SSM - Mental Health (Dec 2022)

Is the chemical imbalance an ‘urban legend’? An exploration of the status of the serotonin theory of depression in the scientific literature

  • Benjamin Ang,
  • Mark Horowitz,
  • Joanna Moncrieff

Journal volume & issue
Vol. 2
p. 100098

Abstract

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The theory that depression is caused by a serotonin abnormality or other chemical imbalance has become widely accepted by the public and is one prominent justification for the use of antidepressants. However, it has been increasingly questioned and there is little evidence it has empirical support. In response, leading psychiatrists suggested it was an ‘urban legend’ that was never taken seriously by the psychiatric profession. To interrogate these claims, we examined the coverage of the serotonin theory of depression in a sample of highly cited and influential academic literature from 1990, when the theory started to be popularized, to 2010 when these responses were articulated. We analysed 30 highly cited reviews of the aetiology of depression in general, 30 highly cited papers on depression and serotonin specifically and a sample of influential textbooks. The majority of the aetiology reviews supported the hypothesis, including some that were entirely devoted to describing research on the serotonin system, and those that reviewed the aetiology of depression more broadly. Research papers on the serotonin system in depression were highly cited and most of them strongly supported the serotonin theory. All textbooks supported the theory, at least in some sections, and devoted substantial coverage to it, although some also acknowledged it remained provisional. The findings suggest that the serotonin theory was endorsed by the professional and academic community. The theory is compared to an exhausted Kuhnian paradigm with professional equivocation about it acting as a means of defending it against encroaching criticism. The analysis suggests that, despite protestations to the contrary, the profession bears some responsibility for the propagation of a theory that has little empirical support and the mass antidepressant prescribing it has inspired.

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