Depression may not be linked to serotonin levels or serotonin activity, according to a major study published yesterday.
The ‘umbrella’ review of systematic reviews and meta-analyses was carried out by Professor Joanna Moncrieff of University College London, UK, and colleagues.
They looked at all published studies covering tens of thousands of participants, examining serotonin and depression.
From this analysis they conclude that levels of serotonin and its breakdown products in the blood or brain fluids showed no differences between people diagnosed with depression and comparable participants without depression.
The researchers went on to look at studies where serotonin levels were artificially lowered in hundreds of participants and found this did not lead to depression.
Large genome studies found no difference in the gene for the serotonin transporter between people with depression and those without.
However, stressful life events "exerted a strong effect on people’s risk of becoming depressed", the team found, adding "the more stressful life events a person had experienced, the more likely they were to be depressed".
Overall, the authors write in Molecular Psychiatry that there is “no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.”
Professor Moncrieff says: “It is always difficult to prove a negative, but I think we can safely say that after a vast amount of research conducted over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities, particularly by lower levels or reduced activity of serotonin.
“The popularity of the ‘chemical imbalance’ theory of depression has coincided with a huge increase in the use of antidepressants.
“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.”
Moncrieff, J. et al. The serotonin theory of depression: a systematic umbrella review of the evidence. Molecular Psychiatry 20 July 2022; doi: 10.1038/s41380-022-01661-0
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