“Depression is a chemical imbalance of Serotonin in the brain!” Debunked. Audio lay summary.

Medicine and Health Sciences: Psychiatry

So, is depression really a ‘chemical imbalance’ in the brain? Well, if you’ve spent any time in North America watching television commercial breaks where certain drugs are hailed to sort depressive symptoms out (you know the adverts where there’s a pretty convincing graphic or animation of our brain chemistry like the one shown here, and an accelerated voice at the end telling you about the vast range of possible unpleasant side effects), you could be forgiven for thinking so. Did you know that this idea has been hotly contested for many years by psychologists and psychiatrists alike? And more recently in 2022 Joanna Moncrieff, a critical psychiatrist from the Division of Psychiatry at University College London in the UK and her colleagues pulled together a lot of scientific data to see if this is actually the case.

The serotonin ‘theory’ (or idea if you like) of depression says that low levels of serotonin are a key cause of depression. Serotonin is a chemical that helps communicate messages between the cells of the brain and throughout the entire body. For many years, the serotonin theory has been influential in the scientific community in guiding the development a group of antidepressants called Selective Serotonin Reuptake Inhibitors (or SSRIs), where an astounding 8.3 million people with symptoms of depression in 2021-22 were prescribed SSRIs usually by their GPs – so, arguably big business for pharmaceutical companies! However, this popularised theory has now been called into question by Joanna and her colleagues who did a systematic ‘umbrella’ or meta-review (so this a review that included a whopping 12 systematic reviews with meta-analyses and 5 other reviews of data from several human studies to see what they say about this theory overall). A systematic review in a nutshell includes a lot of studies and pools their data to look at particular a topic of interest to get a sense of the overall picture. For more information about ‘systematic reviews with meta-analyses’ why not check out our ‘Glossary’ section below?

Joanna and her team did a decent job of searching several respected scientific databases and were interested in a range of serotonin-based studies (for these check out the original paper below), including, for example, measures of serotonin concentration in people’s bodily fluids, brain imaging and post-mortem (after death) studies, to say but a few. They also looked into the relationship between people’s genes and what they’ve experienced throughout their life to work out just how important this ancient molecule actually is.

To cut a long story of careful data collection and analysis short (apologies Joanna!), the results of the study revealed that the data supporting the serotonin theory of depression is limited and pretty inconsistent at best. They found that most studies show the relationship between serotonin levels and depression are generally quite small and unremarkable, and results tend to be mixed. Not only that, Joanna and her team also found that studies looking into people’s serotonin levels after taking SSRI medications have also showed mixed results, where it looks as though for some studies they do boost serotonin levels, but then others they don’t.

Perhaps unsurprisingly, the authors suggest that the serotonin theory has mostly been overstated, and probably to no one’s complete surprise that other social and psychological circumstances are likely to play a much bigger role in depression. Rather than completely throwing the metaphorical ‘biological baby out with the bathwater’ though, they also point out that there are other theories that might explain the biology bit better, including the inflammation theory of depression, which in a nutshell suggests our immune system, if firing much of the time, may contribute to depression.

It’s probably fair to say that this umbrella review was made up of many other individual reviews including quite a lot of low-quality studies that have their own problems in terms of the way that they were done. Joanna and her colleagues acknowledged that they also struggled to answer the question with this data because many studies had not measured other important things that might be responsible for the changes reported in depression, such as past antidepressant use.

That said despite the huge effort and number of studies looking into the serotonin hypothesis up to now, the evidence overwhelmingly seems to suggest that the support for the serotonin theory isn’t great, and that further research needs to be done to better understand if there’s a clear relationship between the amount of serotonin we have and whether we’re depressed, or not. It also invites us to think that, alongside other possible biological theories, we should perhaps be looking a bit more carefully at the social and psychological reasons for why a quarter of people here in the UK at least are struggling with depression. Given that SSRIs don’t seem to boost serotonin in people with depression, and only some people benefit from these medications, is it high time we move on to think about the topic from a completely new point of view?

“Neurotransmitters” is licensed under CC BY 4.0. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/?ref=openverse.


Title of lay summary “Depression is a chemical imbalance of Serotonin in the brain!” Debunked. Audio lay summary.
Lay Summary Author(s)

Dr Anthony Harrison

Vetting Professional Dr. Anja Harrison
Vetting Professional Affiliation(s) / participating organisation(s) 1
Science Area Subject
Key Search Words

Serotonin theory



Selective Serotonin Reuptake Inhibitors (SSRIs)

Chemical imbalance

Key Search Words for Expert Audience
What is the licence for your lay summary? Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) (for all other options selected above)
Provide the full weblink DOI of the published scientific article: https://doi.org/10.1038/s41380-022-01661-0
Title of the original peer-reviewed published article: The serotonin theory of depression: a systematic umbrella review of the evidence
Journal Name: Molecular Psychiatry
Page numbers (if applicable): 1-14
Year of publication: 2022

Joanna Moncrieff

Ruth E. Cooper

Tom Stockmann

Simone Amendola

Michael P. Hengartner

Mark A. Horowitz

Contributors and funders:

SA declares no conflicts of interest. MAH reports being co-founder of a company in April 2022, aiming to help people safely stop antidepressants in Canada. MPH reports royalties from Palgrave Macmillan, London, UK for his book published in December, 2021, called “Evidence-biased Antidepressant Prescription.” JM receives royalties for books about psychiatric drugs, reports grants from the National Institute of Health Research outside the submitted work, that she is co-chairperson of the Critical Psychiatry Network (an informal group of psychiatrists) and a board member of the unfunded organisation, the Council for Evidence-based Psychiatry. Both are unpaid positions. TS is co-chairperson of the Critical Psychiatry Network. RC is an unpaid board member of the International Institute for Psychiatric Drug Withdrawal

Original Article language: English
Article Type: Systematic review without meta-analyses
What licence permission does the original e-print have? For more information on this please see our permissions video): Attribution 4.0 International (CC BY 4.0)

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