Chronic Hypoxia Exposure Worsens Depression

University of Utah Health investigator Perry Renshaw, MD, PhD, and colleagues combine epidemiology, animal models, and human neuroimaging to study how impaired brain bioenergetics affect psychiatric disorders. They first reported a link between altitude and suicide in the U.S., a finding since replicated in three other continents. People living at high altitude are exposed to hypobaric hypoxia, and the partial pressure of oxygen in arterial blood is reduced in people at 4,500ft (Salt Lake City, UT) compared to sea level. Both Hypobaric hypoxia and chronic hypoxic conditions such as pulmonary, cardiovascular, and sleep disorders and smoking are linked to depression. Preclinical studies found that hypobaric hypoxia disrupts brain serotonin and bioenergetic systems, with women being particularly vulnerable. Using magnetic resonance imaging, researchers also found that, compared to sea level, humans at 4,500 feet exhibit deficits in creatine, a high energy neurometabolite. The Renshaw Lab subsequently conducted animal and human studies and observed that targeted creatine supplementation improved brain bioenergetics and reduced depressive symptoms. Future goals aim to define the mechanisms by which hypobaric hypoxia promotes depression and suicide risk, and to test new treatment strategies.