Adaptive hematological profiles and brain structure buffer depression in high-altitude healthy adults

The chronic hypoxic environment at high altitude promotes compensatory changes in the hematological system and may influence depression. However, it remains unclear how hematological compensation affects depression through brain structural mechanisms. In this study, we performed structural magnetic resonance imaging (MRI) on 129 healthy adult participants who had resided at high altitude for an extended period, and collected their routine blood test data along with depression subscale scores from the Symptom Checklist-90 (SCL-90). Cluster analysis based on red blood cell count (RBC), hemoglobin (HGB), and hematocrit (HCT) divided participants into three groups, reflecting varying levels of hematological compensation. Analysis of variance revealed significant group differences in right insula volume (F(2, 126) = 18.42, p < 0.001, partial η² = 0.24) and depression scores (F(2, 126) = 3.37, p = 0.038, partial η² = 0.05). Individuals with higher hematological compensation exhibited significantly larger right insula volumes and lower depression scores. Further mediation analysis revealed a significant indirect effect of hematological compensation on depression via right insula volume. The relative indirect effects were statistically significant (X1: Effect = -0.10, 95 % CI [-0.323, -0.007]; X2: Effect = -0.31, 95 % CI [-0.668, -0.048]). These results suggest that hematological compensation may reduce depression by increasing the volume of right insula. The findings indicate that the right insula may serve as a neural pathway linking physiological adaptation and emotional states, contributing to mental health regulation under chronic hypoxic conditions.