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14 - White matter neurobiology and cognitive dysfunction in major depressive disorder

from Part II - Underlying biological substrates associated with cognitive dysfunction in major depressive disorder

Published online by Cambridge University Press:  05 March 2016

By
Geoffrey Chern-Yee Tan  and
Kang Sim
Edited by
Roger S. McIntyre
Edited in association with
Danielle S. Cha
Roger S. McIntyre
Affiliation:
University of Toronto
Danielle S. Cha
Affiliation:
University of Toronto
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Type
Chapter
Information
Cognitive Impairment in Major Depressive Disorder
Clinical Relevance, Biological Substrates, and Treatment Opportunities
 , pp. 194 - 208
Publisher: Cambridge University Press
Print publication year: 2016

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References

Abe, O., Yamasue, H., Kasai, K., Yamada, H., Aoki, S., Inoue, H., … Ohtomo, K. (2010). Voxel-based analyses of gray/white matter volume and diffusion tensor data in major depression. Psychiatry Research: Neuroimaging, 181(1): 64–70.Google Scholar
Aizenstein, H. J., Butters, M. A., Figurski, J. L., Stenger, V. A., Reynolds, C. F. III, & Carter, C. S. (2005). Prefrontal and striatal activation during sequence learning in geriatric depression. Biological Psychiatry, 58(4): 290–296.CrossRefGoogle ScholarPubMed
Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9(1): 357–381.Google Scholar
Alexopoulos, G. S. (2003). Role of executive function in late-life depression. Journal of Clinical Psychiatry, 64(Suppl. 14): 18–23.Google Scholar
Alexopoulos, G. S., Meyers, B. S., Young, R. C., Campbell, S., Silbersweig, D., & Charlson, M. (1997). “Vascular depression” hypothesis. Archives of General Psychiatry, 54(10): 915–922.CrossRefGoogle ScholarPubMed
Aron, A. R., Behrens, T. E., Smith, S., Frank, M. J., & Poldrack, R. A. (2007). Triangulating a cognitive control network using diffusion-weighted magnetic resonance imaging (MRI) and functional MRI. Journal of Neuroscience, 27(14): 3743–3752.CrossRefGoogle ScholarPubMed
Aston, C., Jiang, L., & Sokolov, B. P. (2004). Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder. Molecular Psychiatry, 10(3): 309–322.Google Scholar
Baird, B., Smallwood, J., Gorgolewski, K. J., & Margulies, D. S. (2013). Medial and lateral networks in anterior prefrontal cortex support metacognitive ability for memory and perception. Journal of Neuroscience, 33(42): 16657–16665.Google Scholar
Beasley, C. L., Honavar, M., Everall, I. P., & Cotter, D. (2009). Two-dimensional assessment of cytoarchitecture in the superior temporal white matter in schizophrenia, major depressive disorder and bipolar disorder. Schizophrenia Research, 115(2): 156–162.CrossRefGoogle ScholarPubMed
Bora, E., Fornito, A., Pantelis, C., & Yücel, M. (2012a). Gray matter abnormalities in major depressive disorder: A meta-analysis of voxel based morphometry studies. Journal of Affective Disorders, 138(1): 9–18.CrossRefGoogle ScholarPubMed
Bora, E., Harrison, B. J., Davey, C. G., Yücel, M., & Pantelis, C. (2012b). Meta-analysis of volumetric abnormalities in cortico-striatal-pallidal-thalamic circuits in major depressive disorder. Psychological Medicine, 42(4): 671–681.CrossRefGoogle ScholarPubMed
Bracht, T., Federspiel, A., Schnell, S., Horn, H., Höfle, O., Wiest, R., … Walther, S. (2012). Cortico-cortical white matter motor pathway microstructure is related to psychomotor retardation in major depressive disorder. PLoS One, 7(12): e52238.Google Scholar
