GERIATRIC DEPRESSION--TREATMENT RESPONSE VARIABILITY

老年抑郁症——治疗反应变异性

• 批准号: 6185642
• 负责人: John T Little
• 金额: $ 15.36万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6185642
• 关键词: age difference; bioimaging /biomedical imaging; brain mapping; brain metabolism; clinical research; clinical trials; deoxyglucose; disease /disorder onset; fluorescent dye /probe; glucose metabolism; human middle age (35-64); human old age (65+); human subject; human therapy evaluation; limbic system; magnetic resonance imaging; major depression; mental disorder chemotherapy; paroxetine; positron emission tomography; prefrontal lobe /cortex; psychopharmacology

This is an application for a Mentored Patient-Oriented Research Career Development Award (K23). The candidate is a geriatric psychiatrist who proposes to acquire the specific skills and knowledge necessary to become an independent investigator and leader in geriatric depression treatment research. Among the aged, major depression is a common problem which causes significant morbidity and mortality. While effective treatments exist for major depression, the speed, extent, and permanence of treatment response are unpredictable and vary widely, thus leaving considerable residual symptoms and disability. The candidate proposes to use the tools of functional neuroimaging to examine the underlying biology of treatment response variability in geriatric depression in order to predict and optimize antidepressant treatment response. Career development activities emphasize an integrative approach and focus on treatment research methodology, functional neuroimaging, and geriatric psychopharmacology. The research plan involves a treatment trial for elders with major depression combined with fluorine-18 deoxyglucose positron emission tomography before and after 10 weeks of acute treatment with paroxetine. Reduction in the Hamilton Depression Scale score will be correlated with cerebral metabolism in neuroanatomical regions of interest. It is hypothesized that pretreatment anterior cingulate hypermetabolism will correlate positively with extent of antidepressant response to acute treatment. Possible sources of variance accounting for treatment response heterogeneity (e.g., cerebrovascular disease reflected as white matter hyperintensities on brain magnetic resonance imaging, age of illness onset, and serum paroxetine concentration) will also be examined. As continuation and maintenance treatment will be offered through the Mental Health Clinical Research Center for the Study of Late-Life Mood Disorders, regional cerebral glucose metabolism before and after acute treatment will also be examined with respect to long-term clinical outcome.

这是一个受过指导的面向患者的研究职业发展奖（K23）的申请。候选人是一位老年精神科医生，他建议获得成为老年抑郁症治疗研究的独立研究者和领导者所必需的特定技能和知识。在老年人中，重度抑郁症是一个常见的问题，会导致明显的发病率和死亡率。尽管存在有效的严重抑郁症治疗方法，但治疗反应的速度，程度和永久性是不可预测的，并且差异很大，因此留下了相当大的残留症状和残疾。候选人建议使用功能性神经影像学的工具检查老年抑郁症治疗反应变异性的潜在生物学，以预测和优化抗抑郁治疗反应。 职业发展活动强调一种综合方法，并专注于治疗研究方法，功能神经影像学和老年心理药理学。 该研究计划涉及对重度抑郁症的长者以及氟-18脱氧葡萄糖正电子发射断层扫描和帕罗西汀急性治疗10周之前的治疗试验。 汉密尔顿抑郁量表评分的降低将与感兴趣的神经解剖区域的脑代谢相关。 假设预处理前扣带回过度代谢将与对急性治疗的抗抑郁反应的程度正相关。 还将检查可能会检查脑磁共振成像，疾病年龄和血清Paroxetine浓度的白质超强度反映的治疗反应异质性异质性异质性方差的可能来源。由于持续和维持治疗将通过心理健康临床研究中心进行晚年情绪障碍研究，因此在急性治疗前后，还将相对于长期临床结果研究区域脑葡萄糖代谢。