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Ischemic basis for deep white matter hyperintensities in major depression: a neuropathological study
Alan J Thomas1, John T O'Brien, Sue Davis
1Department of Psychiatry, Institute for Ageing and Health, University of Newcastle upon Tyne, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, England. a.j.thomas@ncl.ac.uk
Archives of General Psychiatry
|September 7, 2002
Summary
Deep white matter hyperintensities in major depression are primarily ischemic, particularly in the dorsolateral prefrontal cortex. This supports the vascular depression hypothesis in late-life depression.
Area of Science:
- Neuropathology
- Neuroimaging
- Geriatric Psychiatry
Background:
- White matter hyperintensities (WMH) are common in major depression, particularly in frontal deep white matter.
- Previous hypotheses suggested an ischemic origin for WMH in depression, but lacked neuropathological evidence.
- This study aimed to investigate the neuropathological basis of WMH in depression.
Purpose of the Study:
- To neuropathologically examine deep white matter hyperintensities in elderly individuals with and without major depression.
- To determine if these lesions are predominantly ischemic in depressed subjects.
- To identify the specific locations of ischemic lesions in the depressed brain.
Main Methods:
- In vitro MRI and neuropathological analysis of frontal and occipital brain slices from 20 depressed elderly subjects and 20 controls.
- Blind rating of MRI scans and neuropathological examination of stained tissue sections.
- Classification of lesions as ischemic or nonischemic based on neuropathological findings.
Main Results:
- All deep white matter hyperintensities in the depressed group were ischemic, significantly more than in controls (P<.001).
- Smaller punctate lesions (<3 mm) were predominantly ischemic in depressed subjects.
- Ischemic lesions were more frequent in the dorsolateral prefrontal cortex in depressed subjects compared to controls.
Conclusions:
- Deep white matter hyperintensities in depression are largely due to cerebral ischemia.
- Ischemic lesions are more prevalent in the dorsolateral prefrontal cortex in depressed individuals.
- Findings support the vascular depression hypothesis for late-life depression.