Skip to main content Accessibility help
×
Hostname: page-component-848d4c4894-x5gtn Total loading time: 0 Render date: 2024-05-01T08:57:13.781Z Has data issue: false hasContentIssue false

14 - The neuropathology of mood disorders

from Part VII - Affective illness

Published online by Cambridge University Press:  19 January 2010

Paul J Harrison
Affiliation:
Warneford Hospital, Oxford, UK
Rebecca Gittins
Affiliation:
Radcliffe Infirmary, Oxford, UK
Maria A. Ron
Affiliation:
Institute of Neurology, London
Trevor W. Robbins
Affiliation:
University of Cambridge
Get access

Summary

Introduction

Mood (affective) disorders exemplify the distinction made in psychiatric classifications between organic and functional. Hence, in ICD–10, organic mood disorders are those with a ‘presumed direct causation by a cerebral or other physical disorder’. As such, the category includes mood disorders associated with overt neuropathology, e.g. a meningioma, cerebral vasculitis or Huntington's disease. Although ICD–10 emphasizes that functional disorders are not lacking an organic component, they are defined by an absence of demonstrable, established features of this kind. From a neuropathological perspective, until recently there has been no reason to question this basic assumption as it applies to mood disorders: there were few studies, and no convincing data (Jeste et al. 1988). Whilst the neuropathological understanding of mood disorders is still rudimentary, and far from contributing in any diagnostic or clinical sense, structural correlates are beginning to emerge. The focus here is upon the recent postmortem studies of mood disorder, followed by discussion of the methodological and conceptual issues affecting their interpretation.

Anterior cingulate cortex

The anterior cingulate cortex surrounds the corpus callosum on the medial surface of the frontal lobe. It consists mainly of Brodmann area 24 (Figure 14.1, colour plate). It has long been implicated in affective and emotional processing and their disorders because of neuropsychological, anatomical and functional imaging data (Bench et al. 1992; Devinsky et al. 1995; Ebert and Ebmeier 1996; Price 1999).

