Neurobiology and Adverse Outcomes of Neuroticism in Late-life Depression

描述（由申请人提供）：这是一个项目，旨在了解大脑功能，神经质和情绪之间的关系，以及晚年抑郁症的认知结果。神经质是抑郁症中常见的一种临床现象。不太清楚的是神经质在老年抑郁症患者中的情绪和认知后果。此外，对任何年龄段与神经质有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，这本身就与不良结局的风险增加有关，包括较低的缓解率，较高的复发率和痴呆事件风险增加。识别与这些不良结局相关的因素对于预防与持续性抑郁和认知下降相关的发病率以及开发神经信息新颖干预措施至关重要。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和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叶皮层和海马体之间，左眶额皮层和杏仁核之间，以及右背前扣带皮层和右后扣带皮层之间存在联系。我们还发现，随着时间的推移，老年抑郁症受试者的神经质水平较高，抑郁症评分较高，认知能力下降较大。我们计划招募140名老年抑郁症患者和75名老年非抑郁症对照。将在基线和随访期间的规定时间点获得详细的社会心理、功能、临床、精神病学、医学、神经学和认知评估。将进行结构和功能MRI研究。主要的结果测量是情绪和认知的轨迹和神经质的神经相关。所有患者将接受长达24周的标准化治疗，采用标准化两步干预，使用西酞普兰，然后使用安非他酮或去甲文拉法辛。24周后，将使用既定的基于指南的治疗算法对受试者进行随访。分析计划的重点是检查1）与神经质相关的神经链接（基于fMRI 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后果是否由fMRI上观察到的特定大脑变化介导。预计这项研究的结果将确定参与神经质的大脑区域，并将澄清神经质和抑郁症老年人的不良结果之间的关系。 公共卫生相关性：神经质的存在预示着抑郁症的不良结局，但对其生物学基础知之甚少。老年抑郁症是认知能力下降和痴呆症的风险因素。本研究旨在进一步科学地理解抑郁、神经质、持续性抑郁和认知障碍之间的复杂关系。我们的目标是确定老年抑郁症的成年人谁是在风险的负面结果。

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. PUBLIC HEALTH RELEVANCE: Presence of neuroticism predicts poor outcomes of depression, yet little is known about its biological basis. Depression in late life is a risk facto for cognitive decline and dementia. This study seeks to further our scientific understanding of the complex relationships among depression, neuroticism, persistent depression and cognitive impairment. We aim to identify older depressed adults who are at risk for negative outcomes.