Background
Elderly depressed patients have more vascular hyperintensities in frontal white matter
and basal ganglia than elderly control subjects. Cell pathology that might be related
to increased vascular hyperintensities has not been examined.
Methods
Postmortem samples from the orbitofrontal cortex (ORB) were collected in 15 elderly
subjects with major depressive disorder (MDD) and 11 age-matched control subjects.
Cell packing density of neurons and glia, density of pyramidal and nonpyramidal neurons,
and cortical and laminar width were measured.
Results
The overall (layers I–VI) packing density of ORB neurons with pyramidal morphology
was markedly decreased in MDD (by 30%) as compared with control subjects. Further
laminar analysis of pyramidal neurons density revealed significant reductions in layers
IIIc and V in MDD. In contrast, in MDD the density of nonpyramidal neurons and glia
and cortical and laminar width were comparable to control values.
Conclusions
In elderly subjects with depression, the density of pyramidal neurons in the ORB was
particularly low in cortical layers V and III, the origin of prefronto-striatal and
prefronto-cortical and prefronto-amygdalar projections. Degeneration of neurons furnishing
these projections might be related to the white matter hyperintensities previously
observed. Neuronal pathology seems to be more severe in elderly than in younger subjects
with MDD.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Cortical and subcortical afferents to the amygdala of the rhesus monkey (Macaca mulatta).Brain Res. 1980; 190: 347-368
- Executive dysfunction, heart disease burden, and remission of geriatric depression.Neuropsychopharmacology. 2004; 29: 2278-2284
- ‘Vascular depression’ hypothesis.Arch Gen Psychiatry. 1997; 54: 915-922
- Diagnostic and Statistical Manual of Mental Disorders. 4th ed. American Psychiatric Association, Washington, DC1995
- Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys.J Comp Neurol. 1995; 363: 615-641
- Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys.J Comp Neurol. 1995; 363: 642-664
- White matter hyperintensity on magnetic resonance imaging.J Neuropsychiatry Clin Neurosci. 1989; 1: 135-144
- Subcortical hyperintensity on magnetic resonance imaging.Am J Psychiatry. 1990; 147: 187-189
- The density and spatial distribution of GABAergic neurons, labelled using calcium binding proteins, in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia.Biol Psychiatry. 2002; 51: 377-386
- Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder.Cereb Cortex. 2002; 12: 386-394
- Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder.Arch Gen Psychiatry. 2001; 58: 545-553
- A molecular and cellular theory of depression.Arch Gen Psychiatry. 1997; 54: 597-606
- (ver. 2)Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition. Biometrics Research Department, New York State Psychiatric Institute, New York1996
- Mediodorsal nucleus.J Comp Neurol. 1988; 277: 195-213
- Qualitative magnetic resonance imaging findings in geriatric depression. Possible link between later-onset depression and Alzheimer’s disease?.Psychol Med. 1997; 27: 421-431
- Neuroanatomic localization of magnetic resonance imaging signal hyperintensities in geriatric depression.Stroke. 1998; 29: 613-617
- The orbital and medial prefrontal circuit through the primate basal ganglia.J Neurosci. 1995; 15: 4851-4867
- Differential vulnerability of anterior white matter in nondemented aging with minimal acceleration in dementia of the Alzheimer type.Cereb Cortex. 2004; 14: 410-423
- Distinction of early- and late-onset depression in the elderly by their lifetime symptomatology.Int J Geriatr Psychiatry. 2000; 15: 1138-1142
- Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer’s disease: I. Superior frontal and inferior temporal cortex.J Comp Neurol. 1990; 301: 44-54
- Clinical and phenomenological comparisons of late-onset and early-onset depression.Am J Psychiatry. 1995; 152: 785-788
- Neuroanatomic substrates of depression in the elderly.J Geriatr Psychiatry Neurol. 1993; 6: 39-58
- Biological risk factors in late life depression.Biol Psychiatry. 2002; 52: 185-192
