# Brain Bioenergetic Response to Hypoxic Stress in Bipolar Disorder

> **NIH VA I01** · VA SALT LAKE CITY HEALTHCARE SYSTEM · 2021 · —

## Abstract

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.

## Key facts

- **NIH application ID:** 9856936
- **Project number:** 5I01CX000812-07
- **Recipient organization:** VA SALT LAKE CITY HEALTHCARE SYSTEM
- **Principal Investigator:** PERRY FRANKLIN RENSHAW
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2013-07-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856936

## Citation

> US National Institutes of Health, RePORTER application 9856936, Brain Bioenergetic Response to Hypoxic Stress in Bipolar Disorder (5I01CX000812-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9856936. Licensed CC0.

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