Story at a glance

• Researchers from University College London conducted an umbrella review of past meta-studies and systematic analyses of depression’s relationship to serotonin.

• For years, a chemical imbalance of serotonin has been widely viewed as the culprit for depression, resulting in the widespread use of antidepressants.

• The study published this week in the journal Molecular Psychiatry concluded that there’s “no clear evidence” that serotonin levels or serotonin activity is responsible for depression.

A recent review study is pushing back against long-held views in medicine that depression is caused by a serotonin imbalance in the brain.

Researchers from University College London conducted an umbrella review of past meta-studies and systematic analyses of depression’s relationship to serotonin activity that included tens of thousands of participants.

The study published this week in the journal Molecular Psychiatry concluded that there’s “no clear evidence” that serotonin levels or serotonin activity is responsible for depression.

Serotonin is a neurotransmitter that plays a key role in governing mood, sleep, digestion and other body functions. For years, a chemical imbalance of serotonin has been widely viewed as the culprit for depression, resulting in the widespread use of antidepressants like selective serotonin reuptake inhibitors (SSRIs), which boosts serotonin in the brain.

Researchers say the review calls into question the basis for the use of antidepressants.

“It is always difficult to prove a negative, but I think we can safely say that after a vast amount of research conducted over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities, particularly by lower levels or reduced activity of serotonin,” professor Joanna Moncrieff, the study’s lead author, said in a statement.

“Many people take antidepressants because they have been led to believe their depression has a biochemical cause, but this new research suggests this belief is not grounded in evidence.”

Studies analyzed in the review include research comparing levels of serotonin and its breakdown products in the blood or brain fluids, which did not find any significant difference between those diagnosed with depression and healthy participants.

Researchers also looked at studies where serotonin levels were artificially lowered in hundreds of participants by omitting the amino acid required to make serotonin from their diets. The review found lowering serotonin artificially did not produce depression in the study volunteers.

Separate research involved examining gene variation, including gene variation of the serotonin transporter, which is a protein targeted by antidepressants, and found no difference in the genes between people with depression and healthy controls. Other studies examined in the review found the more stressful life events a person experienced, the more likely they were to be depressed.

Mitch Prinstein, chief science officer for the American Psychological Association, said in a statement to Changing America the review’s findings emphasize why it’s critical to advance research to develop and test a variety of personalized psychological treatments.