Expression of messenger RNA (mRNA) for the γ-aminobutyric acid(GABA)–synthesizing enzyme, glutamic acid decarboxylase (GAD), in the prefrontal cortex and the number of GABAergic neurons in the hippocampus are reduced in schizophrenia and bipolar disorder. We tested the hypothesis that the expression of the 2 isoforms, one 65 kd (GAD65) and the other67 kd (GAD67), is differentially affected in the hippocampus in schizophrenia and bipolar disorder.
Hippocampal sections from 15 subjects in 3 groups (control subjects and subjects with schizophrenia and bipolar disorder) were studied using an in situ hybridization protocol with sulfur 35–labeled complementary riboprobes for GAD65 and GAD67 mRNA. Emulsion-dipped slides were analyzed for the density of GAD mRNA–positive neurons in4 sectors of the hippocampus and for the cellular expression level of both GAD mRNAs.
The density of GAD65 and GAD67 mRNA–positive neurons was decreased by 45% and 43%, respectively, in subjects with bipolar disorder, but only 14% and 4%, respectively, in subjects with schizophrenia. The decreased density of GAD65 mRNA–positive neurons in subjects with bipolar disorder was significant in sectors CA2/3 and dentate gyrus, and that of GAD67 mRNA–positive neurons was significant in CA4, but not other hippocampal sectors. Cellular GAD65 mRNA expression was significantly decreased in subjects with bipolar disorder, particularly in CA4, but not in schizophrenic subjects. Cellular GAD67 mRNA expression was normal in both groups.
We have found a region-specific deficit of GAD65 and GAD67 mRNA expression in bipolar disorder.