Morphometric analysis of neuronal and glial cell pathology in the dorsolateral prefrontal cortex in late-life depression.

BACKGROUND: Late-life depression has been associated with cerebrovascular disease and especially with ischaemic white matter hyperintensities on magnetic resonance imaging. Neuroimaging and morphometric studies have identified abnormalities in the dorsolateral prefrontal cortex. AIMS: To examine glial and neuronal density and neuronal volume in the dorsolateral prefrontal cortex in late-life major depression. METHOD: We used the disector and nucleator methods to estimate neuronal density and volume and glial density of cells in the dorsolateral prefrontal cortex in a post-mortem study of 17 individuals with late-life major depression and 10 age-matched controls. RESULTS: We found a reduction in the volume of pyramidal neurones in the whole cortex, which was also present in layer 3 and more markedly in layer 5. There were no comparable changes in non-pyramidal neurones and no glial differences. CONCLUSIONS: Overall, we found a decrease in pyramidal neuronal size in the dorsolateral prefrontal cortex in late-life depression.

A neuropathological study of periventricular white matter hyperintensities in major depression.

BACKGROUND: Signal hyperintensities on magnetic resonance imaging (MRI) are increased in major depression but their pathological basis has never been assessed. We carried out a study of the neuropathological basis of periventricular hyperintensities (PVHs) in major depression. We hypothesised that different pathologies would be associated with the same MRI appearance of PVH and that such causes would be similar in depressed and control subjects. METHODS: In vitro MRI was carried out on coronal slices of brain tissue from 20 elderly subjects with major depression and 20 matched control subjects. PVHs were identified and blindly rated on the films and the tissue was subsequently prepared for neuropathological analysis. Conventional histopathological stains and immunocytochemical stains for glia and macrophages, to identify ischaemic tissue damage, were used. PVHs identified on MRI films were microscopically assessed blind to diagnosis. RESULTS: PVHs were found to be due to one of three main causes: ependymal loss, differing degrees of myelination in adjacent fibre tracts and cerebral ischaemia with associated demyelination. The causes were similar in depressed and control subjects. LIMITATIONS: All depressed subjects had been hospitalised and in spite of scanning 20 subjects only a small number of PVHs were able to be examined in depressed subjects. CONCLUSIONS: The neuropathological basis of PVH was similar in depressed and control subjects, and to previous reports in other diseases. Identical PVHs on MRI can have different causes in depression and this includes cerebral ischaemia.

Neuropathological evidence for ischemia in the white matter of the dorsolateral prefrontal cortex in late-life depression.

BACKGROUND: Signal hyperintensities on magnetic resonance imaging in late-life depression are associated with treatment resistance and poor outcome. These lesions are probably vascular in origin and proposed sites for vascular damage include the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). METHODS: We therefore examined white matter in these areas for microvascular disease and evidence of ischemia using intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). We obtained postmortem tissue from elderly depressed (n = 20) and control (n = 20) subjects and blindly rated microvascular disease and ICAM-1 and VCAM-1 amount using quantitative image analysis in sections of the DLPFC, ACC and occipital cortex (OC; control area). RESULTS: We found a significant increase in ICAM-1 in the deep white matter of the DLPFC in the depressed group (p = 0.01) and a trend towards an increase for VCAM-1 (p = 0.10). In the gyral white matter there was a trend towards significance for both molecules (p = 0.07 and 0.10). No differences were found in the ACC or OC or for microvascular disease in any area. CONCLUSIONS: These findings are consistent with white matter ischemia in the DLPFC and lend support to the 'vascular depression' hypothesis. They implicate the DLPFC as an important site in the pathogenesis of late-life depression and have major implications for the understanding and management of late-life depression and raise the possibility of novel treatments being introduced in the future.

Computed tomography angiography for the evaluation of carotid atherosclerotic plaque: correlation with histopathology of endarterectomy specimens.

BACKGROUND AND PURPOSE: The goal of this study was to determine the efficacy of CT angiography for the characterization of plaque morphology and composition in carotid atherosclerotic disease. METHODS: Fifty-five patients undergoing carotid endarterectomy were imaged preoperatively with single-slice spiral CT angiography. One hundred sixty-five endarterectomy sections were examined histologically at selected levels through the distal common and proximal internal carotid arteries. Plaque density was measured (in Hounsfield units) on axial CT sections, and the presence or absence of ulceration was noted. These observations were compared with the histological findings at corresponding levels. Data were analyzed with 2-sample t tests and 1-way analysis of variance (ANOVA). RESULTS: ANOVA testing showed a statistically significant decrease in CT attenuation values with increasing plaque lipid but with a very high standard deviation of values. No other histological factor showed a statistically significant link with CT attenuation. Plaque ulceration was detected by CT with a sensitivity of 60% and a specificity of 74%. CONCLUSIONS: Analysis of plaque attenuation with single-slice spiral CT does not give useful information concerning plaque composition. The predictive value of CT for the detection of plaque ulceration was moderate. Single-slice CT angiography is insufficiently robust to be a useful tool for the characterization of carotid plaque composition and morphology.