The dynamic human brain : Genetic aspects in schizophrenia and health

Abstract

The general aim of this thesis is to explore the possible mechanisms underlying the individual differences in brain structure and brain structure change in healthy adults and schizophrenia patients. For this purpose, Magnetic Resonance Imaging scans of the brain were acquired in schizophrenia patients, their relatives and healthy comparison subjects. Since all studies are conducted in relatives, we were able to disentangle genetic and environmental influences on the studied phenotypes. Taken together, these studies show that in adulthood the brain continues to be dynamic. In the longitudinal study of healthy participants we demonstrated that brain volume change during a 5-year period through the 3rd to 6th decade of life is heritable. Moreover, the degree of brain loss during that time period is inversely related to the level of intelligence. Interestingly, genes involved in brain loss over time overlap with genes for intelligence and differ from those related to absolute brain volume. Thus, it appears that continued brain maturation in adult life and intellectual development go hand in hand, and both are mediated by common genes. Regarding the progressive brain volume changes in schizophrenia, we conclude that a significant proportion of the progressive brain volume loss that we observed both in schizophrenia patients and their unaffected co-twins during a 5-year interval is at least partly attributable to genes that are implicated in the disease. This implicates that progressive brain tissue loss in schizophrenia can no longer be considered to be solely due to medication intake, smoking or outcome. Finding the (patho)physiological processes underlying these progressive brain changes in schizophrenia is of importance because this knowledge may ultimately enable us to halt or even reverse the disease process.