The serotonin theory of depression : a systematic umbrella review of the evidence

Moncrieff, Joanna; Cooper, Ruth E.; Stockmann, Tom; Amendola, Simone; Hengartner, Michael Pascal; Horowitz, Mark A.

doi:10.1038/s41380-022-01661-0

Please use this identifier to cite or link to this item: https://doi.org/10.21256/zhaw-25367

Full metadata record

DC Field	Value	Language
dc.contributor.author	Moncrieff, Joanna	-
dc.contributor.author	Cooper, Ruth E.	-
dc.contributor.author	Stockmann, Tom	-
dc.contributor.author	Amendola, Simone	-
dc.contributor.author	Hengartner, Michael Pascal	-
dc.contributor.author	Horowitz, Mark A.	-
dc.date.accessioned	2022-07-27T09:28:20Z	-
dc.date.available	2022-07-27T09:28:20Z	-
dc.date.issued	2022-07-20	-
dc.identifier.issn	1359-4184	de_CH
dc.identifier.issn	1476-5578	de_CH
dc.identifier.uri	https://digitalcollection.zhaw.ch/handle/11475/25367	-
dc.description.abstract	The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT1A receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT geneenvironment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use (n = 1869). Two meta analyses of overlapping studies examining the 5-HT1A receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers (n = 566), but weak evidence of an effect in those with a family history of depression (n = 75). Another systematic review (n = 342) and a sample of ten subsequent studies (n = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study (n = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.	de_CH
dc.language.iso	en	de_CH
dc.publisher	Nature Publishing Group	de_CH
dc.relation.ispartof	Molecular Psychiatry	de_CH
dc.rights	http://creativecommons.org/licenses/by/4.0/	de_CH
dc.subject	Depression	de_CH
dc.subject	Serotonin	de_CH
dc.subject	Systematic review	de_CH
dc.subject	Psychiatry	de_CH
dc.subject.ddc	616.8: Neurologie und Krankheiten des Nervensystems	de_CH
dc.title	The serotonin theory of depression : a systematic umbrella review of the evidence	de_CH
dc.type	Beitrag in wissenschaftlicher Zeitschrift	de_CH
dcterms.type	Text	de_CH
zhaw.departement	Angewandte Psychologie	de_CH
zhaw.organisationalunit	Psychologisches Institut (PI)	de_CH
dc.identifier.doi	10.1038/s41380-022-01661-0	de_CH
dc.identifier.doi	10.21256/zhaw-25367	-
zhaw.funding.eu	No	de_CH
zhaw.issue	8	de_CH
zhaw.originated.zhaw	Yes	de_CH
zhaw.pages.end	3256	de_CH
zhaw.pages.start	3243	de_CH
zhaw.publication.status	publishedVersion	de_CH
zhaw.volume	28	de_CH
zhaw.publication.review	Peer review (Publikation)	de_CH
zhaw.webfeed	Klinische Psychologie	de_CH
zhaw.author.additional	No	de_CH
zhaw.display.portrait	Yes	de_CH
Appears in collections:	Publikationen Angewandte Psychologie

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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, 28(8), 3243–3256. https://doi.org/10.1038/s41380-022-01661-0

Moncrieff, J. et al. (2022) ‘The serotonin theory of depression : a systematic umbrella review of the evidence’, Molecular Psychiatry, 28(8), pp. 3243–3256. Available at: https://doi.org/10.1038/s41380-022-01661-0.

J. Moncrieff, R. E. Cooper, T. Stockmann, S. Amendola, M. P. Hengartner, and M. A. Horowitz, “The serotonin theory of depression : a systematic umbrella review of the evidence,” Molecular Psychiatry, vol. 28, no. 8, pp. 3243–3256, Jul. 2022, doi: 10.1038/s41380-022-01661-0.

MONCRIEFF, Joanna, Ruth E. COOPER, Tom STOCKMANN, Simone AMENDOLA, Michael Pascal HENGARTNER und Mark A. HOROWITZ, 2022. The serotonin theory of depression : a systematic umbrella review of the evidence. Molecular Psychiatry. 20 Juli 2022. Bd. 28, Nr. 8, S. 3243–3256. DOI 10.1038/s41380-022-01661-0

Moncrieff, Joanna, Ruth E. Cooper, Tom Stockmann, Simone Amendola, Michael Pascal Hengartner, and Mark A. Horowitz. 2022. “The Serotonin Theory of Depression : A Systematic Umbrella Review of the Evidence.” Molecular Psychiatry 28 (8): 3243–56. https://doi.org/10.1038/s41380-022-01661-0.

Moncrieff, Joanna, et al. “The Serotonin Theory of Depression : A Systematic Umbrella Review of the Evidence.” Molecular Psychiatry, vol. 28, no. 8, July 2022, pp. 3243–56, https://doi.org/10.1038/s41380-022-01661-0.