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Magnetic resonance imaging in late-life depression: vascular and glucocorticoid cascade hypotheses

  • Claire E. Sexton (a1), Marisa Le Masurier (a2), Charlotte L. Allan (a1), Mark Jenkinson (a3), Lisa McDermott (a4), Ukwuori G. Kalu (a1), Lucie L. Herrmann (a5), Kevin M. Bradley (a6), Clare E. Mackay (a1) and Klaus P. Ebmeier (a1)...

Abstract

Background

Late-life depression is a common and heterogeneous illness, associated with structural abnormalities in both grey and white matter.

Aims

To examine the relationship between age at onset and magnetic resonance imaging (MRI) measures of grey and white matter to establish whether they support particular hypotheses regarding the anatomy and aetiology of network disruption in late-life depression.

Method

We studied 36 participants with late-life depression. Grey matter was examined using T 1-weighted MRI and analysed using voxel-based morphometry. The hippocampus was automatically segmented and volume and shape analysis performed. White matter was examined using diffusion tensor imaging and analysed using tract-based spatial statistics.

Results

Later age at onset was significantly associated with reduced fractional anisotropy of widespread tracts, in particular the anterior thalamic radiation and superior longitudinal fasciculus. Earlier age at onset was associated with reduced hippocampal volume normalised to whole brain size bilaterally. However, no significant correlations were detected using hippocampal shape analysis or voxel-based morphometry.

Conclusions

Overall, the results were compatible with the vascular hypothesis, and provided some support for the glucocorticoid cascade hypothesis.

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Copyright

Corresponding author

Klaus P. Ebmeier, University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, UK. Email: klaus.ebmeier@psych.ox.ac.uk

Footnotes

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Declaration of interest

None.

