Boris Chaumette1, Sarojini Sengupta1, Martin Lepage1, Ashok Malla1, Srividya Iyer1, Guy Rouleau1, Marie-Odile Krebs2, Jai Shah1, Ridha Joober1; 1McGill University, Montreal, Canada, 2Inserm U894 - Ste Anne Hospital, Paris (France)
Background Schizophrenia is a progressive illness and cognitive impairments occur since the early phases of the disease and are unresponsive to actual medication. Glutamatergic receptors are good candidates for cognition in psychosis and are targetable by drugs. Methods In a discovery cohort of 144 first-episode of psychosis patients (FEP) recruited in Montreal (Canada), we have genotyped 58 candidate Single Nucleotide Polymorphisms (SNPs) located in NMDA and metabotropic glutamatergic receptors. These SNPs were tested for association with intelligence quotient (IQ) in our cohort. For replication, we used the ICAAR cohort including 121 ultra-high-risk patients (UHR) recruited in Paris (France). Results A polymorphism located in GRM7 gene was significantly associated with performance IQ in the discovery cohort of FEP under an additive model. This association was replicated in the UHR cohort as well as in the merged dataset where this SNP was significantly associated with VIQ, PIQ, and FIQ. The association was significant for the arithmetic subtest of the WAIS and close to significance for the block design and the information subtests. Conclusions This polymorphism seems to be significantly associated with cognitive impairment in early phases of psychosis only. The cognitive decline during later phases of schizophrenia could be linked to other factors. If confirmed, this genetic association may shed light on the biological factors leading to cognitive deficits in early phases of psychosis and could open the way to new therapeutic interventions targeting the glutamatergic pathway.
