Foetal origins of schizophrenia: Testable hypotheses of genetic and environmental influences

Abstract

Although four-fifths of the variance in schizophrenia is attributable to genes, the locus of genetic defect remains elusive. Moreover, genetic investigation provides little detail, beyond suggesting that the contribution of genes is complex, probably polygenic and unlikely to be sufficient in most cases to allow expression of the syndrome (Vincente & Kennedy, 1997). Some apparently genetic effects also need explanation in a more complex model. Population studies show that schizophrenia is more likely to be inherited from an affected mother than from an affected father (Byrne et al, 2002), and increasing paternal age confers increased risk (Malaspina et al, 2001). Other effects are difficult to explain in conventional genetic terms: season of birth, urbanicity and migration are consistently reported to affect rates of schizophrenia in adulthood (Mortensen et al, 1999; Cantor-Graae et al, 2003), as is prenatal exposure to famine (Susser & Lin, 1992). Hypotheses of schizophrenia must be able to account for this interplay of genetic and environmental risk factors.