Fm. Benes et al., DIFFERENCES IN THE SUBREGIONAL AND CELLULAR-DISTRIBUTION OF GABA(A) RECEPTOR-BINDING IN THE HIPPOCAMPAL-FORMATION OF SCHIZOPHRENIC BRAIN, Synapse, 22(4), 1996, pp. 338-349
Recent postmortem studies have reported a marked upregulation of GABA(
A) receptor binding activity in the anterior cingulate and prefrontal
cortices of schizophrenic subjects. Because the hippocampal formation
is a key corticolimbic region that has also been implicated by both po
stmortem and brain imaging studies in the pathophysiology of this diso
rder, the current report has sought to determine whether alterations o
f GABA(A) receptor binding might also be detected in this region from
15 normal controls and 8 schizophrenic subjects. Using a low resolutio
n autoradiographic approach, the results show a significant increase o
f specific GABA(A) receptor binding activity in the area dentata (gran
ule cell layer), CA4, CA3 (str. oriens, str. pyramidale), subiculum, a
nd presubiculum of the schizophrenic group. The magnitude of the incre
ase was greatest in CA3 and lowest in the CA1 sector. When high resolu
tion analyses were performed on emulsion-coverslip preparations, a mod
est increase of binding (43%, P = 0.05) was observed on pyramidal, but
not non-pyramidal neurons in sector CA1. Rather unexpectedly, GABA(A)
binding in sector CA3 was not significantly different on pyramidal ce
lls, but was almost three-fold higher (P = 0.015) on non-pyramidal neu
rons of the schizophrenic group. There was no relationship of age or t
he postmortem interval to the parameters showing significant changes i
n the schizophrenic group. Moreover, patients both with and without ne
uroleptic exposure showed upregulation of GABA(A) receptor binding act
ivity. Taking together the rather modest increase of binding activity
in CA1 and the more marked upregulation in CA3, as well as the differe
ntial changes on pyramidal neurons of CA1 vs. non-pyramidal neurons in
CA3, the findings reported here are consistent with the possibility t
hat a disturbance of brain development could have occurred either peri
natally or perhaps even well into the postnatal period, and have given
rise to discreet subregional and cellular alterations of disinhibitor
y GABAergic modulation in sector CA3 of schizophrenics. Overall, the d
ata reported here provide further evidence that alterations of GABAerg
ic activity may occur in the hippocampal formation of schizophrenic pa
tients. (C) 1996 Wiley-Liss, Inc.