Oxidative stress in geriatric bipolar depression

老年双相抑郁症的氧化应激

• 批准号: 8512108
• 负责人: ATILLA GONENC
• 金额: $ 17.88万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-04 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8512108
• 关键词: Acetylcysteine; Acute; Adolescence; Adult; Adverse effects; Aging; Antidepressive Agents; Antioxidants; Biological Availability; Biological Markers; Bipolar Depression; Bipolar Disorder; Blood - brain barrier anatomy; Brain; Cells; Clinical; Cysteine; Data; Diagnosis; Dietary Supplementation; Disease; Dose; Elderly; Equilibrium; Functional disorder; Glutathione; Human; Impairment; Individual; Intervention; Knowledge; Life; Light; Magnetic Resonance Spectroscopy; Maintenance; Measures; Mental Depression; Mental disorders; Methods; Mood stabilizers; Neurobiology; Neurotransmitters; Oxidative Stress; Patients; Phase; Pilot Projects; Population; Protons; Psyche structure; Publishing; Quality of life; Randomized Controlled Trials; Recurrence; Relative (related person); Relaxation; Research; Resistance; Role; Safety; Severities; Signal Transduction; Supplementation; Testing; Therapeutic; Time; Treatment Efficacy; Unipolar Depression; Work; aged; aging population; depressive symptoms; evidence base; health care service utilization; improved; neuroimaging; novel; older patient; patient population; psychosocial; public health relevance; suicidal risk; therapeutic target; two-dimensional; young adult

DESCRIPTION (provided by applicant): Although bipolar disorder (BPD) usually presents in adolescence or young adulthood, most patients with BPD follow a life-long recurrent course, with ongoing psychosocial and functional deficits and high utilization of health services that persist into later life. Currently, there is a lack of data in geriatric BPD overall and in geriatrc bipolar depression in particular. Bipolar depression, both in adulthood and later life, represents the predominant and least successfully treated phase of this devastating illness and is associated with an elevated risk of suicide. The disease mechanisms that underlie bipolar depression remain unclear and resistance to current treatments is high. N-Acetyl Cysteine (NAC) appears to be a promising therapeutic target and provides a window of treatment opportunity in a field where current treatments are limited or have remained suboptimal. At this point, the mechanism of action of NAC is not entirely understood. While it's been hypothesized that NAC may alter brain glutathione (GSH), main antioxidant important for the maintenance of oxidative balance, this has not been studied in humans or in the context of bipolar depression. The research plans of this proposal aim at identifying the underlying mechanism by which NAC works and include three specific aims. The first aim is to use improved quantitative magnetic resonance spectroscopy methods to determine whether brain GSH levels are altered in older adults with BPD compared to matched controls. A secondary aim is determine whether NAC supplementation will increase GSH levels dose-dependently in the BPD group. A third aim is to determine whether there is an association between the NAC intervention, brain GSH/neurotransmitter levels and depression symptom severity. It is hypothesized that GSH levels will be lower in patients with BPD compared to healthy controls and NAC supplementation will elevate brain GSH reducing oxidative stress and depression symptoms in aging individuals with BPD.

描述（由申请人提供）：虽然双相情感障碍 (BPD) 通常出现在青春期或成年早期，但大多数 BPD 患者会终生复发，伴有持续的社会心理和功能缺陷，并且对健康服务的高度利用会持续到晚年。目前，缺乏关于老年 BPD 的总体数据，特别是老年双相抑郁症的数据。双相抑郁症，无论是在成年期还是晚年，都是这种毁灭性疾病的主要阶段和治疗最不成功的阶段，并且与自杀风险升高有关。双相抑郁症的疾病机制仍不清楚，并且对当前治疗的抵抗力很高。 N-乙酰半胱氨酸（NAC）似乎是一个有前途的治疗靶点，并为当前治疗有限或仍不理想的领域提供了一个治疗机会之窗。目前，NAC 的作用机制尚不完全清楚。虽然有人假设 NAC 可能会改变大脑谷胱甘肽 (GSH)（对维持氧化平衡很重要的主要抗氧化剂），但尚未在人类或双相抑郁症的背景下进行研究。该提案的研究计划旨在确定 NAC 工作的根本机制，并包括三个具体目标。第一个目标是使用改进的定量磁共振波谱方法来确定患有 BPD 的老年人与匹配对照相比，大脑 GSH 水平是否发生改变。次要目标是确定补充 NAC 是否会剂量依赖性地增加 BPD 组的 GSH 水平。第三个目标是确定 NAC 干预、大脑 GSH/神经递质水平和抑郁症状严重程度之间是否存在关联。据推测，与健康对照组相比，BPD 患者的 GSH 水平较低，补充 NAC 会提高大脑 GSH，从而减少老年 BPD 患者的氧化应激和抑郁症状。