Congratulations to Drs. Nicolas Cermakian and Patricia Pelufo Silveira for recently obtaining a Ludmer-MI4 Seed Funding Grant! This grant aimed at supporting a new health research project focusing on the role of infection, immunity and/or the microbiome in the development, prevention or treatment of mental health disorders. The funded project is entitled, Maternal immune activation and circadian disruption as risk factors for mental disorders – using transcriptomics to identify individual differences in susceptibility.
We wish Dr. Cermakian, Dr. Silveira, and their collaborators, Dr. Lalit Srivastava and Dr. Tie Yuan Zhang, success in their endeavours.
Project summary
Schizophrenia is a severe neurodevelopmental disorder with lifetime prevalence ~1%. The occurrence of neurodevelopmental disorders such as schizophrenia and autism spectrum disorders rely on a combination of risk factors, including genetic variants and environmental factors. Exposure to prenatal infections is associated with increased risk for neurodevelopmental disorders. For example, influenza infection during pregnancy first trimester leads to a 7-fold risk of the offspring to develop schizophrenia. Up to 80% of patients with schizophrenia show disrupted sleep and circadian rhythms. This led us to propose circadian disturbances as a possible risk factor for schizophrenia, which our recent findings in mice support. This is important because circadian alterations are common in our modern-day societies (e.g. in shift workers, but also, for a large proportion of the population, with modern lifestyle involving irregular schedules of activity, light exposure and meal timing). Here we plan to identify mechanisms underlying this interaction between an immune-related risk factor (maternal infection) with a new environmental risk factor (circadian disruption). We will study the cellular and molecular bases for this interaction, by looking at the impact of the risk factors on gene expression at the cellular level in mouse brains. Furthermore, to underscore the translational potential of this research, we will use gene expression data to develop a new polygenic score as a tool to detect individual differences in susceptibility to these schizophrenia risk factors in human populations. This work will allow designing novel strategies, taking circadian rhythms into consideration, to prevent schizophrenia and other psychiatric conditions.