Seeing is believing: A structural neuroimaging paradigm of gene-environment interactions in schizophrenia

The study of gene-environment interactions is complicated because of the difficulty measuring environmental exposures. Developmental trauma and cannabis have been associated with schizophrenia risk, but reporting bias may play a role, causing spurious associations. We designed a new paradigm, using structural neuroimaging measures, to investigate GxE in schizophrenia in which reporting bias cannot impact on the findings. Neuroimaging measures in schizophrenia represent expression of genetic risk or better, given that genetic risk moderates environmental sensitivity, gene-environment interactions. Given the fact that biased measures of environmental exposures cannot impact on the brain, the use of neuroimaging phenotypes in studies of GxE may provide direct proof for environmental impact. We hypothesized that if GxE plays a role in the brain alterations in schizophrenia, a direct effect of developmental trauma and cannabis should be present in cases (as they carry schizophrenia genes causing differential sensitivity to environmental exposures) but not in controls. We used the measure of cortical thickness, arguably most sensitive for this purpose, to test these hypotheses in a sample of around 80 cases and 80 controls. For each person, 70 measures of cortical thickness were available. Analysis of the data revealed that both developmental trauma and cannabis impacted on cortical thickness in the cases, but not in the controls, strongly suggesting unconfounded and unbiased contributions of environmental exposures to GxE underlying brain alterations in schizopohrenia.