A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression

Sameer Jauhar; Danilo Arnone; David S. Baldwin; Michael Bloomfield; Michael Browning; Anthony J. Cleare; Phillip Corlett; J. F. William Deakin; David Erritzoe; Cynthia Fu; Paolo Fusar-Poli; Guy M. Goodwin; Joseph Hayes; Robert Howard; Oliver D. Howes; Mario F. Juruena; Raymond W. Lam; Stephen M. Lawrie; Hamish McAllister-Williams; Steven Marwaha; David Matuskey; Robert A. McCutcheon; David J. Nutt; Carmine Pariante; Toby Pillinger; Rajiv Radhakrishnan; James Rucker; Sudhakar Selvaraj; Paul Stokes; Rachel Upthegrove; Nefize Yalin; Lakshmi Yatham; Allan H Young; Roland Zahn; Philip J. Cowen

doi:10.1038/s41380-023-02095-y

A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression

Sameer Jauhar^*, Danilo Arnone, David S. Baldwin, Michael Bloomfield, Michael Browning, Anthony J. Cleare, Phillip Corlett, J. F. William Deakin, David Erritzoe, Cynthia Fu, Paolo Fusar-Poli, Guy M. Goodwin, Joseph Hayes, Robert Howard, Oliver D. Howes, Mario F. Juruena, Raymond W. Lam, Stephen M. Lawrie, Hamish McAllister-Williams, Steven MarwahaDavid Matuskey, Robert A. McCutcheon, David J. Nutt, Carmine Pariante, Toby Pillinger, Rajiv Radhakrishnan, James Rucker, Sudhakar Selvaraj, Paul Stokes, Rachel Upthegrove, Nefize Yalin, Lakshmi Yatham, Allan H Young, Roland Zahn, Philip J. Cowen

^*Corresponding author for this work

Research output: Contribution to journal › Comment/debate › peer-review

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Abstract

A recent “umbrella” review examined various biomarkers relating to the serotonin system, and concluded there was no consistent evidence implicating serotonin in the pathophysiology of depression. We present reasons for why this conclusion is overstated, including methodological weaknesses in the review process, selective reporting of data, over-simplification, and errors in the interpretation of neuropsychopharmacological findings. We use the examples of tryptophan depletion and serotonergic molecular imaging, the two research areas most relevant to the investigation of serotonin, to illustrate this.

Original language	English
Pages (from-to)	3149-3152
Number of pages	4
Journal	Molecular Psychiatry
Volume	28
Issue number	8
Early online date	16 Jun 2023
DOIs	https://doi.org/10.1038/s41380-023-02095-y
Publication status	Published - Aug 2023

Bibliographical note

Acknowledgements:
SJ, AJC, MFJ, PS, NY, AHY and RZ acknowledge this paper represents independent research part funded by the NIHR Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. MBrowning is supported by the Oxford Health NIHR Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. ODH is funded by Medical Research Council-UK (no. MC_A656_5QD30_2135), Maudsley Charity (no. 666), and Wellcome Trust (no. 094849/Z/10/Z) grants to ODH and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of H Lundbeck A/s, the NHS/NIHR or the Department of Health. CF is supported by the Rosetrees Trust 20212104. SS has received grants/research support from NIMH R21(1R21MH119441 – 01A1), NICHD (1R21HD106779 − 01A1) and SAMHSA (FG000470-01). The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or SAMHSA. RU reports grant funding from Medical Research Council (MR/S037675/1), National Institute for Health Research: Health Technology Assessment (NIHR 127700) and speaker fees from Sunovion, Springer Heathcare and Vitaris outside the submitted work. RU holds unpaid officership with the British Association for Pharmacology- Honorary General Secretary 2021-2024 and is Deputy Editor, The British Journal of Psychiatry. PJC is funded as a Clinical Scientist by the Medical Research Council.

