Grant: Operating Grant

Genetic/environmental factors are undoubtedly in cause in schizophrenia (SZ) and bipolar depression (BP). These disorders complexity complicate the identification of involved genes. First, current definitions of SZ and BP include different disease entities, each having its own causes; second, some of these disease entities result from the joint action of many different causes, both genetic and environmental, and third, the clinical manifestations of these disorders are varied and complex to measure. We believe that in order to detect the gene/environment interactions involved in these disorders, analyses should be improved by greater phenotype accuracy. Thus, we investigated cognitive intermediate phenotypes (CIP), considering that CIPs would be closer to genotype than clinical diagnosis. Our study involved a 20-year long accumulated sample of 2500 members from 48 well-characterized multigenerational families of Eastern Quebec that are densely affected by SZ or by BP. This transgenerational sample permitted us to extend our analyses to the young high risk offspring (HRs) for SZ and BP of the third or fourth generations and allowed us to innovatively combine a developmental psychopathology with a genetic approach. The interdisciplinary combination of expertise of our research team allowed us to demonstrate that HRs and non-affected adult relatives (NAARs) displayed important cognitive impairments similar to those observed in adult patients. Moreover, particular cognitive deficits were proved to present distinct generational patterns from childhood to adulthood. In particular, impairments of the visual episodic memory were common to patients and HRs and, as such, act as a predictor of illness. This proposal objective is to characterize further the phenotype in this unique sample by investigating CIPs. This will allow us to look at trajectories of cognitive deficits from childhood to adulthood and at the genetic mechanisms involving cognition in SZ an BP.