The Phenomenology and Antidepressant Treatment of Depressed, Frail Older Adults

描述(申请人提供)：此申请的目的是支持帕特里克·J·布朗博士以患者为中心的研究计划和职业发展，他是哥伦比亚大学接受奖学金培训的学术研究员和临床心理学家。布朗博士的总体目标是发展成为一名独立的研究人员，专注于评估和治疗诊断复杂的老年神经精神障碍患者。抑郁、虚弱的表型是了解如何改善患有诊断复杂的内科和精神疾病的老年患者干预结果的最有希望的途径。这种临床人群的复杂性要求布朗博士接受老年医学原理的交叉培训，以便将这些原理应用于精神病学干预研究。因此，他在以下医生的指导下构建了一个多学科培训计划：史蒂文·鲁斯博士，精神病学家和影响抗抑郁药物疗效的临床、人口和治疗因素方面的权威；马修·毛雷尔博士，对心血管健康和老年患者的无痛有研究兴趣的心脏病专家；琳达·弗里德博士，老年病学家、流行病学家和虚弱概念专家；以及神经心理学、精神药理学、生物统计学和负责任的研究行为顾问。在拟议的奖项期间，布朗博士将通过课程作业、以患者为中心的体验和专家指导获得正式培训，内容包括：1)对虚弱和抑郁常见的生物、神经心理和生理特征的评估和理解；2)治疗干预措施的设计、实施和分析；3)老年研究中的复杂伦理问题。这项研究建议的总体目标是了解抑郁脆弱的表型。虽然抑郁和虚弱分别会给患者和家庭带来可怕的后果，而且似乎在现象学和生理学上是相关的，但虚弱综合征从未在老年抑郁症的背景下进行过明确的研究。根据他的试验数据和这两种疾病的诊断复杂性，布朗博士构建了一个这种表型的模型，并假设在基线上出现特定的脆弱特征会降低对抗抑郁药物治疗的反应。为了研究这一模型，布朗博士将使用抗抑郁药物对抑郁、虚弱的表型进行为期12个月的解构。在这样做的过程中，布朗博士还将评估老年抑郁、虚弱人群中慢性炎症和营养不良的指标，以开始评估表型背后的潜在机制，他还将调查基线虚弱特征对活动水平和残疾的长期改善的影响。在这项提案的最后，布朗博士将能够更好地回答虚弱综合征如何影响老年抑郁症的诊断，以及虚弱综合征是否会减弱抗抑郁药物治疗的反应。有了这些经验和技能，布朗博士将结合从老年医学和精神病学中获得的知识，使用多学科评估技术来完善我们对诊断复杂的患有神经精神障碍的老年患者的理解，并有针对性地进行个性化治疗干预，以最大限度地提高治疗结果。

DESCRIPTION (provided by applicant): The purpose of this application is to support the patient-oriented research program and career development of Patrick J. Brown, PhD, a fellowship-trained academic researcher and clinical psychologist at Columbia University. Dr. Brown's overall goal is to develop into an independent investigator with a focus on the assessment and treatment of diagnostically complex geriatric patients with neuropsychiatric disorders. The depressed, frail phenotype represents the most promising avenue to understand how to improve intervention outcomes for geriatric patients with diagnostically complex medical and psychiatric comorbidity. The complexity of this clinical population requires Dr. Brown receive cross training in the principles of geriatric medicine to apply these principles to psychiatric interventions research. As such, he has constructed a multidisciplinary training plan under the mentorship of Dr. Steven Roose, a psychiatrist and authority on the clinical, demographic, and treatment factors affecting response to antidepressants, Dr. Mathew Maurer, a cardiologist with research interests in cardiovascular health and anergia in older patients, and Dr. Linda Fried, a geriatrician, epidemiologist and expert in the concept of frailty, along with advisors in neuropsychology, psychopharmacology, biostatistics, and responsible conduct in research. During the proposed award, Dr. Brown will obtain formal training via coursework, patient-oriented experiences, and expert tutelage in 1) the assessment and understanding of the biological, neuropsychological, and physical characteristics common to frailty and depression, 2) the design, conduct, and analysis of therapeutic interventions, and 3) the complex ethical issues in geriatric research. The overall goal of this research proposal is to understand the depressed frail phenotype. Although depression and frailty individually result in dire outcomes for patients and families and appear to be phenomenologically and physiologically associated, the syndrome of frailty has never been explicitly studied in the context of late life depression. Based on his pilot data and the diagnostic complexities of these two conditions, Dr. Brown had constructed a model of this phenotype and hypothesized that the presence of specific frailty characteristics at baseline will diminish response to antidepressant treatment. To investigate this model, Dr. Brown will conduct a 12-month deconstruction of the depressed, frail phenotype using antidepressant medication. In doing so, Dr. Brown will also assess markers of chronic inflammation and malnutrition in this older depressed frail population to begin to evaluate the potential mechanisms underlying the phenotype, and he will investigate the impact of baseline frailty characteristics on long-term improvement in activity levels and disability. At the end of this proposal, Dr. Brown will be better able to answer how the syndrome of frailty impacts the diagnosis of late life depression, and whether the syndrome of frailty diminishes response to antidepressant treatment. With this experience and skill set, Dr. Brown will combine the knowledge gained from both geriatric medicine and psychiatry to use multidisciplinary assessment techniques to refine our understanding of diagnostically complex geriatric patients with neuropsychiatric disorders and personalize therapeutic interventions targeted to maximize treatment outcome.