Neurobiology and Adverse Outcomes of Neuroticism in Late-life Depression

描述(由申请者提供)：该项目旨在了解老年抑郁症患者的大脑功能、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一种临床现象。不太清楚的是，老年抑郁症患者神经质的情绪和认知后果。此外，对任何年龄段的神经质相关的生物过程的了解都是有限的。这些问题对晚年抑郁症尤其有意义，抑郁症本身与不良结局的风险增加有关，包括较低的缓解率、较高的复发率和较高的痴呆症事件风险。确定与这些不良结果相关的因素对于预防与持续性抑郁症和认知衰退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)来计算关键种子大脑区域和其他区域之间的静息状态功能连接(RsFC)。我们发现腹内侧额前皮质与海马体、左侧眶前叶皮质与杏仁核、右侧背侧前扣带回皮质与右侧扣带后皮质之间存在联系。我们还发现，随着时间的推移，老年抑郁受试者的神经质越高，抑郁得分越高，认知能力下降越大。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。详细的心理社会、功能、临床、精神病学、医学、神经学和认知评估将在随访期间的基线和确定的时间点获得。将进行结构和功能磁共振研究。主要的结果衡量指标是情绪和认知轨迹以及神经质的神经相关性。所有患者都将接受长达24周的标准化治疗，使用西酞普兰进行标准化的两步干预，然后再进行安非他酮强化治疗或地文拉法辛治疗。24周后，受试者将使用已建立的基于指南的治疗算法进行跟踪。分析计划的重点是检查1)与神经质相关的神经联系(基于功能磁共振rsFC)；2)老年抑郁症患者神经质的纵向情绪和认知后果；3)抑郁症的临床不良情绪和认知结果是否由功能磁共振成像上看到的特定大脑变化介导。预计这项研究的结果将确定与神经质有关的大脑区域，并将澄清神经质与抑郁老年人不良结局之间的关系。

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.