Neurobiology and Adverse Outcomes of Neuroticism in Late-life Depression

描述（由申请人提供）：该项目旨在了解晚年抑郁症患者的脑功能、神经质、情绪和认知结果之间的关系。神经质是抑郁症患者一生中常见的临床现象。老年抑郁症患者神经质的情绪和认知后果尚不清楚。此外，人们对任何年龄段与神经质相关的生物过程的理解都很有限。这些问题在晚年抑郁症中特别有意义，这本身就与不良结果的风险增加有关，包括更低的缓解率，更高的复发率和增加的痴呆风险。识别与这些不良结果相关的因素对于预防与持续抑郁和认知能力下降相关的发病率以及开发神经知情的新干预措施至关重要。在我们的初步数据中，我们使用功能磁共振成像（fMRI）来计算关键种子脑区域与其他区域之间的静息状态功能连接（rsFC）。我们发现腹内侧前额皮质与海马体、左侧眶额皮质与杏仁核、右侧背侧前扣带皮质与右侧后扣带皮质之间存在关联。我们还发现，随着时间的推移，老年抑郁症患者的神经质程度越高，抑郁得分越高，认知能力下降越严重。我们建议招募140名老年抑郁症患者和75名老年非抑郁症对照。详细的社会心理、功能、临床、精神病学、医学、神经学和认知评估将在基线和随访期间的确定时间点进行。将进行结构和功能MRI检查。主要的结果测量是情绪和认知的轨迹以及神经质的神经相关。所有患者将接受长达24周的标准化治疗，采用西酞普兰进行标准化的两步干预，随后使用安非他酮增强或地文拉法辛。24周后，受试者将使用既定的基于指南的治疗算法进行随访。分析计划侧重于检查1)神经连接（基于fMRI rsFC）相关的神经质；老年抑郁症患者神经质情绪与认知的纵向影响；3)抑郁症的临床不良情绪和认知结局是否由fMRI特异性脑变化介导。我们期望这项研究的结果能够确定与神经质有关的大脑区域，并阐明老年抑郁症患者神经质与不良预后之间的关系。

DESCRIPTION (provided by applicant): This is project seeks to understand the relationships between brain function, neuroticism and mood and cognitive outcomes in late life depression. Neuroticism is a clinical phenomenon commonly observed in depression across the life span. Less clear are the mood and cognitive consequences of Neuroticism in older depressed adults. Further, there is only limited understanding of biological processes related to Neuroticism at any age. These questions are particularly meaningful in late life depression, which is itself associated with increased risk of poor outcomes, including lower remission rates, higher relapse rates and increased risk of incident dementia. Identification of factors related to these poor outcomes is essential for preventing the morbidity associated with persistent depression and cognitive decline and for development of neurally informed novel interventions. In our preliminary data, we used functional magnetic resonance imaging (fMRI) to calculate resting state functional connectivity (rsFC) between key seed brains regions and other regions. We found associations between ventromedial prefrontal cortex and the hippocampus, between the left orbitofrontal cortex and the amygdala, and the right dorsal anterior cingulate cortex and the right posterior cingulate cortex. We also found that higher Neuroticism in older depressed subjects was associated with higher depression scores and greater cognitive decline over time. We propose to recruit 140 older depressed patients and 75 older non-depressed controls. Detailed psychosocial, functional, clinical, psychiatric, medical, neurological, and cognitive assessments will be obtained at baseline and at defined points during follow-up. Structural and function MRI studies will be performed. The principal outcome measures are trajectory of mood and cognition and neural correlates of neuroticism. All patients will receive standardized treatment for up to 24 weeks with a standardized two-step intervention using citalopram followed by either bupropion augmentation or desvenlafaxine. After 24 weeks, subjects will be followed using an established guideline-based treatment algorithm. The analysis plan focuses on examining 1) neural links (based on fMRI rsFC) associated Neuroticism; 2) longitudinal mood and cognitive consequences of Neuroticism among older depressed patients; 3) whether the clinical adverse mood and cognitive outcomes of depression are mediated by specific brain changes seen on fMRI. It is expected that results from this study will identify brain regions involved in Neuroticism and will clarify the relationship between Neuroticism and poor outcomes in depressed elderly.