Brain Bioenergetic Response to Hypoxic Stress in Bipolar Disorder

点击翻译按钮获取中文摘要

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.