Depression Not Caused By Low Serotonin, New Study Finds

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.”

Research comparing levels of serotonin and its breakdown products in the blood or brain fluids was one of the studies that was analyzed for this review. The researchers did not find any significant difference in the levels of serotonin or its breakdown products between people who had been diagnosed with depression and healthy participants.

The researchers also examined previous studies in which the serotonin levels were artificially reduced in experiments involving hundreds of participants by omitting from their diets an amino acid that is necessary for the production of serotonin. According to the findings of the review, artificially lowering serotonin did not result in depression in the people who participated in the study.

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.

“This research offers analyses to summarize some well-known facts about depression. First, depression is a very heterogeneous disorder; there are many different expressions of depression that come from a wide array of causal factors and present themselves differently from person to person,” Prinstein said. “Second, there is no single treatment approach that works for everyone with depression.”

More than eight percent of Americans are affected by major depression, making it one of the most prevalent forms of mental illness in the United States.