Cognitive and Affective Neuroscience of Decision-Making in Late-Life Suicide

描述（由申请人提供）：老年自杀的大脑机制尚不清楚，很少有研究者研究老年自杀的神经生物学。特别是，自杀研究领域缺乏对自杀风险的心理和认知标记（绝望，执行控制障碍）与死后和成像研究中确定的大脑标记之间的关系的理解。申请人是一名老年精神病学家，具有晚年自杀和晚年抑郁症治疗的临床背景，他认为自杀是决策过程改变的结果，这一观点得到了初步行为和影像学数据的支持。因此，申请人的职业目标是应用决策基础神经科学的进展来研究晚年自杀的大脑机制，并在未来确定干预目标。这种方法旨在将现有的关于自杀素质的认知研究与基础和临床神经科学联系起来。这将通过功能性磁共振成像（fMRI，包括基于计算模型的fMRI）、决策的神经生物学以及使用神经科学模型识别干预目标的培训来实现。一项关于老年抑郁症自杀未遂者决策的fMRI研究，关注了腹内侧和腹外侧前额叶皮层价值信号处理的中断，将作为拟议训练的媒介。拟议的培训和研究将由CF. Reynolds（导师）、G.J. Siegle的fMRI实验室（联合导师）和L. Clark的成像实验室（英国剑桥）指导的晚期情绪障碍干预和服务研究高级中心提供支持。利用匹兹堡大学的神经成像资源，H.J. Aizenstein将帮助申请人克服老化大脑的MR成像挑战，M.L. Phillips将帮助完善神经模型并发展自杀决策的生命周期视角。K. Szanto将帮助申请人提高临床特征和管理自杀风险。这项工作应该产生一项旨在确定干预目标的ROl。公共卫生相关性（见说明）：在全世界和美国，老年人的自杀率是所有年龄组中最高的——随着美国人口老龄化和合法持有枪支，这一公共负担可能会增加。目前的预防方法没有选择性，主要针对抑郁症。对大脑机制的深入了解将有助于识别有自杀风险的老年人，并开发基于神经科学的干预措施。

DESCRIPTION (provided by applicant): Brain mechanisms of vulnerability to suicide in old age remain unclear, and very few researchers study the neurobiology of late-life'suicide. In particular, the field of suicide research lacks an understanding of how psychoiogicai and cognitive markers of suicidal risk (hopelessness, executive dyscontrol) relate to brain markers identified in post-mortem and imaging studies. The applicant - a geriatric psychiatrist with a clinical background in late-life suicide and in the treatment of late-life depression - views suicide as an outcome of an altered decision process, a view supported by preliminary behavioral and imaging data. Thus, the applicant's career goals are to apply advances in the basic neuroscience of decision-making to investigate the brain mechanisms of late-life suicide and, in the future, to identify intervention targets. This approach aims to bridge existing cognitive research on suicidal diathesis with basic and clinical neuroscience. This will be achieved through training in functional magnetic resonance imaging (fMRI; including computational model-based fMRI), in neurobiology of decision-making, and in using neuroscience models to identify intervention targets. An fMRI study of decision-making in elderly depressed suicide attempters focused on disruptions in the processing of value signals in the ventromedial and ventrolateral prefrontal cortex will serve as a vehicle for proposed training. Proposed training and research will be supported by the Advanced Center for Interventions and Services Research for Late-Life Mood Disorders directed by CF. Reynolds (mentor), G.J. Siegle's fMRI lab (co-mentor), and L. Clark's imaging lab (Cambridge, UK). Taking advantage of the neuroimaging resources at the University of Pittsburgh, H.J. Aizenstein will help the applicant to overcome challenges in MR imaging of the aging brain and M.L. Phillips will aid in refining the neural model and developing a life-span perspective on decision-making in suicide. K. Szanto will help the applicant sharpen clinical characterization and manage suicidal risk. An ROl geared towards identifying intervention targets should result from this work. PUBLIC HEALTH RELEVANCE (See instructions): Worldwide and in the US, the elderly have the highest suicide rate of all age groups - a public burden likely to increase as US population ages and access to firearms is legally upheld. Current prevention approaches are not selective, targeting mainly depression. Insight into brain mechanisms will help identify elderly at risk for suicide and develop neuroscience-based interventions.