Hostname: page-component-586b7cd67f-t8hqh Total loading time: 0 Render date: 2024-11-22T22:33:16.109Z Has data issue: false hasContentIssue false

White-matter tract integrity in late-life depression: associations with severity and cognition

Published online by Cambridge University Press:  16 September 2013

R. A. Charlton*
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, IL, USA
M. Lamar
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, IL, USA
A. Zhang
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, IL, USA
S. Yang
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, IL, USA
O. Ajilore
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, IL, USA
A. Kumar
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, IL, USA
*
*Address for correspondence: R. A. Charlton, Department of Psychology, Goldsmiths University of London, New Cross, SE14 6NW, UK. (Email: [email protected])

Abstract

Background

Although significant changes in both gray and white matter have been noted in late-life depression (LLD), the pathophysiology of implicated white-matter tracts has not been fully described. In this study we examined the integrity of specific white-matter tracts in LLD versus healthy controls (HC).

Method

Participants aged ⩾60 years were recruited from the community. The sample included 23 clinically diagnosed individuals with LLD and 23 HC. White-matter integrity metrics [fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD)] were calculated in the bilateral cingulum and uncinate fasciculus. Depression severity was measured using the Center for Epidemiological Studies Depression Scale (CESD). Composite scores for learning and memory and executive function were created using standardized neuropsychological assessments.

Results

White-matter integrity was lower in LLD versus HC in the bilateral cingulum and right uncinate fasciculus (p⩽0.05). In the whole sample, depression severity correlated with integrity in the bilateral cingulum and right uncinate fasciculus (p ⩽0.05). In patients, depression severity correlated with the integrity of the left uncinate fasciculus (p = 0.03); this tract also correlated with executive function (p = 0.02). Among HC, tract integrity did not correlate with depression scores; however, learning and memory correlated with integrity of the bilateral uncinate fasciculus and bilateral cingulum; executive function correlated with the right uncinate and left cingulum (p ⩽0.05).

