Heritability of Changes in Brain Volume Over Time in Twin Pairs Discordant for Schizophrenia

Context: Structural brain abnormalities have consistently been found in schizophrenia, with increased familial risk for the disease associated with these abnormalities. Some brain volume changes are progressive over the course of the illness. Whether these progressive brain volume changes are mediated by genetic or disease-related factors is unknown. Objective: To investigate whether genetic and/or environmental factors are associated with progressive brain volume changes in schizophrenia. Design: Longitudinal 5-year follow-up in monozygotic (MZ) and dizygotic (DZ) twin pairs discordant for schizophrenia and healthy comparison twin pairs using brain magnetic resonance imaging. Setting: Participants were recruited from the twin pair cohort at the University Medical Center Utrecht. Participants: A total of 92 participants completed the study: 9 MZ and 10 DZ twin pairs discordant for schizophrenia and 14 MZ and 13 DZ healthy twin pairs. Main Outcome Measures: Percentage volume changes of the whole brain; cerebral gray and white matter of the frontal, temporal, parietal, and occipital lobes; cerebellum; and lateral and third ventricles over time between and within twin pairs were compared using repeated measures analysis of covariance. Structural equation modeling was applied to estimate contributions of additive genetic and common and unique environmental factors. Results: Significant decreases over time in whole brain and frontal and temporal lobe volumes were found in patients with schizophrenia and their unaffected co-twins compared with control twins. Bivariate structural equation modeling using cross-trait/cross-twin correlations revealed significant additive genetic influences on the correlations between schizophrenia liability and progressive whole brain (66%; 95% confidence interval [CI], 51%-100%), frontal lobe (76%; 95% CI, 54%-100%), and temporal lobe (79%; CI, 56%-100%) volume change. Conclusion: The progressive brain volume loss found in patients with schizophrenia and their unaffected co-twins is at least partly attributable to genetic factors related to the illness.