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

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The lack of valid biomarkers is a substantial challenge in psychiatric diagnosis. For depressive disorders we have developed a novel, objective approach: The pattern electroretinogram (PERG), a non-invasive measure of the retinal ganglion cell function established in ophthalmology, is reduced by around 50% in patients with depression. The assumed mechanism is a disruption of neurotransmitter homeostasis, involving the dopaminergic system, which modulates visual processing. The project aims at establishing the necessary prerequisites for the successful integration of ganglion cell assessment in daily routine diagnostics of depressive disorders. Some of the main hurdles are of methodological nature: The technically demanding PERG requires proper refraction of the eye, which cannot be guaranteed in daily psychiatric routine. Using the flash-evoked photopic negative response (PhNR), another correlate of ganglion cell function, similar to the PERG, could resolve this problem as it does not rely on good optics. Another obstacle is associated with the use of cornea electrodes, which are not tolerated by some patients. Recent technical innovations allow for recording of ERG signals in response to flash stimuli, including the PhNR, using skin electrodes with an unprecedented signal-to-noise ratio. These electrodes are placed on the facial skin below the eye. Furthermore, suitable commercial devices can facilitate the application outside ophthalmology. One clinical focus of the project concerns differential diagnostics. It is now consensus that rather diverse pathophysiological mechanisms may underlie a single major mental disorder as clustered in ICD-10. Accounting for this, we will assess the capacity of our approach to differentiate among disorders of the depressive spectrum, to distinguish between the different subtypes of affective disorders, and to separate these from autism-spectrum and attention deficit hyperactivity disorders.The project furthermore aims at identifying and elucidating pathophysiological interrelations. Using the flash electroretinogram, functional parameters of other retinal cell types can be assessed. By tracking the modulations of cell responses within the retinal signal transmission cascade in more detail, we will be able to test our hypotheses as to the underlying pathophysiology. These objectives will be accomplished by examining a broad range of patients with different sub-types of affective disorders, in which (1) PhNR and PERG will be compared with respect to their diagnostic potential, (2) different types of electrodes will be tested, and (3) ERG parameters unrelated to ganglion cell function will be assessed to (a) shed light on pathophysiological mechanisms and (b) identify their differential diagnostic potential. The cooperation of the groups involved combines comprehensive methodological competence with distinct expertise in content.