Depression Is Likely Not Caused By A Chemical Imbalance In The Brain, New Study Finds

A comprehensive review of the research on serotonin and depression has revealed the mental health condition is likely not caused by a chemical imbalance.

The theory that depression is caused by an imbalance of the brain chemical called serotonin was first proposed in the 1960s, before being promoted by the pharmaceutical industry in the 1990s as it sought to market a new range of antidepressants.

It gained traction after being endorsed by official institutions such as the American Psychiatric Association, but the authors of the report published in Nature have noted there has not previously been a comprehensive review of the research which could offer firm conclusions on whether the theory is really true.

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In a bid to determine whether an imbalance of serotonin does contribute to depression, the researchers identified and collated existing overviews of evidence from the main areas of research into the topic and found the evidence does not support the 'chemical imbalance' theory.

One area of research included in the study compared levels of serotonin and its breakdown products in the blood or brain fluid, and found no difference between people with depression and those without depression.

Another area focused on serotonin receptors; the proteins which serotonin links up with and which can transmit or inhibit the effects of the chemical.

Research looking into the most commonly investigated serotonin receptor revealed one of two things: either there was no difference between people with and without depression, or serotonin activity was actually increased in people with depression - ultimately proving the exact opposite of the serotonin theory’s prediction.

This research is important because many people take antidepressants because they have been told they have a chemical imbalance. It may be difficult news, but people deserve to know there is no evidence to support this idea

— Dr Joanna Moncrieff (@joannamoncrieff) July 20, 2022

One famous study early on found a relationship between stressful life events and the serotonin transporter gene, which can make the protein which helps to terminate the effect of serotonin, but larger studies indicated no relationship actually exists.

Some of the studies the researchers looked at included people who had experience with antidepressants and revealed evidence the treatment may actually lower the concentration or activity of serotonin. As a result, the authors noted that their research not only suggests the serotonin theory for depression not supported by evidence, but calls into question the basis for the use of antidepressants.

Commenting on the research in IFL Science, authors Joanna Moncrieff and Mark Horowitz, explained: "It is important that people know that the idea that depression results from a 'chemical imbalance' is hypothetical. And we do not understand what temporarily elevating serotonin or other biochemical changes produced by antidepressants do to the brain."

We also found evidence from some studies that suggested long-term antidepressant use may even lower serotonin levels/activity. This underlines how we do not know what antidepressants are doing to the brain, esp in long-term, and should be more wary of prescribing them

— Dr Joanna Moncrieff (@joannamoncrieff) July 20, 2022

The authors concluded that it is impossible to say whether taking antidepressants known as selective serotonin-reuptake inhibitors is worthwhile in treating depression, or 'even completely safe'.

"People need all this information to make informed decisions about whether or not to take antidepressants," the authors concluded.

If you're experiencing distressing thoughts and feelings, the Campaign Against Living Miserably (CALM) is there to support you. They're open from 5pm–midnight, 365 days a year. Their national number is 0800 58 58 58 and they also have a webchat service if you're not comfortable talking on the phone 

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