Oxidative stress in geriatric bipolar depression

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青年期，但大多数BPD患者遵循终身复发过程，持续存在心理社会和功能缺陷，并持续到以后的生活中高度利用卫生服务。目前，缺乏老年BPD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以后的生活中，都是这种毁灭性疾病的主要和最不成功的治疗阶段，并与自杀风险升高有关。双相抑郁症的发病机制尚不清楚，对目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目标，并提供了一个窗口的治疗机会，在目前的治疗是有限的或仍然是次优的领域。在这一点上，NAC的作用机制尚未完全了解。虽然有人假设NAC可能会改变大脑谷胱甘肽（GSH），主要的抗氧化剂对维持氧化平衡很重要，但这还没有在人类或双相抑郁症的背景下进行研究。这项建议的研究计划旨在确定国家行动委员会工作的基本机制，并包括三个具体目标。第一个目的是使用改进的定量磁共振波谱方法来确定与匹配的对照组相比，BPD老年人的脑GSH水平是否改变。第二个目的是确定补充NAC是否会增加BPD组中GSH水平的剂量依赖性。第三个目的是确定NAC干预，脑GSH/神经递质水平和抑郁症症状严重程度之间是否存在关联。据推测，与健康对照相比，BPD患者的GSH水平将较低，NAC补充剂将提高脑GSH，减少BPD老年人的氧化应激和抑郁症状。

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.