Antioxidant uric acid in treated and untreated subjects with major depressive disorder: a meta-analysis and meta-regression
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Pathophysiological mechanisms of major depressive disorder (MDD) seem to be associated with oxidative stress pathways and altered purinergic metabolism. We conducted a systematic review and meta-analysis to estimate if subjects with MDD might have reduced levels of antioxidant uric acid, considering also potential influence of antidepressant treatment. We searched the main Electronic Databases, identifying 14 studies that met our inclusion criteria. Meta-analyses were carried out generating pooled Hedges’ g and mean differences (MDs), using random-effects models. Heterogeneity across studies and risk of publication bias were estimated using standard methods. Relevant sensitivity and meta-regression analyses were conducted. Subjects with MDD had levels of uric acid lower than healthy controls (Hedges’ g = −0.30; p = 0.003). Overall between-study heterogeneity was high (I 2 = 76.3%). The effect was significant among studies including drug naïve/free MDD individuals (Hedges’ g = −0.55; p = 0.023), but not among those involving treated subjects (Hedges’ g = −0.15; p = 0.062). Relevant quality- and heterogeneity-based sensitivity analyses, as well as meta-regressions, confirmed these findings. In addition, uric acid levels significantly, though inconsistently (I 2 = 79.2%), increased after treatment (MD = +0.71 mg/dL; p < 0.001), regardless of follow-up duration (p = 0.518). Our meta-analysis shows that subjects with MDD have lower levels of uric acid. Since antidepressant treatment seems to influence this association, our findings support the hypothesis that uric acid levels may represent a state marker of MDD. Nevertheless, the potential role of additional factors that might clarify the nature of this association deserves further research.
KeywordsMajor depressive disorder Uric acid Antidepressive agents Meta-analysis
We wish to express our great appreciation to all the authors of studies included in the current meta-analysis. A special thanks to Fatih Canan (Department of Psychiatry, Akdeniz University School of Medicine, Antalya, Turkey), Gabriele Ghisleni (Department of Life and Health Sciences, Universidade Catolica de Pelotas, Pelotas, Rio Grande do Sul, Brazil), and Davor Lasic (Department of Psychiatry, University Hospital Centre Split, Split, Croatia), who provided additional, unpublished data.
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Conflict of interest
The authors declare that they have no conflict of interest.
- 6.Kean RB, Spitsin SV, Mikheeva T, Scott GS, Hooper DC (2000) The peroxynitrite scavenger uric acid prevents inflammatory cell invasion into the central nervous system in experimental allergic encephalomyelitis through maintenance of blood-central nervous system barrier integrity. J Immunol 165(11):6511–6518CrossRefPubMedGoogle Scholar
- 11.Jiménez-Fernández S, Gurpegui M, Díaz-Atienza F, Pérez-Costillas L, Gerstenberg M, Correll CU (2015) Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: results from a meta-analysis. J Clin Psychiatry 76(12):1658–1667CrossRefPubMedGoogle Scholar
- 23.Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) Group. JAMA 283(15):2008–2012CrossRefPubMedGoogle Scholar
- 25.Sterne JA, Egger M, Moher D (2008) Addressing reporting biases. In: Higgins JP, Green S (eds) Cochrane handbook for systematic reviews of interventions: Cochrane book series. John Wiley & Sons, Ltd, ChichesterGoogle Scholar
- 30.Keshavarz M, Khosravizadegan F, Bibak A (2016) Serum uric acid levels in different phases of acute severe manic and depressed patients. Arch Neurosci 3(2):e30236Google Scholar
- 32.Wiener C, Rassier GT, Kaster MP, Jansen K, Pinheiro RT, Klamt F, Magalhaes PV, Kapczinski F, Ghisleni G, da Silva RA (2014) Gender-based differences in oxidative stress parameters do not underlie the differences in mood disorders susceptibility between sexes. Eur Psychiatry 29(1):58–63CrossRefPubMedGoogle Scholar
- 37.Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Lawrence Earlbaum Associates, HillsdaleGoogle Scholar