Multimodal MRI Characteristics of Psychotherapy Response in Late Life Depression

项目摘要/摘要：本提案的主要目的是确定多模磁力 磁共振成像(MRI)测量脑血流量(CBF)、皮质萎缩和白质(WM) 异常是老年患者心理治疗反应的预测因素和改变因素 抑郁障碍(LLD)。这将有助于我们的总体目标，即通知新的发展 以及更有效的治疗LLD的方法。严重抑郁障碍(MDD)与巨大的 它是造成全球残疾负担的第四大因素。LLD是 尤其常见，并使人虚弱，高达15%的65岁以上的成年人患有LLD。两者都有 抗抑郁药物和心理治疗干预通常用于治疗LLD，然而显著的 对任何一种治疗都没有反应的个体数量。LLD的治疗结果往往不佳 被认为是大脑结构或功能异常的结果。近几年来几个有效的 心理疗法是专门为LLD设计的，但确定了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患者的心理治疗反应。然而，现有的研究主要集中在单峰神经成像上。 调查，即评估一个因素，如西医异常对治疗反应的影响 而不评估其他因素的影响。这种方法虽然有用，但限制了我们澄清 最显著的神经生物学因素与治疗反应以及这些因素之间的相互关系。 利用多模式MRI方法同时评估几种类型的MRI数据提供了重要的 有机会阐明脑血流量、皮质萎缩和WM异常在 LLD患者的心理治疗反应。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，并 在治疗期间将对抑郁症的严重程度进行评估。所有参与者都将参与核磁共振 在治疗前和治疗12周后再次进行临床评估。117个年龄，性别， 而接受教育的参与者使用相同的神经成像和认知评估来匹配没有学习障碍的参与者 方案将被用来模拟年龄、性别和教育对核磁共振测量的潜在混杂影响 在对LLD参与者进行初步分析之前。使用多模式MRI分析(对照 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GM萎缩和WM异常相比，抑郁症治疗反应的相关性更强。此外，我们预计 以显示抑郁缓解时额叶脑区的脑血流量增加。总而言之，这些发现 可能会对LLD新疗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.