Conclusions

White-matter tract integrity was lower in LLD than in HC and was associated with depression severity across all participants. Tract integrity was associated with cognition in both groups but more robustly among HC.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aizenstein, HJ, Andreescu, C, Edelman, KL, Cochran, J, Price, J, Butters, MA, Karp, J, Patel, M, Reynolds, CF 3rd (2011). fMRI correlates of white matter hyperintensities in late-life depression. American Journal of Psychiatry 168, 10751082.Google Scholar
Alexopoulos, GS, Buckwalter, K, Olin, J, Martinez, R, Wainscott, C, Krishnan, KR (2002 b). Comorbidity of late life depression: an opportunity for research on mechanisms and treatment. Biological Psychiatry 52, 543558.CrossRefGoogle ScholarPubMed
Alexopoulos, GS, Kiosses, DN, Choi, SJ, Murphy, CF, Lim, KO (2002 a). Frontal white matter microstructure and treatment response of late-life depression: a preliminary study. American Journal of Psychiatry 159, 19291932.Google Scholar
Alexopoulos, GS, Meyers, BS, Young, RC, Campbell, S, Silbersweig, D, Charlson, M (1997 a). ‘Vascular depression’ hypothesis. Archives of General Psychiatry 54, 915922.Google Scholar
Alexopoulos, GS, Meyers, BS, Young, RC, Kakuma, T, Silbersweig, D, Charlson, M (1997 b). Clinically defined vascular depression. American Journal of Psychiatry 154, 562565.Google Scholar
Alexopoulos, GS, Murphy, CF, Gunning-Dixon, FM, Latoussakis, V, Kanellopoulos, D, Klimstra, S, Lim, KO, Hoptman, MJ (2008). Microstructural white matter abnormalities and remission of geriatric depression. American Journal of Psychiatry 165, 238244.Google Scholar
Army Individual Test Battery (1944). The Trail Making Test: Manual of Directions and Scoring. War Department, Adjutant General's Office: Washingon, DC.Google Scholar
Bae, JN, MacFall, JR, Krishnan, KR, Payne, ME, Steffens, DC, Taylor, WD (2006). Dorsolateral prefrontal cortex and anterior cingulate cortex white matter alterations in late-life depression. Biological Psychiatry 60, 13561363.Google Scholar
Ballmaier, M, Narr, KL, Toga, AW, Elderkin-Thompson, V, Thompson, PM, Hamilton, L, Haroon, E, Pham, D, Heinz, A, Kumar, A (2008). Hippocampal morphology and distinguishing late-onset from early-onset elderly depression. American Journal of Psychiatry 165, 229237.Google Scholar
Ballmaier, M, Toga, AW, Blanton, RE, Sowell, ER, Lavretsky, H, Peterson, J, Pham, D, Kumar, A (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, 99108.Google Scholar
Barch, DM, D'Angelo, G, Pieper, C, Wilkins, CH, Welsh-Bohmer, K, Taylor, W, Garcia, KS, Gersing, K, Doraiswamy, PM, Sheline, YI (2012). Cognitive improvement following treatment in late-life depression: relationship to vascular risk and age of onset. American Journal of Geriatric Psychiatry 20, 682690.Google Scholar
Bremner, JD, Narayan, M, Anderson, ER, Staib, LH, Miller, HL, Charney, DS (2000). Hippocampal volume reduction in major depression. American Journal of Psychiatry 157, 115118.Google Scholar
Bremner, JD, Vythilingam, M, Vermetten, E, Vaccarino, V, Charney, DS (2004). Deficits in hippocampal and anterior cingulate functioning during verbal declarative memory encoding in midlife major depression. American Journal of Psychiatry 161, 637645.Google Scholar
Budde, MD, Kim, JH, Liang, HF, Russell, JH, Cross, AH, Song, SK (2008). Axonal injury detected by in vivo diffusion tensor imaging correlates with neurological disability in a mouse model of multiple sclerosis. NMR in Biomedicine 21, 589597.Google Scholar
Budde, MD, Xie, M, Cross, AH, Song, SK (2009). Axial diffusivity is the primary correlate of axonal injury in the experimental autoimmune encephalomyelitis spinal cord: a quantitative pixelwise analysis. Journal of Neuroscience 29, 28052813.Google Scholar
Catani, M, Thiebaut de Schotten, M (2008). A diffusion tensor imaging tractography atlas for virtual in vivo dissections. Cortex 44, 11051132.Google Scholar
Charlton, RA, Barrick, TR, Markus, HS, Morris, RG (2010 a). The relationship between episodic long-term memory and white matter integrity in normal aging. Neuropsychologia 48, 114122.Google Scholar
Charlton, RA, Schiavone, F, Barrick, TR, Morris, RG, Markus, HS (2010 b). Diffusion tensor imaging detects age-related white matter change over a two-year follow-up which is associated with working memory decline. Journal of Neurology, Neurosurgery and Psychiatry 81, 1319.Google Scholar
