This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (95)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Neurology  • Magnetic Resonance Imaging  • Depression  • Alert me on articles by topic

A Neuropathological Study

Alan J. Thomas, MRCPsych; John T. O'Brien, DM; Sue Davis, PhD; Clive Ballard, MD; Robert Barber, MD; Rajesh N. Kalaria, FRCPath; Robert H. Perry, FRCPath

Arch Gen Psychiatry. 2002;59:785-792.

Background  White matter hyperintensities on magnetic resonance imaging are increased in major depression in the deep white matter, especially in frontal areas. These lesions have been hypothesized to be ischemic in origin, but there have been no previous neuropathological studies in depression. We investigated the neuropathological basis of these lesions in depression, hypothesizing that they would be more frequently ischemic in origin in depressed subjects.

Methods  We carried out in vitro magnetic resonance imaging on 3 slices of brain tissue (2 frontal, 1 occipital) from 20 elderly subjects who had a history of major depression and 20 elderly controls. The films were blindly rated, and sections were prepared for neuropathological analysis from the same slices and stained conventionally and by means of immunohistochemistry for microglia, macrophages, and astroglia. Lesions on the films were identified in the tissue, blindly described neuropathologically, and subsequently divided into ischemic and nonischemic lesions.

Results  All the deep white matter hyperintensities in the depressed group were found to be ischemic, compared with less than a third of those in the control group, a highly significant difference (P<.001). This difference was due to smaller punctate lesions (<3 mm), which were predominantly ischemic in depressed subjects but not in control subjects. Larger lesions were usually ischemic in both groups. Compared with control subjects, ischemic lesions were significantly more likely to be in the dorsolateral prefrontal cortex compared with the anterior cingulate cortex (P = .003) and the occipital cortex (P = .01) in the depressed subjects.

Conclusions  Deep white matter hyperintensities are more frequently due to cerebral ischemia, and such ischemic lesions are more frequently located at the level of dorsolateral prefrontal cortex in depressed subjects. Our findings strongly support the "vascular depression" hypothesis of late-life depression.

From the Department of Psychiatry (Drs Thomas, O'Brien, Davis, Ballard, Barber, Kalaria, and Perry) and the Institute for Ageing and Health (Drs Thomas, O'Brien, Davis, Ballard, Barber, Kalaria, and Perry), University of Newcastle upon Tyne, Newcastle upon Tyne, England.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Brain Morphology in Older African Americans, Caribbean Hispanics, and Whites From Northern Manhattan
Brickman et al.
Arch Neurol 2008;65:1053-1061.
ABSTRACT | FULL TEXT  

White matter hyperintensities in late life depression: a systematic review
Herrmann et al.
J. Neurol. Neurosurg. Psychiatry 2008;79:619-624.
ABSTRACT | FULL TEXT  

The Brain-Derived Neurotrophic Factor VAL66MET Polymorphism and Cerebral White Matter Hyperintensities in Late-Life Depression
Taylor et al.
AJGP 2008;16:263-271.
ABSTRACT | FULL TEXT  

Regional White Matter Pathology in Mild Cognitive Impairment: Differential Influence of Lesion Type on Neuropsychological Functioning
Delano-Wood et al.
Stroke 2008;39:794-799.
ABSTRACT | FULL TEXT  

Biomarkers of cerebrovascular disease in dementia
MILLS et al.
Br. J. Radiol. 2007;80:S128-S145.
ABSTRACT | FULL TEXT  

White matter changes and late-life depressive symptoms: Longitudinal study
Teodorczuk et al.
Br. J. Psychiatry 2007;191:212-217.
ABSTRACT | FULL TEXT  

The Homocysteine Hypothesis of Depression
Folstein et al.
Am. J. Psychiatry 2007;164:861-867.
ABSTRACT | FULL TEXT  

White Matter Abnormalities in First-Episode, Treatment-Naive Young Adults With Major Depressive Disorder
Ma et al.
Am. J. Psychiatry 2007;164:823-826.
ABSTRACT | FULL TEXT  