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2003

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

Alexopoulos, G S, Meyers, B S, Young, R C, Campbell, S, Silbersweig, D and Charlson, M (1997). ‘Vascular depression’ hypothesis. Arch Gen Psychiatry, 54, 915–22Google Scholar
Altshuler, L L, Bartzokis, G, Grieder, T et al. (2000). An MRI study of temporal lobe structures in men with bipolar disorder or schizophrenia. Biol Psychiatry, 48, 147–62Google Scholar
Ballard, C, McKeith, I, O'Brien, J et al. (2000). Neuropathological substrates of dementia and depression in vascular dementia, with a particular focus on cases with small infarct volumes. Dementia, 11, 59–65Google Scholar
Baumann, B and Bogerts, B (1999). The pathomorphology of schizophrenia and mood disorders: similarities and differences. Schizophr Res, 39, 141–8Google Scholar
Baumann, B, Danos, P, Krell, D et al. (1999). Unipolar-bipolar dichotomy of mood disorders is supported by noradrenergic brainstem system morphology. J Affect Disord, 54, 217–24Google Scholar
Bayer, T A, Buslei, R, Havas, L and Falkai, P (1999). Evidence for activation of microglia in patients with psychiatric illnesses. Neurosci Lett, 271, 126–128Google Scholar
Beckmann, H and Jakob, H (1991). Prenatal disturbances of nerve cell migration in the entorhinal region: a common vulnerability factor in functional psychoses. J Neural Transm, 84, 155–64Google Scholar
Bench, C J, Friston, K J, Brown, R G, Scott, L C, Frackowiak, R S J and Dolan, R J (1992). The anatomy of melancholia – focal abnormalities of cerebral blood flow in major depression. Psychol Med, 22, 607–15Google Scholar
Benes, F M and Lange, N (2001). Two-dimensional versus three-dimensional cell counting: a practical perspective. Trends Neurosci, 24, 11–17Google Scholar
Benes, F M, Todtenkopf, M S, Logiotatos, P and Williams, M (2000). Glutamate decarboxylase65-immunoreactive terminals in cingulate and prefrontal cortices of schizophrenic and bipolar brain. J Chem Neuroanat, 20, 259–69Google Scholar
Benes, F M, Vincent, S L and Todtenkopf, M (2001). The density of pyramidal and non-pyramidal neurons in anterior cingulate cortex of schizophrenic and bipolar subjects. Biol Psychiatry, 50, 395–406Google Scholar
Bernstein, H-G, Krell, D, Baumann, B et al. (1998). Morphometric studies of the entorhinal cortex in neuropsychiatric patients and controls: clusters of heterotopically displaced lamina II neurons are not indicative of schizophrenia. Schizophr Res, 33, 125–32Google Scholar
Bremner, J D, Narayan, M, Anderson, E R, Staib, L H, Miller, H L and Charney, D S (2000). Hippocampal volume reduction in major depression. Am J Psychiatry, 157, 115–17Google Scholar
Brown, E S, Rush, A J and McEwen, B S (1999). Hippocampal remodeling and damage by corticosteroids: implications for mood disorders. Neuropsychopharmacology, 21, 474–84Google Scholar
Chen, G, Rajkowksa, G, Du, F, Seraji-Bozorgzad, N and Manji, H K (2000). Enhancement of hippocampal neurogenesis by lithium. J Neurochem, 75, 1729–34Google Scholar
Cotter, D, Mackay, D, Landau, S, Kerwin, R and Everall, I (2001). Glial cell loss and reduced neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry, 58, 545–53Google Scholar
Coyle, J T and Schwarcz, R (2000). Mind glue – implications of glial cell biology for psychiatry. Arch Gen Psychiatry, 57, 90–3Google Scholar
Devenand, D P, Dwork, A J, Hutchinson, E R, Bolwig, T G and Sackeim, H A (1994). Does ECT alter brain structure?Am J Psychiatry, 151, 957–70Google Scholar
Devinsky, O, Morrell, M J and Vogt, B A (1995). Contributions of anterior cingulate cortex to behaviour. Brain, 118, 279–306Google Scholar
Drevets, W C, Price, J L, Simpson, J R Jr et al. (1997). Subgenual prefrontal cortex abnormalities in mood disorders. Nature, 386, 824–7Google Scholar
Duman, R S, Heninger, G R and Nestler, E J (1997). A molecular and cellular theory of depression. Arch Gen Psychiatry, 54, 597–606Google Scholar
Eastwood, S L and Harrison, P J (2000). Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs. Mol Psychiatry, 5, 425–32Google Scholar
Eastwood, S L and Harrison, P J (2001). Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a western blot study of synaptophysin, GAP-43 and the complexins. Brain Res Bull, 55, 569–78Google Scholar
Ebert, D and Ebmeier, K P (1996). The role of the cingulate gyrus in depression: from functional anatomy to neurochemistry. Biol Psychiatry, 39, 1044–50Google Scholar
Esiri M M and Pearson R C A (2000). Perspectives from other diseases and lesions. In The Neuropathology of Schizophrenia. Progress and Interpretation, ed. P J Harrison and G W Roberts, pp. 257–76. Oxford: Oxford University Press
Ferrier, I N, Stanton, B R, Kelly, T P and Scott, J (1999). Neuropsychological function in euthymic patients with bipolar disorder. Br J Psychiatry, 175, 246–51Google Scholar
Förstl, H, Burns, A, Luthert, P, Cairns, N, Lantos, P and Levy, R (1992). Clinical and neuropathological correlates of depression in Alzheimer's disease. Psychol Med, 22, 877–84Google Scholar
