Glutamate receptor genes: susceptibility factors in schizophrenia and depressive disorders?

Schizophrenia, depression, and bipolar disorder are three major neuropsychiatric disorders that are among the leading causes of disability and have enormous economic impacts on our society. Although several neurotransmitter systems have been suggested to play a role in their etiology, we still have not identified any gene or molecular mechanism that might lead to genetic susceptibility for or protection against these neuropsychiatric disorders. The glutamatergic receptor system, and in particular the N-methyl-D-aspartate (NMDA) receptor complex, has long been implicated in their etiology. I review the current molecular evidence that supports a critical role for the glutamatergic receptor system in schizophrenia and the potential involvement of this receptor system in depression and bipolar disorder. It is likely that mutations in glutamate receptor genes might alter the risk of developing one of these disorders. Potential future research directions designed to identify these mutations and to elucidate their effect on mental health will be discussed.