Gene-environment interactions in the etiology of psychiatric and neurodevelopmental disorders

Huntington's disease and Rett syndrome may be good candidates since patients often show psychiatric symptoms and both have a known, causative single-gene alteration that make it possible to study gene-environment interactions on psychiatric endophenotypes using rodent models of these diseases. This chapter discusses environmental manipulations associated with rodent studies. Environmental enrichment is made up of social and nonsocial components that both have a significant impact on mice. The chapter focuses on brain-derived neurotrophic factor (BDNF) and glucocorticoids in the context of environmental modulation and affective disorders. It describes Rett syndrome and work done in mouse models of Methyl-CpG-binding protein 2 (MeCP2) deficits that have helped to understand the association between this gene, environmental modulation and neurodevelopmental/psychiatric disorders. Although the genetic contribution to phenotype variation in complex brain disorders is often attributed to the different combinations of genes and mutation types involved, an additional factor may be genetic mosaicism.