Grant: Project Grant

A neurodevelopmental origin is likely in schizophrenia, bipolar disorder and recurrent major depression. The pathophysiology remains mysterious mainly due to difficulties in accessing living neuronal tissue in high-risk youths. The study of the retina, by providing such an access, may provide novel insights in etiology, treatment and heterogeneity of these major disorders (Adams & Nasrallah 2018; Silverstein et al 2020). Our progress in ERG have shown that genetically high-risk children (GHRs) may present ERG anomalies (under the form of diminished rod amplitude and cone prolonged latencies) that adult patients also display (Gagné et al 2020). Our reported and pilot findings signpost that ERG may become a powerful catalyst of discovery into the early hits to the developing brain. We are among the major international groups having contributed advances in ERG anomalies as early risk endophenotypes, their longitudinal link with a deterioration of the risk trajectory in GHRs and potential predictivity to a later transition to illness. We aim to investigate further the role of retinal anomalies in the deviant early trajectory heading to schizophrenia, bipolar disorder and recurrent major depression, while taking account of other known childhood risk factors such as cognitive deficits, psychotic-like experiences and childhood trauma. Our short-term objective, in a longitudinal study of 400 GHRs aged 6 to 24 years born to an affected parent, is to test two hypotheses: 1. Longitudinal mechanisms and critical timings marked by rods and cones ERG anomalies may underlie the deterioration of the risk trajectory toward a later transition to illness. 2. Different rod and cone anomalies will have distinctive effects on the risk trajectory and may mark heterogeneity in developmental pathways heading to different outcomes. The mid- or longterm goal is to translate the obtained knowledge into decision trees for early detection and into personalized preventive interventions.