Gene X Environment Interactions in Schizophrenia and Bipolar Disorder: Evidence from Neuroimaging

Pierre Alexis Geoffroy, Bruno Etain, Josselin Houenou

Introduction: Schizophrenia (SZ) and Bipolar disorder (BD) are considered as severe multifactorial diseases, stemming from genetic and environmental influences. Growing evidence supports gene x environment (GxE) interactions in these disorders and neuroimaging studies can help us to understand how those factors mechanistically interact. No reviews synthesized the existing data of neuroimaging studies in these issues. Methods: We conduct a systematic review on the neuroimaging studies exploring GxE interactions relative to SZ or BD in PubMed. Results: First results of the influence of genetic and environmental risks on brain structures came from monozygotic twin pairs concordant and discordant for SZ or BD. Few structural magnetic resonance imaging (sMRI) studies have explored the GxE interactions. No other imaging methods were found. Two main GxE interactions on brain volumes have arisen. First, an interaction between genetic liability to SZ and obstetric complications on gray matter, cerebrospinal fluid, and hippocampal volumes. Second, cannabis use and genetic liability interaction effects on cortical thickness and white matter volumes. Conclusion: Combining GxE interactions and neuroimaging domains is a promising approach. Genetic risk and environmental exposures such as cannabis or obstetrical complications seem to interact leading to specific neuroimaging cerebral alterations in SZ. They are suggestive of GxE interactions that confer phenotypic abnormalities in SZ and possibly BD. We need further, larger neuroimaging studies of GxE interactions for which we may propose a framework focusing on GxE interactions data already known to have a clinical effect such as infections, early stress, urbanicity, and substance abuse.