Brain Bioenergetic Response to Hypoxic Stress in Bipolar Disorder

双相情感障碍患者大脑对缺氧应激的生物能反应

• 批准号: 10291778
• 负责人: PERRY FRANKLIN RENSHAW
• 金额: --
• 依托单位: VA SALT LAKE CITY HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10291778
• 关键词: Acute; Adenosine Triphosphate; Air; Altitude; Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Animals; Area; Atmospheric Pressure; Bioenergetics; Bipolar Disorder; Blood; Boston; Brain; Brain Chemistry; Brain Diseases; Brain scan; Breathing; Buffers; Cells; Cerebrum; Characteristics; Chronic; Cities; Clinical; Cognitive; Consumption; Coupled; Creatine Kinase; Data; Development; Diabetes Mellitus; Diagnostic; Disease; Education; Exhibits; Exposure to; Functional disorder; Genetic Transcription; Glucose; Goals; Healthcare Systems; Homeostasis; Huntington Disease; Hypoxia; Hypoxia Inducible Factor; Individual; Intervention; Learning; Life; Link; Magnetic Resonance Spectroscopy; Magnetism; Measures; Mental disorders; Messenger RNA; Methods; Mission; Mitochondria; Modality; Nature; Neurons; Obesity; Oxidative Phosphorylation; Oxidative Stress; Oxygen; Parkinson Disease; Partial Pressure; Patients; Peripheral; Phosphocreatine; Phosphorus; Photic Stimulation; Prevalence; Production; Progress Reports; Proteins; Publications; Quality of life; Rattus; Reaction; Relapse; Reporting; Research; Respiration; Respiratory Chain; Scanning; Sea; Serum; Site; Sodium Chloride; Source; Spectrum Analysis; Stress; Suicide; Symptoms; System; Techniques; Testing; Therapeutic; Thinness; Transcript; Transcriptional Regulation; Traumatic Brain Injury; United States Department of Veterans Affairs; Veterans; Veterans Health Administration; Visual Cortex; Work; base; clinical center; completed suicide; coping; depressive behavior; deprivation; design; falls; foot; high risk; improved; in vivo; insight; mitochondrial dysfunction; neurobiological mechanism; new therapeutic target; novel; pressure; recruit; response; severe mental illness; side effect; stem; suicidal behavior; suicidal risk; suicide rate; treatment response; treatment-resistant depression

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.

双相情感障碍（BD）是一种慢性精神疾病，缓解率很高。 BD是一种非常普遍的精神病学 疾病，尤其是在退伍军人中。退伍军人事务（VA）医疗保健系统中有超过130,000名退伍军人 一直在寻找BD的治疗。患有BD的人可能会降低生活质量 由于症状的特征，由于疾病而表现出来。自杀是一个主要问题 在VA医疗保健系统中，患有BD的退伍军人有自杀的高风险。 尽管BD和广泛研究工作的盛行率，但其病理生理学仍然存在 尽管已经开发了各种治疗方式，但大约三分之一 BD患者表现出对治疗的反应不足。存在着桥接的迫切需要 BD的神经生物学机制和临床表现之间的差距。过去的研究表明 BD患者的磁共振光谱（MRS）是一种有效的方法，以了解更多有关有关的信息 BD的性质。 神经元线粒体功能障碍诱导的氧化应激已被暗示为潜在的原因 基于足够的先前研究的BD。此外，据报道氧化应激可能是 在高度下由低估缺氧汇总。这可能导致BD以上的自杀率提高 脚高度根据最近的几本出版物。此外，还有动物研究支持 高度对BD的影响。暴露于模拟的低氧缺氧暴露于脑化学的大鼠类似 除了证明抑郁行为增加外，还可以看到BD的个体。 在我们最近的研究中，我们发现生活在现代高度的受试者的大脑化学差异 与生活在低海拔（海平面）的人相比；但是，我们发现生物能没有差异 BD受试者和健康对照之间的代谢物。在这项拟议的研究中，我们将比较差异 在BD的退伍军人如何与健康对照相比，他们的大脑如何弥补了短缺 使用MRS技术持续的低氧条件。总共计划了88个受试者 招聘：44名具有BD的退伍军人和44位健康对照。所有受试者都会接受脑部扫描太太 测量呼吸16％和25％ 氧浓度（分别等于10,000英尺和海平面的氧）。 假设由于缺氧而应对能量产生降低的应对可能较少 相对于健康对照组，具有BD受试者的受试者有效。当前提出的预期结果 研究将阐明BD中的氧化应激，并提出BD的新治疗靶标。