Genes and brain changes in health and disease
background During development the structure of our brain changes, not only in childhood but also thereafter. Using a longitudinal design in twins, we find that genetic factors influence brain volume change, and these differ from the genetic factors that are involved in overall head size. Thus, our brains continue to develop during adulthood under the influence of specific gene systems or expressions. In a longitudinal twin study in monozygotic and dizygotic twinpairs discordant for schizophrenia, Brans et al investigated whether the progressive brain volume changes in schizophrenia are mediated by genetic or environmental (possibly disease-related) factors. Significant decreases over time in whole brain, frontal and temporal lobe volumes were found in schizophrenia patients and in their unaffected co-twins as compared to control twins. Moreover, bivariate structural equation modelling revealed significant additive genetic influences on schizophrenia liability and progressive brain volume changes. Thus, progressive brain volume loss in schizophrenia is at least partly attributable to genetic factors related to the disease. In a third study, the effects of 690 haplotype tagging snps within 132 autosomal myelin- and oligodendrocyte-related genes on cerebral volume were examined in 88 patients with schizophrenia and 94 healthy comparison subjects, all of Dutch descent. We found suggestive evidence for association (P< 0.05) for 24 snps in the total group of subjects, whereas 43 snps were associated when illness was taken into account. This observation suggests an impact of schizophrenia status on the relationship between oligodendrocyte- and myelin- related genes and cerebral volume. Remarkably, a highly significant proportion of the associated snps were snps in Fibroblast Growth Factor (fgf) related genes. This is consistent with earlier reports on fgf system genes. We hypothesize that within a large number of myelin-related genes, genes of the fgf system may contribute particularly to brain volume deficits as found in schizophrenia.