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Structural Changes in the Brain in Depression and Relationship to Symptom Recurrence

Published online by Cambridge University Press:  07 November 2014

J. Douglas Bremner
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Abstract

Depression is an important public health problem affecting about 15% of the general population; however, little is known about possible changes in the brain that might underlie the disorder. Neuroimaging has been a powerful tool to map actual changes in the brain structure of depressed patients that might be directly related to their symptoms of depression. Some imaging studies of brain structure have shown smaller hippocampal volume with the chronicity of depression correlating to a reduction in volume. Although the meaning of these findings is unclear, other studies have shown increased amygdala volume. Studies have found reductions in volume of the frontal cortex, with some studies showing specific reductions in subregions of the frontal cortex, including the orbitofrontal cortex. Findings of an increase in white matter lesions in elderly patients with depression have been replicated and correlated with late-onset depression, as well as impairments in social and cognitive function. These findings point to alterations in a circuit of brain regions hypothesized to include the frontal cortex, hippocampus, amygdala, striatum, and thalamus, that underlie symptoms of depression.

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Feature Article
Information
CNS Spectrums , Volume 7 , Issue 2 , February 2002 , pp. 129 - 139
Copyright
Copyright © Cambridge University Press 2002

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References

1.Steffens, DC, Krishnan, KR. Structural neuroimaging and mood disorders: recent findings, implications for classification, and future directions. Biol Psychiatry. 1998;43:705–712.CrossRefGoogle ScholarPubMed
2.Pearlson, GD, Veroff, AE. Computerised tomographic changes in manicdepressive illness. Lancet. 1981;2:470.CrossRefGoogle ScholarPubMed
3.Andreasen, NC, Swayze, VII, Flaum, M, Alliger, R, Cohen, G. Ventricular abnormalities in affective disorder: clinical and demographic correlates. Arch Gen Psychiatry. 1990;147:893–900.Google ScholarPubMed
4.Kellner, CH, Rubinow, DR, Gold, PW, Post, RM. Relationship of cortisol hypersecretion to brain CT scan alterations in depressed patients. Psychiatry Res. 1983;8:191–197.CrossRefGoogle Scholar
5.Kellner, CH, Rubinow, DR, Post RM. Cerebral ventricular size and cognitive impairment in depression. J Affective Disord. 1986;10:215–219.CrossRefGoogle ScholarPubMed
6.Krishnan, KR, McDonald, WM, Escalona, PR, et al.Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations. Arch Gen Psychiatry. 1992;49:553–557.CrossRefGoogle ScholarPubMed
7.Greenwald, BS, Kramer-Ginsberg, E, Bogerts, B, et al.Qualitative magnetic resonance imaging findings in geriatric depression. Possible link between lateronset depression and Alzheimer's disease? Psychol Med. 1997;27:421–431.CrossRefGoogle ScholarPubMed
8.Husain, MM, McDonald, WM, Doraiswamy, PM, et al.A magnetic resonance imaging study of putamen nuclei in major depression. Psychiatry Res. 1991;40:95–99.CrossRefGoogle ScholarPubMed
9.Lenze, EJ, Sheline, YI. Absence of striatal volume differences between depressed subjects with no comorbid medical illness and matched comparison subjects. Am J Psychiatry. 1999;156:1989–1991.CrossRefGoogle ScholarPubMed
