Living High and Feeling Low: Altitude, Suicide, and Depression

Abstract

After participating in this activity, learners should be better able to:• Assess epidemiologic evidence that increased altitude of residence is linked to increased risk of depression and suicide• Evaluate strategies to address hypoxia-related depression and suicidal ideation ABSTRACT: Suicide and major depressive disorder (MDD) are complex conditions that almost certainly arise from the influences of many interrelated factors. There are significant regional variations in the rates of MDD and suicide in the United States, suggesting that sociodemographic and environmental conditions contribute. Here, we review epidemiological evidence that increases in the altitude of residence are linked to the increased risk of depression and suicide. We consider the possibility that chronic hypobaric hypoxia (low blood oxygen related to low atmospheric pressure) contributes to suicide and depression, which is suggested by animal models, short-term studies in humans, and the effects of hypoxic medical conditions on suicide and depression. We argue that hypobaric hypoxia could promote suicide and depression by altering serotonin metabolism and brain bioenergetics; both of these pathways are implicated in depression, and both are affected by hypoxia. Finally, we briefly examine treatment strategies to address hypoxia-related depression and suicidal ideation that are suggested by these findings, including creatine monohydrate and the serotonin precursors tryptophan and 5-hydroxytryptophan.

Genome-wide significant regions in 43 Utah high-risk families implicate multiple genes involved in risk for completed suicide

“…AGBL2 is an ATP/GTP binding protein implicated in brain structure and function [ 33 ]. SUCLA2 is a mitochondrial tricarboxylic acid cycle protein recently implicated in energy supply to the synapse [ 34 ], and is possibly associated with recent findings linking suicide risk and hypoxia [ 35 ]. APH1B is a transmembrane protein associated with risk of Alzheimer’s [ 36 ] and Parkinson’s [ 37 ] diseases.…”

An Ecological Study on the Spatially Varying Relationship between County-Level Suicide Rates and Altitude in the United States

“…From a biophysiological and psychological perspective, increased suicide rates could be attributed to depression and/or mood instability, related to high-altitude hypoxia [ 33 , 34 , 35 ]. However, systematic physiological responses to ambient oxygen levels are extremely complicated and more research is needed to establish a robust causal link between altitude, hypoxia, mood disorder and suicide risk [ 36 , 37 ].…”

Effect of Altitude on Veteran Suicide Rates

“…Although our findings do not show that higher altitude contributes causally to suicide risk among veterans, they invite speculation about mechanisms that might connect altitude and suicide. Although the slight decrease in arterial oxygen concentration associated with living chronically at moderate elevation has not been shown to have clinical effects, it has been suggested that residing at higher altitudes may result in chronic relative hypoxia, which could in turn impact brain processes such as monoamine synthesis and bioenergetics (Brenner et al, 2011b; Fiedler et al, 2012; Kim et al, 2014b; Kious et al, 2018).…”