A study investigated structural and functional connectivity (SC-FC) coupling in adolescents with major depressive disorder (MDD) and healthy controls. Using diffusion MRI and resting-state fMRI data, researchers found increased SC-FC coupling in the visual network, default mode network, and insula in adolescents with MDD compared to healthy controls. Subgroup analyses revealed specific alterations, such as decreased parahippocampal coupling in those with suicide attempts and increased frontal-limbic coupling in those with major life events. These findings suggest that SC-FC coupling is disrupted in MDD and may be influenced by environmental stressors and behavioral factors. The study highlights the importance of understanding these coupling patterns for better treatment options. The results emphasize the vulnerability of SC-FC coupling to external stressors and its role in shaping future-oriented behavior. The study also underscores the need for further research into the neurobiological basis of MDD and its subgroups.A study investigated structural and functional connectivity (SC-FC) coupling in adolescents with major depressive disorder (MDD) and healthy controls. Using diffusion MRI and resting-state fMRI data, researchers found increased SC-FC coupling in the visual network, default mode network, and insula in adolescents with MDD compared to healthy controls. Subgroup analyses revealed specific alterations, such as decreased parahippocampal coupling in those with suicide attempts and increased frontal-limbic coupling in those with major life events. These findings suggest that SC-FC coupling is disrupted in MDD and may be influenced by environmental stressors and behavioral factors. The study highlights the importance of understanding these coupling patterns for better treatment options. The results emphasize the vulnerability of SC-FC coupling to external stressors and its role in shaping future-oriented behavior. The study also underscores the need for further research into the neurobiological basis of MDD and its subgroups.