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Morphometric changes in early- and late-life major depressive disorder: evidence from postmortem studies

Published online by Cambridge University Press:  22 June 2009

Ahmad A. Khundakar  and
Alan J. Thomas
Ahmad A. Khundakar*
Affiliation:
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, U.K.
Alan J. Thomas
Affiliation:
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, U.K.
*
Correspondence should be addressed to: Ahmad Khundakar, Edwardson Building, Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 6BE, U.K. Phone: +44 (0)191 2481219; Fax: +44 (0)191 2481101. Email: ahmad.khundakar@ncl.ac.uk.
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Abstract

Background: Neuroimaging studies have revealed structural and functional changes in brain regions associated with major depressive disorder (MDD). These abnormalities appear to be more common and extensive in patients with late-life depression than in younger patients. It has therefore been hypothesized that different morphometric and pathological changes may be associated with MDD, depending on age.

Methods: This review stratifies the findings of the various studies on cell morphology in MDD according to age and assesses any possible differences in neuronal and glial cell changes in younger and older age groups.

Results: Recent morphological studies in postmortem tissue have revealed alterations in neuron and glial cell populations in the frontal and subcortical circuitry associated with depression. These may differ by age, with glial reduction consistently reported in younger groups in cortical areas and neuronal changes identified in studies with older subjects.

Conclusions: Apparent differences in the morphological changes between younger and elderly patients may suggest a differing pathological basis in MDD, dependent on age.

Keywords

major depressive disordervascularelderlymorphologypathologyneuronsglial cells
Type
Review Article
Information
International Psychogeriatrics , Volume 21 , Issue 5 , October 2009 , pp. 844 - 854
Copyright
Copyright © International Psychogeriatric Association 2009

