Brain-Behavioral Predictors of Interpersonal Stress Generation and Depression Risk in Adolescent Girls

抑郁症（MDD）发病的风险在青春期急剧增加，特别是女孩。 有必要阐明MDD风险的潜在机制，以改善早期风险检测， 有针对性的预防。压力产生模型假定人际压力产生（I-StressGen）是一种 风险机制，并建议具有先前存在的MDD脆弱性的青年积极促进 在他们的生活中发生人际压力生活事件（即，而这又反过来加剧了他们的焦虑。 MDD风险。虽然I-StressGen对青少年MDD风险的影响是明确的， 导致I-StressGen的确切机制仍不清楚。自我报告研究表明， 在消极的社会交往中的情感反应作为一种有前途的机制，有助于I-StressGen， 尽管这尚未经过直接测试。I-StressGen的潜在神经机制也仍然存在 尽管有研究表明，更大的社会压力与大脑皮层的异常激活有关， 皮质边缘区在任务探测对负面社会互动的反应。因此， 这项研究的目的是对大脑的作用有一个细致的、机械的理解， 在消极的社会交往过程中的行为情感反应，因为它涉及到I-StressGen和随后的 女性青少年的MDD风险。这项拟议的研究将招募90名女性青少年的风险增强样本 (ages 13-15），并将利用神经成像（fMRI）和生态瞬时评估（EMA）来检查大脑 社会情感反应的行为指数作为I-StressGen和抑郁症状的预测因子， 多波一年随访。在这样做的过程中，目前的研究将测试是否情感反应， 在神经（目标1）和现实世界的行为（目标2）水平的社会互动预测I- StressGen，以及I-StressGen是否介导了这种社会情感反应与 女性青少年抑郁症状的预期增加（目标3）。拟议的研究和平行 培训计划将使候选人能够建立在她目前在青少年压力和MDD风险方面的专业知识基础上， 在四个关键领域发展新技能：（1）fMRI，（2）EMA，（3）高级统计多层次建模，（4） 专业发展。伊利诺伊大学芝加哥分校丰富的学术环境， 候选人的导师团队在功能磁共振成像方法，发展情感， 神经科学，EMA和先进的统计技术将有助于成功实施拟议的 学习和培训计划。这些技能的获得将是启动候选人的独立 作为一名翻译科学家的职业生涯，专注于描绘青少年MDD风险的大脑行为机制 在现实世界的人际压力下。这项研究的结果将为未来的发展提供信息 赠款重点是表征社会情感的大脑和行为机制， 轨迹有助于出现适应不良的压力过程和抑郁症发作在青春期。

Risk for major depressive disorder (MDD) onset dramatically increases during adolescence, particularly for girls. There is a vital need to elucidate the underlying mechanisms of MDD risk to improve early risk detection and targeted preventions. The stress generation model posits interpersonal stress generation (I-StressGen) as a mechanism of risk and proposes that youth with preexisting MDD vulnerabilities actively contribute to the occurrence of interpersonal stressful life events in their lives (i.e., I-StressGen), which in turn exacerbates their risk for MDD. Although the impact of I-StressGen on prospective MDD risk in adolescents is well-established, the precise mechanisms contributing to I-StressGen remain unclear. Self-report research indicates increased affective reactivity during negative social interactions as a promising mechanism contributing to I-StressGen, though this has not been directly tested. The underlying neural mechanisms of I-StressGen also remain unexamined, despite work suggesting that greater social stress is associated with aberrant activation in corticolimbic regions during tasks probing response to negative social interactions. Therefore, the overarching goal of the proposed study is to obtain a fine-grained, mechanistic understanding of the role of brain and behavioral affective reactivity during negative social interactions as it relates to I-StressGen and subsequent MDD risk in female adolescents. The proposed study will enroll a risk-enhanced sample of 90 female adolescents (ages 13-15) and will utilize neuroimaging (fMRI) and ecological momentary assessment (EMA) to examine brain and behavior indices of socio-affective reactivity as predictors of I-StressGen and depression symptoms across a multi-wave one year follow-up. In doing so, the current study will test whether affective reactivity during negative social interactions at the neural (Aim 1) and real-world behavioral (Aim 2) level prospectively predicts I- StressGen, and whether I-StressGen mediates the relation between this socio-affective reactivity and prospective increases in female adolescents’ depression symptoms (Aim 3). The proposed study and parallel training plan will allow the Candidate to build upon her current expertise in adolescent stress and MDD risk and develop new skills in four key areas: (1) fMRI, (2) EMA, (3) advanced statistical multilevel modeling, and (4) professional development. The rich academic environment at the University of Illinois at Chicago coupled with the collective expertise of the Candidate’s mentorship team in fMRI methodology, developmental affective neuroscience, EMA, and advanced statistical techniques will facilitate successful implementation of the proposed study and training plan. The acquisition of these skills will be integral to launching the Candidate’s independent career as a translational scientist focused on delineating brain-behavioral mechanisms of adolescent MDD risk within the context of real-world interpersonal stress. Results from this study will inform the development of future grants focused on characterizing socio-affective brain and behavior mechanisms and aberrant developmental trajectories contributing to the emergence of maladaptive stress processes and MDD onset in adolescence.