Bias in Peripheral Depression BiomarkersCarvalho A.F.a · Köhler C.A.a · Brunoni A.R.b, c · Miskowiak K.W.d · Herrmann N.e, f · Lanctôt K.L.e-g · Hyphantis T.N.h · Quevedo J.i-k · Fernandes B.S.l, m · Berk M.l, n
aTranslational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, bInterdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, and cLaboratory of Neurosciences (LIM-27), Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil; dPsychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; eNeuropsychopharmacology Research Group, Sunnybrook Health Sciences Center, fDepartment of Psychiatry, and gDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, Ont., Canada; hDepartment of Psychiatry, Division of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece; iCenter for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, and jCenter of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, Tex., USA; kLaboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, Brazil; lIMPACT Strategic Research Centre, School of Medicine and Barwon Health, Deakin University, Geelong, Vic., Australia; mLaboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; nDepartment 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
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Article / Publication Details
Background: To aid in the differentiation of individuals with major depressive disorder (MDD) from healthy controls, numerous peripheral biomarkers have been proposed. To date, no comprehensive evaluation of the existence of bias favoring the publication of significant results or inflating effect sizes has been conducted. Methods: Here, we performed a comprehensive review of meta-analyses of peripheral nongenetic biomarkers that could discriminate individuals with MDD from nondepressed controls. PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched through April 10, 2015. Results: From 15 references, we obtained 31 eligible meta-analyses evaluating biomarkers in MDD (21,201 cases and 78,363 controls). Twenty meta-analyses reported statistically significant effect size estimates. Heterogeneity was high (I2 ≥50%) in 29 meta-analyses. We plausibly assumed that the true effect size for a meta-analysis would equal the one of its largest study. A significant summary effect size estimate was observed for 20 biomarkers. We observed an excess of statistically significant studies in 21 meta-analyses. The summary effect size of the meta-analysis was higher than the effect of its largest study in 25 meta-analyses, while 11 meta-analyses had evidence of small-study effects. Conclusions: Our findings suggest that there is an excess of studies with statistically significant results in the literature of peripheral biomarkers for MDD. The selective publication of ‘positive studies' and the selective reporting of outcomes are possible mechanisms. Effect size estimates of meta-analyses may be inflated in this literature.
© 2016 S. Karger AG, Basel
Article / Publication Details
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