Reduced dysbindin (DTNBP1) mRNA in hippocampus of patients with schizophrenia

Dysbindin has been implicated as an etiological factor in schizophrenia by genetic linkage studies, genetic association studies and molecular studies of postmortem brains of patients with schizophrenia. In this report, we tested if alterations in dysbindin mRNA were found in the hippocampus of patients with schizophrenia by using in situ hybridization. We found significantly reduced dysbindin mRNA in the dentate gyrus, CA4 and CA3, but not CA1, subregions of the hippocampus of patients with schizophrenia as compared with normal controls. Additionally, we found that dysbindin mRNA levels strongly and positively correlated with synaptophysin and spinophilin mRNA levels, which are known to be reduced in patients with schizophrenia. Our results suggest that reductions in dysbindin protein previously found in the hippocampus of patients with schizophrenia may be because of decreased dysbindin mRNA. The significant reduction of dysbindin mRNA found in the hippocampus confirms and extends our initial findings that dysbindin mRNA is significantly reduced in the frontal cortex and tends to be decreased in the midbrain of patients with schizophrenia (Weickert et al. 2004). Taken together, our results suggest that dysbindin mRNA reduction is not anatomically restricted, but may be anatomically specific, in the brains of patients with schizophrenia. Furthermore, subfield-specific reductions in dysbindin mRNA may lead to subfield-specific synaptic pathology in the hippocampus of patients with schizophrenic.