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The anatomy of melancholia – focal abnormalities of cerebral blood flow in major depression

  • Christopher J. Bench (a1), Karl J. Friston (a1), Richard G. Brown (a1), Lynette C. Scott (a1), Richard S. J. Frackowiak (a1) and Raymond J. Dolan (a1)...


Using positron emission tomography (PET) and 15Oxygen, regional cerebral blood flow (rCBF) was measured in 33 patients with primary depression, 10 of whom had an associated severe cognitive impairment, and 23 age-matched controls. PET scans from these groups were analysed on a pixel-by-pixel basis and significant differences between the groups were identified on Statistical Parametric Maps (SPMs). In the depressed group as a whole rCBF was decreased in the left anterior cingulate and the left dorsolateral prefrontal cortex (P < 0·05 Bonferroni-corrected for multiple comparisons). Comparing patients with and without depression-related cognitive impairment, in the impaired group there were significant decreases in rCBF in the left medial frontal gyrus and increased rCBF in the cerebellar vermis (P < 0·05 Bonferroni-corrected). Therefore an anatomical dissociation has been described between the rCBF profiles associated with depressed mood and depression-related cognitive impairment. The pre-frontal and limbic areas identified in this study constitute a distributed anatomical network that may be functionally abnormal in major depressive disorder.


Corresponding author

1 Address for correspondence: Dr Christopher J. Bench, MRC Cyclotron Unit, Hammersmith Hospital, DuCane Road, London W12 0HS.


