Neurocircuitry of Emotion: Distinguishing Late Life Anxiety and Depression

描述(由申请人提供)：本申请旨在描述晚年焦虑和抑郁障碍的神经基础。在美国，60岁以上的成年人中有多达15%的人患有焦虑或抑郁障碍。这些晚年的障碍使人丧失能力，降低了生活质量，损害了认知过程，增加了发病率和死亡率。人们对老年人这些疾病背后的神经回路知之甚少，随着衰老过程而发生的神经退行性变化使这个问题变得更加复杂。增加对晚年情绪和焦虑症的神经基础的表征对于增加我们对a)这些疾病的病因；b)它们的鉴别诊断；c)它们与年龄相关的神经退化和认知衰退的关系；d)脆弱性和恢复力因素；e)治疗反应的预测因素；以及f)建立针对特定神经回路的合理疗法的基础是至关重要的。我们建议通过在老年抑郁和焦虑患者中进行研究来提供这个急需的神经生物学基础，我们已经利用创新的fMRI范式来识别年轻人中抑郁和焦虑的不同神经底物，这些神经底物既表征和区分这些疾病。为了实现我们在神经回路水平上描述晚年MDD和GAD的目标，我们将把这些神经成像探针应用于160名老年人(60岁)，他们平均分为四组：仅GAD组、仅MDD组、GAD/MDD并存组和健康对照组，同时研究与情绪调节相关的非情绪认知控制过程，并通过神经心理测试评估一系列认知功能。基于我们的初步数据和关于年龄相关认知下降的考虑，我们的具体目标是：目标1：检查情绪处理和调节的fMRI测量是否与晚年GAD和晚年MDD的神经回路受损模式有关。目的2：研究共病老年GAD和MDD的神经回路异常是否相加。目的3：研究GAD和MDD患者晚年情绪加工的异常是否与认知加工中的执行控制受损有关。

DESCRIPTION (provided by applicant): This application aims to delineate the neural basis of late life anxiety and depressive disorders. As many as 15% of adults over the age of 60 years in the U.S. suffer from anxiety or depressive disorders. These disorders in late life are disabling, reduce the quality of life, impair cognitive processing and increase morbidity and mortality. Little is known about the neurocircuitry underlying these disorders in older adults, an issue that is further complicated by the neurodegenerative changes that accompany the aging process. Increased characterization of the neural basis of late life mood and anxiety disorders is essential for increasing our understanding of a) the etiology of these disorders; b) their differential diagnosis; c) their relationship to age- related neurodegeneration and cognitive decline; d) vulnerability and resilience factors; e) predictors of treatment response; and also for the f) establishment of the basis for development of rational therapeutics targeting defined neural circuits. We propose to provide this much-needed neurobiological foundation by investigating in patients with late life depression and anxiety innovative fMRI paradigms that we have utilized to identify differential neural substrates of depression and anxiety in young adults that both characterize and distinguish these disorders. To achieve our objective of characterizing late life MDD and GAD at a neural circuit level, we will apply these neuroimaging probes to 160 older adults (>60 years old) falling equally into four groups: GAD only, MDD only, comorbid GAD/MDD and healthy controls, while also examining non- emotional cognitive control processes that parallel emotion regulatory ones, and assessing a range of cognitive functions through neuropsychological testing. Our Specific Aims, based on our preliminary data and considerations regarding age-related cognitive decline, are: Aim 1: To examine if fMRI measures of emotional processing and regulation are associated with different patterns of impaired neurocircuitry in late life GAD versus late life MDD. Aim 2: To examine if neurocircuitry abnormalities in co-morbid late life GAD and MDD are additive. Aim 3: To examine if dysregulation of emotional processing in late life GAD and MDD is due to impaired executive control during cognitive processing.