Buyukdura, J. S., McClintock, S. M., & Croarkin, P. E. (2011). Psychomotor retardation in depression: Biological underpinnings, measurement, and treatment. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35(2): 395–409.CrossRefGoogle ScholarPubMed
Caligiuri, M. P. & Ellwanger, J. (2000). Motor and cognitive aspects of motor retardation in depression. Journal of Affective Disorders, 57(1–3): 83–93.CrossRefGoogle ScholarPubMed
Chantiluke, K., Halari, R., Simic, M., Pariante, C. M., Papadopoulos, A., Giampietro, V., & Rubia, K. (2012). Fronto-striato-cerebellar dysregulation in adolescents with depression during motivated attention. Biological Psychiatry, 71(1): 59–67.CrossRefGoogle ScholarPubMed
Chen, C.-S., Chiang, I., Li, C.-W., Lin, W.-C., Lu, C.-Y., Hsieh, T.-J., … Kuo, Y.-T. (2009). Proton magnetic resonance spectroscopy of late-life major depressive disorder. Psychiatry Research: Neuroimaging, 172(3): 210–214.Google Scholar
Cooney, R. E., Joormann, J., Eugène, F., Dennis, E. L., & Gotlib, I. H. (2010). Neural correlates of rumination in depression. Cognitive, Affective, & Behavioral Neuroscience, 10(4): 470–478.CrossRefGoogle ScholarPubMed
Cotter, D., Mackay, D., Chana, G., Beasley, C., Landau, S., & Everall, I. P. (2002). Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. Cerebral Cortex, 12(4): 386–394.CrossRefGoogle ScholarPubMed
Crowell, A. L., Riva-Posse, P., Garlow, S. J., & Mayberg, H. S. (2014). Toward an understanding of the neural circuitry of major depressive disorder through the clinical response to deep brain stimulation of different anatomical targets. Current Behavioral Neuroscience Reports, 1(2): 55–63.CrossRefGoogle Scholar
Dannlowski, U., Ohrmann, P., Konrad, C., Domschke, K., Bauer, J., Kugel, H., … Baune, B. T. (2009). Reduced amygdala–prefrontal coupling in major depression: Association with MAOA genotype and illness severity. International Journal of Neuropsychopharmacology, 12(1): 11–22.CrossRefGoogle ScholarPubMed
DeRubeis, R. J., Siegle, G. J., & Hollon, S. D. (2008). Cognitive therapy versus medication for depression: Treatment outcomes and neural mechanisms. Nature Reviews Neuroscience, 9(10): 788–796.CrossRefGoogle ScholarPubMed
Disner, S. G., Beevers, C. G., Haigh, E. A. P., & Beck, A. T. (2011). Neural mechanisms of the cognitive model of depression. Nature Reviews Neuroscience, 12(8): 467–477.CrossRefGoogle ScholarPubMed
Draganski, B., Kherif, F., Klöppel, S., Cook, P. A., Alexander, D. C., Parker, G. J. M., … Frackowiak, R. S. J. (2008). Evidence for segregated and integrative connectivity patterns in the human basal ganglia. Journal of Neuroscience, 28(28): 7143–7152.Google Scholar
Drevets, W. C., Savitz, J., & Trimble, M. (2008). The subgenual anterior cingulate cortex in mood disorders. CNS Spectrums, 13(8): 663–681.CrossRefGoogle ScholarPubMed
Elliott, R., Rubinsztein, J. S., Sahakian, B. J., & Dolan, R. J. (2002). The neural basis of mood-congruent processing biases in depression. Archives of General Psychiatry, 59(7): 597–604.CrossRefGoogle ScholarPubMed
Etkin, A., Egner, T., Peraza, D. M., Kandel, E. R., & Hirsch, J. (2006). Resolving emotional conflict: A role for the rostral anterior cingulate cortex in modulating activity in the amygdala. Neuron, 51(6): 871–882.Google Scholar
Eugène, F., Joormann, J., Cooney, R. E., Atlas, L. Y., & Gotlib, I. H. (2010). Neural correlates of inhibitory deficits in depression. Psychiatry Research: Neuroimaging, 181(1): 30–35.Google Scholar
