Brain Chemistry and Altitude in Bipolar Disorder

描述（由申请人提供）： 双相情感障碍是一种流行的严重精神疾病，其特征是抑郁和躁狂交替发作。在退伍军人事务部（VA），2004年有近80，000名退伍军人接受了双相情感障碍的治疗，比1999年增加了40%。双相情感障碍对退伍军人造成了巨大的医疗负担，并且与VA系统中任何精神疾病的最高医疗保健费用相关。此外，在男性退伍军人中，双相情感障碍是自杀的重要危险因素。 世界卫生组织将双相情感障碍列为全球医疗残疾的第六大原因。尽管进行了数十年的研究，但对这种疾病的了解仍然很少，并且没有新的治疗方法可以超过锂对大多数患者的有效性。有一个关键的需要研究旨在了解双相情感障碍的神经生物学，以改善我们的诊断和治疗策略。 大脑pH值与情感功能密切相关，并受到一系列内部和外部因素的影响。一个这样的环境因素可以是海拔。极端海拔与吸入氧分压降低有关，这种低压缺氧导致严重的认知障碍。然而，海拔高度的适度变化对大脑化学的影响还没有得到很好的理解。最近的出版物显示，在美国，海拔高度与自杀率的增加有关，这种自杀率从大约2,000英尺的适度海拔高度开始，这种影响在双相情感障碍中可能最强。在内源性因素方面，假设双相情感障碍的脑pH值降低可能代表疾病的生物学特征。在双相情感障碍中，脑pH值降低与脑乳酸盐和谷氨酸盐水平的改变有关。需要研究来澄清双相情感障碍患者的情绪、脑化学和海拔高度之间的关系。 为了满足这一需求，我们建议使用磁共振波谱（MRS）神经成像与临床评估，研究脑pH值，谷氨酸，乳酸和海拔高度的退伍军人与双相情感障碍之间的关系。该提案采用了一种新颖的横断面研究设计，在两个海拔高度对双相情感障碍受试者进行脑部扫描：湖城（4,700英尺）和马萨诸塞州贝尔蒙特（44英尺）。共将入组120例受试者，包括40例抑郁双相情感障碍受试者（每个研究中心20例）、40例情感正常双相情感障碍受试者（每个研究中心20例）和40例健康对照受试者（每个研究中心20例）。所有受试者将接受MRS脑部扫描，以测量其脑部pH值、谷氨酸盐和乳酸盐水平。 这项研究将为双极障碍患者的脑化学、情绪状态和海拔高度之间的相互关系提供深入的了解。这项研究的结果可能有助于科学家开发新的诊断方法，或为患有双相情感障碍的退伍军人开发新的治疗方法。

DESCRIPTION (provided by applicant): Bipolar disorder is a prevalent and severe psychiatric disorder marked by alternating episodes of depression and mania. In the Department of Veterans Affairs (VA), nearly 80,000 Veterans received care for bipolar disorder in 2004, a 40% increase from 1999. Bipolar disorder imposes a substantial medical burden on Veterans, and is associated with the highest health care costs of any psychiatric disorder in the VA system. Moreover, in male Veterans bipolar disorder is a significant risk factor for suicide. The World Health Organization ranks bipolar disorder as the sixth leading cause of global medical disability. Despite decades of research, the illness remains poorly understood, and no new treatment has surpassed lithium's effectiveness for the majority of patients. There is a critical need for research studies aimed at understanding the neurobiology of bipolar disorder, to improve our diagnostic and treatment strategies. Brain pH is closely linked to affective functioning, and is influenced by a range of internal and external factors. One such environmental factor may be altitude. Extreme altitudes are associated with a decreased partial pressure of inspired oxygen, and this hypobaric hypoxia results in significant cognitive impairment. However, the effect of moderate changes in altitude on brain chemistry is not well understood. Recent publications show that within the U.S., altitude is associated with an increased rate of suicide that begins at the modest altitude of ~2,000 feet, an effect that may be strongest in bipolar disorder. In terms of endogenous factors, it is hypothesized that decreased brain pH in bipolar disorder may represent a biologic trait of the illness. Decreased brain pH has been linked to altered brain lactate and glutamate levels in bipolar disorder. Research is needed to clarify the relationship between mood, brain chemistry and altitude in bipolar disorder. To address this need, we propose to use magnetic resonance spectroscopy (MRS) neuroimaging together with clinical assessments, to study the relationship between brain pH, glutamate, lactate and altitude in Veterans with bipolar disorder. The proposal features a novel cross-sectional study design, in which brain scans will be performed on subjects with bipolar disorder at two altitudes: Salt Lake City, UT (4,700 feet) and Belmont, MA (44 feet). A total of 120 subjects will be enrolled, including 40 depressed bipolar subjects (20 per site), 40 euthymic bipolar subjects (20 per site), and 40 healthy controls (20 per site). All subjects will undergo MRS brain scans to measure their brain pH, glutamate and lactate levels. The proposed study will provide insight into the interrelationship of brain chemistry, mood state and altitude in bipoar disorder. The results of the study may help scientists develop new diagnostic methods, or new treatment approaches for Veterans with bipolar disorder.