Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-10T05:10:56.678Z Has data issue: false hasContentIssue false
  • English
  • Français

Is the Mechanism of Prefrontal Hypofunction in Depression the Same as in Schizophrenia?

Regional Cerebral Blood Flow During Cognitive Activation

Published online by Cambridge University Press:  02 January 2018

Karen Faith Berman ,
Allen R. Doran ,
David Pickar  and
Daniel R. Weinberger
Karen Faith Berman*
Affiliation:
Unit on Positron Emission Tomography, Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Neuroscience Center at Saint Elizabeth's, Washington, DC, 20032, USA
Allen R. Doran
Affiliation:
Experimental Therapeutics Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD 20892, USA
David Pickar
Affiliation:
Experimental Therapeutics Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD 20892, USA
Daniel R. Weinberger
Affiliation:
Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Neuroscience Center at Saint Elizabeth's, Washington, DC, 20032, USA
*
∗ Correspondence
Get access Rights & Permissions [Opens in a new window]

Abstract

To test the hypothesis that depressed and schizophrenic patients have a common pathophysiological mechanism for hypofunction of the prefrontal cortex (‘hypofrontality’), we measured regional cortical blood flow (rCBF) in ten depressed patients, ten patients with schizophrenia, and 20 age- and sex-matched normal controls. Blood flow was measured during three different cognitive conditions: a resting state, a simple number-matching sensorimotor control task, and the Wisconsin Card Sorting test (WCS). The schizophrenic patients had lower prefrontal rCBF during the WCS. There were no differences in global or regional flow between the depressed patients and the normal subjects during any testing condition. Analysis of rCBF lateralisation showed that during the WCS normal subjects had relatively more left parietal blood flow than depressed patients, who had more right parietal blood flow. Since the testing condition that has most consistently revealed hypofrontality in schizophrenia (i.e. the WCS) was not associated with abnormal rCBF in the depressed patients, these data suggest that the pathophysiological mechanisms underlying prefrontal hypofunction in depression and schizophrenia are different.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 162 , Issue 2 , February 1993 , pp. 183 - 192
Copyright
Copyright © Royal College of Psychiatrists, 1993 