Fales, C. L., Barch, D. M., Rundle, M. M., Mintun, M. A., Snyder, A. Z., Cohen, J. D., … Sheline, Y. I. (2008). Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression. Biological Psychiatry,63(4): 377–384.Google Scholar
Fornage, M., Debette, S., Bis, J. C., Schmidt, H., Ikram, M. A., Dufouil, C., … Launer, L. J. (2011). Genome-wide association studies of cerebral white matter lesion burden. Annals of Neurology, 69(6): 928–939.Google Scholar
Greicius, M. (2008). Resting-state functional connectivity in neuropsychiatric disorders. Current Opinion in Neurology, 21(4): 424–430.Google Scholar
Greicius, M. D., Flores, B. H., Menon, V., Glover, G. H., Solvason, H. B., Kenna, H., … Schatzberg, A. F. (2007). Resting-state functional connectivity in major depression: Abnormally increased contributions from subgenual cingulate cortex and thalamus. Biological Psychiatry, 62(5): 429–437.CrossRefGoogle ScholarPubMed
Halari, R., Simic, M., Pariante, C. M., Papadopoulos, A., Cleare, A., Brammer, M., … Rubia, K. (2009). Reduced activation in lateral prefrontal cortex and anterior cingulate during attention and cognitive control functions in medication-naïve adolescents with depression compared to controls. Journal of Child Psychology and Psychiatry, 50(3): 307–316.Google Scholar
Hamilton, J. P. & Gotlib, I. H. (2008). Neural substrates of increased memory sensitivity for negative stimuli in major depression. Biological Psychiatry, 63(12): 1155–1162.Google Scholar
Heller, A. S., Johnstone, T., Shackman, A. J., Light, S. N., Peterson, M. J., Kolden, G. G., … Davidson, R. J. (2009). Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation. Proceedings of the National Academy of Sciences of the United States of America, 106(52): 22445–22450.Google Scholar
Johansen-Berg, H., Gutman, D. A., Behrens, T. E. J., Matthews, P. M., Rushworth, M. F. S., Katz, E., … Mayberg, H. S. (2008). Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression. Cerebral Cortex, 18(6): 1374–1383.CrossRefGoogle ScholarPubMed
Johnston-Wilson, N. L., Sims, C. D., Hofmann, J. P., Anderson, L., Shore, A. D., Torrey, E. F., & Yolken, R. H. (2000). Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. Molecular Psychiatry, 5(2): 142–149.Google Scholar
Johnstone, T., Van Reekum, C. M., Urry, H. L., Kalin, N. H., & Davidson, R. J. (2007). Failure to regulate: Counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression. Journal of Neuroscience, 27(33): 8877–8884.CrossRefGoogle ScholarPubMed
Krishnan, K., Taylor, W. D., McQuoid, D. R., MacFall, J. R., Payne, M. E., Provenzale, J. M., & Steffens, D. C.(2004). Clinical characteristics of magnetic resonance imaging-defined subcortical ischemic depression. Biological Psychiatry, 55(4): 390–397.Google Scholar
Kumar, A., Gupta, R. C., Albert, T. M., Alger, J., Wyckoff, N., & Hwang, S. (2004). Biophysical changes in normal-appearing white matter and subcortical nuclei in late-life major depression detected using magnetization transfer. Psychiatry Research: Neuroimaging, 130(2): 131–140.CrossRefGoogle ScholarPubMed
Lee, R. S. C., Hermens, D. F., Porter, M. A., & Redoblado-Hodge, M. A. (2012). A meta-analysis of cognitive deficits in first-episode major depressive disorder. Journal of Affective Disorders, 140(2): 113–124.CrossRefGoogle ScholarPubMed
