Using fMRI of Autobiographical Memory Recall to Determine Risk and Resilience Endophenotypes in Familial Major Depressive Disorder

使用自传体记忆回忆的功能磁共振成像确定家族性重度抑郁症的风险和弹性内表型

• 批准号: 9912202
• 负责人: Kym Young
• 金额: $ 56.75万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-12 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9912202
• 关键词: Affect; American; Amygdaloid structure; Antidepressive Agents; Brain; Brain region; Clinical; Cognitive deficits; Cross-Sectional Studies; Data; Diagnosis; Disease; Electroencephalography; Emotional; Exhibits; Family; Female; Functional Magnetic Resonance Imaging; Future; Goals; High Prevalence; Imaging technology; Individual; Intervention; Major Depressive Disorder; Memory; Mental Depression; Neurosciences; Participant; Patient Self-Report; Patients; Pattern; Population; Preventive Intervention; Recording of previous events; Recovery; Research; Residual state; Risk; Sampling; Scientist; Sex Differences; Specificity; Stimulus; Structure; Symptoms; System; Technology; Time; Training; Work; base; depressive symptoms; endophenotype; experience; follow-up; functional MRI scan; hemodynamics; high risk; improved; insight; longitudinal design; male; memory recall; neural correlate; neurobiological mechanism; neurofeedback; prevent; psychosocial; resilience; response; sex; treatment response; young adult

Abstract Major depressive disorder (MDD) is a highly disabling condition affecting 60 million Americans. Patients with MDD experience difficulty recalling autobiographical memories (AMs), and this cognitive deficit is related to poor psychosocial functioning. Patients with MDD exhibit blunted amygdala hemodynamic activity during positive AM recall and enhanced activity during negative AM recall relative to healthy individuals, and training to directly increase the amygdala response during positive AM recall improves depressive symptoms, implicating the amygdala hemodynamic response during positive AM recall as a causal mechanism underlying recovery from MDD. Furthermore, in cross-sectional studies looking at individuals at high-risk for developing MDD based on personal or family history, amygdala activity during positive AM recall is significantly associated with the presence of depressive symptoms. We aim to examine whether this correctable mechanism also convers vulnerability or resilience to developing MDD in a longitudinal design following young adults at high- risk for developing MDD. Healthy individuals with a first-degree family relative diagnosed with MDD (n=150) and healthy controls (n=50) will perform an autobiographical memory task while undergoing functional magnetic resonance imaging (fMRI). Participants will then be followed for two years to determine whether criteria for MDD are met. Our goal is to determine whether amygdala activity (Aim 1) and its interaction with activity in other regions implicated in self-referential processing (including the precuneus Aim 2) during positive AM recall is associated with risk or resilience in a sample of participants at high-risk for receiving an MDD diagnosis. Furthermore, as MDD is more prevalent in females than males, and as the relationship between AM recall deficits and depressive symptoms is only evident in females, we expect sex to moderate the relationship between overgeneral AM, regional hemodynamic activity, and depressive symptoms (Aim 3). The long term goal of this research is to identify neuroscience-based interventions that can prevent the onset of depression and thus prevent a lifetime of illness, as well as to better identify individuals in need of preventative interventions. As fMRI is expensive and not widely available for clinical use, we will also collect concurrent EEG data during fMRI in order to determine if reliable signatures of amygdala activity can be identified (Exploratory Aim) so that more widely available and affordable technology can be used in the future.

抽象的 重度抑郁症（MDD）是一种影响6000万美国人的高度残疾疾病。患者 MDD经历难以召回自传记忆（AMS），而这种认知赤字与 不良的社会心理功能。 MDD患者在杏仁核血液动力学活动中表现出钝化的患者 相对于健康个体的负AM召回期间的积极召回和增强活动和训练 为了直接增加杏仁核反应在阳性召回期间，可以改善抑郁症状， 在正AM回忆中暗示杏仁核血流动力学反应是作为因果机制的基础机制 从MDD恢复。此外，在横截面研究中，研究高风险的人开发 MDD基于个人或家族史，正面召回期间的杏仁核活动显着相关 存在抑郁症状。我们的目的是检查是否也可以正确的机制 在高成年人的年轻人之后，在纵向设计中对发展MDD的脆弱性或韧性 开发MDD的风险。具有诊断为MDD的一级家庭的健康个体（n = 150） 健康控制（n = 50）将执行自传记忆任务，同时进行功能 磁共振成像（fMRI）。然后将遵循参与者两年来确定是否 满足MDD的标准。我们的目标是确定杏仁核活动（AIM 1）及其与之相互作用是否 在阳性期间涉及自指加工（包括前后目标2）的其他地区的活动 AM召回与高风险的参与者样本中的风险或弹性有关，以接受MDD 诊断。此外，由于MDD在女性中比男性更为普遍，并且作为AM之间的关系 召回缺陷和抑郁症状仅在女性中很明显，我们希望性别减轻关系 在过度的AM，区域血流动力学活性和抑郁症状之间（AIM 3）。长期 这项研究的目标是确定基于神经科学的干预措施，以防止抑郁症发作 从而防止疾病的终生，并更好地识别需要预防的人 干预措施。由于fMRI很昂贵，并且不广泛用于临床使用，我们还将收集并发 fMRI期间的脑电图数据，以确定是否可以识别出可靠的杏仁核活性特征 （探索目的），以便将来可以使用更广泛的可用技术。