Modelling Genetic and Environmental Influences on Brain Volume in Twins with Schizophrenia

Abstract

BACKGROUND: Whole brain and grey matter volumes are reduced in schizophrenia. How these pathological abnormalities are influenced by schizophrenia’s genetic and environmental risk remains less clear. METHODS: We investigated the relationship between genetic, common and unique environmental risk on brain volumes in monozygotic and dizygotic twin pairs varying in their concordance for schizophrenia, and healthy control twins. Total brain, grey and white matter volumes were established from structural magnetic resonance images using an automated alogorithm in SPM8 from 86 twin pairs (n=168). Hippocampal volumes were measured manually in the same sample. Between group differences in brain volumes were tested before full genetic modelling in Mx. RESULTS: We found that whole brain, grey, white and right hippocampal volumes were smaller in probands with schizophrenia compared to healthy controls. Well co-twins from DZ discordant pairs also had smaller hippocampal volumes compared to the healthy controls. Whole brain, grey and white matter volumes were heritable, while hippocampal volume was subject to significant common environmental effects. All of the brain volumes tested had a significant negative phenotypic correlation with schizophrenia. Lower birth weight and hypoxia were both associated with lower whole brain volumes, and with lower white and grey matter volumes respectively. There were no significant effects in the patients of cumulative antipsychotic exposure. DISCUSSION: Our data suggest that total brain, grey, white matter and hippocampal volume reductions are associated with schizophrenia. Whole brain and white matter volumes were most strongly linked to genetic effects. Hippocampal volume reductions appear to be particularly sensitive to environmental effects.