Lui, S., Wu, Q., Qiu, L., Yang, X., Kuang, W., Chan, R. C. K., … Gong, Q. (2011). Resting-state functional connectivity in treatment-resistant depression. American Journal of Psychiatry, 168(6): 642–648.Google Scholar
Ma, N., Li, L., Shu, N., Liu, J., Gong, G., He, Z., … Zhang, Z. (2007). White matter abnormalities in first-episode, treatment-naive young adults with major depressive disorder. American Journal of Psychiatry, 164(5): 823–826.Google Scholar
MacLeod, C., Mathews, A., & Tata, P. (1986). Attentional bias in emotional disorders. Journal of Abnormal Psychology, 95(1): 15–20.Google Scholar
Mayberg, H. S. (2009). Targeted electrode-based modulation of neural circuits for depression. Journal of Clinical Investigation, 119(4): 717–725.Google Scholar
Mayberg, H. S., Liotti, M., Brannan, S. K., McGinnis, S., Mahurin, R. K., Jerabek, P. A., … Lancaster, J. L. (1999). Reciprocal limbic-cortical function and negative mood: Converging PET findings in depression and normal sadness. American Journal of Psychiatry, 156(5): 675–682.Google Scholar
Mayberg, H. S., Lozano, A. M., Voon, V., McNeely, H. E., Seminowicz, D., Hamani, C., … Kennedy, S. H. (2005). Deep brain stimulation for treatment-resistant depression. Neuron, 45(5): 651–660.Google Scholar
McCormick, L. M., Ponto, L. L. B., Pierson, R. K., Johnson, H. J., Magnotta, V., & Brumm, M. C. (2007). Metabolic correlates of antidepressant and antipsychotic response in patients with psychotic depression undergoing electroconvulsive therapy. Journal of ECT, 23(4): 265–273.Google Scholar
Millan, M. J., Agid, Y., Brüne, M., Bullmore, E. T., Carter, C. S., Clayton, N. S., … DeRubeis, R. J. (2012). Cognitive dysfunction in psychiatric disorders: Characteristics, causes and the quest for improved therapy. Nature Reviews Drug Discovery, 11(2): 141–168.Google Scholar
Minett, T. S. C., Dean, J. L., Firbank, M., English, P., & O’Brien, J. T. (2005). Subjective memory complaints, white-matter lesions, depressive symptoms, and cognition in elderly patients. American Journal of Geriatric Psychiatry, 13(8): 665–671.CrossRefGoogle ScholarPubMed
Modirrousta, M. & Fellows, L. K. (2008). Medial prefrontal cortex plays a critical and selective role in “feeling of knowing” meta-memory judgments. Neuropsychologia, 46(12): 2958–2965.Google Scholar
Murata, T., Kimura, H., Omori, M., Kado, H., Kosaka, H., Iidaka, T., … Wada, Y. (2001). MRI white matter hyperintensities, 1H-MR spectroscopy and cognitive function in geriatric depression: A comparison of early-and late-onset cases. International Journal of Geriatric Psychiatry, 16(12): 1129–1135.Google Scholar
Niogi, S., Mukherjee, P., Ghajar, J., & McCandliss, B. D. (2010). Individual differences in distinct components of attention are linked to anatomical variations in distinct white matter tracts. Frontiers in Neuroanatomy, 4: 2.Google Scholar
O’Driscoll, K. & Leach, J. P. (1998). “No longer Gage”: an iron bar through the head – early observations of personality change after injury to the prefrontal cortex. British Medical Journal, 317(7174): 1673–1674.Google Scholar
O’Sullivan, M., Barrick, T. R., Morris, R. G., Clark, C. A., & Markus, H. S. (2005). Damage within a network of white matter regions underlies executive dysfunction in CADASIL. Neurology, 65(10): 1584–1590.Google Scholar
Papakostas, G. I., Iosifescu, D. V., Renshaw, P. F., Lyoo, I. K., Lee, H. K., Alpert, J. E., … Fava, M. (2005). Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part II). Psychiatry Research: Neuroimaging, 140(3): 301–307.Google Scholar
