Brain Chemistry and Altitude in Bipolar Disorder

双相情感障碍的脑化学和海拔

• 批准号: 8543917
• 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 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8543917
• 关键词: Acidosis; Address; Adult; Advocate; Affect; Affective; Alkalosis; Altitude; Anterior; Biological; Biological Markers; Bipolar Depression; Bipolar Disorder; Blood gas; Brain; Brain Chemistry; Brain scan; Caring; Cerebrum; Cities; Clinical; Clinical assessments; Cross-Sectional Studies; DSM-V; Data; Depressed mood; Depression and Suicide; Diagnosis; Diagnostic; Diagnostic Procedure; Disabled Persons; Discipline; Disease; Education; Effectiveness; Endogenous Factors; Energy Metabolism; Enrollment; Environmental Risk Factor; Functional disorder; Glutamates; Glutamine; Goals; Health Care Costs; Homeostasis; Human; Hyperventilation; Hypoxia; Impaired cognition; Incidence; Individual; Lead; Link; Lithium; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Major Depressive Disorder; Manic; Measurement; Measures; Medical; Mental Depression; Mental disorders; Mission; Moods; National Institute of Mental Health; Neurobiology; Occipital lobe; Oxygen; Oxygen Consumption; Partial Pressure; Patients; Phosphorus; Population; Protons; Publications; Publishing; Relative (related person); Reporting; Research; Research Design; Risk Factors; Schizophrenia; Scientist; Sea; Site; Sodium Chloride; Strategic Planning; Suicide; Symptoms; Syndrome; System; Therapeutic; Unemployment; United States Department of Veterans Affairs; Veterans; World Health Organization; base; cingulate cortex; depressive symptoms; disability; foot; frontal lobe; improved; in vivo; insight; male; meter; mitochondrial dysfunction; neuroimaging; novel; novel diagnostics; programs; public health relevance; reducing suicide; research study; suicide rate; trait; treatment response; treatment strategy; volunteer

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.

描述（由申请人提供）： 躁郁症是一种普遍且严重的精神病，以抑郁和躁狂症的交替发作为特征。在退伍军人事务部（VA）中，近80,000名退伍军人在2004年接受了双相情感障碍的护理，比1999年增加了40％。双相情感障碍对退伍军人施加了实质性的医疗负担，并且与VA系统中任何精神病的最高医疗保健费用有关。此外，在男性退伍军人中，躁郁症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个主要原因。尽管进行了数十年的研究，但这种疾病的理解仍然很少，并且没有新的治疗方法超过锂对大多数患者的有效性。旨在了解躁郁症的神经生物学的研究迫切需要研究，以改善我们的诊断和治疗策略。 脑pH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。这样的环境因素可能是高度。极端高度与受启发的氧气的局部压力降低有关，而这种低碱性缺氧导致严重的认知障碍。但是，高度变化对脑化学的影响尚不清楚。最近的出版物表明，在美国，高度与自杀率的增加有关，该自杀率始于〜2,000英尺的适度高度，这在双相情感障碍中可能最强。就内源性因素而言，假设躁郁症的脑pH降低可能代表了疾病的生物学特征。脑pH的降低与双相情感障碍中脑乳酸和谷氨酸水平的改变有关。需要进行研究以阐明双相情感障碍的情绪，大脑化学和高度之间的关系。 为了满足这一需求，我们建议使用磁共振光谱（MRS）神经影像以及临床评估，以研究患有双相情感障碍的退伍军人的脑pH，谷氨酸，乳酸和高度之间的关系。该提案采用了一种新颖的横断面研究设计，其中将对在两个高度的双相情感障碍受试者进行脑部扫描：犹他州盐湖城（4,700英尺）和马萨诸塞州的贝尔蒙特（44英尺）。总共将招募120名受试者，其中包括40名抑郁症受试者（每个位置20名），40名正常双极受试者（每个位置20个）和40个健康对照（每个位置20个）。所有受试者都将接受脑扫描太太以测量其脑pH，谷氨酸和乳酸水平。 拟议的研究将洞悉双重疾病中脑化学，情绪状态和海拔高度的相互关系。该研究的结果可能有助于科学家开发新的诊断方法，或针对双相情感障碍的退伍军人的新治疗方法。