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Psychosis Immune Mechanism Stratified Medicine Study (PIMS)
Upthegrove, R., Wood, S., Gkoutos, G. & Barnes, N.
Medical Research Council
1/12/19 → 31/10/25
Project: Research Councils

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Jauhar, S., Arnone, D., Baldwin, D. S., Bloomfield, M., Browning, M., Cleare, A. J., Corlett, P., Deakin, J. F. W., Erritzoe, D., Fu, C., Fusar-Poli, P., Goodwin, G. M., Hayes, J., Howard, R., Howes, O. D., Juruena, M. F., Lam, R. W., Lawrie, S. M., McAllister-Williams, H., ... Cowen, P. J. (2023). A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression. Molecular Psychiatry, 28(8), 3149-3152. https://doi.org/10.1038/s41380-023-02095-y

@article{7d39709125294b4da83c0839a61879cd,

title = "A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression",

abstract = "A recent “umbrella” review examined various biomarkers relating to the serotonin system, and concluded there was no consistent evidence implicating serotonin in the pathophysiology of depression. We present reasons for why this conclusion is overstated, including methodological weaknesses in the review process, selective reporting of data, over-simplification, and errors in the interpretation of neuropsychopharmacological findings. We use the examples of tryptophan depletion and serotonergic molecular imaging, the two research areas most relevant to the investigation of serotonin, to illustrate this.",

author = "Sameer Jauhar and Danilo Arnone and Baldwin, {David S.} and Michael Bloomfield and Michael Browning and Cleare, {Anthony J.} and Phillip Corlett and Deakin, {J. F. William} and David Erritzoe and Cynthia Fu and Paolo Fusar-Poli and Goodwin, {Guy M.} and Joseph Hayes and Robert Howard and Howes, {Oliver D.} and Juruena, {Mario F.} and Lam, {Raymond W.} and Lawrie, {Stephen M.} and Hamish McAllister-Williams and Steven Marwaha and David Matuskey and McCutcheon, {Robert A.} and Nutt, {David J.} and Carmine Pariante and Toby Pillinger and Rajiv Radhakrishnan and James Rucker and Sudhakar Selvaraj and Paul Stokes and Rachel Upthegrove and Nefize Yalin and Lakshmi Yatham and Young, {Allan H} and Roland Zahn and Cowen, {Philip J.}",

note = "Acknowledgements: SJ, AJC, MFJ, PS, NY, AHY and RZ acknowledge this paper represents independent research part funded by the NIHR Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. MBrowning is supported by the Oxford Health NIHR Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. ODH is funded by Medical Research Council-UK (no. MC_A656_5QD30_2135), Maudsley Charity (no. 666), and Wellcome Trust (no. 094849/Z/10/Z) grants to ODH and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the author(s) and not necessarily those of H Lundbeck A/s, the NHS/NIHR or the Department of Health. CF is supported by the Rosetrees Trust 20212104. SS has received grants/research support from NIMH R21(1R21MH119441 – 01A1), NICHD (1R21HD106779 − 01A1) and SAMHSA (FG000470-01). The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or SAMHSA. RU reports grant funding from Medical Research Council (MR/S037675/1), National Institute for Health Research: Health Technology Assessment (NIHR 127700) and speaker fees from Sunovion, Springer Heathcare and Vitaris outside the submitted work. RU holds unpaid officership with the British Association for Pharmacology- Honorary General Secretary 2021-2024 and is Deputy Editor, The British Journal of Psychiatry. PJC is funded as a Clinical Scientist by the Medical Research Council.",

year = "2023",

month = aug,

doi = "10.1038/s41380-023-02095-y",

language = "English",

volume = "28",

pages = "3149--3152",

journal = "Molecular Psychiatry",

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Jauhar, S, Arnone, D, Baldwin, DS, Bloomfield, M, Browning, M, Cleare, AJ, Corlett, P, Deakin, JFW, Erritzoe, D, Fu, C, Fusar-Poli, P, Goodwin, GM, Hayes, J, Howard, R, Howes, OD, Juruena, MF, Lam, RW, Lawrie, SM, McAllister-Williams, H, Marwaha, S, Matuskey, D, McCutcheon, RA, Nutt, DJ, Pariante, C, Pillinger, T, Radhakrishnan, R, Rucker, J, Selvaraj, S, Stokes, P, Upthegrove, R, Yalin, N, Yatham, L, Young, AH, Zahn, R & Cowen, PJ 2023, 'A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression', Molecular Psychiatry, vol. 28, no. 8, pp. 3149-3152. https://doi.org/10.1038/s41380-023-02095-y

TY - JOUR

T1 - A leaky umbrella has little value

T2 - evidence clearly indicates the serotonin system is implicated in depression

AU - Jauhar, Sameer

AU - Arnone, Danilo

AU - Baldwin, David S.