Goodwin, G M (1997). Neuropsychological and neuroimaging evidence for the involvement of the frontal lobes in depression. J Psychopharmacol, 11, 115–22Google Scholar
Greenwald, B S, Kramer-Ginsberg, E, Krishnan, K R, Ashtari, M, Auerbach, C and Patel, M (1998). Neuroanatomic localization of magnetic resonance imaging signal hyperintensities in geriatric depression. Stroke, 29, 613–17Google Scholar
Hamakawa, H, Kato, T, Shioiri, T, Inubushi, T and Kato, N (1999). Quantitative proton magnetic resonance spectroscopy of the bilateral frontal lobes in patients with bipolar disorder. Psychol Med, 29, 639–44Google Scholar
Harrison, P J (1999). The neuropathological effects of antipsychotic drugs. Schizophr Res, 40, 87–99Google Scholar
Harrison, P J and Eastwood, S L (2001). Neuropathological studies of synaptic connectivity in the hippocampal formation in schizophrenia. Hippocampus, 11, 508–19Google Scholar
Harrison P J and Kleinman J E (2000). Methodological issues. In The Neuropathology of Schizophrenia. Progress and Interpretation, ed. P J Harrison and G W Roberts, pp. 339–50. Oxford: Oxford University Press
Harrison P J and Lewis D A (in press). The neuropathology of schizophrenia. In Schizophrenia, 2nd edn, ed. S Hirsch and D R Weinberger. Oxford: Blackwell Science
Harrison P J and Roberts G W (2000). The Neuropathology of Schizophrenia: Progress and Interpretation. Oxford: Oxford University Press
Hirayasu, Y, Shenton, M E, Salisbury, D F et al. (1999). Subgenual cingulate cortex volume in first-episode psychosis. Am J Psychiatry, 156, 1091–3Google Scholar
Honer, W G, Falkal, P, Chen, C, Arango, V, Mann, J J and Dwork, A J (1999). Synaptic and plasticity-associated proteins in anterior frontal cortex in severe mental illness. Neuroscience, 91, 1247–55Google Scholar
Hoogendijk, W J G, Sommer, I E C, Pool, C W et al. (1999). Lack of association between depression and loss of neurons in the locus coeruleus in Alzheimer disease. Arch Gen Psychiatry, 56, 45–51Google Scholar
Jeste, D V, Lohr, J B and Goodwin, F K (1988). Neuroanatomical studies of major affective disorders. A review and suggestions for future research. Br J Psychiatry, 153, 444–59Google Scholar
Kessing, L V (1998). Cognitive impairment in the euthymic phase of affective disorder. Psychol Med, 28, 1027–38Google Scholar
Klimek, V, Stockmeier, C, Overholser, J et al. (1997). Reduced levels of norepinephrine transporters in the locus coeruleus in major depression. J Neurosci, 17, 8451–8Google Scholar
Korbo, L (1999). Glial cell loss in the hippocampus of alcoholics. Alcohol Clin Exp Res, 23, 164–8Google Scholar
Kövari, E, Giannakopoulos, P, Hof, P R and Bouras, C (1999). Structural changes in the subgenual prefrontal cortex in schizophrenia and mood disorders. Soc Neurosci Abstr, 25, 817Google Scholar
Kril, J J and Halliday, G M (1999). Brain shrinkage in alcoholics: a decade on and what have we learned?Prog Neurobiol, 58, 381–7Google Scholar
Lucassen, P J, Müller, M B, Holsboer, F et al. (2001). Hippocampal apoptosis in major depression is a minor event and absent from subareas at risk for glucocorticoid overexposure. Am J Pathol, 158, 453–68Google Scholar
Madhav, T R, Pei, Q, Grahame-Smith, D G and Zetterström, T S C (2000). Repeated electroconvulsive shock promotes the sprouting of serotonergic axons in the lesioned rat hippocampus. Neuroscience, 97, 677–83Google Scholar
Madsen, T M, Treschow, A, Bengzon, J, Bolwig, T G, Lindvall, O and Tingström, A (2000). Increased neurogenesis in a model of electroconvulsive therapy. Biol Psychiatry, 47, 1043–9Google Scholar
Maes M and Meltzer H Y (1995). The serotonin hypothesis of major depression. In Psychopharmacology: the Fourth Generation of Progress, ed. F E Bloom and D J Kupfer, pp. 933–44. New York: Raven Press
Magistretti, P J (2000). Cellular bases of functional brain imaging: insights from neuron-glia metabolic coupling. Brain Res, 886, 108–12Google Scholar
Malberg, J E, Eisch, A J, Nestler, E J and Duman, R S (2000). Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci, 20, 9104–10Google Scholar
Manji, H K, Moore, G J and Chen, G (2000). Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers: implications for the pathophysiology and treatment of manic-depressive illness. Biol Psychiatry, 48, 740–54Google Scholar
Masliah, E and Terry, R D (1993). The role of synaptic proteins in the pathogenesis of disorders of the central nervous system. Brain Pathol, 3, 77–86Google Scholar
Merriam, E P, Thase, M E, Haas, G L, Keshavan, M S and Sweeney, J A (1999). Prefrontal cortical dysfunction in depression determined by Wisconsin Card Sorting Test performance. Am J Psychiatry, 156, 780–2Google Scholar
Miguel-Hidalgo, J J, Baucom, C, Dilley, G et al. (2000). Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder. Biol Psychiatry, 48, 861–73Google Scholar
O'Brien, J T, Ames, D and Schweitzer, I (1996). White matter changes in depression and Alzheimer's disease: a review of magnetic resonance imaging studies. Int J Geriatr Psychiatry, 11, 681–94Google Scholar