- Clinical characteristics of magnetic resonance imaging-defined subcortical ischemic depression.Biol Psychiatry. 2004; 55: 390-397
- Atrophy and high intensity lesions.Neuropsychopharmacology. 2000; 22: 264-274
- Late-onset minor and major depression.Proc Natl Acad Sci U S A. 1998; 95: 7654-7658
- Autonomous neurobiological pathways to late-life major depressive disorder.Neuropsychopharmacology. 2002; 26: 229-236
- Neuroanatomical substrates of late-life minor depression. A quantitative magnetic resonance imaging study.Arch Neurol. 1997; 54: 613-617
- Anatomic evaluation of the orbitofrontal cortex in major depressive disorder.Biol Psychiatry. 2004; 55: 353-358
- Reduction of orbital frontal cortex volume in geriatric depression.Biol Psychiatry. 2000; 48: 971-975
- Subcortical lesion severity and orbitofrontal cortex volume in geriatric depression.Biol Psychiatry. 2003; 54: 529-533
- Medial orbital frontal lesions in late-onset depression.Biol Psychiatry. 2001; 49: 803-806
- BDNF and 5-HT.Trends Neurosci. 2004; 27: 589-594
- Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder.Biol Psychiatry. 2000; 48: 861-873
- Glial reduction in the subgenual prefrontal cortex in mood disorders.Proc Natl Acad Sci U S A. 1998; 95: 13290-13295
- Decreased somal size of deep layer 3 pyramidal neurons in the prefrontal cortex of subjects with schizophrenia.Arch Gen Psychiatry. 2001; 58: 466-473
- Direct and indirect pathways from the amygdala to the frontal lobe in rhesus monkeys.J Comp Neurol. 1981; 198: 121-136
- Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression.Biol Psychiatry. 1999; 45: 1085-1098
- Neuronal and glial somal size in the prefrontal cortex.Arch Gen Psychiatry. 1998; 55: 215-224
- The laminar pattern of connections between prefrontal and anterior temporal cortices in the Rhesus monkey is related to cortical structure and function.Cereb Cortex. 2000; 10: 851-865
- Thinning of the cerebral cortex in aging.Cereb Cortex. 2004; 14: 721-730
- The possibility of neurotoxicity in the hippocampus in major depression.Biol Psychiatry. 2000; 48: 755-765
- Callosal and intrahemispheric connectivity of the prefrontal association cortex in rhesus monkey.J Comp Neurol. 1984; 226: 403-420
- Abnormally high neuronal density in the schizophrenic cortex.Arch Gen Psychiatry. 1995; 52: 805-818
- Evidence for progression in frontal cortical pathology in late-stage Huntington’s disease.J Comp Neurol. 2004; 468: 190-204
- Hippocampal atrophy in recurrent major depression.Proc Natl Acad Sci U S A. 1996; 93: 3908-3913
- Untreated depression and hippocampal volume loss.Am J Psychiatry. 2003; 160: 1516-1518
- Age-dependent reductions in the level of glial fibrillary acidic protein in the prefrontal cortex in major depression.Neuropsychopharmacology. 2004; 29: 2088-2096
- Structural neuroimaging and mood disorders.Biol Psychiatry. 1998; 43: 705-712
- Cerebrovascular disease and depression symptoms in the cardiovascular health study.Stroke. 1999; 30: 2159-2166
- Hippocampal volume and incident dementia in geriatric depression.Am J Geriatr Psychiatry. 2002; 10: 62-71
- Cellular changes in the postmortem hippocampus in major depression.Biol Psychiatry. 2004; 56: 640-650
- Structural brain investigations in affective disorders.in: Soares J.C. Brain Imaging in Affective Disorders. Marcel Dekker, New York2003: 53-78
- Evidence of white matter tract disruption in MRI hyperintensities.Biol Psychiatry. 2001; 50: 179-183
- Smaller orbital frontal cortex volumes associated with functional disability in depressed elders.Biol Psychiatry. 2003; 53: 144-149
- Ischemic basis for deep white matter hyperintensities in major depression.Arch Gen Psychiatry. 2002; 59: 785-792
- Regional frontal cortical volumes decrease differentially in aging.Neuroimage. 2002; 17: 657-669
- A voxel-based morphometric study to determine individual differences in gray matter density associated with age and cognitive change over time.Cereb Cortex. 2004; 14: 966-973
- Depression in later life.J Affect Disord. 2001; 65: 19-26
Article info
Publication history
Published online: June 16, 2005
Accepted:
April 8,
2005
Received in revised form:
March 29,
2005
Received:
November 10,
2004
Identification
Copyright
© 2005 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
