A systematic umbrella review, reported in the journal Nature, has challenged the long-held idea that low or inactive levels of serotonin are responsible for depression.

The research - The serotonin theory of depression: a systematic umbrella review of the evidence - reviewed existing research to examine the evidence on the relationship between serotonin levels and depression. Included in the review were studies on:

• Serotonin receptors and transporters in the brain in people with and without depression
• Concentrations of serotonin in the blood in people with and without depression
• The artificial lowering of serotonin to see if it would provoke depression
• Genetics: studies involving tens of thousands of participants (with and without depression) looking for any differences in gene instructions for serotonin transporters.

The researchers concluded:

The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.

An excellent commentary by two of the researchers can be found at The Conversation - Depression is probably not caused by a chemical imbalance in the brain – new study