AU - Bloomfield, Michael

AU - Browning, Michael

AU - Cleare, Anthony J.

AU - Corlett, Phillip

AU - Deakin, J. F. William

AU - Erritzoe, David

AU - Fu, Cynthia

AU - Fusar-Poli, Paolo

AU - Goodwin, Guy M.

AU - Hayes, Joseph

AU - Howard, Robert

AU - Howes, Oliver D.

AU - Juruena, Mario F.

AU - Lam, Raymond W.

AU - Lawrie, Stephen M.

AU - McAllister-Williams, Hamish

AU - Marwaha, Steven

AU - Matuskey, David

AU - McCutcheon, Robert A.

AU - Nutt, David J.

AU - Pariante, Carmine

AU - Pillinger, Toby

AU - Radhakrishnan, Rajiv

AU - Rucker, James

AU - Selvaraj, Sudhakar

AU - Stokes, Paul

AU - Upthegrove, Rachel

AU - Yalin, Nefize

AU - Yatham, Lakshmi

AU - Young, Allan H

AU - Zahn, Roland

AU - Cowen, Philip J.

N1 - Acknowledgements: SJ, AJC, MFJ, PS, NY, AHY and RZ acknowledge this paper represents independent research part funded by the NIHR Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. MBrowning is supported by the Oxford Health NIHR Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. ODH is funded by Medical Research Council-UK (no. MC_A656_5QD30_2135), Maudsley Charity (no. 666), and Wellcome Trust (no. 094849/Z/10/Z) grants to ODH and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of H Lundbeck A/s, the NHS/NIHR or the Department of Health. CF is supported by the Rosetrees Trust 20212104. SS has received grants/research support from NIMH R21(1R21MH119441 – 01A1), NICHD (1R21HD106779 − 01A1) and SAMHSA (FG000470-01). The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or SAMHSA. RU reports grant funding from Medical Research Council (MR/S037675/1), National Institute for Health Research: Health Technology Assessment (NIHR 127700) and speaker fees from Sunovion, Springer Heathcare and Vitaris outside the submitted work. RU holds unpaid officership with the British Association for Pharmacology- Honorary General Secretary 2021-2024 and is Deputy Editor, The British Journal of Psychiatry. PJC is funded as a Clinical Scientist by the Medical Research Council.

PY - 2023/8

Y1 - 2023/8

N2 - A recent “umbrella” review examined various biomarkers relating to the serotonin system, and concluded there was no consistent evidence implicating serotonin in the pathophysiology of depression. We present reasons for why this conclusion is overstated, including methodological weaknesses in the review process, selective reporting of data, over-simplification, and errors in the interpretation of neuropsychopharmacological findings. We use the examples of tryptophan depletion and serotonergic molecular imaging, the two research areas most relevant to the investigation of serotonin, to illustrate this.

AB - A recent “umbrella” review examined various biomarkers relating to the serotonin system, and concluded there was no consistent evidence implicating serotonin in the pathophysiology of depression. We present reasons for why this conclusion is overstated, including methodological weaknesses in the review process, selective reporting of data, over-simplification, and errors in the interpretation of neuropsychopharmacological findings. We use the examples of tryptophan depletion and serotonergic molecular imaging, the two research areas most relevant to the investigation of serotonin, to illustrate this.

U2 - 10.1038/s41380-023-02095-y

DO - 10.1038/s41380-023-02095-y

M3 - Comment/debate

SN - 1359-4184

VL - 28

SP - 3149

EP - 3152

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 8

ER -

A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression

Abstract

Bibliographical note

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Projects

Psychosis Immune Mechanism Stratified Medicine Study (PIMS)

Cite this