10.Aylward, EH, Roberts-Twillie, JV, Barta, PE, et al.Basal ganglia volumes and white matter hyperintensities in patients with bipolar disorder. Am J Psychiatry. 1994;151:687–693.Google ScholarPubMed
11.Bremner, JD, Narayan, M, Anderson, ER, et al.Hippocampal volume reduction in major depression. Am J Psychiatry. 2000;157:115–118.CrossRefGoogle ScholarPubMed
12.Krishnan, KR, Doraiswamy, PM, Lurie, SN, et al.Pituitary size in depression. J Clin Endocrinol Metab. 1991;72:256–259.CrossRefGoogle ScholarPubMed
13.Nemeroff, CB, Krishnan, KR, Reed, D, Leder, R, Beam, C, Dunnick, NR. Adrenal gland enlargement in depression. A computed tomographic study. Arch Gen Psychiatry. 1992;49:384–387.CrossRefGoogle ScholarPubMed
14.Krishnan, KR, Goli, V, Ellinwood, EH, et al.Leukoencephalopathy in patients diagnosed as major depressive. Biol Psychiatry. 1988;23:519–522.CrossRefGoogle ScholarPubMed
15.McDonald, WM, Krishnan, KR, Doraiswamy, PM, Blazer, DG. Occurrence of subcortical hyperintensities in elderly subjects with mania. Psychiatry Res. 1991;40:211–220.CrossRefGoogle ScholarPubMed
16.Lenze, E, Cross, D, McKeel, D, Neuman, RJ, Sheline, YI. White matter hyperintensities and gray matter lesions in physically healthy depressed subjects. Am J Psychiatry. 1999;156:1602–1607.CrossRefGoogle ScholarPubMed
17.Greenwald, BS, Kramer-Ginsberg, E, Krishnan, KR, et al.Neuroanatomical localization of magnetic resonance imaging signal hyperintensities in geriatric depression. Stroke. 1998;29:613–617.CrossRefGoogle ScholarPubMed
18.Hickie, I, Scott, E, Wilhelm, K, Brodaty, H. Subcortical hyperintensities on magnetic resonance imaging in patients with severe depression—a longitudinal evaluation. Biol Psychiatry. 1997;42:367–374.CrossRefGoogle ScholarPubMed
19.Iidaka, T, Nakajima, T, Kawamoto, K, et al.Signal hyperintensities on brain magnetic resonance imaging in elderly depressed patients. Eur Neurol. 1996;36:293–299.CrossRefGoogle ScholarPubMed
20.Greenwald, BS, Kramer-Ginsburg, E, Krishnan, RR, Ashtari, M, Aupperle, PM, Patel, M. MRI signal hyperintensities in geriatric depression. Am J Psychiatry. 1996;153:1212–1215.Google ScholarPubMed
21.Hickie, I, Scott, E, Mitchell, P, Wilhelm, K, Austin, MP, Bennett, B. Subcortical hyperintensities on magnetic resonance imaging: clinical correlates and prognostic significance in patients with severe depression. Biol Psychiatry. 1995;37:151–160.CrossRefGoogle ScholarPubMed
22.Salloway, S, Malloy, P, Kohn R, et al. MRI and neuropsychological differences in early- and late-life-onset geriatric depression. Neurology. 1996;46:1567–1574.CrossRefGoogle ScholarPubMed
23.Fujikawa, T, Yokota, N, Muraoka, M, Yamawaki, S. Response of patients with major depression and silent cerebral infarction to antidepressant drug therapy, with emphasis on central nervous system adverse reactions. Stroke. 1996;27:2040–2042.CrossRefGoogle ScholarPubMed
24.Cahn, DA, Malloy, PF, Salloway, S, et al.Subcortical hyperintensities on MRI and activities of daily living in geriatric depression. J Neuropsychiatry Clin Neurosci. 1996;8:404–411.Google ScholarPubMed
25.Fujikawa, T, Yanai, I, Yamawaki, S. Psychosocial stressors in patients with major depression and silent cerebral infarction. Stroke. 1997;28:1123–1125.CrossRefGoogle ScholarPubMed
26.Lesser, IM, Boone, KB, Mehringer, CM, et al.Cognition and white matter hyperintensities in older depressed patients. Am J Psychiatry. 1996;153:1280–1287.Google ScholarPubMed
27.Narayan, M, Bremner, JD, Kumar, A. Neuroanatomical substrates of late-life mental disorders. J Geriatr Psychiatry Neurol. 1999;12:95–106.CrossRefGoogle ScholarPubMed
