Written by Jessica Helmer

March 14th, 2023

The commonly held belief that depression is caused by a chemical imbalance in the brain, specifically a lack of serotonin, has come under scrutiny in a recent review. The serotonin theory of depression, which states that depression is caused by a lack of serotonin in the brain, has been a basis for SSRI medications that aim to increase serotonin levels. However, a new review of the literature has suggested this is not the case. Moncrieff et al. (2022) took meta-analyses (research that quantitatively combines the results from multiple studies) from different areas of serotonin research to assess the support for the serotonin theory of depression and found that the results were unconvincing. Meta-analyses of studies measuring serotonin levels in cerebrospinal fluid (CSF), which is considered an effective way of measuring biomarkers, found no link between serotonin levels and depression. Meta-analyses of studies on 5-HT receptors, which inhibit the release of serotonin, so we would expect to see more activity there for people with depression, found no relationship between 5-HT activity and depression. The review continued with three more ways that the field has looked for a relationship between serotonin and depression, and for each area, the most recent, high-quality meta-analyses showed no statistically significant relationship. 

These findings are important – at least 80% of the population believes that the field has established that a lack of serotonin or other chemical imbalances are causes of depression. Confidence in the serotonin theory of depression is linked to more pessimistic views about depression and influences treatment decisions. These findings challenge the widely-held belief that depression is caused by a lack of serotonin, and highlight the need for further research in this field. 

Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2022). The serotonin theory of depression: a systematic umbrella review of the evidence. Molecular Psychiatry. https://doi.org/10.1038/s41380-022-01661-0