Abstract
Major depressive disorder (MDD) is one of the most common consequences of chronic stress. Still, there is currently no reliable biomarker to detect individuals at risk to develop the disease. Recently, the retina emerged as an effective way to investigate psychiatric disorders using the electroretinogram (ERG). In this study, cone and rod ERGs were performed in male and female C57BL/6 mice before and after chronic social defeat stress (CSDS). Mice were then divided as susceptible or resilient to stress. Our results suggest that CSDS reduces the amplitude of both oscillatory potentials and a-waves in the rods of resilient but not susceptible males. Similar effects were revealed following the analysis of the cone b-waves, which were faster after CSDS in resilient mice specifically. In females, rod ERGs revealed age-related changes with no change in cone ERGs. Finally, our analysis suggests that baseline ERG can predict with an efficacy up to 71% the expression of susceptibility and resilience before stress exposition in males and females. Overall, our findings suggest that retinal activity is a valid biomarker of stress response that could potentially serve as a tool to predict whether males and females will become susceptible or resilient when facing CSDS.
Highlights
Affecting more than 300 million people worldwide (World Health Organization, 2018), major depressive disorder (MDD) is a leading cause of disability imposing a major burden on modern societies (Ferrari et al, 2013; World Health Organization, 2018)
Our analysis revealed a main effect of phenotype (F(2,87) = 56.0, p < 0.001) highlighting that 10 days of chronic social defeat stress (CSDS) induced social avoidance (SI ratio < 1) in 25 males and 14 females while the remaining 10 males and 14 females continued to interact with CD1 targets (Figures 1B,C)
We tested if the phenotypes of susceptibility and resilience to CSDS are associated with specific ERG alterations and whether baseline ERG signals could detect which males and females undergoing CSDS would develop such phenotypes
Summary
Affecting more than 300 million people worldwide (World Health Organization, 2018), major depressive disorder (MDD) is a leading cause of disability imposing a major burden on modern societies (Ferrari et al, 2013; World Health Organization, 2018). It has been suggested that men and women respond differently to antidepressant treatment (Kornstein et al, 2000; Khan et al, 2005). Early diagnostic of MDD is critical to decrease the longterm prevalence of the disease, which is why the research of an accurate biomarker tool to help clinicians diagnose depression has become increasingly prominent in the last decades. Such a tool would benefit preclinical animal studies allowing researchers to investigate the pathology during its early development.
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