Genetics of schizophrenia: from animal models to clinical studies

Genetic epidemiological studies strongly suggest that additive and interactive genes, each with small effects, mediate the genetic vulnerability for schizophrenia. With the human genome working draft at hand, candidate gene (and ultimately large-scale genome-wide) association studies are gaining renewed interest in the effort to unravel the complex genetics of schizophrenia. In the absence of an unequivocally established biological theory for schizophrenia, identifying candidate genes to be tested in an association paradigm remains a challenging task. We maintain that it is possible to use animal models to map genes or loci involved in behavioural traits that are relevant to schizophrenia. The human genes (or syntenic loci) homologous to those identified in mice can subsequently be tested in patients with schizophrenia who have been carefully phenotyped for traits "isomorphic" to the ones modelled in mice. If confirmed in humans, these genes may be further analyzed in the animal model to identify their role and the biological network they are involved in. To tackle the complex and intimidating problem of the genetics of schizophrenia, it may be necessary to go from animal models to human studies and vice versa; this strategy has been proven to be efficient in less complicated, though complex, human diseases.