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%患有焦虑或抑郁症。这些疾病在晚年是致残的，降低生活质量，损害认知过程，增加发病率和死亡率。对老年人这些疾病背后的神经回路知之甚少，这一问题因伴随衰老过程的神经退行性变化而进一步复杂化。增加对晚年情绪和焦虑障碍的神经基础的表征对于增加我们对以下内容的理解是至关重要的：a）这些障碍的病因学; B）它们的鉴别诊断; c）它们与年龄相关的神经变性和认知衰退的关系; d）脆弱性和恢复力因素; e）治疗反应的预测因子;并且还用于f）建立用于开发靶向限定的神经回路的合理疗法的基础。我们建议提供这种急需的神经生物学基础，通过调查老年抑郁症和焦虑症患者的创新功能磁共振成像范例，我们已经利用这些范例来识别年轻人的抑郁症和焦虑症的差异神经基质，这些基质都是这些疾病的特征和区别。为了实现我们在神经回路水平上表征晚年MDD和GAD的目标，我们将这些神经成像探针应用于160名老年人（60岁以上），平均分为四组：仅GAD，仅MDD，共病GAD/MDD和健康对照，同时还检查与情绪调节过程平行的非情绪认知控制过程，并通过神经心理学测试评估一系列认知功能。我们的具体目标，根据我们的初步数据和考虑与年龄相关的认知能力下降，是：目的1：检查是否fMRI措施的情绪处理和调节与不同的模式受损的神经回路在晚年GAD与晚年MDD。目的2：检查共病晚年GAD和MDD的神经回路异常是否是相加的。目的3：研究老年广泛性焦虑症和抑郁症患者的情绪加工失调是否是由于认知加工过程中的执行控制受损所致。

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.