Recent neuroimaging studies indicate changes exist in gross morphology and metabolic activity of the left prefrontal cortex (orbitofrontal and/or dorsolateral) of subjects with depression and schizophrenia. The investigator's recent studies have demonstrated changes in cell architecture in prefrontal cortex which are associated with schizophrenia, providing a morphopathological basis for abnormalities reported in neuroimaging studies on schizophrenic cortex. However, cytoarchitectonic studies of the prefrontal cortex have not been undertaken on depression to date. Thus, based on neuroimaging studies demonstrating gross morphological and metabolic changes in prefrontal cortex in depressive brains the investigator hypothesizes that cytoarchitectonic changes occur in left prefrontal cortex in major depression. Furthermore, multiple lines of evidences implicate dysfunction of monoamine systems in the pathology of affective disorders. Frontal cortex may be a site of this pathology since this region is an important postsynaptic target of monoamine projection systems. Therefore, the investigator also hypothesizes that cytoarchitectonic changes in frontal cortex are accompanied by alterations in neurochemical organization of monoamine systems in this region.
The specific aims of this project will: 1) examine the quantitative cytoarchitecture of the dorsolateral prefrontal cortex in postmortem brain tissue of suicide victims with major depression and compare it to that of nonsuicide major depressive subjects, nondepressed schizophrenics and age- and sex-matched nonpsychiatric controls; 2) establish quantitative cytoarchitectonic criteria for the orbitofrontal cortex in normal human brain and examine the cytoarchitecture of this cortex in the four diagnostic groups; 3) reveal the autoradiographic densitometry of catecholaminergic and serotonergic receptors in prefrontal cortex of the four groups; 4) and compare neuronal and receptor densities for individual cortical layers. To accomplish these aims the investigator will use a direct, 3-dimensional image analyzer to measure cytoarchitectonic parameters (neuronal and glial density, cell size, laminar width) and a computerized imaging device to conduct densitometric analyses of receptors in individual layers of the very same prefrontal regions in the same subjects. The proposed project will detect alterations in neuronal organization (cytoarchitecture and/or chemoarchitecture) of prefrontal cortex which may underlie the neuropathology of depression. This information may elucidate potential neuronal sites for the development of novel antidepressant treatments. In addition, this project will support specificity of the investigator's previous morphopathological findings with respect to schizophrenia and define whether the same or different prefrontal regions are involved in the neuropathology of schizophrenia and major depression.
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