Multimodal MRI Characteristics of Psychotherapy Response in Late Life Depression

项目总结/摘要：本提案的主要目的是识别多模态磁共振成像 脑血流量（CBF）、皮质萎缩和白色物质（WM）的共振成像（MRI）测量 异常，这是预测，并改变了，心理治疗的反应，晚年生活主要 抑郁症（LLD）。这将有助于我们的总体目标，即为新的发展提供信息。 以及更有效的治疗LLD的方法重度抑郁症（MDD）与巨大的 是全球残疾负担的第四大贡献者。LLD为 特别常见和使人衰弱，高达15%的65岁以上的成年人患有LLD。两 抗抑郁药和心理治疗干预通常用于治疗LLD，然而， 许多人对任何一种治疗都没有反应。LLD的不良治疗结果通常 被认为是大脑结构或功能异常的结果。近年来，一些有效的 心理治疗是专门为LLD设计的，但确定神经生物学因素的影响 对LLD的心理治疗反应尚未进行评估。现存的文献和我们的初步数据 提示CBF、皮质萎缩和WM异常可能是导致 LLD的心理治疗反应。然而，现有的研究主要集中在单峰神经成像 研究，即评价一个因素（如WM异常）对治疗反应的影响 而不考虑其他因素的影响。这种方法虽然有用，但限制了我们澄清 与治疗反应相关的最突出的神经生物学因素以及这些因素的相互关系。 利用多模态MRI方法同时评估几种类型的MRI数据， 有机会澄清CBF、皮质萎缩和WM异常对 LLD的心理治疗反应。在这项研究中，我们将招募110名患有LLD的老年人，他们没有服用 抗抑郁药所有LLD参与者将参加为期12周的心理治疗干预， 在治疗期间将进行抑郁症严重程度的评估。所有参与者将参加MRI 以及治疗前和治疗12周后的临床评价。117名年龄、性别、 使用相同的神经成像和认知评估， 将使用方案模拟年龄、性别和教育对MRI测量的潜在混杂效应 在对LLD参与者进行初步分析之前。使用多模态MRI分析（控制 认知功能和其他临床特征），我们希望证明CBF将显示出更强的 与抑郁症治疗反应的相关性高于GM萎缩和WM异常。此外，我们预计 表明随着抑郁症的缓解，额叶脑区的CBF增加。总的来说，这些发现 可能对LLD新治疗方法的开发产生重大影响。

PROJECT SUMMARY/ABSTRACT: The primary aim of this proposal is to identify multimodality magnetic resonance imaging (MRI) measures of cerebral blood flow (CBF), cortical atrophy, and white matter (WM) abnormalities, which are predictors of, and altered by, psychotherapy treatment response for late life major depressive disorder (LLD). This will contribute to our overall goal, which is to inform the development of new and more effective treatments for LLD. Major depressive Disorder (MDD) is associated with tremendous personal suffering and is the 4th leading contributor to the global burden of disability worldwide. LLD is particularly common and debilitating with up to 15% of adults over the age of 65 suffering from LLD. Both antidepressants and psychotherapy interventions are commonly utilized to treat LLD, however a significant number of individuals do not respond to either type of treatment. Poor treatment outcomes in LLD are often posited to be the result of structural or functional brain abnormalities. In recent years several effective psychotherapies have been designed specifically for LLD but determining the impact of neurobiological factors on psychotherapy response in LLD has not been evaluated. The extant literature and our preliminary data suggest that CBF, cortical atrophy, and WM abnormalities may be important factors contributing to psychotherapy response in LLD. The existing studies, however, have focused on unimodal neuroimaging investigations, i.e. evaluating the impact of one factor such as WM abnormalities on treatment response without evaluating for the effects of other factors. This approach, while useful, limits our ability to clarify the most salient neurobiological factors associated with treatment response and the interrelations of these factors. Utilizing multimodal MRI methods to evaluate several types of MRI data simultaneously offers a significant opportunity to clarify the relative contributions of CBF, cortical atrophy, and WM abnormalities on psychotherapy response in LLD. For this study we will recruit 110 older adults with LLD who are not taking antidepressants. All LLD participants will be enrolled in a 12-week psychotherapy intervention and assessments of depression severity will be conducted during treatment. All participants will participate in MRI and clinical evaluations prior to treatment and again after 12 weeks of treatment. Data for 117 age, gender, and education matched participants without LLD using the same neuroimaging and cognitive assessment protocols will be used to model potential confounding effects of age, gender, and education on MRI measures prior to conducting our primary analyses in LLD participants. Using multimodal MRI analyses (controlling for cognitive functioning and other clinical characteristics) we expect to demonstrate that CBF will show stronger associations with depression treatment response than GM atrophy and WM abnormalities. Further, we expect to show that CBF increases in frontal brain regions with remission of depression. Collectively these findings may have a significant impact on the development of new treatments for LLD.