Oxidative stress in geriatric bipolar depression

描述(申请人提供)：尽管双相情感障碍(BPD)通常出现在青春期或青壮年，但大多数BPD患者都会经历终生反复发作的过程，持续存在心理社会和功能缺陷，并对健康服务的高利用率持续到晚年。目前，在老年性BPD总体上，特别是在老年性双相抑郁方面，缺乏数据。在成年和晚年，双相抑郁是这种毁灭性疾病的主要阶段，也是治疗最不成功的阶段，并与自杀风险增加有关。双相抑郁的发病机制尚不清楚，对当前治疗方法的抵抗力很高。N-乙酰半胱氨酸(NAC)似乎是一个很有前途的治疗靶点，并在当前治疗有限或仍处于次优状态的领域提供了一个治疗机会之窗。在这一点上，NAC的作用机制还不完全清楚。虽然已经假设NAC可能改变大脑谷胱甘肽(GSH)，这是维持氧化平衡的主要抗氧化剂，但这还没有在人类或双相抑郁的背景下进行研究。这项建议的研究计划旨在确定新来港儿童工作的基本机制，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与匹配的对照组相比，患有BPD的老年人的大脑GSH水平是否发生了变化。第二个目的是确定补充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，BPD患者的GSH水平将低于健康对照组，补充NAC将提高脑GSH水平，减轻BPD老年患者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.