The role of brain activity and connectivity in the association between immune function and depressive symptoms, and the effect of pubertal timing: A longitudinal study of adolescent girls.

项目摘要/摘要 研究表明，免疫功能与抑郁症有关，尽管造成这种情况的原因 联系尚不清楚。一个重要的步骤是研究神经过程，因为有研究表明 抑郁症患者的神经功能异常及其与炎症、脑活动和抑郁的关系 心情。然而，这在青少年中还没有被研究过，尽管青春期早期是一种敏感的 大脑发育和组织的发育期。免疫功能障碍可能对大脑有很大影响 功能，这反过来可能增加抑郁情绪升高的风险；然而，临时性的 这些关联的方向仍然不清楚。此外，青春期发育也显示出 与大脑发育和精神健康症状的出现有关，并缓解 免疫功能与抑郁症状的相关性。对于女孩来说，青春期可能特别突出， 从青春期开始，抑郁症的发病率增加到男孩的两倍，而女性的性激素 与更强的免疫反应有关。我的初步数据显示，发育较早的女孩有负面影响 脑岛、纹状体和前扣带回皮质炎症反应与脑活动的关系 情绪面孔加工，这反过来又与抑郁症状负相关。然而， 在这一领域缺乏纵向研究，这使得很难确定免疫功能和变化是否 大脑功能先于情绪变化和青春期临床抑郁症的出现，并且 青春期的时机和节奏如何影响这些联系。大脑连通性的发展也没有 已经被探索过了。我对提议的K01的培训目标是在功能磁共振成像和静态连接方面进行培训 分析，并理解相关的纵向发展神经科学模型 心理神经免疫学，这将使我成为一名独立的调查员。这些目标将通过以下方式实现 得到来自成熟和经验丰富的指导和顾问团队的支持，并通过研究 这项研究的目的是前瞻性地检查免疫学、脑功能和连接性，以及 对青春期早期女孩的抑郁进行研究，并确定青春期对这些联系的影响。 具体地说，这项研究将从N=170名11岁、 12.5岁和14岁，还没有关于免疫的任何具体研究问题 功能正常。首先，在每个时间点，我将评估炎症、大脑 活跃性和连接性，抑郁症状，以及青春期时机的调节作用。第二，我会 研究纵向发育模式，如大脑活动和连接性的变化 免疫功能与抑郁之间的联系的中介，或预测它们的轨迹 变量。第三，我会对女生进行一个分研究，检查炎症反应和大脑活动 在功能核磁共振社会评估应激源期间。总体而言，这项研究将确定 从发育和神经生物学的角度来看，炎症，并将确立我作为一个独立的 这一领域的研究科学家。

Project Summary/Abstract Research has shown that immune function is associated with depression, although the reasons for this link are unclear. One important step is to investigate neural processes, given that there is research implicating abnormal neural function in depression, and associations between inflammation, brain activity, and depressed mood. However, this has not yet been explored in adolescents, even though early adolescence is a sensitive developmental period of brain growth and organization. Immune dysfunction may have a strong effect on brain function during this time, which in turn, may increase risk for elevated depressed mood; however, the temporal direction of these associations remains unclear. In addition, pubertal development has also shown to be associated with both brain development and the onset of mental health symptoms, and to moderate the association between immune function and depressive symptoms. Puberty may be especially salient for girls, as rates of depression increase to twice that of boys starting at puberty, and female sex hormones are associated with a stronger immune response. My pilot data shows that earlier developing girls have a negative correlation between inflammation and brain activity in the insula, striatum and anterior cingulate cortex during emotional face processing, which in turn is negatively associated with depressive symptoms. However, longitudinal research in this area is lacking, making it difficult to determine if immune function and changes in brain function precede changes in mood and the emergence of clinical depression during adolescence, and how pubertal timing and tempo may affect these associations. Development of brain connectivity has also not been explored. My training goals for the proposed K01 are to train in fMRI and resting-state connectivity analysis, and to understand longitudinal developmental neuroscience models relevant to psychoneuroimmunology, which will establish me as an independent investigator. These goals will be met by having support from an established and experienced mentoring and advisor team, and through the research aims of this study, which are to prospectively examine immunology, brain function and connectivity, and depression in girls in early adolescence, and to determine the effect that puberty has on these associations. Specifically, the study will collect data from an established longitudinal cohort of N=170 adolescent girls, at 11, 12.5, and 14 years old, which does not yet have any specific research questions regarding immune functioning. First, at each time point, I will assess cross-sectional associations between inflammation, brain activity and connectivity, and depressive symptoms, and the moderating effect of pubertal timing. Second, I will investigate longitudinal developmental patterns, such as changes in brain activity and connectivity as a mediator of the association between immune function and depression, or prediction of trajectories of these variables. Third, I will conduct a sub-study of 64 girls to examine inflammatory responses to and brain activity during an fMRI social-evaluative stressor. Overall, this study will identify mental health outcomes of inflammation from a developmental and neurobiological perspective, and will establish me as an independent research scientist in this area.