Evidence-based umbrella review of 162 peripheral biomarkers for major mental disorders

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Abstract

The literature on non-genetic peripheral biomarkers for major mental disorders is broad, with conflicting results. An umbrella review of meta-analyses of non-genetic peripheral biomarkers for Alzheimer’s disease, autism spectrum disorder, bipolar disorder (BD), major depressive disorder, and schizophrenia, including first-episode psychosis. We included meta-analyses that compared alterations in peripheral biomarkers between participants with mental disorders to controls (i.e., between-group meta-analyses) and that assessed biomarkers after treatment (i.e., within-group meta-analyses). Evidence for association was hierarchically graded using a priori defined criteria against several biases. The Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to investigate study quality. 1161 references were screened. 110 met inclusion criteria, relating to 359 meta-analytic estimates and 733,316 measurements, on 162 different biomarkers. Only two estimates met a priori defined criteria for convincing evidence (elevated awakening cortisol levels in euthymic BD participants relative to controls and decreased pyridoxal levels in participants with schizophrenia relative to controls). Of 42 estimates which met criteria for highly suggestive evidence only five biomarker aberrations occurred in more than one disorder. Only 15 meta-analyses had a power >0.8 to detect a small effect size, and most (81.9%) meta-analyses had high heterogeneity. Although some associations met criteria for either convincing or highly suggestive evidence, overall the vast literature of peripheral biomarkers for major mental disorders is affected by bias and is underpowered. No convincing evidence supported the existence of a trans-diagnostic biomarker. Adequately powered and methodologically sound future large collaborative studies are warranted.

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Author and article information

Contributors

André F. Carvalho:

ORCID: http://orcid.org/0000-0002-2500-5671

andrefc7@hotmail.com

Journal

Journal ID (nlm-ta): Transl Psychiatry

Journal ID (iso-abbrev): Transl Psychiatry

Title: Translational Psychiatry

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2158-3188

Publication date (Electronic): 18 May 2020

Publication date PMC-release: 18 May 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 152

Affiliations

[1 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Department of Psychiatry, , University of Toronto, ; Toronto, ON Canada

[2 ]ISNI 0000 0000 8793 5925, GRID grid.155956.b, Centre for Addiction & Mental Health (CAMH), ; Toronto, ON Canada

[3 ]ISNI 0000 0004 1757 3470, GRID grid.5608.b, Neuroscience Department, , University of Padova, ; Padova, Italy

[4 ]ISNI 0000 0004 1757 3470, GRID grid.5608.b, Neuroscience Center, , University of Padova, ; Padova, Italy

[5 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, , King’s College London, ; London, UK

[6 ]ISNI 0000 0000 8793 5925, GRID grid.155956.b, Centre for Addiction & Mental Health (CAMH), ; Toronto, ON Canada

[7 ]Krembil Centre for NeuroInformatics, Toronto, ON Canada

[8 ]ISNI 0000 0004 0474 0188, GRID grid.417199.3, Division of Dermatology, , Women’s College Hospital, ; Toronto, ON Canada

[9 ]ISNI 0000 0000 9439 0839, GRID grid.37640.36, Physiotherapy Department, , South London and Maudsley NHS Foundation Trust, ; London, UK

[10 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, , King’s College London, ; De Crespigny Park, London, UK

[11 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, , King’s College London, ; London, UK

[12 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program, , Sunnybrook Research Institute, ; Toronto, ON Canada

[13 ]ISNI 0000 0004 1937 0722, GRID grid.11899.38, Service of Interdisciplinary Neuromodulation, Laboratory of Neurosciences (LIM-27) and National Institute of Biomarkers in Psychiatry (INBioN), Department and Institute of Psychiatry, , University of São Paulo, ; São Paulo, SP Brazil

[14 ]ISNI 0000 0004 1937 0722, GRID grid.11899.38, Department of Internal Medicine, , Faculdade de Medicina da Universidade de São Paulo, ; São Paulo, Brazil

[15 ]ISNI 0000 0004 1757 3470, GRID grid.5608.b, Neuroscience Department, , University of Padova, ; Padova, Italy

[16 ]ISNI 0000 0004 1757 3470, GRID grid.5608.b, Neuroscience Center, , University of Padova, ; Padova, Italy

[17 ]ISNI 0000 0000 9206 2401, GRID grid.267308.8, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center, ; Houston, TX USA

[18 ]Department of Mental Health ULSS 8 “Berica”, Vicenza, Italy

[19 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Department of Psychiatry, University of Toronto, ; Toronto, ON Canada

[20 ]ISNI 0000 0000 8793 5925, GRID grid.155956.b, Centre for Addiction & Mental Health (CAMH), ; Toronto, ON Canada

[21 ]ISNI 0000 0001 2162 9922, GRID grid.5640.7, Pain and Rehabilitation Centre, and Department of Medical and Health Sciences, , Linköping University, ; SE-581 85 Linköping, Sweden

[22 ]ISNI 0000 0000 9939 5719, GRID grid.1029.a, NICM Health Research Institute, , Western Sydney University, ; Westmead, Australia

[23 ]ISNI 0000000121662407, GRID grid.5379.8, Division of Psychology and Mental Health, , Faculty of Biology, Medicine and Health, University of Manchester, ; Manchester, UK

