The low-serotonin theory of depression had no solid evidence

A team at University College London reviewed decades of research across the main lines of evidence used to support that theory, including serotonin levels in blood and spinal fluid, receptor binding studies, and genetic studies of the serotonin transporter.

Across the umbrella review of multiple large meta-analyses, the researchers found no consistent evidence that depressed people have lower serotonin activity or concentration than people who are not depressed. Genetic studies looking at variants in serotonin-related genes found no reliable link to depression either.

The review does not mean antidepressants that affect serotonin cannot help some patients, since drugs can work through mechanisms other than the one originally assumed, and some patients clearly benefit from them. It does mean the simple chemical-imbalance explanation, repeated for decades in textbooks, advertising, and doctor's offices, was never well supported by the actual research behind it, a point some other researchers in the field have disputed.

The imbalance story was never proven.