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

摘要 重度抑郁症（MDD）是一种影响6000万美国人的高度致残性疾病。患者 MDD经历回忆自传体记忆（AM）的困难，这种认知缺陷与 社会心理功能差。MDD患者表现出杏仁核血流动力学活动迟钝， 相对于健康个体，积极的AM回忆和在消极的AM回忆期间增强的活动，以及训练 在积极的AM回忆期间直接增加杏仁核反应可以改善抑郁症状， 暗示杏仁核血流动力学反应在积极上午回忆作为一个因果机制， 从MDD中恢复。此外，在横断面研究中， 基于个人或家族史的MDD，在积极AM回忆期间杏仁核活动显著相关 有抑郁症状我们的目标是研究这种可纠正的机制是否也 在一项纵向设计中，将易感性或弹性转化为发展中的MDD， 开发MDD的风险。一级亲属诊断为MDD的健康个体（n=150） 和健康对照组（n=50）将进行自传体记忆任务，同时进行功能性记忆。 磁共振成像（fMRI）。参与者将被跟踪两年，以确定是否 符合MDD标准。我们的目标是确定杏仁核活动（Aim 1）及其与 在积极的自我参照过程中，参与自我参照处理的其他区域（包括楔前叶目标2）的活动 在接受MDD的高风险参与者样本中，AM回忆与风险或弹性相关 诊断.此外，由于MDD在女性中比男性更普遍，并且AM与 回忆缺陷和抑郁症状仅在女性中明显，我们预计性别会缓和这种关系 过度广泛的AM、局部血流动力学活动和抑郁症状之间的关系（目的3）。长期 这项研究的目的是确定以神经科学为基础的干预措施，可以防止抑郁症的发作 从而预防终身疾病，并更好地识别需要预防的个人， 干预措施。由于功能磁共振成像是昂贵的，并没有广泛用于临床使用，我们还将收集同期 功能磁共振成像期间的EEG数据，以确定是否可以识别杏仁核活动的可靠特征 （探索性目标），以便今后能够使用更广泛获得和负担得起的技术。

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.