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.
Thomas
Alan J
AJ
Department of Psychiatry and Institute for Ageing and Health, University of Newcastle upon Tyne, UK. a.j.thomas@ncl.ac.uk
Perry
Robert
R
Kalaria
Rajesh N
RN
Oakley
Arthur
A
McMeekin
William
W
O'Brien
John T
JT
D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000032:analysis; D003866:Depressive Disorder / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006179:Gyrus Cinguli / Q000737:chemistry / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008297:Male; D009778:Occipital Lobe / Q000098:blood supply / Q000737:chemistry / Q000473:pathology; D017397:Prefrontal Cortex / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003094:Collagen