28.Sheline, YI. 3D MRI studies of neuroanatomical changes in unipolar major depression: the role of stress and medical comorbidity. Biol Psychiatry. 2000;48:791–800.CrossRefGoogle ScholarPubMed
29.Swayze, VW II, Andreasen, NC, Alliger, RJ, Yuh, WT, Ehrhardt, JC. Subcortical and temporal structures in affective disorder and schizophrenia: a magnetic resonance imaging study. Biol Psychiatry. 1992;31:221–240.CrossRefGoogle ScholarPubMed
30.Altshuler, LL, Conrad, A, Hauser, P, Li, X, et al.Reduction of temporal lobe volume in bipolar disorder: a preliminary report of magnetic resonance imaging [letter]. Arch Gen Psychiatry. 1991;48:482–483.Google ScholarPubMed
31.Krishnan, KRR, Doraiswamy, PM, Figiel, GS, et al.Hippocampal abnormalities in depression. J Neuropsychiatry Clin Neurosci. 1991;3:387–391.Google ScholarPubMed
32.Sha, PJ, Ebmeier, KP, Glabus, MF, et al.Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression. Br J Psychiatry. 1998;527–532.CrossRefGoogle Scholar
33.Axelson, DA, Doraiswamy, PM, McDonald, WM, et al.Hypercortisolemia and hippocampal changes in depression. Psychiatry Res. 1993;47:163–173.CrossRefGoogle ScholarPubMed
34.Sheline, Y, Wang, P, Gado, M, et al.Hippocampal atrophy in major depression. Proc Natl Acad Sci U S A. 1996;93:3908–3913.CrossRefGoogle ScholarPubMed
35.Sheline, YI, Sanhavi, M, Mintun, MA, et al.Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci. 1999;19:5034–5043.CrossRefGoogle Scholar
36.Vakili, K, Pillay, SS, Lafer, B, et al.Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study. Biol Psychiatry. 2000;47:1087–1090.CrossRefGoogle ScholarPubMed
37.Mervaala, E, Fohr, J, Kononen, M, et al.Quantitative MRI of the hippocampus and amygdala in severe depression. Psychol Med. 2000;30:117–125.CrossRefGoogle ScholarPubMed
38.Steffens, DC, Byrum, CE, McQuoid, DR, et al.Hippocampal volume in geriatric depression. Biol Psychiatry. 2000;48:301–309.CrossRefGoogle ScholarPubMed
39.Ashtari, M, Greenwald, BS, Kramer-Ginsberg, E, et al.Hippocampal/amygdala volumes in geriatric depression. Psychol Med. 1999;29:629–638.CrossRefGoogle ScholarPubMed
40.Pantel, J, Schroder, J, Essig, M, et al.Quantitative magnetic resonance imaging in geriatric depression and primary degenerative dementia. J Affect Disord. 1997;42:69–83.CrossRefGoogle ScholarPubMed
41.Bremner, JD, Randall, PR, Scott, TM, et al.MRI-based measurement of hippocampal volume in posttraumatic stress disorder. Am J Psychiatry. 1995;152:973–981.Google ScholarPubMed
42.Bremner, JD, Randall, P, Vermetten, E, et al.MRI-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse: a preliminary report. Biol Psychiatry. 1997;41:23–32.CrossRefGoogle Scholar
43.Gurvits, TG, Shenton, MR, Hokama, H, et al.Magnetic resonance imaging study of hippocampal volume in chronic combat-related posttraumatic stress disorder. Biol Psychiatry. 1996;40:192–199.CrossRefGoogle ScholarPubMed
44.Stein, MB, Koverola, C, Hanna, C, et al.Hippocampal volume in women victimized by childhood sexual abuse. Psychol Med. 1997;27:951–959.CrossRefGoogle ScholarPubMed
45.Bremner, JD. Does stress damage the brain? Biol Psychiatry. 1999;45:797–805.CrossRefGoogle ScholarPubMed
46.Tebartz van Elst, L, Woermann, F, Lemieux, L, et al.Amygdala enlargement in dysthymia—a volumetric study of patients with temporal lobe epilepsy. Biol Psychiatry. 1999;46:1614–1623.CrossRefGoogle ScholarPubMed
47.Stratowski, SM. Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Arch Gen Psychiatry. 1999;56:254–260.CrossRefGoogle Scholar
