Abstract
Introduction: The human brain is a highly oxygen-dependent organ. Low environmental oxygen availability (e.g., hypobaric hypoxia at altitude) is a major challenge to the brain and numerous endogenous cellular and systemic hypoxia responses therefore are in place to mitigate hypoxic stress. When the dose of the hypoxic stress surpasses the adaptive capabilities of the brain, cerebral forms of high-altitude illnesses can develop, the prevalence of which increases with the altitude. Hypoxia can also trigger psychotic symptoms. Despite that, the effects of altitude exposures on people with pre-existing mental disorders are surprisingly scarcely investigated. Methods: In this narrative review we summarize the literature on the brain’s responses to hypoxia and put them in the context of somatic high-altitude illnesses and mental consequences of altitude exposure from an interdisciplinary perspective. Results: We identify knowledge gaps with high clinical relevance related to the safety of altitude exposures, particularly for individuals with mental disorders. Conclusions: Taken together, research into the vulnerability of people with neuropsychiatric disorders and the risk of developing mental symptoms in different populations (diseased, healthy, athletes) at altitude is urgently needed to provide appropriate evidence-based counselling and treatment.