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Altshuler, L. L., Conrad, A., Hauser, P., Li, X., Guze, B. H., Denikoff, K., Tourtellotte, W. & Post, R. (1991). Reduction of temporal lobe volume in bipolar disorder: a preliminary report of magnetic resonance imaging. Archives of General Psychiatry 48, 482483.
Baleydier, C. & Mauguiére, F. (1980). The duality of the cingulated gyrus in the monkey. Brain 103, 525554.
Baxter, L. R., Phelps, M. E., Mazziotta, J. C., Schwartz, J. M., Gerner, R. H., Selin, C. E. & Sumida, R. M. (1985). Cerebral metabolic rates for glucose in mood disorders. Studies with positron emission tomography and fluorodeoxyglucose F18. Archives of General Psychiatry 42, 441447.
Baxter, L. R., Schwartz, J. M., Phelps, M. E., Mazziotta, J. C., Guze, B. H., Selin, C. E., Gerner, R. H. & Sumida, R. M. (1989). Reduction of prefrontal cortex metabolism common to three types of depression. Archives of General Psychiatry 46, 243250.
Buchsbaum, M. S., DeLisi, L. E., Holcomb, H. H., Cappelletti, J., King, A. C., Johnson, J., Hazlett, E., Dowling-Zimmerman, S., Post, R. M., Morihisa, J., Carpenter, W., Cohen, R., Pickar, D., Weinberger, D. R., Margolin, R. & Kessler, R. M. (1984). Anteroposterior gradients in cerebral glucose use in schizophrenia and affective disorders. Archives of General Psychiatry 41, 11591166.
Dolan, R. J., Calloway, S. P. & Mann, A. H. (1985). Cerebral ventricular size in depressed subjects. Psychological Medicine 15, 873878.
Dolan, R. J., Calloway, S. P., Thacker, P. & Mann, A. H. (1986). The cerebral cortical appearance in depressed subjects. Psychological Medicine 16, 775779.
Endicott, J. & Spitzer, R. L. (1978). A diagnostic interview. The Schedule for Affective Disorders and Schizophrenia. Archives of General Psychiatry 35, 837844.
Fazekas, F., Alavi, A., Chawluk, J. B., Zimmerman, R. A., Hackney, D., Bilaniuk, L., Rosen, M., Alves, W. M., Hurtig, H. I., Jamieson, D. G., Kushner, M. J. & Reivich, M. (1989). Comparison of CT, MR and PET in Alzheimer's dementia and normal aging. Journal of Nuclear Medicine 30, 16071615.
Flor-Henry, P. (1979). On certain aspects of the localization of the cerebral systems regulating and determining emotion. Biological Psychiatry 14, 677698.
Foltz, E. L. & White, L. E. Jr (1962). Pain ‘relief’ by frontal cingulotomy. Journal of Neurosurgery 19, 89100.
Frackowiak, R. S. J., Lenzi, G.-L., Jones, T. & Heather, J. D. (1980). Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using 15O and positron emission tomography: theory, procedure, and normal values. Journal of Computer Assisted Tomography 4, 727736.
Frackowiak, R. S. J., Pozzilli, C., Legg, N. J., Du Boulay, G. H., Marshall, J., Lenzi, G. L. & Jones, T. (1981). Regional cerebral oxygen supply and utilization in dementia. A clinical and physiological study with Oxygen-15 and positron tomography. Brain 104, 753778.
Friston, K. J. & Frackowiak, R. S. J. (1991). Imaging functional anatomy. In Brain Work and Metal Activity, Alfred Benzon Symposium 31 (ed. Lassen, N. A., Ingvar, D. H.Raichle, M. E. and Friberg, L.), pp. 267277. Munksgaard: Copenhagen.
Friston, K. J., Passingham, R. E., Nutt, J. G., Heather, J. D., Sawle, G. V. & Frackowiak, R. S. J. (1989). Localisation in PET images: direct fitting of the intercommissural (AC-PC) line. Journal of Cerebral Blood Flow and Metabolism 9, 690695.
Friston, K. J., Frith, C. D., Liddle, P. F., Dolan, R. J., Lammertsma, A. A. & Frackowiak, R. S. J. (1990). The relationship between global and local changes in PET scans. Journal of Cerebral Blood Flow and Metabolism 10, 458466.
Friston, K. J., Frith, C. D., Liddle, P. F. & Frackowiak, R. S. J. (1991). Comparing functional (PET) images: the assessment of significant change. Journal of Cerebral Blood Flow and Metabolism 11, 690699.
Hachinski, V. C., Iliff, L. D., Zilhka, E., Du Boulay, G. H., McAllister, V. L., Marshall, J., Ross Russell, R. W. & Symon, L. (1975). Cerebral blood flow in dementia. Archives of Neurology 32, 632637.
Hamilton, M. (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.
Hamilton, N. G., Frick, R. B., Takahashi, T. & Hopping, M. W. (1983). Psychiatric symptoms and cerebellar pathology. American Journal of Psychiatry 140, 13221326.
Heath, R. G. & Harper, J. W. (1974). Ascending projections of the cerebellar fastigial nucleus to the hippocampus, amygdala, and other temporal lobe sites: evoked potential and histological studies in monkeys and cats. Experimental Neurology 45, 268287.
Heath, R. G., Dempsey, C. W., Fontana, C. J. & Myers, W. A. (1978). Cerebellar stimulation: effects on septal region, hippocampus, and amygdala of cats and rats. Biological Psychiatry 13, 501529.
Heath, R. G., Franklin, D. E. & Shraberg, D. (1979). Gross pathology of the cerebellum in patients diagnosed and treated as functional psychiatric disorders. Journal of Nervous and Mental Disease 167, 585591.
Helgason, L. (1977). Psychiatric services and mental illness in Iceland. Acta Psychiatrica Scandinavica Suppl. 268.
House, A., Dennis, M., Warlow, C., Hawton, K. & Molyneux, A. (1990). Mood disorders after stroke and their relation to lesion location. A CT scan study. Brain 113, 11131129.
Liddle, P. F., Friston, K. J., Hirsch, S. R. & Frackowiak, R. S. J. (1990). Regional cerebral metabolic activity in chronic schizophrenia. Schizophrenia Research 3, 2324.