Footnotes

References

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1 Alexopoulos, GS. Frontostriatal and limbic dysfunction in late-life depression. Am J Geriatr Psychiatry 2002; 10: 687–95.
2 Sexton, CE, Mackay, CE, Ebmeier, KP. A systematic review and meta-analysis of magnetic resonance imaging studies in late-life depression. Am J Geriatr Psychiatry 2012; Feb 29 (Epub ahead of print).
3 Sexton, CE, Mackay, CE, Ebmeier, KP. A systematic review of diffusion tensor imaging studies in affective disorders. Biol Psychiatry 2009; 66: 814–23.
4 Sexton, CE, Allan, CL, Le Masurier, M, McDermott, LM, Kalu, UG, Herrmann, LL, et al. Magnetic resonance imaging in late-life depression: multi-modal examination of network disruption. Arch Gen Psychiatry 2012; in press.
5 Shimony, JS, Sheline, YI, D'Angelo, G, Epstein, AA, Benzinger, TL, Mintun, MA, et al. Diffuse microstructural abnormalities of normal-appearing white matter in late life depression: a diffusion tensor imaging study. Biol Psychiatry 2009; 66: 245–52.
6 Pantel, J, Schroder, J, Essig, M, Popp, D, Dech, H, Knopp, MV, et al. Quantitative magnetic resonance imaging in geriatric depression and primary degenerative dementia. J Affect Disord 1997; 42: 6983.
7 Taylor, WD, Steffens, DC, Payne, ME, MacFall, JR, Marchuk, DA, Svenson, IK, et al. Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression. Arch Gen Psychiatry 2005; 62: 537–44.
8 Avila, R, Ribeiz, S, Duran, FL, Arrais, JP, Moscoso, MA, Bezerra, DM, et al. Effect of temporal lobe structure volume on memory in elderly depressed patients. Neurobiol Aging 2009; 32: 1857–67.
9 Alexopoulos, GS, Meyers, BS, Young, RC, Campbell, S, Silbersweig, D, Charlson, M. ‘Vascular depression’ hypothesis. Arch Gen Psychiatry 1997; 54: 915–22.
10 Herrmann, L, Lemasurier, M, Ebmeier, K. White matter hyperintensities in late life depression: a systematic review. J Neurol Neurosurg Psychiatry 2008; 79: 619–24.
11 Chen, CS, Chen, CC, Kuo, YT, Chiang, IC, Ko, CH, Lin, HF. Carotid intima-media thickness in late-onset major depressive disorder. Int J Geriatr Psychiatry 2006; 21: 3642.
12 Smith, PJ, Blumenthal, JA, Babyak, MA, Doraiswamy, PM, Hinderliter, A, Hoffman, BM, et al. Intima-media thickness and age of first depressive episode. Biol Psychol 2009; 80: 361–4.
13 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.
14 Thomas, AJ, Perry, R, Kalaria, RN, Oakley, A, McMeekin, W, O'Brien, JT. Neuropathological evidence for ischemia in the white matter of the dorsolateral prefrontal cortex in late-life depression. Int J Geriatr Psychiatry 2003; 18: 713.
15 Bae, JN, MacFall, JR, Krishnan, KR, Payne, ME, Steffens, DC, Taylor, WD. Dorsolateral prefrontal cortex and anterior cingulate cortex white matter alterations in late-life depression. Biol Psychiatry 2006; 60: 1356–63.
16 Sapolsky, RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 2000; 57: 925–35.
17 Sapolsky, RM, Krey, LC, McEwen, BS. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev 1986; 7: 284301.
18 Bell-McGinty, S, Butters, MA, Meltzer, CC, Greer, PJ, Reynolds, CF, Becker, JT. Brain morphometric abnormalities in geriatric depression: long-term neurobiological effects of illness duration. Am J Psychiatry 2002; 159: 1424–7.
19 Sheline, YI, Wang, PW, Gado, MH, Csernansky, JG, Vannier, MW. Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA 1996; 93: 3908–13.
20 Andreescu, C, Butters, MA, Begley, A, Rajji, T, Wu, M, Meltzer, CC, et al. Gray matter changes in late life depression – a structural MRI analysis. Neuropsychopharmacology 2008; 33: 2566–72.
21 Janssen, J, Hulshoff Pol, HE, de Leeuw, FE, Schnack, HG, Lampe, IK, Kok, RM, et al. Hippocampal volume and subcortical white matter lesions in late life depression: comparison of early and late onset depression. J Neurol Neurosurg Psychiatry 2007; 78: 638–40.
22 O'Brien, JT, Lloyd, A, McKeith, I, Gholkar, A, Ferrier, N. A longitudinal study of hippocampal volume, cortisol levels, and cognition in older depressed subjects. Am J Psychiatry 2004; 161: 2081–90.
23 Weber, K, Giannakopoulos, P, Delaloye, C, de Bilbao, F, Moy, G, Moussa, A, et al. Volumetric MRI changes, cognition and personality traits in old age depression. J Affect Disord 2010; 124: 275–82.
24 Ashtari, M, Greenwald, BS, Kramer-Ginsberg, E, Hu, J, Wu, H, Patel, M, et al. Hippocampal/amygdala volumes in geriatric depression. Psychol Med 1999; 29: 629–38.
25 Steffens, DC, Byrum, CE, McQuoid, DR, Greenberg, DL, Payne, ME, Blitchington, TF, et al. Hippocampal volume in geriatric depression. Biol Psychiatry 2000; 48: 301–9.
26 Butters, MA, Young, JB, Lopez, O, Aizenstein, HJ, Mulsant, BH, Reynolds, CF, et al. Pathways linking late-life depression to persistent cognitive impairment and dementia. Dialogues Clin Neurosci 2008; 10: 345–57.
27 Caraci, F, Copani, A, Nicoletti, F, Drago, F. Depression and Alzheimer's disease: neurobiological links and common pharmacological targets. Eur J Pharmacol 2010; 626: 6471.
28 Byers, AL, Yaffe, K. Depression and risk of developing dementia. Nat Rev Neurol 2011; 7: 323–31.
29 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM-IV). APA, 1994.
30 D'Agostino, RB, Wolf, PA, Belanger, AJ, Kannel, WB. Stroke risk profile: adjustment for antihypertensive medication. The Framingham Study. Stroke 1994; 25: 40–3.
31 Hamilton, M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967; 6: 278–96.
32 Yesavage, JA, Brink, TL, Rose, TL, Lum, O, Huang, V, Adey, M, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 1982; 17: 3749.
33 Mioshi, E, Dawson, K, Mitchell, J, Arnold, R, Hodges, JR. The Addenbrooke's Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry 2006; 21: 1078–85.
34 Folstein, MF, Folstein, SE, McHugh, PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–98.