Delis, DC, Kaplan, E, Kramer, JH (2001). The Delis-Kaplan Executive Function System. Psychological Corporation: San Antonio, TX.Google Scholar
Delis, DC, Kramer, JH, Kaplan, E, Ober, BA (2000). California Verbal Learning Test. Psychological Corporation: San Antonio, TX.Google Scholar
Elderkin-Thompson, V, Mintz, J, Haroon, E, Lavretsky, H, Kumar, A (2006). Executive dysfunction and memory in older patients with major and minor depression. Archives of Clinical Neuropsychology 22, 261270.Google Scholar
Folstein, MF, Folstein, SE, McHugh, PR (1975). ‘Mini-mental State’. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189198.Google Scholar
Fujikawa, T, Yamawaki, S, Touhouda, Y (1993). Incidence of silent cerebral infarction in patients with major depression. Stroke 24, 16311634.Google Scholar
Golden, CJ (1978). Stroop Color and Word Test: A Manual for Clinical and Experimental Uses. Skoelting: Chicago, IL.Google Scholar
Hamilton, MA (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 23, 5662.Google Scholar
Herrmann, LL, Le Masurier, M, Ebmeier, KP (2008). White matter hyperintensities in late life depression: a systematic review. Journal of Neurology, Neurosurgery and Psychiatry 79, 619624.Google Scholar
Janssen, J, Hulshoff Pol, HE, Schnack, HG, Kok, RM, Lampe, IK, de Leeuw, FE, Kahn, RS, Heeren, TJ (2007). Cerebral volume measurements and subcortical white matter lesions and short-term treatment response in late life depression. International Journal of Geriatric Psychiatry 22, 468474.Google Scholar
Jiang, H, van Zijl, PC, Kim, J, Pearlson, GD, Mori, S (2006). DtiStudio: resource program for diffusion tensor computation and fiber bundle tracking. Computer Methods and Programs in Biomedicine 81, 106116.Google Scholar
Kennedy, KM, Raz, N (2009). Aging white matter and cognition: differential effects of regional variations in diffusion properties on memory, executive functions, and speed. Neuropsychologia 47, 915927.Google Scholar
Korten, NCM, Comijs, HC, Lamers, F, Penninx, BWJH (2012). Early and late onset depression in young and middle aged adults: differential symptomatology, characteristics and risk factors? Journal of Affective Disorders 138, 259267.Google Scholar
Krishnan, KR (2002). Biological risk factors in late life depression. Biological Psychiatry 52, 185192.Google Scholar
Kumar, A, Mintz, J, Bilker, W, Gottlieb, G (2002). Autonomous neurobiological pathways to late-life major depressive disorder: clinical and pathophysiological implications. Neuropsychopharmacology 26, 229236.Google Scholar
Lamar, M, Charlton, RA, Morris, RG, Markus, HS (2010). The impact of subcortical white matter disease on mood in euthymic older adults: a diffusion tensor imaging study. American Journal of Geriatric Psychiatry 18, 634642.Google Scholar
Lamar, M, Charlton, RA, Zhang, A, Kumar, A (2012). Differential associations between types of verbal memory and prefrontal brain structure in healthy aging and late life depression. Neuropsychologia 50, 18231829.Google Scholar
Metwalli, NS, Benatar, M, Nair, G, Usher, S, Hu, X, Carew, JD (2010). Utility of axial and radial diffusivity from diffusion tensor MRI as markers of neurodegeneration in amyotrophic lateral sclerosis. Brain Research 1348, 156164.Google Scholar
Metzler-Baddeley, C, Jones, DK, Belaroussi, B, Aggleton, JP, O'Sullivan, MJ (2011). Frontotemporal connections in episodic memory and aging: a diffusion MRI tractography study. Journal of Neuroscience 31, 1323613245.Google Scholar
O'Sullivan, M, Summers, PE, Jones, DK, Jarosz, JM, Williams, SC, Markus, HS (2001). Normal-appearing white matter in ischemic leukoaraiosis: a diffusion tensor MRI study. Neurology 57, 23072310.Google Scholar
Petrides, M, Alivistatos, B (2002). Differential activation of the human orbital, mid-ventrolateral, and mid-dorsolateral prefrontal cortex during the processing of visual stimuli. Proceedings of the National Academy of Sciences USA 99, 56495654.Google Scholar
Pujol, J, Bello, J, Deus, J, Martí-Vilalta, JL, Capdevila, A (1997). Lesions in the left arcuate fasciculus region and depressive symptoms in multiple sclerosis. Neurology 49, 11051110.Google Scholar