MacLean, P. D. (1952). Some psychiatric implications of physiological studies on frontotemporal portion of limbic system (visceral brain). Electroencephalography and Clinical Neurophysiology 4, 407418.
Marsden, C. D. & Harrison, M. J. G. (1972). Outcome of investigation of patients with presenile dementia. British Medical Journal ii, 249252.
Martin, A. J., Friston, K. J.,Colebatch, J. G. & Frackowiak, R. S. J. (1991). Decreases in regional cerebral blood flow with normal aging. Journal of Cerebral Blood Flow and Metabolism 11, 684689.
Martinot, J. L., Hardy, P., Feline, A., Huret, J. D., MazoyerB., Attar-Levy, D. B., Attar-Levy, D., PappataS. & Syrota, A. S. & Syrota, A. (1990). Left prefrontal glucose hypometabolism in the depressed state: a confirmation. American Journal of Psychiatry 147, 13131317.
Mesulam, M.-M. (1986). Frontal cortex and behavior. Annals of Neurology 19, 320325.
Montgomery, S. A. & Åsberg, M. (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry 134, 382389.
Nielsen, J. (1976). The Samso project from 1957 to 1974. Acta Psychiatrica Scandinavica 54, 198222.
Oldfield, R. C. (1971). The assessment and analysis of handedness; the Edinburgh inventory. Neuropsychologia 9, 97113.
Pandya, D. N., Van Hoesen, G. W. & Mesulam, M.-M. (1981). Efferent connections of the cingulate gyrus in the Rhesus monkey. Experimental Brain Research 42, 319330.
Papez, J. W. (1937). A proposed mechanism of emotion. Archives of Neurology and Psychiatry 79, 217224.
Pardo, J. V., Pardo, P. J., Janer, K. W. & Raichle, M. E. (1990). The anterior cingulate cortex mediates processing selection in the Stroop attentional conflict paradigm. Proceedings of the National Academy of Sciences 87, 256259.
Pearlson, G. D., Rabins, P. V., Kim, W. S., Speedie, L. J., Moberg, P. J., Burns, A. & Bascom, M. J. (1989). Structural brain CT changes and cognitive deficits in elderly depressives with and without reversible dementia (‘pseudodementia’). Psychological Medicine 19, 573584.
Powell, E. & Hines, G. (1974). The limbic system: an interface. Behavioral Biology 12, 149164.
Raichle, M. E. (1987). In Handbook of Physiology, section 1, Nervous System, vol. 5, Higher Functions of the Brain (ed. Plum, F.), pp. 643669. Oxford University Press: New York.
Reiman, E. M., Raichle, M. E., Robins, E., Mintun, M., Fusselman, M. J., Fox, P. T., Price, J. L. & Hackman, K. A. (1989). Neuroanatomical correlates of a lactate-induced anxiety attack. Archives of General Psychiatry 46, 493500.
Robins, L. N., Helzer, J. E., Weissman, M. M., Orvaschel, H., Gruenbuerg, E., Burke, J. D. Jr, & Regier, D. A. (1984). Lifetime prevalence of specific psychiatric disorders in three sites. Archives of General Psychiatry 41, 949958.
Robinson, R. G., Starr, L. B., Kudos, K. L. & Price, T. R. (1983). A two-year longitudinal study of post-stroke mood disorders: findings during the initial evaluation. Stroke 14, 736741.
Robinson, R. G., Kubos, K. L., Starr, L. B., Rao, K. & Price, T. R. (1984). Mood disorders in stroke patients. Importance of location of lesion. Brain 107, 8191.
Sackeim, H. A., Prohovnik, I., Moeller, J. R., Brown, R. P., Apter, S., Prudic, J., Devanand, D. P. & Mukherjee, S. (1990). Regional cerebral blood flow in mood disorders. I. Comparison of major depressives and normal controls at rest. Archives of General Psychiatry 47, 6070.
Schwartz, J. M., Baxter, L. R., Mazziotta, J. C., Gerner, R. H. & Phelps, M. E.(1987). The differential diagnosis of depression. Relevance of Positron Emission Tomography studies of cerebral glucose metabolism to the bipolar–unipolar dichotomy. Journal of the American Medical Association 258, 13681374.
Sharpe, M., Hawton, K., House, A., Molyneux, A., Sandercock, P., Bamford, J. & Warlow, C. (1990). Mood disorders in long-term survivors of stroke: associations with brain lesion location and volume. Psychological Medicine 20, 815828.
Spinks, T. J., Jones, T., Gilardi, M. C. & Heather, J. D. (1988). Physical performance of the latest generation of commercial positron scanner. IEEE Transactions on Nuclear Science 35, 721725.
Spitzer, R. L., Endicott, J. & Robins, E. (1977). Research Diagnostic Criteria for a Selected Group of Functional Disorders. Biometrics Research Division, New York State Psychiatric Institute: New York.
Talairach, J. & Tournoux, P. (1988). Co-Planar Stereotaxic Atlas of the Human Brain. Georg Thieme Verlag: Stuttgart.
van Praag, H. M. (1982). The significance of biological factors in the diagnosis of depressions. II. Hormonal variables. Comprehensive Psychiatry 23, 216226.
van Praag, H. M., Korf, J. & Puite, J. (1970). 5-hydroxyindoleacetic acid levels in the cerebrospinal fluid of depressed patients treated with probenecid. Nature 225, 12591260.
Weinberger, D. R., Berman, K. F. & Zec, R. F. (1986). Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. 1. Regional cerebral blood flow evidence. Archives of General Psychiatry 43, 114124.

The anatomy of melancholia – focal abnormalities of cerebral blood flow in major depression

  • Christopher J. Bench (a1), Karl J. Friston (a1), Richard G. Brown (a1), Lynette C. Scott (a1), Richard S. J. Frackowiak (a1) and Raymond J. Dolan (a1)...


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