and pubertal timing and tempo moderate associations between estrogen and neural and behavioral response to stimuli that activate positive and negative valence systems. Approach: Urine samples are available for 150 late adolescent girls participating in a longitudinal study who have completed an fMRI assessment of response to emotional stimuli. Urine samples were collected immediately prior to the scanning session and then stored at -40°. Data on exposure to stressors (e.g., negative family events, abuse, trauma), depression symptoms, and pubertal development were collected prospectively beginning in childhood and continuing through late adolescence. The goal of the present application is to assay the urine for an estrogen metabolite, and test the association between estrogen levels and individual differences in neural and behavioral response to positive/negative face emotion and reward/loss, as well as models of moderation. Investigators: Dr. Kathryn Keenan serves as the PI with Co-investigators Drs. C. Neill Epperson and Mary Jane De Souza, both of whom are experts in the interface of ovarian hormones, mood, and behavior, Dr. Erika Forbes, an expert in using fMRI to probe neural response to emotional stimuli in adolescents, and biostatistician, Kristen Wroblewski. Impact: The sample size would be one of the largest to date and will yield sufficient power for testing models of moderation. Hormone levels will be assessed directly and immediately prior to the assessment of functioning of positive and negative valence systems, thus obviating the significant limitation of inferring level from phase of cycle. Multimodal assessments of functioning are completed within each subject, providing an opportunity to test more refined models of how hormones impact psychological processes. The leveraging of the prospectively collected data from the parent grants provides an unprecedented opportunity to identify factors that may increase neural sensitivity to ovarian hormones, which will significantly extend the existing literature in this area. The results from the proposed study have the potential to impact clinical practice paradigms by specifying clinical targets within each of the two emotion systems, elucidating the role of mood in the physiological disturbance, and identifying a subgroup who may be particularly vulnerable to hormone related dysfunction in emotion systems.