48.Altschuler, LL, Bartzokis, G, Grieder, T, et al.Amygdala enlargement in bipolar disorder and hippocampal reduction in schizophrenia: an MRI study demonstrating neuroanatomic specificity. Arch Gen Psychiatry. 1998;55:663–664.Google Scholar
49.Sheline, YI, Gado, MH, Price, JL. Amygdala core nuclei volumes are decreased in recurrent major depression. Neuroreport. 1998;9:2023–2028.CrossRefGoogle ScholarPubMed
50.Drevets, WC, Price, JL, Simpson, JR Jr, et al.Subgenual prefrontal cortex abnormalities in mood disorders. Nature. 1997;386:824–827.CrossRefGoogle ScholarPubMed
51.Ongur, D, Drevets, WC, Price, JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci U S A. 1998;95:13290–13295.CrossRefGoogle ScholarPubMed
52.Coffey, CE, Wilkinson, WE, Weiner, RD, et al.Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study. Arch Gen Psychiatry. 1993;50:7–16.CrossRefGoogle ScholarPubMed
53.Kumar, A, Schweizer, E, Jin, Z, et al.Neuroanatomical substrates of late-life minor depression. A quantitative magnetic resonance imaging study. Arch Neurol. 1997;54:613–617.CrossRefGoogle ScholarPubMed
54.Kumar, A, Zin, Z, Bilker, W, et al.Late onset minor and major depression: early evidence for common neuroanatomical substrates detected by using MRI. Proc Natl Acad Sci U S A. 1998;95:7654–7658.CrossRefGoogle ScholarPubMed
55.Steingard, RJ, Renshaw, PF, et al.Structural abnormalities in brain magnetic resonance images of depressed children. J Am Acad Child Adolesc Psychiatry. 1996;35:307–311.CrossRefGoogle ScholarPubMed
56.Bremner, JD, Innis, RB, Salomon, RM, et al.PET measurement of cerebral metabolic correlates of depressive relapse. Arch Gen Psychiatry. 1997;54:364–374.CrossRefGoogle Scholar
57.Rajkowska, NA, Miguel-Hidalgo, JJ, Wei, J, et al.Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry. 1999;45:1085–1098.CrossRefGoogle ScholarPubMed
58.Bremner, JD, Vythilingam, M, Vermetten, E, et al.Reduced volume of orbitofrontal cortex in major depression. Biol Psychiatry. 2002. In press.Google Scholar
59.Lai, TJ, Payne, ME, Byrum, CE, et al.Reduction of orbital frontal cortex volume in geriatric depression. Biol Psychiatry. 2000;48:971–975.CrossRefGoogle ScholarPubMed
60.Auer, DP, Putz, B, Kraft, E, Lipinski, B, Schill, J, Holsboer, F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry. 2000;47:305–313.CrossRefGoogle Scholar
61.Carroll, BJ, Curtis, GC, Davies, BM, et al.Urinary free cortisol excretion in depression. J Psychol Med. 1976;6:43–50.CrossRefGoogle ScholarPubMed
62.Nemeroff, CB, Widerlov, E, Bissette, G, et al.Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science. 1984;226:1342–1343.CrossRefGoogle ScholarPubMed
63.Sapolsky, RM, Uno, H, Rebert, CS, et al.Hippocampal damage associated with prolonged glucocorticoid exposure in primates. J Neurosci. 1990;10:2897–2902.CrossRefGoogle ScholarPubMed
64.Sapolsky, RM. Why stress is bad for your brain. Science. 1996;273:749–750.CrossRefGoogle ScholarPubMed
65.McEwen, BS, Angulo, J, Cameron, H, et al.Paradoxical effects of adrenal steroids on the brain: protection versus degeneration. Biol Psychiatry. 1992;31:177–199.CrossRefGoogle ScholarPubMed
66.Smith, MA, Makino, S, Kvetnansky, R, et al.Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNA in the hippocampus. J Neurosci. 1995;15:1768–1777.CrossRefGoogle ScholarPubMed
67.Nibuya, M, Morinobu, S, Duman, RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci. 1995;15:7539–7547.CrossRefGoogle ScholarPubMed
68.Duman, RS, Heninger, GR, Nestler, EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry. 1997;54:597–606.CrossRefGoogle ScholarPubMed
