Twin studies on childhood externalizing behavior and schizophrenia

Abstract

Mental disorders are abnormal patterns of mental or behavioral activities causing suffering, harm or disabilities. These illnesses can put great burden on patients and their families, and also on the healthcare system and society. However, the etiology of mental disorders remains unclear, after decades of research. In order to help understand both the genetic and environmental contributions to disease, twin studies are often employed. Twin registries are built to collect and effectively utilize twin samples. Structural equation modelling is used to explore structural relationships among variables in the data. Assumptions of the model are set up according to established knowledge of quantitative genetics. The present thesis explores the aetiology of mental disorders via the twin design, using structural equation modeling, in two separate studies. The first study focuses on attention deficit and hyperactivity disorder and conduct disorder, mental problems most common in childhood and adolescence. Information on hyperactivity/inattention and conduct disorder traits was collected from a population-based twin registry in China. Genetic models exploring the genetic and environmental factors overlapping the two traits were employed. The problem of rater bias in questionnaire data was also explored. The results indicated that the two classes of traits were separate entities with substantial overlapping genetic components. The information from parents and teachers had low level of agreement, although each contributes meaningful information. The second study focuses on schizophrenia, which is a chronic and severe mental disorder mostly affecting adults. The concept of the endophenotype, which reflects the mechanisms by which genetic effects lead to disorder, is introduced and employed to help understand the etiology of schizophrenia, Data was collected from a case-based twin registry of European countries. Multivariate models were used to estimate the correlation between schizophrenia and candidate endophenotypes (cognitition and brain volumes), partitioned into genetic and environmental components. Reciprocal causation models were explored to infer the direction of causation between schizophrenia and the endophenotypes. Cognition as measured by IQ and memory was found to exert causal influence on schizophrenia. Parameter estimates indicated that schizophrenia risk decreased in a log-linear fashion as IQ score increases, with schizophrenia risk dropping 3.92% for every point increase of IQ. This thesis demonstrates the utility of the twin study to dissect genetic and environmental components of complex diseases. Knowledge gained from the studies conducted may aid in diagnosis and potentially improve treatment of schizophrenia, ADHD, and conduct disorder.