Please use this identifier to cite or link to this item: https://doi.org/10.21256/zhaw-25367
Publication type: Article in scientific journal
Type of review: Peer review (publication)
Title: The serotonin theory of depression : a systematic umbrella review of the evidence
Authors: Moncrieff, Joanna
Cooper, Ruth E.
Stockmann, Tom
Amendola, Simone
Hengartner, Michael Pascal
Horowitz, Mark A.
et. al: No
DOI: 10.1038/s41380-022-01661-0
10.21256/zhaw-25367
Published in: Molecular Psychiatry
Volume(Issue): 28
Issue: 8
Page(s): 3243
Pages to: 3256
Issue Date: 20-Jul-2022
Publisher / Ed. Institution: Nature Publishing Group
ISSN: 1359-4184
1476-5578
Language: English
Subjects: Depression; Serotonin; Systematic review; Psychiatry
Subject (DDC): 616.8: Neurology, diseases of nervous system
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.
URI: https://digitalcollection.zhaw.ch/handle/11475/25367
Fulltext version: Published version
License (according to publishing contract): CC BY 4.0: Attribution 4.0 International
Departement: Applied Psychology
Organisational Unit: Psychological Institute (PI)
Appears in collections:Publikationen Angewandte Psychologie

Files in This Item:
File Description SizeFormat 
2022_Moncrieff-etal_Serotonin-theory-depression-systematical-review.pdf634.17 kBAdobe PDFThumbnail
View/Open
Show full item record
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.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.