Depression, Serotonin, and the Chemical Imbalance Story

A major umbrella review published in Molecular Psychiatry examined the serotonin theory of depression and found no consistent evidence that depression is caused by low serotonin levels or reduced serotonin activity. The review looked across several major research areas, including serotonin metabolites, serotonin receptors, serotonin transporters, tryptophan depletion, serotonin-related genes, and gene-stress interaction studies.

This does not mean depression is imaginary. It does not mean biology is irrelevant. It means the common “chemical imbalance” explanation is too narrow. Depression appears to involve a complex interaction of biology, stress, environment, psychology, trauma, sleep, behavior, and emotional regulation.

For Zero Point, this matters because the question changes. Instead of asking only, “What chemical is missing?” we ask, “What is keeping the whole system outside its workable range?” Medication may help some people reduce symptoms or stabilize enough to function, but medication alone does not automatically address the conditions that keep the system dysregulated.