Glutamate decarboxylase(65)-immunoreactive terminals in cingulate and prefrontal cortices of schizophrenic and bipolar brain

Recent postmortem studies have been suggesting that a defect of GABAergic n eurotransmission might occur in the corticolimbic system of subjects with s chizophrenia and bipolar disorder. To explore this possibility, a method fo r immunolocalizing the 65 kdalton isoform of glutamate decarboxylase (GAD(6 5)) has been developed and applied to the anterior cingulate (ACCx) and pre frontal (PFCx) cortices of 12 normal controls (CONs), 12 schizophrenics (SZ s) and 5 manic depressive (MDs) subjects. A computer-assisted technique was employed under strictly blind conditions to determine the density of GAD(6 5)-IR terminals in apposition with pyramidal (PNs) and nonpyramidal (NPs) n eurons and in neuropil (NPL) of layers II, III, V and VI of each cortical r egion. For SZs, no difference in the numerical density of CAD(65)-IR termin als in contact with either PNs or NPs or in NPL of layers II-VI in ACCx or PFCx was detected. There were also no differences in the size of either PNs and NPs that could have influenced the nature of these findings. Using a p ixel count analysis, the size of IR terminals was, however, found to be inc reased in layers II (10.3%) and III (15.8%) of SZs, but only in subjects tr eated with neuroleptic drugs. For MDs, the density of GAD(65)-IR terminals was significantly reduced in all four layers of ACCx, but these differences were most significant in layers II (27.8%) and III (37.2%), whether or not the subjected were treated with neuroleptics. Tn PFCx, the MDs showed simi lar differences in terminal density for PNs and NPs but not neuropil in the four laminae examined. The MD group showed no differences in either the si ze of cell bodies or IR terminals. Age and PMI did not account for any of t he differences between the CONs vs SZs and MDs. Overall, the results of thi s study, though preliminary, suggest that there may be complex changes in G ABAergic terminals in SZ and MD, ones that may vary with respect to primary diagnosis and neuroleptic exposure. (C) 2000 Elsevier Science B.V. All rig hts reserved.