Do low serotonin levels cause depression?

Do low serotonin levels cause depression?
© iStock/stefanamer

Are low serotonin levels a cause of depression? There is no clear evidence that serotonin levels impact the risk of depression.

University College London (UCL) performed a major review of prior meta-analyses and systematic reviews surrounding low serotonin levels and depression. The researchers suggest that it is unlikely that a chemical imbalance causes depression, and their findings question the role of antidepressants.

Most antidepressants are selective serotonin reuptake inhibitors (SSRIs), originally marketed as correcting low serotonin levels. Currently, there is no other accepted pharmacological mechanism by which antidepressants affect the symptoms of depression.

The review is published in Molecular Psychiatry.

Reviewing low serotonin levels and depression studies

The researchers set out to analyse relevant studies about serotonin and depression. The review involved thousands of participants.

Research has shown that levels of serotonin and its breakdown products in the blood or brain fluids did not influence the number of people diagnosed with depression and healthy control participants.

Furthermore, in studies on serotonin receptors and the serotonin transporter, which is the protein targeted by most antidepressants, the researchers found weak and inconsistent evidence suggestive of high levels of serotonin activity in people with depression. However, the researchers said these findings are potentially explained by antidepressant use in people diagnosed with depression since such effects were not reliably ruled out.

The authors analysed studies where serotonin levels were artificially lowered by depriving the participant’s diet of the amino acid required to create serotonin. These studies have claimed that low serotonin levels are linked to depression. Another meta-analysis conducted in 2007 and some recent studies found that lowering serotonin using this method did not produce depression in hundreds of healthy volunteers. There was weak evidence in a small subgroup of people with a family history of depression, but this only involved 75 participants.

Large studies involving thousands of participants looked at gene variation, including the gene for the serotonin transporter. They found no difference in these genes between people with depression and healthy controls. These studies analysed stressful life events, which subsequently increased the risk of people becoming depressed – the more stressful a life event is, this caused higher levels of depression. One famous early study discovered a relationship between stressful events, the type of serotonin transporter gene a person had and the chance of depression. However, more comprehensive studies suggest this was a false finding.

No link between serotonin activity and depression

After reviewing relevant studies, the UCL researchers conclude that there is “no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.”

The researchers noted that their findings are crucial as studies have indicated that 85-90% of the public believe that depression is caused by low serotonin or a chemical imbalance. Several scientists are seeing that a chemical imbalance is an over-simplification. The chemical imbalance theory also can affect the likelihood of recovery and mood management without medical intervention for patients with depression.

The researchers found evidence from a large meta-analysis that people using antidepressants had low levels of serotonin in their blood. They concluded that this partly supports the possibility that long-term antidepressant use reduces serotonin levels. The researchers say this may imply that the increase in serotonin that some antidepressants produce in the short term could lead to compensatory changes in the brain that produce the opposite effect in the long-term. However, the study did not analyse the efficacy of antidepressants, and the researchers support further research into treatments that focus on managing stressful and traumatic life events without medical intervention.

Professor Moncrieff said: “Our view is that patients should not be told that depression is caused by low serotonin or by a chemical imbalance, and they should not be led to believe that antidepressants work by targeting these unproven abnormalities. We do not understand what antidepressants are doing to the brain exactly and giving people this sort of misinformation prevents them from making an informed decision about whether to take antidepressants or not.”




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