BackgroundFrontal alpha asymmetry (FAA) has frequently been reported as potential discriminator between depressed and healthy individuals, although contradicting results have been published. The aim of the current study was to provide an up to date meta-analysis on the diagnostic value of FAA in major depressive disorder (MDD) and to further investigate discrepancies in a large cross-sectional dataset.MethodsSCOPUS database was searched through February 2017. Studies were included if the article reported on both MDD and controls, provided an FAA measure involving EEG electrodes F3/F4, and provided data regarding potential covariates. Hedges' d was calculated from FAA means and standard deviations (SDs). Potential covariates, such as age and gender, were explored. Post hoc analysis was performed to elucidate interindividual differences that could explain interstudy discrepancies.Results16 studies were included (MDD: n = 1883, controls: n = 2161). After resolving significant heterogeneity by excluding studies, a non-significant Grand Mean effect size (ES) was obtained (d = − 0.007;CI = [− 0.090]–[0.075]). Crosssectional analyses showed a significant three-way interaction for Gender × Age × Depression severity in the depressed group, which was prospectively replicated in an independent sample.ConclusionsThe main result was a non-significant, negligible ES, demonstrating limited diagnostic value of FAA in MDD. The high degree of heterogeneity across studies indicates covariate influence, as was confirmed by crosssectional analyses, suggesting future studies should address this Gender × Age × Depression severity interaction. Upcoming studies should focus more on prognostic and research domain usages of FAA rather than a pure diagnostic tool.

HighlightsFrontal alpha asymmetry (FAA) is moderately stable over time.Antidepressant response prediction with FAA remains consistent, even after 8 weeks of treatment.FAA is a differential predictor of antidepressant response robust to state and drug effects.