In women with major depressive disorder, baseline prefrontal N-acetylaspartate levels and rich club hub connectivity are lower than in healthy women, indicating a neurobiological signature associated with altered brain energy metabolism and structural network organization.

Brain cells in the prefrontal area don't have enough energy to make a key molecule called N-acetylaspartate, which is needed to keep neurons healthy. Without enough energy, the wiring between the brain's most important hubs gets weaker because building and maintaining those connections requires a lot of power. This leads to both lower levels of N-acetylaspartate and less efficient communication between major brain regions.