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

抑郁母亲及其女儿的大脑行为情绪标记

• 批准号: 9750809
• 负责人: Katie L Burkhouse
• 金额: $ 19.09万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750809
• 关键词: Address; Affect; Affective; Age; Amygdaloid structure; Behavior; Behavioral; Behavioral Mechanisms; Biological; Brain; Chicago; Child; Chronic; Corpus striatum structure; Coupled; Data; Daughter; Depressed mood; Development; Ecological momentary assessment; Emotional; Emotions; Environment; Exhibits; Face; Family; Female; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Illinois; Individual; Laboratories; Life; Link; Major Depressive Disorder; Measures; Mental Depression; Mentorship; Methodology; Methods; Mothers; Motivation; Mydriasis; Onset of illness; Parents; Peripheral; Phenotype; Population; Prevention; Preventive Intervention; Protocols documentation; Psychiatry; Psychopathology; Recording of previous events; Recurrence; Regulation; Research; Rewards; Risk; Risk Factors; Risk Marker; Sampling; Statistical Models; Stimulus; Testing; Time; Training; Universities; Work; Youth; affective neuroscience; behavior measurement; brain behavior; career; child depression; clinically significant; depressive symptoms; design; disorder risk; emerging adult; experience; flexibility; follow-up; girls; high risk; high risk population; imaging study; intergenerational; longitudinal analysis; longitudinal design; maternal depression; multilevel analysis; negative affect; neural circuit; neurobehavioral; neuromechanism; offspring; prevent; programs; prospective; recruit; relating to nervous system; response; social; transmission process

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.

抑郁母亲的女儿患重度抑郁症 (MDD) 的风险极高 (HR) 到了成年早期。为了针对这一人力资源群体制定更有针对性、机械化的预防工作，至关重要 澄清与这种风险有关的家族机制。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感和动机处理过程中的特征。尽管可复制 研究结果记录了这种效应，但尚不清楚 HR 后代的神经回路激活是否受到干扰 反映了他们抑郁的母亲的情况，代表了传播抑郁风险的神经特征 从母亲到女儿。目前还不清楚这种神经特征是否以及如何与反应性相关 和现实世界中情感的调节，这是理解其临床意义和识别的关键 预防和干预的大脑行为目标。在当前的K23申请中，候选人建议 检查 40 名母亲样本中社会情感和动机处理的神经行为标记 有复发性 MDD (rMDD) 病史及其非 MDD、HR 女儿（13-16 岁），以及 40 名患有 MDD 的母亲 无精神病理学史，其女儿无 MDD、低风险 (LR)。通过结合神经和行为 通过纵向设计的测量，考生将测试神经区域是否与负面社交相关 情绪和动机处理 (a) 将 HR 与 LR 二元区分开来，并且在母亲之间是一致的 和他们的女儿，代表一个家庭风险标记，（b）可以预测后代的行为评级 使用生态瞬时评估（EMA）在实验室外进行情感处理，并且（c）是 与多波随访中后代抑郁症状的轨迹相关。在当前 在提案中，候选人力求建立在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培训来降低青少年抑郁风险：1) 发展 情感神经科学和功能磁共振成像 (fMRI) 方法，2) 生态学 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精神病学系拥有优越的环境， 从事跨学科培训。候选人的导师团队（Phan 博士、Keenan 博士和 Mermelstein 博士）以及 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 方法的使用以及统计专业知识 多层次和纵向分析。拟议的研究将为更大的 R01 研究的设计提供信息 是否可以改变风险的神经和行为机制来预防抑郁症的发展 HR的后代。这项研究加上完成已确定的培训目标将有效推动 候选人致力于建立一个独立的研究计划，重点是识别行为大脑风险 青年抑郁症的表型和预防干预措施。