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References

Ahlbom, E., Gogvadze, V., Chen, M., Celsi, G. and Ceccatelli, S. (2000). Prenatal exposure to high levels of glucocorticoids increases the susceptibility of cerebellar granule cells to oxidative stress-induced cell death. Proceedings of the National Academy of Science, 97, 14726–14730.CrossRefGoogle ScholarPubMed
Alexander, G. E., DeLong, M. R. and Strick, P. L. (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9, 357–381.CrossRefGoogle ScholarPubMed
Alexopoulos, G. S., Meyers, B. S., Young, R. C., Kakuma, T., Silbersweig, D. and Charlson, M. (1997). Clinically defined vascular depression. American Journal of Psychiatry, 154, 562–565.Google ScholarPubMed
Ali, S., Stone, M. A., Peters, J. L., Davies, M. J. and Khunti, K. (2006). The prevalence of co-morbid depression in adults with Type 2 diabetes: a systematic review and meta-analysis. Diabetic Medicine, 23, 1165–1173.CrossRefGoogle ScholarPubMed
Baldwin, R. C. and O'Brien, J. (2002). Vascular basis of late-onset depressive disorder. British Journal of Psychiatry, 180, 157–160.CrossRefGoogle ScholarPubMed
Ballmaier, M. et al. (2004). Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex. American Journal of Psychiatry, 161, 99–108.CrossRefGoogle ScholarPubMed
Bonelli, R. M. and Cummings, J. L. (2007). Frontal-subcortical circuitry and behavior. Dialogues in Clinical Neuroscience, 9, 141–151.CrossRefGoogle ScholarPubMed
Bowley, M. P., Drevets, W. C., Ongur, D. and Price, J. L. (2002). Low glial numbers in the amygdala in major depressive disorder. Biological Psychiatry, 52, 404–412.CrossRefGoogle ScholarPubMed
Cadepond, F. et al. (2002). Steroid receptors in various glial cell lines expression and functional studies. Annals of the New York Academy of Science, 973, 484–487.CrossRefGoogle ScholarPubMed
Cotter, D. R., Pariante, C. M. and Everall, I. P. (2001). Glial cell abnormalities in major psychiatric disorders: the evidence and implications. Brain Research Bulletin, 55, 585–595.CrossRefGoogle ScholarPubMed
Cotter, D., Hudson, L. and Landau, S. (2005). Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia. Bipolar Disorders, 7, 358–369.CrossRefGoogle ScholarPubMed
Davis, S., Thomas, A., Perry, R., Oakley, A., Kalaria, R. N. and O'Brien, J. T. (2002). Glial fibrillary acidic protein in late life major depressive disorder: an immunocytochemical study. Journal of Neurology, Neurosurgery and Psychiatry, 73, 556–560.CrossRefGoogle ScholarPubMed
de Groot, J. C., de Leeuw, F. E., Oudkerk, M., Hofman, A., Jolles, J. and Breteler, M. M. (2000). Cerebral white matter lesions and depressive symptoms in elderly adults. Archives of General Psychiatry, 57, 1071–1076.CrossRefGoogle ScholarPubMed
Drevets, W. C., Price, J. L. and Furey, M. L. (2008). Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Structure and Function, 213, 93–118.CrossRefGoogle ScholarPubMed
Gittins, R. and Harrison, P. J. (2004a). Neuronal density, size and shape in the human anterior cingulate cortex: a comparison of Nissl and NeuN staining. Brain Research Bulletin, 63, 155–160.CrossRefGoogle ScholarPubMed
Gittins, R. and Harrison, P. J. (2004b). A quantitative morphometric study of the human anterior cingulate cortex. Brain Research, 1013, 212–222.CrossRefGoogle ScholarPubMed
Herrmann, L. L., Le Masurier, M. and Ebmeier, K. P. (2008). White matter hyperintensities in late life depression: a systematic review. Journal of Neurology Neurosurgery and Psychiatry, 79, 619–624.CrossRefGoogle ScholarPubMed
Inazu, M., Takeda, H., Ikoshi, H., Sugisawa, M., Uchida, Y. and Matsumiya, T. (2001). Pharmacological characterization and visualization of the glial serotonin transporter. Neurochemistry International, 39, 39–49.CrossRefGoogle ScholarPubMed
Khundakar, A. A. and Zetterstrom, T. S. (2006). Biphasic change in BDNF gene expression following antidepressant drug treatment explained by differential transcript regulation. Brain Research, 1106, 12–20.CrossRefGoogle ScholarPubMed
Khundakar, A. A., Morris, C. M., Oakley, A. E., McMeekin, W. and Thomas, A. J. (2009). Morphometric analysis of neuronal and glial cell pathology in the dorsolateral prefrontal cortex in late-life depression. British Journal of Psychiatry, In press.CrossRefGoogle Scholar
Kim, M. J., Hamilton, J. P. and Gotlib, I. H. (2008). Reduced caudate gray matter volume in women with major depressive disorder. Psychiatry Research, 164, 114–122.CrossRefGoogle ScholarPubMed
Krishnan, M. S. et al. (2006). Relationship between periventricular and deep white matter lesions and depressive symptoms in older people: the LADIS Study. International Journal of Geriatric Psychiatry, 21, 983–989.CrossRefGoogle ScholarPubMed
Krystal, J. H., et al. (2002). Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Molecular Psychiatry, 7 (Suppl. 1), S71–S80.CrossRefGoogle ScholarPubMed
Laping, N. J., Teter, B., Nichols, N. R., Rozovsky, I. and Finch, C. E. (1994). Glial fibrillary acidic protein: regulation by hormones, cytokines, and growth factors. Brain Pathology, 4, 259–275.CrossRefGoogle ScholarPubMed
