Novel variants in the promoter region of the CREB gene in schizophrenic patients

Cyclic AMP-responsive element-binding protein (CREB) is one of the messenge r molecules involved in intracellular signal transduction pathways used by most dopamine and serotonin receptor subtypes. In addition, CREB stimulates the expression of a number of genes, alterations in the expression of whic h may be associated with schizophrenia. The promoter region of the human CR EB gene was therefore analyzed to identify genetic variants that may lead t o the modification of CREB expression and contribute to schizophrenia. Eigh ty unrelated schizophrenics and 100 healthy controls were screened for gene tic variants of the CREB gene by SSCP analysis, followed by direct sequenci ng of PCR products. Two novel variants (-933T-->C and -413G-->A) were found only in schizophrenics. A patient with the -933T-->C variant had unusual c linical characteristics in addition to typical schizophrenic symptoms.