Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients

Previous neuropathological studies have revealed that the corticolimbic sys tem of schizophrenic patients expresses abnormal levels of various synaptic molecules, which are known to be influenced by the neuronal differentiatio n factors, neurotrophins. Therefore, we determined levels of neurotrophins and their receptors in the postmortem brains of schizophrenic patients and control subjects in relation to molecular impairments in schizophrenia. Amo ng the neurotrophins examined, levels of brain-derived neurotrophic factor (BDNF) were elevated specifically in the anterior cingulate cortex and hipp ocampus of schizophrenic patients, but levels of nerve growth factors and n eurotrophin-3 showed no change in any of the regions examined. In parallel, the expressions of TrkB receptor and calbindin-D, which are both influence d by BDNF, were reduced significantly in the hippocampus or the prefrontal cortex. However, neuroleptic treatment did not appear to mimic the neurotro phic change. Neither withdrawal of drug treatment in patients nor chronic a dministration of haloperidol to rats altered levels of BDNF. These findings suggest that neurotrophic abnormality is associated with the corticolimbic structures of schizophrenic patients and might provide the molecular subst rate for pathological manifestations of the illness.