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Regional Specificity in the Neuropathologic Substrates of Schizophrenia
A Morphometric Analysis of Broca's Area 44 and Area 9
Lynn D. Selemon, PhD;
Jasna Mrzljak, MD;
Joel E. Kleinman, MD, PhD;
Mary M. Herman, MD;
Patricia S. Goldman-Rakic, PhD
Arch Gen Psychiatry. 2003;60:69-77.
Background Numerous recent studies of postmortem schizophrenic brains have reported the presence of structural abnormalities in the dorsolateral prefrontal cortex (dlPFC) that are consistent with a reduction of neuropil. Ventrolateral prefrontal areas have been studied less extensively, and therefore it is not clear whether these cortices exhibit pathologic abnormalities of the same type and magnitude. Because thought disturbances in schizophrenic patients involve language processing, we have performed a morphometric analysis of Broca's area in the ventral frontal lobe.
Methods Neuronal and glial density and somal size were assessed via stereologic cell counting in postmortem samples of Broca's area 44 in 9 schizophrenic patients and 14 normal controls. Cell density was reexamined in dorsolateral prefrontal area 9 as an internal control.
Results We did not detect abnormalities in overall or laminar neuronal density, glial density, cortical thickness, or somal size in area 44 of schizophrenic patients. In contrast, neuronal density in area 9 exhibited a 12% increase in the schizophrenic cohort, replicating previous findings. In addition, there was a significant effect of disease on laminar neuronal density in area 9, with neuronal density tending to be higher (7%-29%) in all layers.
Conclusions The absence of significant cytoarchitectonic abnormalities in Broca's area in the same brains in which the dlPFC exhibited an increase in neuronal density suggests that the neuropil deficit is a regionally specific pathologic finding in schizophrenia and indicates that the dlPFC is a particularly vulnerable target of the disease process.
From the Department of Neurobiology, Yale University School of Medicine, New Haven, Conn (Drs Selemon, Mrzljak, and Goldman-Rakic); and Clinical Brain Disorders Branch, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, Bethesda, Md (Drs Kleinman and Herman).
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