Atrophy and High Intensity Lesions Complementary Neurobiological Mechanisms in Late-Life Major Depression
Abstract
The primary objective of our study was to examine the role of atrophy, high intensity lesions and medical comorbidity in the pathophysiology of major depressive disorder in the elderly (late-life MDD). Our sample was comprised of 51 patients with late-life MDD and 30 non-depressed controls. All subjects were scanned on 1.5 tesla magnetic resonance imaging scanner (MRI) and absolute and normalized measures of brain and lesion volumes were obtained and used for comparison between groups. Patients with MDD had significantly smaller frontal lobe volumes, together with larger whole brain lesion volumes when compared with controls (p < .05). Whole brain lesion volumes correlated significantly (r = 0.41, p = .006) with overall medical comorbidity. The odds ratio (OR) for existing MDD increases significantly with a decrease in frontal lobe volume and an increase in whole brain lesion volumes (p < .05). Our findings suggest that atrophy and high intensity lesions represent relatively independent pathways to late-life MDD. While medical disorders lead to neuropathological changes that are captured on MR imaging as high intensity signals, atrophy may represent a relatively autonomous phenomenon. These findings have broad implications for the pathophysiology of mood disorders and suggest that complementary neurobiological processes may lead to cumulative neuronal injury thereby predisposing to clinical depression.
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MDD subjects have smaller normalized frontal lobe volumes compared with nondepressed controls after controlling for age, gender and total cumulative illness rating scale score.
“MDD subjects have smaller normalized frontal lobe volumes when compared with the nondepressed controls after controlling for age, gender and “total cumulative illness rating scale score” [61].”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [61]
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Brain Network Dysfunction in Late-Life Depression
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Localization of age-associated white matter hyperintensities in late-life depression
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Is vascular depression a distinct sub-type of depressive disorder? A review of causal evidence
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Artery-vein separation via MRA-An image processing approach
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Animal models for the study of depressive disorder
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Depression with late onset is associated with right frontal lobe atrophy
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Hippocampal changes and white matter lesions in early-onset depression
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Making sense of neuroimaging in psychiatry
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Protein Binding in Patients With Late-Life Depression
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Self-citationIs major depression a neurologic disorder with psychiatric symptoms?
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Cognitive Deficits in Geriatric Depression
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Anterior cingulate dysfunction in geriatric depression
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Amygdala Volume in Late-Life Depression: Relationship with Age of Onset
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Proton magnetic resonance spectroscopy of late-life major depressive disorder
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Widespread Effects of Hyperintense Lesions on Cerebral White Matter Structure
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Longitudinal Association of Initiation/Perseveration and Severity of Geriatric Depression
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White matter hyperintensities and chronicity of depression
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Three-Dimensional Surface Mapping of the Caudate Nucleus in Late-Life Depression
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Psychiatric Disease in the Twenty-First Century: The Case for Subcortical Ischemic Depression
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Subtypes of Mild Cognitive Impairment Among the Elderly With Major Depressive Disorder in Remission
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Progression of Subcortical Ischemic Disease From Vascular Depression to Vascular Dementia
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Kumar, A. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00331-1 · Cited by 52 · see citing works
Self-citationTaylor, W. D., Zhao, Z., Ashley‐Koch, A., Payne, M. E., Steffens, D. C., Krishnan, R. R., Hauser, E., & MacFall, J. R. (2013) · Human Brain Mapping · doi:10.1002/hbm.21445 · Cited by 50 · see citing works
Neuropsychiatric Significance of Subcortical Hyperintensity
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Salo, K. I., Scharfen, J., Wilden, I. D., Schubotz, R. I., & Holling, H. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.01241 · Cited by 48 · see citing works
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Psychotic major depression in older people: a systematic review
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Brain levels of high-energy phosphate metabolites and executive function in geriatric depression
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Multimodal Brain Connectivity Analysis in Unmedicated Late-Life Depression
Tadayonnejad, R., Yang, S., Kumar, A., & Ajilore, O. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096033 · Cited by 41 · see citing works
Self-citationData From the VITA Study Do Not Support the Concept of Vascular Depression
Rainer, M. K., Mucke, H. A., Zehetmayer, S., Krampla, W. W., Kuselbauer, T., Weissgram, S., Jungwirth, S., Tragl, K., & Fischer, P. A. (2006) · American Journal of Geriatric Psychiatry · doi:10.1097/01.jgp.0000218326.91287.66 · Cited by 40 · see citing works
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Aging and brain activation with working memory tasks: an fMRI study of connectivity
Cook, I. A., Bookheimer, S. Y., Mickes, L., Leuchter, A. F., & Kumar, A. (2007) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1678 · Cited by 38 · see citing works
Self-citationAge of onset of depression and quantitative neuroanatomic measures: absence of specific correlates
Kumar, A., Bilker, W. B., Jin, Z., Udupa, J. K., & Gottlieb, G. L. (1999) · Psychiatry Research Neuroimaging · doi:10.1016/s0925-4927(99)00021-9 · Cited by 37 · see citing works
Self-citationCurrent Understanding of the Neurobiology and Longitudinal Course of Geriatric Depression
Weisenbach, S. L., & Kumar, A. (2014) · Current Psychiatry Reports · doi:10.1007/s11920-014-0463-y · Cited by 35 · see citing works
Self-citationStructural Neuroimaging of Geriatric Depression
Benjamin, S., & Steffens, D. C. (2011) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2011.02.001 · Cited by 35 · see citing works
Structural MRI Changes of the Brain in Depression
Kanner, A. M. (2004) · Clinical EEG and Neuroscience · doi:10.1177/155005940403500111 · Cited by 36 · see citing works
Grool, A. M., van der Graaf, Y., Mali, W. P. T. M., Geerlings, M. I., & on behalf of the SMART Study Group (2011) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2010.232413 · Cited by 35 · see citing works
- Authors
- Kumar, A.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Kumar, A
- Venue
- Neuropsychopharmacology
- Published
- 2000-03
- Volume
- 22
- Issue
- 3
- Pages
- 264-274
- ISSN
- 0893-133X (ISSN-L)
- OpenAlex
- W2004128631
- Cited by
- 181
- References
- 71
- Citations by year
- 2025: 3 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 3 · 2017: 6 · 2016: 1 · 2015: 3 · 2014: 5 · 2013: 9 · 2012: 9
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH-52129, P30MH052129, MH-55115, R01MH055115)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- brain atrophy, comorbidities, frontal lobe volume, neurodegeneration, mood disorders, depression pathophysiology, older adults
- MeSH terms
- Aged, Atrophy, Brain, Depressive Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Reference Values, Regression Analysis, Sex Characteristics, Age of Onset
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