. 2020 May 18;10(1):152.

doi: 10.1038/s41398-020-0835-5.

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

André F Carvalho^#^{1

2}, Marco Solmi^#^{3

4

5}, Marcos Sanches^{6

7}, Myrela O Machado⁸, Brendon Stubbs^{9

10}, Olesya Ajnakina¹¹, Chelsea Sherman¹², Yue Ran Sun¹², Celina S Liu¹², Andre R Brunoni^{13

14}, Giorgio Pigato^{3

4}, Brisa S Fernandes¹⁵, Beatrice Bortolato¹⁶, Muhammad I Husain^{17

6}, Elena Dragioti¹⁸, Joseph Firth^{19

20}, Theodore D Cosco^{21

22}, Michael Maes^{23

24}, Michael Berk^{24

25

26

27}, Krista L Lanctôt^{17

6

12

28

29}, Eduard Vieta³⁰, Diego A Pizzagalli³¹, Lee Smith³², Paolo Fusar-Poli^{5

33

34}, Paul A Kurdyak^{17

35

36}, Michele Fornaro³⁷, Jürgen Rehm^{17

36

38

39

40

41

42}, Nathan Herrmann^{17

12

28}

Affiliations

¹ Department of Psychiatry, University of Toronto, Toronto, ON, Canada. andrefc7@hotmail.com.
² Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada. andrefc7@hotmail.com.
³ Neuroscience Department, University of Padova, Padova, Italy.
⁴ Neuroscience Center, University of Padova, Padova, Italy.
⁵ Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁶ Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada.
⁷ Krembil Centre for NeuroInformatics, Toronto, ON, Canada.
⁸ Division of Dermatology, Women's College Hospital, Toronto, ON, Canada.
⁹ Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK.
¹⁰ Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, UK.
¹¹ Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹² Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.
¹³ 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 Department of Internal Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
¹⁵ Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center, Houston, TX, USA.
¹⁶ Department of Mental Health ULSS 8 "Berica", Vicenza, Italy.
¹⁷ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
¹⁸ Pain and Rehabilitation Centre, and Department of Medical and Health Sciences, Linköping University, SE-581 85, Linköping, Sweden.
¹⁹ NICM Health Research Institute, Western Sydney University, Westmead, Australia.
²⁰ Division of Psychology and Mental Health, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
²¹ Gerontology Research Center, Simon Fraser University, Vancouver, Canada.
²² Oxford Institute of Population Ageing, University of Oxford, Oxford, UK.
²³ Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
²⁴ IMPACT Strategic Research Center, Deakin University, Geelong, Australia.
²⁵ Orygen, the National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia.
²⁶ Centre for Youth Mental Health, University of Melbourne, Melbourne, VIC, Australia.
²⁷ Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
²⁸ Sunnybrook Research Institute, Toronto, ON, Canada.
²⁹ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
³⁰ Psychiatry and Psychology Department of the Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
³¹ Department of Psychiatry & McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA.
³² The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, UK.
³³ OASIS Service, South London and Maudsley National Health Service Foundation Trust, London, UK.
³⁴ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
³⁵ Canada Institute for Clinical Evaluative Sciences (ICES), Toronto, ON, Canada.
³⁶ Institute for Mental Health Policy Research, Centre for Addiction and Mental Health (CAMH), Toronto, Canada.
³⁷ Department of Neuroscience, Reproductive Science and Dentistry, Section of Psychiatr, University School of Medicine Federico II, Naples, Italy.
³⁸ Campbell Family Mental Health Research Institute, CAMH, Toronto, Canada.
³⁹ Addiction Policy, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁴⁰ Institute of Clinical Psychology and Psychotherapy & Center for Clinical Epidemiology and Longitudinal Studies, Technische Universität Dresden, Dresden, Germany.
⁴¹ Institute of Medical Science, University of Toronto, Toronto, Canada.
⁴² Department of International Health Projects, Institute for Leadership and Health Management, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation.

^# Contributed equally.

PMID: 32424116
PMCID: PMC7235270
DOI: 10.1038/s41398-020-0835-5

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

André F Carvalho et al. Transl Psychiatry. 2020.

. 2020 May 18;10(1):152.

doi: 10.1038/s41398-020-0835-5.

