Glymphatic System in Adolescents with Major Depressive Disorder: No Dysfunction and No Association with Poor Sleep Quality

The purpose of this study was to investigate the relationship between glymphatic function and sleep quality in adolescents with Major Depressive Disorder (MDD). Previous research has linked glymphatic dysfunction to MDD in adults, often associated with sleep disturbances, but the relationship between these factors in adolescents remains unclear. This study utilized Diffusion Tensor Imaging analysis along the perivascular space (DTI-ALPS) to assess glymphatic system function and the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep quality in adolescents. A total of 138 participants were included: 80 first-episode and medication-naive patients with MDD (total 80: 9 with mild MDD, 28 with moderate MDD, 43 with severe MDD), and 58 healthy controls. Pearson correlation analysis was performed to examine the relationship between sleep quality and glymphatic function. The results showed adolescents with MDD demonstrated poor sleep quality, whereas healthy controls exhibited normal sleep quality. However, no significant impairment in glymphatic function was observed. Furthermore, no clear correlation was found between sleep quality and glymphatic function in the adolescent MDD group. This study provides novel insights into the neurobiological mechanisms of adolescent MDD, suggesting that the glymphatic system may not contribute to its pathogenesis in the same way as in adults. However, this cross-sectional study, with its small sample size and single-center design, limits the generalizability of the findings. Future research should adopt longitudinal, multicenter, and larger-scale designs to further investigate these relationships in more depth.