Decreased density of tyrosine hydroxylase–immunoreactive axons in the entorhinal cortex of schizophrenic subjects

Background: We recently reported a laminar-specific reduction in the density of tyrosine hydroxylase (TH)-immunoreactive axons in the prefrontal cortex of subjects with schizophrenia. In this report, we extend these investigations to the entorhinal cortex (ERC), another candidate site of dysfunction in this disorder. Methods: Using immunocytochemical techniques and blind quantitative analyses, we determined the density of TH-immunoreactive axons in the rostral subdivision of the ERC from seven matched pairs of schizophrenic and control subjects. Results: The relative density of TH-labeled axons was significantly decreased by over 60% in layers 3 and 6, but not in layer 1, of the ERC in schizophrenic subjects. In contrast, in the prefrontal cortex of the same subjects, labeled axon density was significantly decreased by 62% only in layer 6. Furthermore, the length of TH-labeled axons did not differ between six matched pairs of nonschizophrenic psychiatric and control subjects in any layer of the ERC. Finally, the density of TH-labeled axons in the ERC of cynomolgus monkeys chronically treated with haloperidol was not reduced relative to control animals. Conclusions: These findings reveal regional- and laminar-specific alterations in TH-immunoreactive axons that appear to be specific to the pathophysiology of schizophrenia.