Increased density of GAD65/67 immunoreactive neurons in the posterior subiculum and parahippocampal gyrus in treated patients with chronic schizophrenia

Alterations of glutamic acid decarboxylase (GAD) play a crucial role in schizophrenic pathology. While GAD has been studied in several brain regions, its expression in the posterior hippocampus formation has not been investigated in schizophrenia.We studied the brains of 17 patients with chronic schizophrenia and 15 controls. Using the optical dissector method we counted GAD65/67 immunoreactive neurons and pyramidal cells in the posterior hippocampus, subiculum, and parahippocampal gyrus, and measured the cortical thickness in posterior subiculum and parahippocampal gyrus. Patients had received typical neuroleptics for the mean of 20.8 years.In the patients we observed a significant increase of GAD immunoreactive neurons in the subiculum (left/right P = 0.004) and the parahippocampal gyrus (left P = 0.001, right P = 0.006). The hippocampus showed no or only subtle trends towards higher GAD densities. The density of pyramidal neurons and cortical thickness did not differ between the groups. A significant association between GAD density and the duration of illness was found in women with schizophrenia.The current data on GAD65/67 indicates a dysregulation of the GABAergic system in schizophrenia patients that may be associated with cognitive decline. However, a long term effect of neuroleptics on the GABAergic system cannot be excluded.