O'Brien, J, Thomas, A, Ballard, C et al. (2001). Cognitive impairment in depression is not associated with neuropathologic evidence of increased vascular or Alzheimer-type pathology. Biol Psychiatry, 49, 130–6Google Scholar
Öngür, D, Drevets, W C and Price, J L (1998). Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA, 95, 13290–5Google Scholar
Pei, Q, Burnet, P J W and Zetterström, T S C (1998). Changes in mRNA abundance of microtubule-associated proteins in the rat brain following electroconvulsive shock. Neuroreport, 9, 391–4Google Scholar
Perry R H (1994). A guide to the cortical regions. In Neuropsychiatric Disorders, ed. G W Roberts, P N Leigh and D R Weinberger, pp. 1.1–1.10. London: Wolfe
Price, J L (1999). Prefrontal cortical networks related to visceral function and mood. Ann N Y Acad Sci, 877, 383–96Google Scholar
Rajkowska, G (2000). Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry, 48, 766–77Google Scholar
Rajkowska, G and Goldman-Rakic, P S (1995). Cytoarchitectonic definition of prefrontal areas in the normal human cortex. II. Variability in locations of areas 9 and 46 and relationship to the Talairach coordinate system. Cereb Cortex, 5, 323–37Google Scholar
Rajkowska, G, Miguel-Hidalgo, J J, Wei, J R et al. (1999). Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry, 45, 1085–98Google Scholar
Rajkowska, G, Halaris, A and Selemon, L D (2001). Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biol Psychiatry, 49, 741–52Google Scholar
Ressler, K J and Nemeroff, C B (1999). Role of norepinephrine in the pathophysiology and treatment of mood disorder. Biol Psychiatry, 46, 1219–33Google Scholar
Rocha, E, Achaval, M, Santos, P and Rodnight, R (1998). Lithium treatment causes gliosis and modifies the morphology of hippocampal astrocytes in rats. Neuroreport, 9, 3971–4Google Scholar
Rosoklija, G, Toomayan, G, Ellis, S P et al. (2000). Structural abnormalities of subicular dendrites in subjects with schizophrenia and mood disorders – preliminary findings. Arch Gen Psychiatry, 57, 349–56Google Scholar
Sapolsky, R M (2000). Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry, 57, 925–35Google Scholar
Schneider, J A and Mirra, S S (1994). Neuropathologic correlates of persistent neurologic deficit in lithium intoxication. Ann Neurol, 36, 928–31Google Scholar
Selemon, L D, Lidow, M S and Goldman-Rakic, P S (1999). Increased volume and glial density in primate prefrontal cortex associated with chronic antipsychotic drug exposure. Biol Psychiatry, 46, 161–72Google Scholar
Shah, P J, Ebmeier, K P, Glabus, M F and Goodwin, G M (1998). Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression – controlled magnetic resonance imaging study. Br J Psychiatry, 172, 527–32Google Scholar
Sheline, Y I (2000). 3D MRI studies of neuroanatomic changes in unipolar major depression: the role of stress and medical comorbidity. Biol Psychiatry, 48, 791–800Google Scholar
Sheline, Y I, Wang, P W, Gado, M H, Csernansky, J G and Vannier, M W (1996). Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA, 93, 3908–13Google Scholar
Sheline, Y I, Sanghavi, M, Mintun, M A and Gado, M H (1999). Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci, 19, 5034–43Google Scholar
Steward, O (1994). Electroconvulsive seizures upregulate astroglial gene expression selectively in the dentate gyrus. Mol Brain Res, 25, 217–24Google Scholar
Strakowski, S M, DelBello, M P, Sax, K W et al. (1999). Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Arch Gen Psychiatry, 56, 254–60Google Scholar
Sweeney, J A, Kmiec, J A and Kupfer, D J (2000). Neuropsychologic impairments in bipolar and unipolar mood disorders on the CANTAB neurocognitive battery. Biol Psychiatry, 48, 674–84Google Scholar
Torrey, E F, Webster, M, Knable, M, Johnston, N and Yolken, R H (2000). The Stanley Foundation brain collection and Neuropathology Consortium. Schizophr Res, 44, 151–5Google Scholar
Ullian, E M, Sapperstein, S, Christopherson, K and Barres, B A (2001). Control of synapse number by glia. Science, 291, 657–61Google Scholar
Underwood, M D, Khaibulina, A A, Ellis, S P et al. (1999). Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims. Biol Psychiatry, 46, 473–83Google Scholar
Vaidya, V A, Siuciak, J A, Du, F and Duman, R S (1999). Hippocampal mossy fiber sprouting induced by chronic electroconvulsive seizures. Neuroscience, 89, 157–66Google Scholar
Videbech, P (1997). MRI findings in patients with affective disorder: a meta-analysis. Acta Psychiatr Scand, 96, 157–68Google Scholar
Vogt, B A, Nimchinsky, E A, Vogt, L J and Hof, P R (1995). Human cingulate cortex: surface features, flat maps, and cytoarchitecture. J Comp Neurol, 359, 490–506Google Scholar
Winsberg, M E, Sachs, N, Tate, D L, Adalsteinsson, E, Spielman, D and Ketter, T A (2000). Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder. Biol Psychiatry, 47, 475–81Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×