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. (C) 2003 Elsevier B.V. All rights reserved.