McQuade, R. and Young, A. H. (2000). Future therapeutic targets in mood disorders: the glucocorticoid receptor. British Journal of Psychiatry, 177, 390–395.CrossRefGoogle ScholarPubMed
Middleton, F. A. and Strick, P. L. (2002). Basal-ganglia “projections” to the prefrontal cortex of the primate. Cerebral Cortex, 12, 926–935.CrossRefGoogle Scholar
Miguel-Hidalgo, J. J. et al. (2000). Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder. Biological Psychiatry, 48, 861–873.CrossRefGoogle ScholarPubMed
O'Brien, J. T., Ames, D., Schweitzer, I., Colman, P., Desmond, P. and Tress, B. (1996). Clinical and magnetic resonance imaging correlates of hypothalamic-pituitary-adrenal axis function in depression and Alzheimer's disease. British Journal of Psychiatry, 168, 679–687.CrossRefGoogle ScholarPubMed
Ongur, D., Drevets, W. C. and Price, J. L. (1998). Glial reduction in the subgenual prefrontal cortex in mood disorders. Proceedings of the National Academy of Science of the United States of America, 95, 13290–13295.CrossRefGoogle ScholarPubMed
Palomero-Gallagher, N., Vogt, B. A., Schleicher, A., Mayberg, H. S. and Zilles, K. (2008). Receptor architecture of human cingulate cortex: evaluation of the four-region neurobiological model. Human Brain Mapping. E-published ahead of print, November 2008; doi: 10.1002/hbm.20667.CrossRefGoogle Scholar
Plante, G. E. (2005). Depression and cardiovascular disease: a reciprocal relationship. Metabolism, 54, 45–48.CrossRefGoogle ScholarPubMed
Rajkowska, G. et al. (1999). Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biological Psychiatry, 45, 1085–1098.CrossRefGoogle ScholarPubMed
Rajkowska, G., Miguel-Hidalgo, J. J., Dubey, P., Stockmeier, C. A. and Krishnan, K. R. (2005). Prominent reduction in pyramidal neurons density in the orbitofrontal cortex of elderly depressed patients. Biological Psychiatry, 58, 297–306.CrossRefGoogle ScholarPubMed
Sapolsky, R. M., Romero, L. M. and Munck, A. U. (2000). How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocrine Reviews, 21, 55–89.Google ScholarPubMed
Sheline, Y. I. et al. (2008). Regional white matter hyperintensity burden in automated segmentation distinguishes late-life depressed subjects from comparison subjects matched for vascular risk factors. American Journal of Psychiatry, 165, 524–532.CrossRefGoogle ScholarPubMed
Steffens, D. C., Helms, M. J., Krishnan, K. R. and Burke, G. L. (1999). Cerebrovascular disease and depression symptoms in the cardiovascular health study. Stroke, 30, 2159–2166.CrossRefGoogle ScholarPubMed
Stockmeier, C. A. et al. (2004). Cellular changes in the postmortem hippocampus in major depression. Biological Psychiatry, 56, 640–650.CrossRefGoogle ScholarPubMed
Taylor, W. D. et al. (2007). Orbitofrontal cortex volume in late life depression: influence of hyperintense lesions and genetic polymorphisms. Psychological Medicine, 37, 1763–1773.CrossRefGoogle ScholarPubMed
Teodorczuk, A. et al. (2007). White matter changes and late-life depressive symptoms: longitudinal study. British Journal of Psychiatry, 191, 212–217.CrossRefGoogle ScholarPubMed
Thomas, A. J. et al. (2000). Elevation in late-life depression of intercellular adhesion molecule-1 expression in the dorsolateral prefrontal cortex. American Journal of Psychiatry, 157, 1682–1684.CrossRefGoogle ScholarPubMed
Thomas, A. J. et al. (2002). Ischemic basis for deep white matter hyperintensities in major depression: a neuropathological study. Archives of General Psychiatry, 59, 785–792.CrossRefGoogle ScholarPubMed
Thomas, A. J., Davis, S., Morris, C., Jackson, E., Harrison, R. and O'Brien, J. T. (2005). Increase in interleukin-1beta in late-life depression. American Journal of Psychiatry, 162, 175–177.CrossRefGoogle ScholarPubMed
Virgin, C. E. Jr., et al. (1991). Glucocorticoids inhibit glucose transport and glutamate uptake in hippocampal astrocytes: implications for glucocorticoid neurotoxicity. Journal of Neurochemistry, 57, 1422–1428.CrossRefGoogle ScholarPubMed
Vogt, B. A., Finch, D. M. and Olson, C. R. (1992). Functional heterogeneity in cingulate cortex: the anterior executive and posterior evaluative regions. Cerebral Cortex, 2, 435–443.Google ScholarPubMed
West, M. J. (1999). Stereological methods for estimating the total number of neurons and synapses: issues of precision and bias. Trends in Neuroscience, 22, 51–61.CrossRefGoogle ScholarPubMed
Young, K. A., Holcomb, L. A., Yazdani, U., Hicks, P. B. and German, D. C. (2004). Elevated neuron number in the limbic thalamus in major depression. American Journal of Psychiatry, 161, 1270–1277.CrossRefGoogle ScholarPubMed
Zafra, F., Hengerer, B., Leibrock, J., Thoenen, H. and Lindholm, D. (1990). Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocampus is mediated by non-NMDA glutamate receptors. European Molecular Biology Organization Journal, 9, 3545–3550.CrossRefGoogle ScholarPubMed