Brain Bioenergetic Response to Hypoxic Stress in Bipolar Disorder

双相情感障碍(BD)是一种复发率高的慢性精神疾病。BD是一种高度流行的精神疾病 紊乱，尤指退伍军人。退伍军人事务部(VA)医疗系统中的13万多名退伍军人 一直在寻求BD的治疗。患有BD的人的生活质量可能会下降 由于这种疾病所表现出的症状的特点。自杀是一个主要的担忧 在退伍军人管理局的医疗系统中，患有BD的退伍军人自杀的风险很高。 尽管BD的流行和广泛的研究努力，其病理生理学仍然 复杂而晦涩难懂。尽管已经开发出各种治疗方式，但约有三分之一的 BD患者对治疗的反应不充分。存在着弥合的迫切需要 BD的神经生物学机制与临床表现之间的差距。过去的研究表明 磁共振波谱(MRS)在BD患者中是了解更多信息的有效方法 BD的本质。 由神经元线粒体功能障碍引起的氧化应激被认为是一个潜在的原因 基于大量先前研究的BD。此外，据报道，氧化应激可能是 高原低压缺氧加重。这可能会导致BD的自杀率增加到2000以上 根据最近的几份出版物，脚的高度。此外，还有动物研究支持 海拔高度对BD的影响暴露在模拟低压缺氧下的大鼠显示出类似于 在BD患者中可以看到，除了表现出更多的抑郁行为外。 在我们最近的研究中，我们发现居住在中等海拔地区的受试者的大脑化学成分有所不同 与生活在低海拔(海平面)的人相比，我们发现在生物能量方面没有区别 BD受试者与健康对照组之间的代谢产物。在这项拟议的研究中，我们将比较差异 关于患有BD的退伍军人与健康对照组相比，他们的大脑如何弥补大脑中 使用MRS技术耐受低氧条件下的能量。计划的科目总数为88个 招募：44名患有BD的退伍军人和44名健康对照。所有受试者都将接受MRS脑部扫描 测量呼吸中16%和25%的脑生物能(磷酸肌酸和三磷酸腺苷水平) 氧浓度(分别等于10,000英尺和海平面上的氧)。 据推测，应对因缺氧而导致的能源生产减少的时间可能会更少 相对于健康对照组，BD受试者的有效率。当前建议的预期结果 这项研究将阐明BD的氧化应激，并建议BD的新治疗靶点。

Bipolar disorder (BD) is a chronic mental illness with high rates of relapse. BD is a highly prevalent psychiatric disorder, especially in veterans. More than 130,000 veterans in the Veterans Affairs (VA) healthcare system have been seeking treatment for BD. Individuals suffering with BD are likely to have diminished quality of life due to characteristics of symptoms which manifest as a result of the disorder. Suicide is a major concern within the VA healthcare system, and veterans suffering with BD are at high risk for committing suicide. Despite the prevalence of BD and widespread research efforts, its pathophysiology remains complicated and obscure. Although various therapeutic modalities have been developed, about one third of BD patients have demonstrated an inadequate response to treatment. There exists a critical need to bridge the gap between neurobiological mechanisms and clinical manifestations of BD. Past research has shown magnetic resonance spectroscopy (MRS) in patients with BD to be an effective approach to learn more about the nature of BD. Oxidative stress induced by neuronal mitochondrial dysfunction has been implicated as a potent cause of BD based on ample prior research. Moreover, it has been reported that oxidative stress could be aggravated by hypobaric hypoxia at altitude. This may result in an increased suicide rate in BD above 2,000 feet altitude according to several recent publications. Additionally, there are animal studies supporting altitude’s effects on BD. Rats exposed to simulated hypobaric hypoxia exhibited brain chemistry similar to that seen in individuals with BD, in addition to demonstrating increased depressive behavior. In our recent study, we found a difference in the brain chemistry of subjects living in moderate altitude compared to those living at low altitude (sea level); however, we found no difference in bioenergetic metabolites between BD subjects and healthy controls. In this proposed study, we will compare the difference in how veterans with BD compare to healthy controls in how their brains compensate for the shortage of energy enduring hypoxic conditions using MRS techniques. A total number of 88 subjects are planned for recruitment: 44 veterans with BD and 44 healthy controls. All subjects will undergo MRS brain scans to measure brain bioenergetics (phosphocreatine and adenosine triphosphates levels) in breathing 16% and 25% oxygen concentrations (equal to oxygen at 10,000 feet and sea level, respectively). It is hypothesized that coping with decreased energy production as a result of hypoxia may be less efficient in the subjects with BD, relative to healthy controls. The anticipated results of the current proposed study will elucidate the oxidative stress in BD and suggest new therapeutic targets for BD.