Schizophrenia susceptibility genes and their neurodevelopmental implications: focus on neuregulin 1.

On the basis of epidemiological as well as neurobiological evidence, schizophrenia has been conceptualized as a neurodevelopmental disorder. It is also known to have a large heritable component and a complex genetic architecture. Many putative susceptibility genes have recently been identified, arising both from positional cloning and candidate gene approaches. The evidence is strong for neuregulin 1, dysbindin and DISC1, and moderate for several others. However, there are key unanswered questions. For example, concerning the molecular basis of genetic association, multiple, mostly non-coding, variants have been found within the genes, complicating discussion as to the strength and interpretation of the data. Second, there is speculation whether the genes converge on common pathways, notably glutamatergic synaptic transmission. Additional questions concern the emerging evidence for epistasis, the clinico-genetic correlates, and the extent to which the genes confer schizophrenia risk via their roles in neurodevelopment. Here, the genetic advances and their neurodevelopmental implications are summarised, with a particular focus on neuregulin 1.