Resting-state EEG activity as a Biomarker and Treatment Target in Depression: A Systematic Review and Meta-analysis

Depression is a highly prevalent and disabling disorder affecting approximately 5% of the adult population worldwide. Despite its impact, the underlying pathophysiology remains insufficiently understood, and current treatments are only partially effective. Brain-based biomarkers offer promise for clarifying mechanisms of depression and guiding novel treatment approaches, including neuromodulation. EEG is particularly attractive for this purpose due to its wide availability, cost-effectiveness, and potential for direct neuromodulatory targeting. We conducted a PROSPERO-registered systematic review in accordance with PRISMA guidelines to assess resting-state EEG biomarkers in adult patients with depression, diagnosed according to DSM-IV/V or ICD-10/11. Included studies reported cross-sectional or correlational data on quantitative EEG measures such as power, cordance, peak frequency, and alpha asymmetry. Semiquantitative analyses using modified albatross plots and meta-analyses were performed. Study quality was assessed with a modified Newcastle-Ottawa Scale. Fifty-two studies met the inclusion criteria. Findings indicated increased low- frequency (delta, theta) and high-frequency (beta, gamma) power, and left frontal alpha asymmetry in depressed patients compared to healthy controls. Meta-analysis confirmed a significant increase in beta power. However, results regarding disease severity correlations and data on peak alpha frequency and cordance were insufficient for interpretation. Risk of bias across studies was high. Our results support increased beta and potentially also theta oscillations and alpha asymmetry as candidate diagnostic EEG biomarkers for depression. These oscillations may reflect disrupted corticolimbic control and reward processing and partially overlap with mechanisms implicated in chronic pain and fatigue. Further investigation is warranted into their potential as diagnostic tools and neuromodulatory treatment targets.