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

Background: We recently reported a laminar-specific reduction in the densit y of tyrosine hydroxylase (TH)immunoreactive axons in the prefrontal cortex of subjects with schizophrenia. In this report, we extend these investigat ions to the entorhinal cortex (ERC), another candidate site of dysfunction in this disorder Methods: Using immunocytochemical techniques and blind quantitative analyse s, we determined the density of TH-immunoreactive axons in the rostral subd ivision of the ERC from seven matched pairs of schizophrenic and control su bjects. Results: The relative density of TH-labeled axons was significantly decreas ed by over 60% in layers 3 and 6 but not in layer I, of the ERC in schizoph renic subjects. In contrast, in the prefrontal cortex of the same subjects, labeled axon density was significantly decreased by 62% only in layer 6. F urthermore, the length of TH-labeled axons did not differ between six match ed pairs of nonschizophrenic psychiatric and control subjects in any layer of the ERC. Finally, the density of TH-labeled axons in the ERC of cynomolg us monkeys chronically treated with haloperidol was not reduced relative to control animals. Conclusions: These findings reveal regional- and laminar-specific alteratio ns in TH-immunoreactive axons that appear to be specific to the pathophysio logy of schizophrenia. (C) 2000 Society of Biological Psychiatry.