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Morphometric analysis of neuronal and glial cell pathology in the dorsolateral prefrontal cortex in late-life depression

  • Ahmad Khundakar (a1), Christopher Morris (a1), Arthur Oakley (a1), William McMeekin (a2) and Alan J. Thomas (a3)...

Abstract

Background

Late-life depression has been associated with cerebrovascular disease and especially with ischaemic white matter hyperintensities on magnetic resonance imaging. Neuroimaging and morphometric studies have identified abnormalities in the dorsolateral prefrontal cortex.

Aims

To examine glial and neuronal density and neuronal volume in the dorsolateral prefrontal cortex in late-life major depression.

Method

We used the disector and nucleator methods to estimate neuronal density and volume and glial density of cells in the dorsolateral prefrontal cortex in a post-mortem study of 17 individuals with late-life major depression and 10 age-matched controls.

Results

We found a reduction in the volume of pyramidal neurones in the whole cortex, which was also present in layer 3 and more markedly in layer 5. There were no comparable changes in non-pyramidal neurones and no glial differences.

Conclusions

Overall, we found a decrease in pyramidal neuronal size in the dorsolateral prefrontal cortex in late-life depression.

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Copyright

Corresponding author

Alan J. Thomas, Wolfson Research Centre, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK. Email: a.j.thomas@ncl.ac.uk

Footnotes

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Declaration of interest

None.

Footnotes

References

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1 Baldwin, R. Depressive disorders. In Oxford Textbook of Old Aga Psychiatry (eds Jacoby, R, Oppenheimer, C, Dening, T, et al): 529–56. Oxford University Press, 2008.
2 Alexopoulos, GS, Meyers, BS, Young, RC, Campbell, S, Silbersweig, D, Charlson, M. ‘Vascular depression’ hypothesis. Arch Gen Psychiatry 1997; 54: 915–22.
3 O'Brien, JT, Thomas, AJ. Depression in the elderly. In Unipolar Depression: A Lifetime Perspective (ed Goodyear, I). Oxford University Press, 2003.
4 Salloway, S, Malloy, P, Kohn, R, Gillard, E, Duffy, J, Rogg, J, et al. MRI and neuropsychological differences in early- and late-life-onset geriatric depression. Neurology 1996; 46: 1567–74.
5 Miguel-Hidalgo, JJ, Baucom, C, Dilley, G, Overholser, JC, Meltzer, HY, Stockmeier, CA, et al. Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder. Biol Psychiatry 2000; 48: 861–73.
6 Rajkowska, G, Miguel-Hidalgo, JJ, Wei, J, Dilley, G, Pittman, SD, Meltzer, HY, et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 1999; 45: 1085–98.
7 Thomas, AJ, Ferrier, IN, Kalaria, RN, Woodward, SA, Ballard, C, Oakley, A, et al. Elevation in late-life depression of intercellular adhesion molecule-1 expression in the dorsolateral prefrontal cortex. Am J Psychiatry 2000; 157: 1682–4.
8 Thomas, AJ, Ferrier, IN, Kalaria, RN, Davis, S, O'Brien, JT. Cell adhesion molecule expression in the dorsolateral prefrontal cortex and anterior cingulate cortex in major depression in the elderly. Br J Psychiatry 2002; 181: 129–34.
9 Thomas, AJ, O'Brien, JT, Davis, S, Ballard, C, Barber, R, Kalaria, RN, et al. Ischemic basis for deep white matter hyperintensities in major depression: a neuropathological study. Arch Gen Psychiatry 2002; 59: 785–92.
10 Rajkowska, G, Miguel-Hidalgo, JJ, Dubey, P, Stockmeier, CA, Krishnan, KR. Prominent reduction in pyramidal neurons density in the orbitofrontal cortex of elderly depressed patients. Biol Psychiatry 2005; 58: 297306.
11 Thomas, AJ, Ferrier, IN, Kalaria, RN, Perry, RH, Brown, A, O'Brien, JT. A neuropathological study of vascular factors in late-life depression. J Neurol Neurosurg Psychiatry 2001; 70: 83–7.
12 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM–IV). APA, 1994.
13 Perry, RH. Coronal Maps of Brodmann Areas in the Human Brain. Wolfe, 1993.
14 Gundersen, HJ, Bagger, P, Bendtsen, TF, Evans, SM, Korbo, L, Marcussen, N, et al. The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS 1988; 96: 857–81.
15 Sterio, DC. The unbiased estimation of number and sizes of arbitrary particles using the disector. J Microsc 1984; 134: 127–36.
16 Gundersen, HJ. The nucleator. J Microsc 1988; 151: 321.
17 Cotter, D, Mackay, D, Landau, S, Kerwin, R, Everall, I. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry 2001; 58: 545–53.
18 Kaufer, DI, Lewis, DA. Frontal lobe anatomy and cortical connectivity. In The Human Frontal Lobes (eds Miller, BL, Cumming, JL): 2744. Guilford Press, 1999.
19 Duman, RS. Role of neurotrophic factors in the etiology and treatment of mood disorders. Neuromolecular Med 2004; 5: 1125.
20 Evans, SJ, Choudary, PV, Neal, CR, Li, JZ, Vawter, MP, Tomita, H, et al. Dysregulation of the fibroblast growth factor system in major depression. Proc Natl Acad Sci USA 2004; 101: 15506–11.
21 O'Brien, JT, Ames, D, Schweitzer, I, Colman, P, Desmond, P, Tress, B. Clinical and magnetic resonance imaging correlates of hypothalamic–pituitary–adrenal axis function in depression and Alzheimer's disease. Br J Psychiatry 1996; 168: 679–87.
22 Sapolsky, RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 2000; 57: 925–35.
23 Cotter, D, Hudson, L, Landau, S. Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia. Bipolar Disord 2005; 7: 358–69.
24 Taylor, WD, Steffens, DC, MacFall, JR, McQuoid, DR, Payne, ME, Provenzale, JM, et al. White matter hyperintensity progression and late-life depression outcomes. Arch Gen Psychiatry 2003; 60: 1090–6.
25 Davis, S, Thomas, A, Perry, R, Oakley, A, Kalaria, RN, O'Brien, JT. Glial fibrillary acidic protein in late life major depressive disorder: an immunocytochemical study. J Neurol Neurosurg Psychiatry 2002; 73: 556–60.
26 Aston, C, Jiang, L, Sokolov, BP. Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder. Mol Psychiatry 2005; 10: 309–22.
27 Hamidi, M, Drevets, WC, Price, JL. Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes. Biol Psychiatry 2004; 55: 563–9.

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Morphometric analysis of neuronal and glial cell pathology in the dorsolateral prefrontal cortex in late-life depression

  • Ahmad Khundakar (a1), Christopher Morris (a1), Arthur Oakley (a1), William McMeekin (a2) and Alan J. Thomas (a3)...
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