Discussing the "chemical imbalance" theory of major depressive disorder (MDD), particularly focusing on the serotonin hypothesis, and explore alternative mechanisms and treatments. A key theme is the strong challenge to the long-standing idea that depression is caused simply by low serotonin levels, citing a major 2022 systematic review which found no convincing evidence for this etiology. Sources detail the history and development of monoamine-based antidepressant drugs, such as SSRIs and SNRIs, and note that these drugs affect neurotransmitters like serotonin and norepinephrine, though their mechanism is likely related to modulating emotional processing and promoting synaptic plasticity rather than directly fixing a simple deficit. Finally, we introduce the emerging focus on the glutamatergic system (involving compounds like ketamine) as a rapi ...