Radloff, LS (1977). The CES-D scale: a self-report depression scale for research in the general population. Applied Pscyhological Measurement 1, 385401.Google Scholar
Rapp, MA, Rieckmann, N, Lessman, DA, Tang, CY, Paulino, R, Burg, MM, Davidson, KW (2010). Persistent depressive symptoms after acute coronary syndrome are associated with compromised white matter integrity in the anterior cingulate: a pilot study. Psychotherapy and Psychosomatics 79, 149155.Google Scholar
Sexton, CE, McDermott, L, Kalu, UG, Herrmann, LL, Bradley, KM, Allan, CL, Le Masurier, M, MacKay, CE, Ebmeier, KP (2012). Exploring the pattern and neural correlates of neuropsychological impairment in late-life depression. Psychological Medicine 42, 11951202.Google Scholar
Shah, PJ, Ebmeier, KP, Glabus, MF, Goodwin, GM (1998). Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression. Controlled magnetic resonance imaging study. British Journal of Psychiatry 172, 527532.Google Scholar
Sheline, YI, Sanghavi, M, Mintun, MA, Gado, MH (1999). Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. Journal of Neuroscience 19, 50345043.Google Scholar
Shimony, JS, Sheline, YI, D'Angelo, G, Epstein, AA, Benzinger, TLS, Mintun, MA, McKinstry, RC, Snyder, AZ (2009). Diffuse microstructural abnormalities of normal-appearing white matter in late life depression: a diffusion tensor imaging study. Biological Psychiatry 66, 245252.Google Scholar
Song, SK, Sun, SW, Ramsbottom, MJ, Chang, C, Russell, J, Cross, AH (2002). Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. NeuroImage 17, 14291436.Google Scholar
Song, SK, Yoshino, J, Le, TQ, Lin, SJ, Sun, SW, Cross, AH, Armstrong, RC (2005). Demyelination increases radial diffusivity in corpus callosum of mouse brain. NeuroImage 26, 132140.Google Scholar
Spitzer, RL, Williams, JBW, Gibbon, M, First, MB (1992). The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Archives of General Psychiatry 49, 624629.Google Scholar
Sun, SW, Neil, JJ, Song, SK (2003). Relative indices of water diffusion anisotropy are equivalent in live and formalin-fixed mouse brains. Magnetic Resonance in Medicine 50, 743748.Google Scholar
Taylor, WD, MacFall, JR, Gerig, G, Krishnan, KRR (2007). Structural integrity of the uncinate fasciculus in geriatric depression: relationship with age of onset. Neuropsychiatric Disease and Treatment 3, 669674.Google Scholar
Taylor, WD, MacFall, JR, Payne, ME, McQuoid, DR, Provenzale, JM, Steffens, DC, Krishnan, KR (2004). Late-life depression and microstructural abnormalities in dorsolateral prefrontal cortex white matter. American Journal of Psychiatry 161, 12931296.Google Scholar
Taylor, WD, MacFall, JR, Steffens, DC, Payne, ME, Provenzale, JM, Krishnan, KR (2003). Localization of age-associated white matter hyperintensities in late-life depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry 27, 539544.Google Scholar
Wakana, S, Caprihan, A, Panzenboeck, MM, Fallon, JH, Perry, M, Gollub, RL, Hua, K, Zhang, J, Jiang, H, Dubey, P, Blitz, A, van Zijl, P, Mori, S (2007). Reproducibility of quantitative tractography methods applied to cerebral white matter. NeuroImage 36, 630644.Google Scholar
Wechsler, D (1997). Wechsler Adult Intelligence Scale – Third Edition (WAIS-III). Psychological Corporation: San Antonio, TX.Google Scholar
Wechsler, D, Wycherley, RJ, Benjamin, L, Callanan, M, Lavender, T, Crawford, JR, Mockler, D (1998). Wechsler Memory Scale – III (WMS-III). Psychological Corporation: London, UK.Google Scholar
Wheeler-Kingshott, CA, Cercignani, M (2009). About ‘axial’ and ‘radial’ diffusivities. Magnetic Resonance in Medicine 61, 12551260.Google Scholar
Wolf, PA, D'Agostino, RB, Belanger, AJ, Kannel, WB (1991). Probability of stroke: a risk profile from the Framingham Study. Stroke 22, 312318.Google Scholar
Woods, RP, Grafton, ST, Holmes, CJ, Cherry, SR, Mazziotta, JC (1998). Automated image registration: I. General methods and intrasubject, intramodality validation. Journal of Computer Assisted Tomography 22, 139152.Google Scholar
Zhang, A, Leow, A, Ajilore, O, Lamar, M, Yang, S, Joseph, J, Medina, J, Zhan, L, Kumar, A (2012). Quantitative tract-specific measures of uncinate and cingulum in major depression using diffusion tensor imaging. Neuropsychopharmacology 37, 959967.Google Scholar
Supplementary material: File

Charlton Supplementary Material

Table

Download Charlton Supplementary Material(File)
File 44.5 KB