title: Adipokines as emerging depression biomarkers: a systematic review and meta-analysis.
abstract: Adiponectin, leptin and resistin may play a role in the pathophysiology of major depressive disorder (MDD). However, differences in peripheral levels of these hormones are inconsistent across diagnostic and intervention studies. Therefore, we performed meta-analyses of diagnostic studies (i.e., MDD subjects versus healthy controls) and intervention investigations (i.e., pre-vs. post-antidepressant treatment) in MDD. Adiponectin (N = 1278; Hedge's g = -0.35; P = 0.16) and leptin (N = 893; Hedge's g = -0.018; P = 0.93) did not differ across diagnostic studies. Meta-regression analyses revealed that gender and depression severity explained the heterogeneity observed in adiponectin diagnostic studies, while BMI and the difference in BMI between MDD individuals and controls explained the heterogeneity of leptin diagnostic studies. Subgroup analyses revealed that adiponectin peripheral levels were significantly lower in MDD participants compared to controls when assayed with RIA, but not ELISA. Leptin levels were significantly higher in individuals with mild/moderate depression versus controls. Resistin serum levels were lower in MDD individuals compared to healthy controls (N = 298; Hedge's g = -0.25; P = 0.03). Leptin serum levels did not change after antidepressant treatment. However, heterogeneity was significant and sample size was low (N = 108); consequently meta-regression analysis could not be performed. Intervention meta-analyses could not be performed for adiponectin and resistin (i.e., few studies met inclusion criteria). In conclusion, this systematic review and meta-analysis underscored that relevant moderators/confounders (e.g., BMI, depression severity and type of assay) should be controlled for when considering the role of leptin and adiponectin as putative MDD diagnostic biomarkers.
authors.affiliation: Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil. Electronic address: andrefc7@terra.com.br.
authors.forename: André F
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil.
authors.forename: Davi Q C
authors.initials: DQ
authors.lastname: Rocha
authors.affiliation: Departments of Pharmacology and Psychiatry, University of Toronto, Toronto, ON, Canada; Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, ON, Canada.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
authors.affiliation: Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil.
authors.forename: Lucas M
authors.initials: LM
authors.lastname: Mesquita
authors.affiliation: Memory Research Laboratory, Brain Institute (ICe), Federal University of Rio Grande do Norte (UFRN), Natal, RN, Brazil.
authors.forename: Cristiano A
authors.initials: CA
authors.lastname: Köhler
authors.affiliation: Department of Psychiatry, Medical School, University of Ioaninna, Ioaninna, Greece.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Hyphantis
authors.affiliation: Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil.
authors.forename: Paulo M G
authors.initials: PM
authors.lastname: Sales
authors.affiliation: National Institute of Mental Health (NIMH), Bethesda, USA; Laboratory of Neuroscience, LIM-27, Department and Institute of Psychiatry, University of São Paulo, USP, Brazil; Center for Interdisciplinary Research in Applied Neuroscience (NAPNA), USP, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado-Vieira
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Vic., Australia; Florey Institute of Neuroscience and Mental Health, Australia; Orygen Youth Health Research Centre, University of Melbourne, Parkville, Vic., Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
mesh_terms: D054392:Adipokines / Q000097:blood*; D000928:Antidepressive Agents / Q000627:therapeutic use; D015992:Body Mass Index; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D003865:Major Depressive Disorder / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D006801:Humans; D011863:Radioimmunoassay
chemical_list: D054392:Adipokines; D000928:Antidepressive Agents
keywords: Adiponectin; Biomarkers; Leptin; Major depressive disorder; Meta-analysis; Resistin