No Evidence Low Serotonin Causes Depression?

There is no convincing evidence that low serotonin levels are the primary cause of depression

Red Flags that You May Be Slipping Back into Depression- Photo: thedawnrehab.com

This is the conclusion of an “exhaustive” review by UK investigators, which upends the widely held belief that depression is the result of lower levels, or reduced activity, of the chemical. Researchers say the results call antidepressant use into question.

“We found no consistent evidence in the main avenues of serotonin research that there is an association between serotonin and depression, and we found no support for the hypothesis that lower serotonin activity or concentrations are responsible for depression,” senior author Mark Horowitz, GDPsych, MBBS (Hons), Ph.D., of the Division of Psychiatry, University College London, UK, told Medscape Medical News.

“It’s not an evidence-based statement to say that depression is caused by low serotonin; if we were more honest and transparent with patients, we should tell them that an antidepressant might have some use in numbing their symptoms, but it’s extremely unlikely that it will be the solution or cure for their problem,” he said.

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The study was published online on July 20 in Molecular Psychiatry.

Amplified by Industry

The theory that low serotonin levels may be the cause of depression was first proposed in the 1960s, but the investigators note that it was only one of several hypotheses. Nevertheless, the report, caught on and has been “influential for decades and provides an important justification for the use of antidepressants.”

The authors add that with the advent of selective reuptake inhibitors in the 1990s, the serotonin hypothesis was widely publicized. Recent surveys show that 80% or more of the public now believe this theory.

“Most people think that depression is caused by a ‘chemical imbalance’ in their brains or by low serotonin, and this is what many doctors tell patients who are depressed,” Horowitz said.

“It has been known in academic circles that no good evidence has ever been found of low serotonin in depression, but drug company marketing has amplified the ‘chemical imbalance’ and low serotonin hypotheses,” he continued.

Settling the Question

Horowitz and colleagues “wanted to settle this question” by conducting a comprehensive systematic umbrella review of all studies through December 2020 as to whether low serotonin levels are associated with depression. They investigated the following six hypotheses:

  • Lower levels of serotonin and its metabolite 5-HIAA are found in body fluids of people with depression.
  • Altered serotonin receptor levels occur in people with depression.
  • Higher levels of SERT occur in people with depression.
  • The induction of depression occurs through tryptophan depletion (which lowers available serotonin).
  • Higher levels of the SERT gene occur in people with depression.
  • There is an interaction between the SERT gene and stress in people with depression.

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