Schizophrenia susceptibility genes: emergence of positional candidates and future directions

Schizophrenia is a devastating psychiatric disorder that affects ∼1% of the population worldwide. It is characterized by so-called ‘positive symptoms’ – including delusions and hallucinations – ‘negative symptoms’ – including blunted emotions and social isolation – and cognitive deficits – including impairments in attention and working memory. Studies of the inheritance of schizophrenia have revealed that it is a multifactorial disease that is characterized by multiple genetic susceptibility elements, each contributing a modest degree of risk. Linkage studies have identified several potential schizophrenia susceptibility loci, and in recent years major progress has been made in the identification of positional candidate susceptibility genes from these loci. A central goal of future research will be to use this genetic knowledge to generate specific animal models, characterize genetic interactions, investigate the disease pathophysiology and assist drug-discovery efforts.