White Matter Hyperintensities Rather Than Lacunar Infarcts Are Associated With Depressive Symptoms in Older People: The LADIS Study
O'Brien et al.
AJGP 2006;14:834-841.
ABSTRACT | FULL TEXT  

Vascular Nutritional Correlates of Late-Life Depression
Payne et al.
AJGP 2006;14:787-795.
ABSTRACT | FULL TEXT  

Depression and Comorbidity
O'Brien
AJGP 2006;14:187-190.
FULL TEXT  

Brain white-matter hyperintensities and treatment outcome in major depressive disorder
IOSIFESCU et al.
Br. J. Psychiatry 2006;188:180-185.
ABSTRACT | FULL TEXT  

Successful Mental Health Aging: Results From a Longitudinal Study of Older Australian Men
Almeida et al.
AJGP 2006;14:27-35.
ABSTRACT | FULL TEXT  

Frontal white matter anisotropy and symptom severity of late-life depression: a magnetic resonance diffusion tensor imaging study
Nobuhara et al.
J. Neurol. Neurosurg. Psychiatry 2006;77:120-122.
ABSTRACT | FULL TEXT  

Depressive Psychosis: Clinical Usefulness of MR Spectroscopy Data in Predicting Prognosis
Kado et al.
Radiology 2006;238:248-255.
ABSTRACT | FULL TEXT  

Generalized atherosclerosis, cognitive decline, and depressive symptoms in old age
Vinkers et al.
Neurology 2005;65:107-112.
ABSTRACT | FULL TEXT  

Effects of Acute Tryptophan Depletion on Mood and Cognitive Functioning in Older Recovered Depressed Subjects
Porter et al.
AJGP 2005;13:607-615.
ABSTRACT | FULL TEXT  

Dilatation of the Virchow-Robin Space Is a Sensitive Indicator of Cerebral Microvascular Disease: Study in Elderly Patients with Dementia
Patankar et al.
Am. J. Neuroradiol. 2005;26:1512-1520.
ABSTRACT | FULL TEXT  

Cerebrovascular Disease and Late-Life Depression
Kales et al.
AJGP 2005;13:88-98.
ABSTRACT | FULL TEXT  

Increase in Interleukin-1{beta} in Late-Life Depression
Thomas et al.
Am. J. Psychiatry 2005;162:175-177.
ABSTRACT | FULL TEXT  

A Volumetric Study of MRI Signal Hyperintensities in Late-Life Depression
Firbank et al.
AJGP 2004;12:606-612.
ABSTRACT | FULL TEXT  

Neuropathological Study of the Dorsal Raphe Nuclei in Late-Life Depression and Alzheimer's Disease With and Without Depression
Hendricksen et al.
Am. J. Psychiatry 2004;161:1096-1102.
ABSTRACT | FULL TEXT  

Hippocampal volume change in depression: late- and early-onset illness compared
Lloyd et al.
Br. J. Psychiatry 2004;184:488-495.
ABSTRACT | FULL TEXT  

Prognostic value of frontal functional neuroimaging in late-onset severe major depression
NAVARRO et al.
Br. J. Psychiatry 2004;184:306-311.
ABSTRACT | FULL TEXT  

Anterior Cingulate, Gyrus Rectus, and Orbitofrontal Abnormalities in Elderly Depressed Patients: An MRI-Based Parcellation of the Prefrontal Cortex
Ballmaier et al.
Am. J. Psychiatry 2004;161:99-108.
ABSTRACT | FULL TEXT  

White Matter Hyperintensity Progression and Late-Life Depression Outcomes
Taylor et al.
Arch Gen Psychiatry 2003;60:1090-1096.
ABSTRACT | FULL TEXT  

Changes in DWI and MRS associated with white matter hyperintensities in elderly subjects
Firbank et al.
Neurology 2003;61:950-954.
ABSTRACT | FULL TEXT