Brain Plasticity, Intelligence and Schizophrenia: influence of genes and environment

This thesis shows that the adult human brain has plastic properties. These plastic properties are at least in part heritable and have functional significance. Identifying genes and environmental factors implicated in brain plasticity is an important next step to optimize brain development in health and in psychiatric diseases, such as schizophrenia. These conclusions are based on 5 studies. Structural brain plasticity was based on a longitudinal design with magnetic resonance imaging. Heritability was measured using structural equation modeling in monozygotic and dizygotic twins discordant for schizophrenia and in healthy twins. Functional significance was based on the intelligence quotient. In a meta-analysis that included over 2000 individuals it was revealed that brain volume changes throughout life (Hedman et al, Human Brain Mapping, 2013). There is a wave of growth in adolescence and possibly another wave of growth in adulthood. In addition, there are periods of brain volume shrinkage. Structural brain plasticity is at least in part heritable, with estimates up to 50 percent heritability for volumes, based on a longitudinal magnetic resonance imaging study in monozygotic and dizygotic twins (Hedman et al, in preparation). These brain volume changes have functional significance. Adults with a higher intelligence show attenuated brain loss and more pronounced brain growth. Genes involved in brain volume changes in healthy adults overlap in part with genes for intelligence. Thus, it appears that continued dynamic brain change in adulthood and intelligence act together in concert, and both are mediated in part by common genes. It is known that there is progressive brain tissue loss in schizophrenia, which is at least in part heritable (Brans et al, Arch Gen Psychiatry, 2008). Cortically, the progressive loss of thickness in schizophrenia was found to be particularly prominent in the left superior temporal cortex, which is at least partly attributable to genes involved in the disease (Hedman et al, under review). Cortical surface area and surface area change are heritable, but not associated with higher genetic (or environmental) liability for schizophrenia. Thus, in schizophrenia there is diminished structural brain plasticity. In this thesis no direct associations between brain plasticity and functional significance were investigated in schizophrenia. However, a meta-analysis focusing on intelligence quotient change, it was revealed that schizophrenia is characterized by a relative lack of gain in global cognitive abilities over time (Hedman et al, Schizophrenia Research, 2013). Moreover, patients with schizophrenia in the chronic phases of the disease, but not the discordant co-twins, show a lack of increase in intelligence quotient over time, thus reflecting that it is probably due to environmental (non-genetic) factors related to the disease (Hedman et al, Psychological Medicine, 2012)