Retinal electrophysiology in mood disorders: Toward clinically relevant biomarkers. A systematic review and meta-analysis.

Abstract

Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are associated with substantial disability and frequent misdiagnosis, particularly in early stages and in the differential diagnosis between unipolar and bipolar depression. Current diagnosis remains largely based on clinical assessment, highlighting the need for objective biomarkers to improve early detection and diagnostic accuracy. The retina, sharing structural and neurochemical properties with the brain, is a promising candidate. To assess its function, Electroretinography (ERG) is widely used. This study aimed to systematically review and quantitatively synthesise ERG findings in mood disorders and genetically high-risk populations. PubMed, Web of Science, Embase and APA PsycINFO were searched up to 25 November 2025 (PROSPERO: 1234381). Methodological quality was assessed using a modified Newcastle-Ottawa Scale. Random-effects meta-analyses were conducted for full-field ERG parameters in MDD without reported specifiers. Thirty-two studies (n = 1334) were included, with five in the meta-analysis. Mood disorders were generally associated with reduced ERG amplitudes and prolonged implicit times. In MDD, a significant prolongation of b-wave implicit time under mixed scotopic conditions was observed (g = 0.23, 95% CI 0.00-0.46), while other parameters were non-significant. BD and seasonal affective disorder studies suggested mood-state-dependent retinal alterations, and high-risk offspring showed ERG abnormalities associated with subclinical and cognitive features. Overall, ERG shows consistent but heterogeneous alterations in mood disorders and may have potential value for early detection, differential diagnosis and stratification but further longitudinal and methodologically harmonized studies are required to clarify its clinical utility.