Brain-Behavior Markers of Emotion in Depressed Mothers and Their Daughters

抑郁母亲的女儿患严重抑郁障碍的风险极高(HR) 在成年初期。要为这一人力资源人群制定更有针对性、更有机制的预防工作，这是至关重要的 以阐明这一风险所涉及的家族机制。先前的研究表明，功能失调的神经回路 描述了HR后代在消极的社会情绪和动机过程中的特征。尽管可复制 记录这种效应的研究结果，目前还不清楚是否干扰了HR后代的神经回路激活 反映了她们抑郁的母亲的情况，代表了抑郁症风险的神经信号，这种信号是通过传播的 从母亲到女儿。这种神经信号是否以及如何与反应性有关也在很大程度上是未知的。 以及对真实世界中情感的调节，这是理解其临床意义和识别 用于预防和干预的大脑行为目标。在目前的K23申请中，候选人提议 对40名母亲进行社会情绪和动机加工的神经行为标记物检测 有复发性MDD(RMDD)病史和她们的非MDD，HR女儿(13-16岁)和40名患有 无精神病史和他们的非MDD、低风险(LR)女儿。通过将神经和行为相结合 采用纵向设计，考生将测试神经区域是否牵涉到负面社会- 情绪和动机加工(A)区分HR和LR二联体，并且在母亲之间是一致的 和他们的女儿，代表着一个家族风险标记，(B)预测后代的行为评级 在实验室外使用生态瞬时评估(EMA)进行情感处理，以及(C) 与子代抑郁症状在多波随访中的轨迹有关。在当前 建议，候选人寻求建立在她的多层次分析的坚实基础上来研究情感 通过在三个新领域获得额外的培训来处理和青少年抑郁风险：1)发展 情感神经科学和功能磁共振成像(FMRI)方法，2)生态 瞬时评估(EMA)，以及3)针对嵌套、多方法、纵向数据的高级统计建模。 伊利诺伊大学芝加哥分校的精神病学系是一个出色的环境，在这里 参与跨学科培训。候选人的指导团队(Phan博士、Keenan博士和Mermelstein博士)和 顾问团队(Hedeker博士和Gotlib博士)在发展情感神经科学方面拥有丰富的经验 方法(包括功能磁共振成像)、纵向高风险设计、EMA方法的使用以及以下方面的统计专业知识 多层次和纵向分析。拟议的研究将为设计更大规模的R01研究提供参考 是否可以改变神经和行为的风险机制来预防抑郁症的发展 人力资源的后代。这项研究加上已确定的培训目标的完成将有效地推动 建立一个独立的研究计划，专注于识别行为-大脑风险 青年抑郁症的表型和预防性干预。

Daughters of depressed mothers are at extremely high risk (HR) for developing major depressive disorder (MDD) by early adulthood. To develop more targeted, mechanistic prevention efforts for this HR population, it is essential to clarify the familial mechanisms implicated in this risk. Prior studies suggest that a dysfunctional neural circuit characterizes HR offspring during negative social-emotional and motivational processing. Despite replicable findings documenting this effect, it is not clear whether disrupted neural circuit activation among HR offspring mirrors that of their depressed mothers, representing a neural signature of depression risk that is transmitted from the mother to the daughter. It is also largely unknown if and how this neural signature relates to reactivity and regulation of affect in the real world, which is key to understanding its clinical significance and identifying brain-behavior targets for prevention and intervention. In the current K23 application, the candidate proposes to examine neurobehavioral markers of social-emotional and motivational processing in a sample of 40 mothers with a history of recurrent MDD (rMDD) and their non-MDD, HR daughters (ages 13-16), and 40 mothers with no history of psychopathology and their non-MDD, low risk (LR) daughters. By combining neural and behavioral measures with a longitudinal design, the candidate will test whether neural regions implicated in negative social- emotional and motivational processing (a) differentiate HR from LR dyads and are concordant between mothers and their daughters, representing a familial risk marker, (b) are predictive of offspring’s behavioral ratings of affective processing outside of the laboratory using Ecological Momentary Assessment (EMA), and (c) are associated with the trajectory of offspring’s depressive symptoms over a multi-wave follow-up. In the current proposal, the candidate seeks to build upon her strong foundation in multiple levels of analysis to study affective processing and youth depression risk by gaining additional training in three new domains: 1) Developmental affective neuroscience and functional magnetic resonance imaging (fMRI) methodology, 2) Ecological momentary assessment (EMA), and 3) Advanced statistical modeling for nested, multi-method, longitudinal data. The Department of Psychiatry at the University of Illinois at Chicago is an outstanding environment in which to engage in interdisciplinary training. The candidate's mentorship team (Drs. Phan, Keenan, and Mermelstein) and consultant team (Drs. Hedeker and Gotlib) have extensive experience in developmental affective neuroscience methods (including fMRI), longitudinal high risk designs, use of EMA methods, and statistical expertise in multilevel and longitudinal analyses. The proposed study will inform the design of larger R01 studies examining whether neural and behavioral mechanisms of risk can be altered to prevent the development of depression in HR offspring. This study coupled with completion of the identified training goals will effectively propel the candidate towards establishing an independent program of research focused on identifying behavioral-brain risk phenotypes and preventative interventions for youth depression.