[24 ]ISNI 0000 0004 1936 7494, GRID grid.61971.38, Gerontology Research Center, , Simon Fraser University, ; Vancouver, Canada

[25 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Oxford Institute of Population Ageing, , University of Oxford, ; Oxford, UK

[26 ]ISNI 0000 0001 0244 7875, GRID grid.7922.e, Department of Psychiatry, Faculty of Medicine, , Chulalongkorn University, ; Bangkok, Thailand

[27 ]ISNI 0000 0001 0526 7079, GRID grid.1021.2, IMPACT Strategic Research Center, , Deakin University, ; Geelong, Australia

[28 ]GRID grid.488501.0, Orygen, the National Centre of Excellence in Youth Mental Health, ; Melbourne, VIC Australia

[29 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, Centre for Youth Mental Health, , University of Melbourne, ; Melbourne, VIC Australia

[30 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, Florey Institute for Neuroscience and Mental Health, , University of Melbourne, ; Melbourne, VIC Australia

[31 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Department of Psychiatry, , University of Toronto, ; Toronto, ON Canada

[32 ]ISNI 0000 0000 8793 5925, GRID grid.155956.b, Centre for Addiction & Mental Health (CAMH), ; Toronto, ON Canada

[33 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program, , Sunnybrook Research Institute, ; Toronto, ON Canada

[34 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Sunnybrook Research Institute, ; Toronto, ON Canada

[35 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Department of Pharmacology and Toxicology, , University of Toronto, ; Toronto, ON Canada

[36 ]ISNI 0000 0004 1762 4012, GRID grid.418264.d, Psychiatry and Psychology Department of the Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, , CIBERSAM, ; Barcelona, Catalonia Spain

[37 ]ISNI 000000041936754X, GRID grid.38142.3c, Department of Psychiatry & McLean Hospital, , Harvard Medical School, ; Belmont, MA 02478 USA

[38 ]ISNI 0000 0001 2299 5510, GRID grid.5115.0, The Cambridge Centre for Sport and Exercise Sciences, , Anglia Ruskin University, ; Cambridge, UK

[39 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, , King’s College London, ; London, UK

[40 ]OASIS Service, South London and Maudsley National Health Service Foundation Trust, London, UK

[41 ]ISNI 0000 0004 1762 5736, GRID grid.8982.b, Department of Brain and Behavioral Sciences, , University of Pavia, ; Pavia, Italy

[42 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Department of Psychiatry, , University of Toronto, ; Toronto, ON Canada

[43 ]ISNI 0000 0000 8849 1617, GRID grid.418647.8, Canada Institute for Clinical Evaluative Sciences (ICES), ; Toronto, ON Canada

[44 ]ISNI 0000 0000 8793 5925, GRID grid.155956.b, Institute for Mental Health Policy Research, , Centre for Addiction and Mental Health (CAMH), ; Toronto, Canada

[45 ]ISNI 0000 0001 0790 385X, GRID grid.4691.a, Department of Neuroscience, Reproductive Science and Dentistry, Section of Psychiatr, , University School of Medicine Federico II, ; Naples, Italy

[46 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Department of Psychiatry, , University of Toronto, ; Toronto, ON Canada

[47 ]ISNI 0000 0000 8793 5925, GRID grid.155956.b, Institute for Mental Health Policy Research, , Centre for Addiction and Mental Health (CAMH), ; Toronto, Canada

[48 ]ISNI 0000 0000 8793 5925, GRID grid.155956.b, Campbell Family Mental Health Research Institute, CAMH, ; Toronto, Canada

[49 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Addiction Policy, Dalla Lana School of Public Health, , University of Toronto, ; Toronto, ON Canada

[50 ]ISNI 0000 0001 2111 7257, GRID grid.4488.0, Institute of Clinical Psychology and Psychotherapy & Center for Clinical Epidemiology and Longitudinal Studies, , Technische Universität Dresden, ; Dresden, Germany

[51 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Institute of Medical Science, , University of Toronto, ; Toronto, Canada

[52 ]ISNI 0000 0001 2288 8774, GRID grid.448878.f, Department of International Health Projects, Institute for Leadership and Health Management, , I.M. Sechenov First Moscow State Medical University, ; Moscow, Russian Federation

[53 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Department of Psychiatry, , University of Toronto, ; Toronto, ON Canada

[54 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program, , Sunnybrook Research Institute, ; Toronto, ON Canada

[55 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Sunnybrook Research Institute, ; Toronto, ON Canada

Author information

André F. Carvalho http://orcid.org/0000-0002-2500-5671

Andre R. Brunoni http://orcid.org/0000-0002-6310-3571

Muhammad I. Husain http://orcid.org/0000-0001-5771-5750

Diego A. Pizzagalli http://orcid.org/0000-0002-7772-1143

Paolo Fusar-Poli http://orcid.org/0000-0003-3582-6788

Article

Publisher ID: 835

DOI: 10.1038/s41398-020-0835-5

PMC ID: 7235270

PubMed ID: 32424116

SO-VID: 0c02ef28-8a7b-483c-9b4a-04f5a6643cf0

License:

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