Ponds, R. W. H. M. & Jolles, J. (1996). Memory complaints in elderly people: The role of memory abilities, metamemory, depression, and personality. Educational Gerontology: An International Quarterly, 22(4): 341–357.CrossRefGoogle Scholar
Posner, M. I. & Petersen, S. E. (1989). The attention system of the human brain: DTIC document. St. Louis, MO: Washington University.Google Scholar
Posner, M. I. & Rothbart, M. K. (2007). Research on attention networks as a model for the integration of psychological science. Annual Review of Psychology, 58: 1–23.Google Scholar
Prins, N. D., Van Dijk, E. J., den Heijer, T., Vermeer, S. E., Jolles, J., Koudstaal, P. J., … Breteler, M. M. B. (2005). Cerebral small-vessel disease and decline in information processing speed, executive function and memory. Brain, 128(9): 2034–2041.Google Scholar
Qin, J., Wei, M., Liu, H., Yan, R., Luo, G., Yao, Z., & Lu, Q. (2014). Abnormal brain anatomical topological organization of the cognitive-emotional and the frontoparietal circuitry in major depressive disorder. Magnetic Resonance in Medicine, 72(5): 1397–1407.Google Scholar
Rajkowska, G. & Miguel-Hidalgo, J. J. (2007). Gliogenesis and glial pathology in depression. CNS & Neurological Disorders: Drug Targets, 6(3): 219–233.Google Scholar
Ratiu, P., Talos, I.-F., Haker, S., Lieberman, D., & Everett, P. (2004). The tale of Phineas Gage, digitally remastered. Journal of Neurotrauma, 21(5): 637–643.Google Scholar
Rigucci, S., Serafini, G., Pompili, M., Kotzalidis, G. D., & Tatarelli, R. (2010). Anatomical and functional correlates in major depressive disorder: The contribution of neuroimaging studies. World Journal of Biological Psychiatry, 11(2): 165–180.Google Scholar
Russo, S. J. & Nestler, E. J. (2013). The brain reward circuitry in mood disorders. Nature Reviews Neuroscience, 14(9): 609–625.Google Scholar
Sacher, J., Neumann, J., Fünfstück, T., Soliman, A., Villringer, A., & Schroeter, M. L. (2012). Mapping the depressed brain: A meta-analysis of structural and functional alterations in major depressive disorder. Journal of Affective Disorders, 140(2): 142–148.Google Scholar
Sepulcre, J., Masdeu, J. C., Sastre-Garriga, J., Goñi, J., Vélez-de-Mendizábal, N., Duque, B., … Villoslada, P. (2008). Mapping the brain pathways of declarative verbal memory: Evidence from white matter lesions in the living human brain. Neuroimage, 42(3): 1237–1243.Google Scholar
Sheline, Y. I., Price, J. L., Yan, Z., & Mintun, M. A. (2010). Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proceedings of the National Academy of Sciences of the United States of America, 107(24): 11020–11025.Google Scholar
Shizukuishi, T., Abe, O., & Aoki, S. (2013). Diffusion tensor imaging analysis for psychiatric disorders. Magnetic Resonance in Medical Sciences, 12(3): 153–159.Google Scholar
Siegle, G. J., Thompson, W., Carter, C. S., Steinhauer, S. R., & Thase, M. E. (2007). Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: Related and independent features. Biological Psychiatry, 61(2): 198–209.Google Scholar
Simpson, J. E., Hosney, O., Wharton, S. B., Heath, P., Holden, H., Fernando, M. S., … Ince, P. G. (2009). Microarray RNA expression analysis of cerebral white matter lesions reveals changes in multiple functional pathways. Stroke, 40(2): 369–375.Google Scholar
Surguladze, S., Brammer, M. J., Keedwell, P., Giampietro, V., Young, A. W., Travis, M. J., … Phillips, M. L. (2005). A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biological Psychiatry, 57(3): 201–209.Google Scholar
