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Retinal ganglion cell function as objective biomarker for subgroups of depressive disorders

Subject Area Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
Term from 2021 to 2024
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 462923710
 
Final Report Year 2025

Final Report Abstract

The project aimed to evaluate methodological and differential diagnostic aspects of functional retina assessments in the context of psychiatric diagnostics. Initially, previously reported results of reduced pattern electroretinogram (PERG) amplitudes in depression were replicated. Furthermore, an influence of the stimulus pattern was observed, similar to early glaucoma. This analogy was also seen in the PERG ratio (amplitude ratio of two checker sizes), a parameter known from early glaucoma diagnostics, which exhibits reduced interindividual variability. A central question concerned the suitability of the photopic negative response (PhNR) from the flash electroretinogram (fERG) as a methodologically easier substitute for the PERG. In individuals with depression, we found reductions in the PERG ratio, the a-wave amplitude (reflecting photoreceptor and bipolar cell responses) from the fERG, the contrast sensitivity and suppression, as well as a thinning in the outer nuclear layer (ONL), housing the photoreceptor cell bodies, as additionally assessed via optical coherence tomography (OCT). Contrary to our expectations, the PhNR was not attenuated, suggesting a specific, non-generalized dysfunction in retinal ganglion cell responses in depression. Although the PhNR cannot replace the PERG for evaluating ganglion cell function in depression, the attenuated a-wave in the fERG indicates additional pathophysiological modulations. From a practical perspective, it is noteworthy that these effects were detectable using an easily applicable handheld device and skin electrodes. The utility of the observed OCT alterations could further complement functional assessments and provide insights into neurodegenerative processes. Our results further align with findings in Parkinson’s disease (reductions in the a-wave, contrast suppression, and ONL thickness), further supporting the hypothesis of dopaminergic system involvement in retinal alterations in depression. Regarding the potential of fERG assessments for differential diagnostics, no differences were observed between first-episode and recurrent depression. A distinction from adults with autism appears possible, as no fERG modulations were observed in this group. Although the project results showed that the retinal evaluations cannot discriminate between first manifestation and recurrent depressive disorder and that the PhNR is not suitable for ganglion cell integrity evaluation in depression, the project was able to unravel additional retinal modulations and alterations in visual information processing in depression. This novel evidence provides additional insights into pathophysiology and may have the potential to aid psychiatric diagnosis.

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