ELEVATED NEURONAL DENSITY IN PREFRONTAL AREA-46 IN BRAINS FROM SCHIZOPHRENIC-PATIENTS - APPLICATION OF A 3-DIMENSIONAL, STEREOLOGIC COUNTING METHOD

Neuropsychologic testing in schizophrenic patients has underscored the prominence of dysfunction in cognitive processes associated with the dorsolateral prefrontal cortex. Quantitative cytometric analysis of ar ea 46 was undertaken in brains from schizophrenic patients to determin e whether there are morphologic changes underlying these cognitive def icits. Postmortem brain specimens from 9 schizophrenic patients, 10 no rmal subjects, and 8 Huntington's diseased patients were fixed in form alin and celloidin embedded. A direct, three-dimensional counting meth od was used to determine cell density and cortical thickness in Nissl- stained sections of area 46. Overall neuronal density was 21% greater in brains from schizophrenic patients in comparison to normal controls . Significant elevations in neuronal density were observed in layers I I, III, IV, and VI. The cortical ribbon was slightly (8%) but not sign ificantly thinner However, layer II exhibited disproportionate thinnin g compared with all other layers. In brains from Huntington's diseased patients, increases in neuronal(35%) and glial (61%) density with sub stantial cortical thinning (30%) were observed. The neuropathology of area 46 in schizophrenia is similar in direction and magnitude to that previously described in area 9 (Selemon et al. [1995] Arch. Gen. Psyc hiatry 52:805-818), except for the abnormalities in layer II, which ar e specific to area 46. In contrast to Huntington's disease, in which c ortical atrophy and gliosis are present, no evidence for cortical cell loss was uncovered in the schizophrenic cohort. The observed elevatio n in neuronal density suggests that a reduction in interneuronal neuro pil may constitute the anatomical substrate for prefrontal cortical dy sfunction in schizophrenia. (C) 1998 Wiley-Liss, Inc.