Tao, H., Guo, S., Ge, T., Kendrick, K. M., Xue, Z., Liu, Z., & Feng, J. (2011). Depression uncouples brain hate circuit. Molecular Psychiatry, 18(1): 101–111.Google Scholar
Taylor, W. D., Aizenstein, H. J., & Alexopoulos, G. S. (2013). The vascular depression hypothesis: Mechanisms linking vascular disease with depression. Molecular Psychiatry, 18(9): 963–974.CrossRefGoogle ScholarPubMed
Tham, M. W., Woon, P. S., Sum, M. Y., Lee, T.-S., & Sim, K. (2011). White matter abnormalities in major depression: Evidence from post-mortem, neuroimaging and genetic studies. Journal of Affective Disorders, 132(1): 26–36.Google Scholar
Thomas, A. J., O’Brien, J. T., Davis, S., Ballard, C., Barber, R., Kalaria, R. N., & Perry, R. H. (2002). Ischemic basis for deep white matter hyperintensities in major depression: A neuropathological study. Archives of General Psychiatry, 59(9): 785–792.Google Scholar
Tullberg, M., Fletcher, E., DeCarli, C., Mungas, D., Reed, B. R., Harvey, D. J., … Jagust, W. J. (2004). White matter lesions impair frontal lobe function regardless of their location. Neurology, 63(2): 246–253.Google Scholar
Turken, A. U., Whitfield-Gabrieli, S., Bammer, R., Baldo, J., Dronkers, N. F., & Gabrieli, J. D. E. (2008). Cognitive processing speed and the structure of white matter pathways: Convergent evidence from normal variation and lesion studies. NeuroImage, 42(2): 1032–1044.Google Scholar
Van den Heuvel, D. M. J., Ten Dam, V. H., de Craen, A. J. M., Admiraal-Behloul, F., Olofsen, H., Bollen, E. L. E. M., … Westendorp, R. G. J. (2006). Increase in periventricular white matter hyperintensities parallels decline in mental processing speed in a non-demented elderly population. Journal of Neurology, Neurosurgery, and Psychiatry, 77(2): 149–153.Google Scholar
Van Horn, J. D., Irimia, A., Torgerson, C. M., Chambers, M. C., Kikinis, R., & Toga, A. W. (2012). Mapping connectivity damage in the case of Phineas Gage. PloS One, 7(5): e37454.Google Scholar
Van Petten, C., Plante, E., Davidson, P. S. R., Kuo, T. Y., Bajuscak, L., & Glisky, E. L. (2004). Memory and executive function in older adults: Relationships with temporal and prefrontal gray matter volumes and white matter hyperintensities. Neuropsychologia, 42(10): 1313–1335.Google Scholar
Veer, I. M., Beckmann, C. F., Van Tol, M.-J., Ferrarini, L., Milles, J., Veltman, D. J., … Rombouts, S. A. R. B. (2010). Whole brain resting-state analysis reveals decreased functional connectivity in major depression. Frontiers in Systems Neuroscience, 4: 41.Google Scholar
Walther, S., Hügli, S., Höfle, O., Federspiel, A., Horn, H., Bracht, T., … Müller, T. J. (2012). Frontal white matter integrity is related to psychomotor retardation in major depression. Neurobiology of Disease,47(1): 13–19.Google Scholar
Watkins, E. & Brown, R. G. (2002). Rumination and executive function in depression: An experimental study. Journal of Neurology, Neurosurgery, and Psychiatry, 72(3): 400–402.Google Scholar
World Health Organization (2001). Mental Health: A Call for Action by World Health Ministers. Geneva: WHO.Google Scholar
Zou, K., Huang, X., Li, T., Gong, Q., Li, Z., Ou-yang, L., … Sun, X. (2008). Alterations of white matter integrity in adults with major depressive disorder: A magnetic resonance imaging study. Journal of Psychiatry & Neuroscience, 33(6): 525–530.Google Scholar

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