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.

项目总结/摘要 研究表明，免疫功能与抑郁症有关，尽管其原因 联系不清楚。重要的一步是研究神经过程，因为有研究表明， 抑郁症的神经功能异常，以及炎症、大脑活动和抑郁症之间的关系 心情然而，这还没有在青少年中进行过探索，尽管青春期早期是一个敏感的阶段。 大脑的生长和组织的发展阶段。免疫功能障碍可能对大脑产生强烈影响 在这段时间内，功能，这反过来可能会增加抑郁情绪升高的风险;然而，时间 这些协会的方向仍然不清楚。此外，青春期发育也被证明是 与大脑发育和精神健康症状的发作相关，并减轻 免疫功能和抑郁症状之间的联系。青春期对女孩来说可能特别突出， 从青春期开始，抑郁症的发病率就增加到男孩的两倍， 与更强的免疫反应有关。我的试验数据显示发育较早的女孩 脑内炎症与纹状体、前扣带皮层活动的相关性 情绪面孔处理，这反过来又与抑郁症状呈负相关。然而，在这方面， 这一领域缺乏纵向研究，因此难以确定免疫功能和 大脑功能先于情绪变化和青春期临床抑郁症的出现， 青春期的时间和克里思如何影响这些关联。大脑连接的发展也没有 被探索。我对K 01的培训目标是在功能磁共振成像和静息状态连接方面进行培训 分析，并了解纵向发展神经科学模型相关， 心理神经免疫学，这将使我成为一个独立的调查员。这些目标将通过 拥有成熟且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，大脑功能和连接， 抑郁症的女孩在青春期早期，并确定青春期对这些协会的影响。 具体而言，该研究将从一个已建立的纵向队列中收集数据，该队列包括N=170名11岁的青春期女孩， 12.5岁和14岁，还没有任何关于免疫的具体研究问题。 功能首先，在每个时间点，我将评估炎症、脑损伤和脑损伤之间的横截面关联。 活动和连接，抑郁症状，以及青春期时间的调节作用。第二，我会 研究纵向发展模式，如大脑活动和连接的变化， 免疫功能和抑郁症之间的关联的调解人，或预测这些轨迹 变量第三，我将对64名女孩进行一项子研究，以检查炎症反应和大脑活动 在功能磁共振成像社会评价压力源。总的来说，这项研究将确定心理健康的结果， 炎症从发展和神经生物学的角度来看，并将建立我作为一个独立的 科学家在这个领域。

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.