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For more than half a century, major depressive disorder (MDD) has largely been interpreted through a neurochemical lens. The prevailing framework focused on deficiencies or imbalances in serotonin, norepinephrine, and dopamine, leading to generations of therapies designed to modulate synaptic signaling. While these approaches improved outcomes for many patients, they have not fundamentally solved the problem of durable remission. A significant proportion of patients remain treatment resistant, and relapse rates continue to challenge long-term disease management.
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