The electroretinogram (ERG), a non-invasive electrophysiological tool used in ophthalmology, is increasingly applied to investigate neural correlates of depression. The present study aimed to reconsider previous findings in major depressive disorder (MDD) reporting (1) a diminished contrast sensitivity and (2) a reduced patten ERG (PERG) amplitude ratio, and additionally, to assess (3) the photopic negative response (PhNR) from the flash ERG (fERG), with the RETeval® device, a more practical option for clinical routine use. We examined 30 patients with a MDD and 42 healthy controls (HC), assessing individual contrast sensitivity thresholds with an optotype-based contrast test. Moreover, we compared the PERG ratio, an established method for early glaucoma detection, between both groups. The handheld ERG device was used to measure amplitudes and peak times of the fERG components including a-wave, b-wave and PhNR in both MDD patients and HCs. MDD patients exhibited diminished contrast sensitivity together with a reduced PERG ratio, compared to HC. With the handheld ERG device, we found reduced a-wave amplitudes in MDD, whereas no significant differences were observed in the fERG b-wave or PhNR between patients and controls. The reduced contrast sensitivity and PERG ratio in MDD patients supports the hypothesis that depression is associated with altered visual processing. The findings underscore the PERG’s potential as a possible objective marker for depression. The reduced a-wave amplitude recorded with the RETeval® system in MDD patients might open new avenues for using handheld ERG devices as simplified approaches for advancing depression research compared to the PERG.

Background: Optical coherence tomography (OCT) has emerged as a significant non-invasive imaging technique in psychiatric research, allowing for detailed structural assessment of the retinal layers. While OCT has been promising for monitoring neurodegeneration in Alzheimer’s and Parkinson’s diseases, results in major depressive disorder (MDD) remain inconsistent. Building on findings of attenuated electroretinogram (ERG) responses in MDD, indicating functional retinal alterations, this study investigated whether structural retinal changes, such as thinning of retinal layers, also occur in patients with MDD and whether these changes are associated with the severity of depressive symptoms. Methods: OCT examinations were conducted on 31 MDD patients and 60 healthy controls (HC). The thickness and volumes of macular retinal layers were analyzed and correlated with depressive symptoms. Results: The thickness of the outer nuclear layer (ONL) was significantly reduced in MDD patients (p = 0.003) and negatively correlated with depressive symptoms (BDI-II scores; p = 0.001). The thickness and volume of the ganglion cell and inner plexiform layer were further inversely associated with depressive symptoms in MDD patients (BDI-II and MADRS scores; p < 0.02). Conclusions: ONL thinning in MDD suggests possible neurodegenerative processes that may disturb signal transmission downstream, as indicated by altered ERG responses in MDD. Further research is essential to determine the reversibility of these structural changes following remission. Structural retinal analysis with OCT offers the potential to complement functional ERG examinations and represents a promising approach for developing diagnostic and therapeutic monitoring tools for MDD.