69.Duman, RS, Malberg, J, Nakagawa, S. Regulation of adult neurogenesis by psychotropic drugs and stress. J Pharmacol Exp Ther. 2001;299:401–407.Google ScholarPubMed
70.Gould, E, Tanapat, P, McEwen, BS, et al.Proliferation of granule cell precursors in the dentate gyms of adult monkeys is diminished by stress. Proc Natl Acad Sci U S A. 1998;95:3168–3171.CrossRefGoogle Scholar
71.Wolkowitz, OM, Reus, VI, Weingartner, H, et al.Cognitive effects of corticosteroids. Am J Psychiatry. 1990;147:1297–1303.Google ScholarPubMed
72.Newcomer, JW, Craft, S, Hershey, T, et al.Glucocorticoid-induced impairment in declarative memory performance in adult humans. J Neurosci. 1994;14:2047–2053.CrossRefGoogle ScholarPubMed
73.Kirschbaum, C, Wolf, OT, May, M, et al.Stress- and treatment-induced elevations of cortisol levels associated with impaired declarative memory in healthy adults. Life Sci. 1996;58:1475–1483.CrossRefGoogle ScholarPubMed
74.Lupien, SJ, Gaudreau, S, Tchiteya, BM, et al.Stress-induced declarative memory impairment in healthy elderly subjects: relationship to cortisol reactivity. J Clin Endocrinol Metab. 1997;82:2070–2075.Google ScholarPubMed
75.Bentson, J, Reza, M, Winter, J, et al.Steroids and apparent cerebral atrophy on computed tomography scans. J Comput Assist Tomogr. 1978;2:16–23.CrossRefGoogle ScholarPubMed
76.Okuno, T, Ito, M, Konishi, Y, et al.Cerebral atrophy following ACTH therapy. J Comput Assist Tomogr. 1980;4:20–23.CrossRefGoogle ScholarPubMed
77.Starkman, MN, Gebarksi, SS, Berent, S, et al.Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome. Biol Psychiatry. 1992;32:756–765.CrossRefGoogle ScholarPubMed
78.Burt, DB, Zembar, MJ, Niederehe, G. Depression and memory impairment: a meta-analysis of the association, its pattern, and specificity. Psychol Bull. 1995;117:285–305.CrossRefGoogle ScholarPubMed
79.Bartfai, A, Asberg, M, Martensson, B, et al.Memory effects of clomipramine treatment: relationship to CSF monoamine metabolites and drug concentrations in plasma. Biol Psychiatry. 1991;30:1073–1092.CrossRefGoogle ScholarPubMed
80.Rubinow, DR, Post, RM, Savard, R, et al.Cortisol hypersecretion and cognitive impairment in depression. Arch Gen Psychiatry. 1984;41:279–283.CrossRefGoogle ScholarPubMed
81.Wolkowitz, OM, Reus, VI, Roberts, E, et al.Dehydroepiandosterone (DHEA) treatment of depression. Biol Psychiatry. 1997;41:311–318.CrossRefGoogle Scholar
82.Sass, KJ, Spencer, DD, Kim, JH, et al.Verbal memory impairment correlates with hippocampal pyramidal cell density. Neurology. 1990;40:1694–1697.CrossRefGoogle ScholarPubMed
83.Rothschild, A, Benes, F, Hebben, N, et al.Relationships between brain CT scan findings and cortisol in psychotic and nonpsychotic depressed patients. Biol Psychiatry. 1989;26:565–575.CrossRefGoogle ScholarPubMed
84.Alexopoulos, GS, Meyers, BS, Young, RC, et al.The course of geriatric depression with “reversible dementia”: a controlled study. Am J Psychiatry. 1993;150:1693–1699.Google ScholarPubMed
85.Sapolsky, R, Krey, L, McEwen, B. Prolonged glucocorticoid exposure reduces hippocampal neuron number implications for aging. J Neurosci. 1985;5:1221–1226.CrossRefGoogle ScholarPubMed
86.O'Brien, JT, Ames, D, Schweitzer, I, et al.Clinical and magnetic resonance imaging correlates of hypothalamic-pituitary-adrenal axis function in depression and Alzheimer's disease. Br J Psychiatry. 1996;168:679–687.CrossRefGoogle ScholarPubMed
87.Rao, VP, Krishnan, KRR, Goli, V, et al.Neuroanatomical changes and hypothalamo-pituitary-adrenal axis abnormalities. Biol Psychiatry. 1989;26:729–732.CrossRefGoogle ScholarPubMed