In Pursuit of the Molecular Neuropathology of Schizophrenia-Reply

In reply  Each of the three commentaries on our article¹ raises important issues for discussion.Lee and Tobin² claim a discrepancy between our findings of reduced glutamic acid decarboxylase messenger RNA (GAD mRNA) levels in the prefrontal cortex of schizophrenics and the lack of similar changes in GAD enzyme activity reported by Hanada et al.³ This is not surprising, given the fact that GAD enzyme is unstable and its activity is influenced by confounding factors such as autolysis time⁴ and cause of death.^3,5 Two other studies reported decreased GAD activity in schizophrenics,^6,7 but one only found decreased GAD activity in schizophrenics who did not die a sudden death.⁵ The GAD mRNA is far more resistant to autolysis, and localization by in situ hybridization was successful in all patients and controls included in this study. In the same specimens, staining of GAD enzyme by means