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Bias in emerging biomarkers for bipolar disorder

Published online by Cambridge University Press:  19 May 2016

A. F. Carvalho ,
C. A. Köhler ,
B. S. Fernandes ,
J. Quevedo ,
K. W. Miskowiak ,
A. R. Brunoni ,
R. Machado-Vieira ,
M. Maes ,
E. Vieta  and
M. Berk
A. F. Carvalho*
Affiliation:
Department of Psychiatry and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
C. A. Köhler
Affiliation:
Department of Psychiatry and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
B. S. Fernandes
Affiliation:
IMPACT Strategic Research Centre, Deakin University, School of Medicine and Barwon Health, Geelong - VIC, Australia Department of Biochemistry, Laboratory of Calcium Binding Proteins in the Central Nervous System, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
J. Quevedo
Affiliation:
Department of Psychiatry and Behavioral Sciences, Center for Experimental Models in Psychiatry, The University of Texas Medical School at Houston, Houston, TX, USA Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil
K. W. Miskowiak
Affiliation:
Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
A. R. Brunoni
Affiliation:
Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil Department and Institute of Psychiatry, Service of Interdisciplinary Neuromodulation (SIN), Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil
R. Machado-Vieira
Affiliation:
Laboratory of Neuroscience, LIM- 27, Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, NIH, Bethesda, MD, USA
M. Maes
Affiliation:
IMPACT Strategic Research Centre, Deakin University, School of Medicine and Barwon Health, Geelong - VIC, Australia
E. Vieta
Affiliation:
Bipolar Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain
M. Berk
Affiliation:
IMPACT Strategic Research Centre, Deakin University, School of Medicine and Barwon Health, Geelong - VIC, Australia Department of Psychiatry, Florey Institute of Neuroscience and Mental Health, Orygen, The National Centre of Excellence in Youth Mental Health and Orygen Youth Health Research Centre, University of Melbourne, Parkville, VIC, Australia
*
*Address for correspondence: A. F. Carvalho, MD, PhD, Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Rua Prof. Costa Mendes, 1608, 4 andar, 60430-040, Fortaleza, CE, Brazil. (Email: andrefc7@terra.com.br; andrefc7@hotmail.com)
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Abstract

Background

To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD.

Method

The Pubmed/Medline, EMBASE and PsycInfo electronic databases were searched up to May 2015. Two independent authors conducted searches, examined references for eligibility, and extracted data. Meta-analyses in any language examining peripheral non-genetic biomarkers in participants with BD (across different mood states) compared to unaffected controls were included.

Results

Six references, which examined 13 biomarkers across 20 meta-analyses (5474 BD cases and 4823 healthy controls) met inclusion criteria. Evidence for excess of significance bias (i.e. bias favoring publication of ‘positive’ nominally significant results) was observed in 11 meta-analyses. Heterogeneity was high for (I2 ⩾ 50%) 16 meta-analyses. Only two biomarkers met criteria for suggestive evidence namely the soluble IL-2 receptor and morning cortisol. The median power of included studies, using the effect size of the largest dataset as the plausible true effect size of each meta-analysis, was 15.3%.

Conclusions

Our findings suggest that there is an excess of statistically significant results in the literature of peripheral biomarkers for BD. Selective publication of ‘positive’ results and selective reporting of outcomes are possible mechanisms.

Keywords

Biasbiomarkersbipolar disordermeta-analysispsychiatryreview
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 11 , August 2016 , pp. 2287 - 2297
Copyright
Copyright © Cambridge University Press 2016 

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