Schizophrenia : a consequence of gene-environment interactions?

Schizophrenia is a multi-factorial disease characterized by a high heritability and environmental risk factors (e.g., social stress and cannabis use). It is the combined action of multiple genes of small effect size (Owen et al., 2005) and a number of environmental risk factors (McGrath et al., 2004), which causes the development of this mental disorder (Mackay-Sim et al., 2004). This is conceptualized in the “Two-Hit Hypothesis” of schizophrenia, which predicts that genetic and environmental risk factors interactively (GxE interaction) cause the development of the disorder (Bayer et al., 1999; Caspi and Moffitt, 2006). GxE interactions occur when the expression of an individual's genetic predisposition is dependent on the environment they are living in or when environmental influences on a trait differ according to an individual's genome (Tsuang et al., 2004). Human studies have confirmed that nature and nurture are both important in the development of schizophrenia: the concordance rate in monozygotic twins is only around 50% (Tsuang et al., 2001) and genome wide association studies fail to identify major genetic candidates for schizophrenia (Sanders et al., 2008) suggesting an important role of environmental factors in the development of this disorder.