Neuropsychiatric disorders (schizophrenia and affective disorders) are studied with the use of postmortem human brain tissue. 146 brains were collected in the last year. Molecular biological techniques (in situ hybridization and RNase protection assays) as well as autoradiography and immunocytochemistry were used to examine three brain regions (n. accumbens/striatum, hippocampus/ entorhinal cortex (ERC) and dorsolateral prefrontal cortex (DLPFC)) thought to be relevant to schizophrenia and affective disorders. The most promising results are as follows: (1) decreases in mRNA for glutamate transporter in hippocampus and ERC of schizophrenics as well as a number of mRNAs for neuromodulators of glutamate neurons (CCK, TRH and proline transporter); (2) decreases in mRNA for GAP-43, a synaptic membrane protein, in DLPFC of schizophrenics; and (3) decreases in mRNA for brain derived neurotrophic factor (BDNF), a brain development protein, in DLPFC of schizophrenics. The abnormalities in the mRNAs for the glutamate transporter as well related peptides suggest that there are abnormal efferent connections from hippocampus and ERC to other cortical and subcortical structures (possibly DLPFC and n. accumbens) in the brains of schizophrenic patients. The abnormalities in mRNAs for BDNF and GAP-43 in DLPFC suggest further problems with the connections from DLPFC to striatum and thalamus in schizophrenics. Taken together, these results support the hypothesis that there is an abnormal neural circuit involving the hippocampus/ ERC-DLPFC-striatum/ n. accumbens in the brains of schizophrenics.
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