ScienceWeek

Science 26 October 2007:
Vol. 318. no. 5850, pp. 576 - 577
DOI: 10.1126/science.1150196

http://scienceweek.com/2007/071028a.htm

Neuroscience: Maternal Effects on Schizophrenia Risk

Paul H. Patterson

Understandably, there is great enthusiasm surrounding the search for candidate genes that increase the risk for devastating mental disorders such as schizophrenia. Progress is being made on several fronts, such as identifying genes that regulate potential molecular pathways underlying brain development. Genetic variants are also being associated with brain functions during particular cognitive tasks. What is equally important, though, and at risk of being lost in this gene fervor, is a balanced view of the variety of risk factors for mental illness. Many mental disorders are now referred to as "genetic diseases" as if they were autosomal dominant, like Huntington's disease, in which inheriting a genetic mutation causes the disorder in every person. In the case of schizophrenia, recent epidemiological and animal studies are taking understanding of environmental influences to the molecular level.

Much of the emphasis on the genetics of schizophrenia comes from twin studies, where the incidence of the disorder in genetically identical (monozygotic) twins is 50%. This 50% concordance leaves considerable room for nongenetic influences. However, even that figure may be an overestimate of the role of genetic influence (1). Several lines of evidence point to a key role for maternal environment.

Not widely appreciated in deducing the importance of genes from twin studies is the fact that two-thirds of monozygotic twins share a placenta, which is a key environmental factor. Individual placentas vary with respect to the transport of various nutrients and hormones (2), which affects normal development. Interestingly, X-chromosome inactivation is affected by placental status (3) and, in the largest study of its kind, so is IQ (4). It is therefore possible that the placental environment can influence the expression of genes that are linked to neurodevelopment and schizophrenia. Moreover, indirect evidence suggests that monozygotic twins sharing a placenta have a higher concordance for schizophrenia than monozygotic twins with separate placentas (5, 6). It would be extremely informative to directly assess placental status in twin studies of schizophrenia, and there are twin registries where this could be done (7).

BOOK SOURCES:

biology of schizophrenia
fetal environment
genes and mental illness
development of the fetal nervous system