Brain and behavior
Exploring Associations Between Hypoxia, Serum Erythropoietin, and Cognition in Patients With Mood Disorders and Healthy Individuals
By Ørum BER, Schandorff JM, Damgaard V and 6 others.
Abstract
Purpose
Moderate repeated hypoxia (MRH) has shown neuroprotective and neuroplastic effects, partly mediated by erythropoietin (EPO) via hypoxia-inducible factors (HIFs). This study examined the effects of 3 weeks of daily 3.5-h normobaric hypoxia (12% O2) versus normoxia (20% O2) combined with cognitive training on oxygen saturation (SpO2), cerebral side effects, hematology (including EPO and brain-derived neurotrophic factor [BDNF]), and cognitive learning. We also assessed SpO2 associations with side effects, hematology, and learning outcomes, as well as potential clinical and demographic predictors of hypoxic response.
Method
Data from 84 healthy participants (HP) and 24 participants with remitted mood disorders (MD) in the ongoing ALTIBRAIN trial (NCT06121206) were analyzed. HP were randomized to MRH or normoxia (with/without cognitive training), while MD participants were randomized to MRH with cognitive training or treatment as usual. Finding: MRH reduced SpO2 (97.5% ± 1.0% to 85.9% ± 2.9%, p < 0.001), but this effect attenuated over time (p < 0.001). Side effects (e.g., dizziness and headaches) were slightly higher in MRH (p = 0.044) but declined over time (p < 0.001). Reticulocyte, hemoglobin, and thrombocyte levels increased (p ≤ 0.029), while EPO decreased (p = 0.003) and BDNF remained unchanged (p > 0.60). MRH slightly flattened cognitive learning curves (p < 0.001). MD participants experienced marginally higher side effects (p = 0.006), but overall tolerability was good.