Authors

Affiliations

¹ Department of Psychiatry, University of Toronto, Toronto, ON, Canada. andrefc7@hotmail.com.
² Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada. andrefc7@hotmail.com.
³ Neuroscience Department, University of Padova, Padova, Italy.
⁴ Neuroscience Center, University of Padova, Padova, Italy.
⁵ Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁶ Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada.
⁷ Krembil Centre for NeuroInformatics, Toronto, ON, Canada.
⁸ Division of Dermatology, Women's College Hospital, Toronto, ON, Canada.
⁹ Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK.
¹⁰ Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, UK.
¹¹ Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹² Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.
¹³ 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 Department of Internal Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
¹⁵ Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center, Houston, TX, USA.
¹⁶ Department of Mental Health ULSS 8 "Berica", Vicenza, Italy.
¹⁷ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
¹⁸ Pain and Rehabilitation Centre, and Department of Medical and Health Sciences, Linköping University, SE-581 85, Linköping, Sweden.
¹⁹ NICM Health Research Institute, Western Sydney University, Westmead, Australia.
²⁰ Division of Psychology and Mental Health, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
²¹ Gerontology Research Center, Simon Fraser University, Vancouver, Canada.
²² Oxford Institute of Population Ageing, University of Oxford, Oxford, UK.
²³ Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
²⁴ IMPACT Strategic Research Center, Deakin University, Geelong, Australia.
²⁵ Orygen, the National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia.
²⁶ Centre for Youth Mental Health, University of Melbourne, Melbourne, VIC, Australia.
²⁷ Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
²⁸ Sunnybrook Research Institute, Toronto, ON, Canada.
²⁹ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
³⁰ Psychiatry and Psychology Department of the Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
³¹ Department of Psychiatry & McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA.
³² The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, UK.
³³ OASIS Service, South London and Maudsley National Health Service Foundation Trust, London, UK.
³⁴ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
³⁵ Canada Institute for Clinical Evaluative Sciences (ICES), Toronto, ON, Canada.
³⁶ Institute for Mental Health Policy Research, Centre for Addiction and Mental Health (CAMH), Toronto, Canada.
³⁷ Department of Neuroscience, Reproductive Science and Dentistry, Section of Psychiatr, University School of Medicine Federico II, Naples, Italy.
³⁸ Campbell Family Mental Health Research Institute, CAMH, Toronto, Canada.
³⁹ Addiction Policy, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁴⁰ Institute of Clinical Psychology and Psychotherapy & Center for Clinical Epidemiology and Longitudinal Studies, Technische Universität Dresden, Dresden, Germany.
⁴¹ Institute of Medical Science, University of Toronto, Toronto, Canada.
⁴² Department of International Health Projects, Institute for Leadership and Health Management, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation.

^# Contributed equally.

PMID: 32424116
PMCID: PMC7235270
DOI: 10.1038/s41398-020-0835-5

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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Conflict of interest statement

A.F.C., Marco Solmi, M. Sanches, M.O.M., B.S., O.A., C.S., J.S., C.S.L., A.R.B., G.P., B.S.F., B.B., M.I.H., E.D., J.F., T.D.C., M.M., L.S., P.F.-P., P.A.K., M.F., J.R., and N.H. have no conflicts of interest to declare. M.B. has been a speaker for Astra Zeneca, Lundbeck, Merck, Pfizer, and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Lundbeck Merck, Pfizer and Servier. K.L.L. has received consulting fees from AbbVie, Lundbeck/Otsuka, Pfizer, ICG Pharma, and Kondor in the last 3 years. E.V. has served as consultant, advisor or CME speaker for the following entities: AB-Biotics, Abbott, Allergan, Angelini, AstraZeneca, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Farmindustria, Ferrer, Forest Research Institute, Gedeon Richter, Glaxo-Smith-Kline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, SAGE, Sanofi-Aventis, Servier, Shire, Sunovion, Takeda. Over the past 3 years, D.A.P. has received consulting fees from Akili Interactive Labs, BlackThorn Therapeutics, Boehringer Ingelheim, Compass, Posit Science, and Takeda Pharmaceuticals and an honorarium from Alkermes for activities unrelated to the current work.

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

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

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