35 Sahakian, BJ, Owen, AM, Morant, NJ, Eagger, SA, Boddington, S, Crayton, L, et al. Further analysis of the cognitive effects of tetrahydroaminoacridine (THA) in Alzheimer's disease: assessment of attentional and mnemonic function using CANTAB. Psychopharmacology (Berl) 1993; 110: 395401.
36 Wechsler, D. Wechsler Adult Intelligence Scale. The Psychological Corporation, 1997.
37 McKenna, P, Warrington, EK. Testing for nominal dysphasia. J Neurol Neurosurg Psychiatry 1980; 43: 781–8.
38 Brandt, J. The Hopkins verbal learning test: development of a new memory test with six equivalent forms. Clin Neuropsychol 1991; 5: 125–42.
39 Osterrieth, PA. Le test de copie d'une figure complexe. Arch Psychol 1944; 30: 206356.
40 Reitan, R. Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills 1958; 8: 271–6.
41 Sexton, CE, McDermott, L, Kalu, UG, Herrmann, LL, Bradley, KM, Allan, CL, et al. Exploring the pattern and neural correlates of neuropsychological impairment in late-life depression. Psychol Med 2011; Oct 26 (Epub ahead of print).
42 Lyness, JM, Pearson, JL, Lebowitz, BD, Kupfer, DJ. Age at onset or late-life depression: a research agenda report of a MacArthur Foundation-NIMH Workshop. Am J Geriatr Psychiatry 1994; 2: 48.
43 Smith, SM, Jenkinson, M, Woolrich, MW, Beckmann, CF, Behrens, TE, Johansen-Berg, H, et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 2004; 23 (suppl 1): S20819.
44 Smith, SM. Fast robust automated brain extraction. Hum Brain Mapp 2002; 17: 143–55.
45 Patenaude, B, Smith, SM, Kennedy, DN, Jenkinson, M. A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage 2011; 56: 907–22.
46 Ashburner, J, Friston, KJ. Voxel-based morphometry – the methods. Neuroimage 2000; 11: 805–21.
47 Good, CD, Johnsrude, IS, Ashburner, J, Henson, RNA, Friston, KJ, Frackowiak, RSJ. A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage 2001; 14: 2136.
48 Jenkinson, M, Bannister, P, Brady, M, Smith, S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 2002; 17: 825–41.
49 Jenkinson, M, Smith, S. A global optimisation method for robust affine registration of brain images. Med Image Anal 2001; 5: 143–56.
50 Andersson, JLR, Jenkinson, M, Smith, S. Non-Linear Optimisation. FMRIB Technical Report TR07JA1. FMRIB, 2007 (www.fmrib.ox.ac.uk/analysis/techrep/).
51 Andersson, JLR, Jenkinson, M, Smith, S. Non-Linear Registration, aka Spatial Normalisation. FMRIB Technical Report TR07JA2. FMRIB, 2007 (www.fmrib.ox.ac.uk/analysis/techrep/).
52 Rueckert, D, Sonoda, LI, Hayes, C, Hill, DL, Leach, MO, Hawkes, DJ. Nonrigid registration using free-form deformations: application to breast MR images. IEEE Trans Med Imaging 1999; 18: 712–21.
53 Nichols, TE, Holmes, AP. Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 2002; 15: 125.
54 Smith, SM, Nichols, TE. Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 2009; 44: 8398.
55 Smith, SM, Jenkinson, M, Johansen-Berg, H, Rueckert, D, Nichols, TE, Mackay, CE, et al. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 2006; 31: 1487–505.
56 Mori, S, Wakana, S, Nagae-Poetscher, LM, van Zijl, PCM. MRI Atlas of Human White Matter. Elsevier BV, 2005.
57 Thomas, AJ, Kalaria, RN, O'Brien, JT. Depression and vascular disease: what is the relationship? J Affect Disord 2004; 79: 8195.
58 Paranthaman, R, Greenstein, AS, Burns, AS, Cruickshank, JK, Heagerty, AM, Jackson, A, et al. Vascular function in older adults with depressive disorder. Biol Psychiatry 2010; 68: 133–9.
59 Richardson, J, Kerr, SR, Shaw, F, Kenny, RA, O'Brien, JT, Thomas, AJ. A study of orthostatic hypotension in late-life depression. Am J Geriatr Psychiatry 2009; 17: 996–9.
60 Vasudev, A, O'Brien, JT, Tan, MP, Parry, SW, Thomas, AJ. A study of orthostatic hypotension, heart rate variability and baroreflex sensitivity in late-life depression. J Affect Disord 2011; 131: 374–8.
61 Gerritsen, L, Comijs, HC, van der Graaf, Y, Knoops, AJ, Penninx, BW, Geerlings, MI. Depression, hypothalamic pituitary adrenal axis, and hippocampal and entorhinal cortex volumes – the SMART medea study. Biol Psychiatry 2011; 70: 373–80.
62 McEwen, BS. Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol 2008; 583: 174–85.
63 Wang, Z, Neylan, TC, Mueller, SG, Lenoci, M, Truran, D, Marmar, CR, et al. Magnetic resonance imaging of hippocampal subfields in posttraumatic stress disorder. Arch Gen Psychiatry 2010; 67: 296303.
64 Chen, MC, Hamilton, JP, Gotlib, IH. Decreased hippocampal volume in healthy girls at risk of depression. Arch Gen Psychiatry 2010; 67: 270–6.
65 de Geus, EJ, van't Ent, D, Wolfensberger, SP, Heutink, P, Hoogendijk, WJ, Boomsma, DI, et al. Intrapair differences in hippocampal volume in monozygotic twins discordant for the risk for anxiety and depression. Biol Psychiatry 2007; 61: 1062–71.
66 Prusoff, BA, Merikangas, KR, Weissman, MM. Lifetime prevalence and age of onset of psychiatric disorders: recall 4 years later. J Psychiatr Res 1988; 22: 107–17.
67 Wiener, P, Alexopoulos, GS, Kakuma, T, Meyers, BS, Rosenthal, E, Chester, J. The limits of history-taking in geriatric depression. Am J Geriatr Psychiatry 1997; 5: 116–25.
68 Koolschijn, PCMP, van Haren, NEM, Lensvelt-Mulders, GJLM, Hulshoff Pol, HE, Kahn, RS. Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Hum Brain Mapp 2009; 30: 3719–35.
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Magnetic resonance imaging in late-life depression: vascular and glucocorticoid cascade hypotheses

  • Claire E. Sexton (a1), Marisa Le Masurier (a2), Charlotte L. Allan (a1), Mark Jenkinson (a3), Lisa McDermott (a4), Ukwuori G. Kalu (a1), Lucie L. Herrmann (a5), Kevin M. Bradley (a6), Clare E. Mackay (a1) and Klaus P. Ebmeier (a1)...
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