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

摘要 严重抑郁障碍(MDD)是一种严重致残的疾病，影响着6000万美国人。患有疾病的患者 MDD在回忆自传体记忆(AM)方面存在困难，这种认知缺陷与以下因素有关 心理社会功能不佳。MDD患者杏仁核血流动力学活动迟钝 与健康个体相比，积极的AM回忆和在消极的AM回忆期间增强的活动，以及培训 在积极的AM回忆过程中直接增加杏仁核的反应可以改善抑郁症状， AM回忆阳性时杏仁核血流动力学反应是潜在的致病机制 从MDD中恢复。此外，在对高危人群进行的横断面研究中， 基于个人或家族病史，AM回忆阳性期间杏仁核活动与MDD显著相关 伴随抑郁症状的出现。我们的目标是检查这个可纠正的机制是否也 在纵向设计中转换易患MDD的脆弱性或恢复力，遵循青壮年高 开发MDD的风险。有一级亲属被诊断为MDD的健康个体(n=150) 而健康对照组(n=50)将在经历功能性记忆的同时执行自传体记忆任务 磁共振成像(FMRI)。然后对参与者进行为期两年的跟踪调查，以确定 符合MDD的标准。我们的目标是确定杏仁核的活动(目标1)及其与 阳性期间涉及自我参照加工的其他区域的活动(包括楔前目标2) AM召回与接受MDD高危参与者样本中的风险或复原力相关 诊断。此外，由于MDD在女性中比男性更常见，以及AM与 记忆缺陷和抑郁症状只在女性中明显，我们希望性行为能缓和这种关系 广泛AM、局部血流动力学活动和抑郁症状之间的关系(目标3)。从长远来看 这项研究的目标是确定基于神经科学的干预措施，可以预防抑郁症的发生 从而预防终生疾病，以及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价格昂贵，而且不能广泛应用于临床，我们还将收集并发 FMRI期间的脑电数据，以确定是否可以识别杏仁核活动的可靠特征 (探索性目标)，以便在未来可以使用更广泛和负担得起的技术。

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.