alt Hacker NewsSee also: The Serotonin Theory of Depression: a Systematic Umbrella Review of the Evidence (2022). It's worth reading the introduction and results in full, but here are two important quotes (footnote markers removed):
> Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. Most studies found no evidence of reduced serotonin activity in people with depression compared to people without, and methods to reduce serotonin availability using tryptophan depletion do not consistently lower mood in volunteers. High quality, well-powered genetic studies effectively exclude an association between genotypes related to the serotonin system and depression, including a proposed interaction with stress.
> The chemical imbalance theory of depression is still put forward by professionals, and the serotonin theory, in particular, has formed the basis of a considerable research effort over the last few decades. The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities, and this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood. The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue anti-depressant medication and may discourage people from dis-continuing treatment, potentially leading to lifelong dependence on these drugs.
Replies
The conclusions in that were not universally accepted, and some critiques were rather damning:
https://www.kcl.ac.uk/news/a-response-to-the-serotonin-theor...
Personally, I both agree that SSRI antidepressants were likely overprescribed early on, and disagree with the notion that the chemical imbalance theory is unsupported. N = 1, they can absolutely work. It took a few to find one that really did, hence I am certain it is not a placebo effect.
The "chemical imbalance" theory is objectively wrong, but still useful in that it conveys the fact that mental disorders have physical causes. It's a purposeful simplification.
Thanks for the paper, it is actually quite crazy to think about when SSRI are basically the standard to treat depression.
I recently read a book about "The brain energy theory of mental illnesses"[1] which encapsulates depression and found it pretty compelling.
It seems to be a relatively new and active area of research[2], so there is hope!
[1]: https://books.google.fr/books/about/Brain_Energy.html?id=GIx... [2]: https://pubmed.ncbi.nlm.nih.gov/38183680/