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

Altshuler, L. L., Conrad, A., Hauser, P., et al (1991) Reduction of temporal lobe volume in bipolar disorder: a preliminary report of magnetic resonance imaging. Archives of General Psychiatry, 48, 482–483.Google Scholar
American Psychiatric Association (1980) Diagnostic and Statistical Manual of Mental Disorders (3rd edn) (DSM-III). Washington, DC: APA.Google Scholar
Baxter, L. R. Jr., Phelps, M. E., Mazziotta, J. C., et al (1985) Cerebral metabolic rates for glucose in mood disorders. Archives of General Psychiatry, 42, 441–447.Google Scholar
Baxter, L. R. Jr., Schwartz, J. M., Phelps, M. E., et al (1989) Reduction of prefrontal cortex glucose metabolism is common to three types of depression. Archives of General Psychiatry, 46, 243–250.Google Scholar
Beckmann, H. & Jakob, H. (1991) Prenatal disturbances of cell migration in the entorhinal region: a common vulnerability factor in functional psychoses? Journal of Neural Transmission, 84, 155–164.Google Scholar
Berman, K. F. & Weinberger, D. R. (1986) Cerebral blood flow studies in schizophrenia. In Handbook of Schizophrenia, The Neurology of Schizophrenia (eds Nasrallah, H. & Weinberger, D. R.), pp. 277–307. Amsterdam: Elsevier North Holland Press.Google Scholar
Berman, K. F., Zec, R. F., & Weinberger, D. R. (1986) Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia: II. Role of neuroleptic treatment, attention, and mental effort. Archives of General Psychiatry, 43, 126–135.Google Scholar
Berman, K. F., Rosenbaum, S. C. W., Brasher, C. A., et al (1987) Regional cerebral blood flow during auditory discrimination in schizophrenia. Abstracts of the Society for Neuroscience, 13, 1344.Google Scholar
Berman, K. F., Illowsky, B. P. & Weinberger, D. R. (1988a) Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. IV, Further evidence for regional and behavioral specificity. Archives of General Psychiatry, 45, 616–622.Google Scholar
Berman, K. F., Schapiro, M. B., Friedland, R. P., et al (1988b) Cerebral function during cognition in Down syndrome. Proceedings of the 141st Annual Meeting of the American Psychiatric Association. Washington, DC: APA.Google Scholar
Berman, K. F. & Weinberger, D. R. (1990) Lateralisation of cortical function during cognitive tasks: regional cerebral blood flow studies of normal individuals and patients with schizophrenia. Journal of Neurology, Neurosurgery, and Psychiatry, 53, 150–160.CrossRefGoogle ScholarPubMed
Berman, K. F. & Weinberger, D. R. (1991) Functional localization in the brain in schizophrenia. In American Psychiatric Press Review of Psychiatry, Vol. 10 (eds Tasman, A. & Goldfinger, S. M.), pp. 24–59. Washington, DC: American Psychiatric Press.Google Scholar
Berman, K. F., Randolph, C., Gold, J., et al (1991) Physiological activation of frontal lobe studied with positron emission tomography and oxygen-15 water during working memory tasks. Journal of Cerebral Blood Flow and Metabolism, 11 (suppl. 2), 851s.Google Scholar
Berman, K. F., Torrey, E. F., Daniel, D. G., et al (1992) Regional cerebral blood flow in monozygotic twins discordant and concordant for schizophrenia. Archives of General Psychiatry, 49, 927–934.Google Scholar
Buchsbaum, M. S., DeLisi, L. E., Holcomb, H. H., et al (1984) Anteroposterior gradients in cerebral glucose in schizophrenia and affective disorders. Archives of General Psychiatry, 41, 1159–1166.CrossRefGoogle ScholarPubMed
Chabrol, H., Barrere, M., Guell, A., et al (1986) Hyperfrontality of cerebral blood flow in depressed adolescents. American Journal of Psychiatry, 143, 263–264.Google Scholar
Cohen, R. M., Semple, W. E., Gross, M., et al (1987) Dysfunction in a prefrontal substrate of sustained attention in schizophrenia. Life Sciences, 40, 2031–2039.CrossRefGoogle Scholar
Cohen, R. M., Semple, W. E., Gross, M., et al (1989) Evidence for common alterations in cerebral glucose metabolism in major affective disorders and schizophrenia. Neuropsychopharmacology, 2, 241–254.Google Scholar
Copolla, R., Buchsbaum, M. S. & Rigal, F. (1982) Computer generation of surface distribution maps of measures of brain activity. Computers in Biological Medicine, 12, 191–199.Google Scholar
Davis, S. M., Ackerman, R. H., Correia, J. A., et al (1983) Cerebral blood flow and cerebrovascular CO2 reactivity in stroke-age normal controls. Neurology, 33, 391–399.Google Scholar
Deshmukh, V. D. & Meyer, J. S. (1978) Noninvasive Measurement of Cerebral Blood Flow in Man. New York: Prentice Hall.Google Scholar
Fox, P. T., Mintun, M. A., Reiman, E. M., et al (1988) Enhanced detection of focal brain responses using intersubject averaging and change distribution analysis of subtracted PET images. Journal of Cerebral Blood Flow and Metabolism, 8, 642–653.Google Scholar
Fuster, J. (1989) The Prefrontal Cortex. New York: Raven Press.Google Scholar
Goldberg, T. E., Weinberger, D. R., Berman, K. F., et al (1987) Further evidence for dementia of the prefrontal type in schizophrenia. Archives of General Psychiatry, 44, 1008–1014.Google Scholar
Gruzelier, J. & Flor-Henry, P. (1979) Hemispheric Asymmetries of Function in Psychopathology. New York: Elsevier North Holland Press.Google Scholar
Gur, R. E., Skolnick, B. E., Gur, R. C., et al (1984) Brain function in psychiatric disorders, II. Regional cerebral blood flow in medicated unipolar depressives. Archives of GeneraI Psychiatry, 41, 695–699.Google Scholar
Hamilton, M. (1967) Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology, 6, 278–296.CrossRefGoogle ScholarPubMed
Kling, A. S., Metter, E. J., Riege, W. H., et al (1986) Comparison of PET measurement of local brain glucose metabolism and CAT measurement of brain atrophy in chronic schizophrenia and depression. American Journal of Psychiatry, 143, 175–180.Google Scholar
Kolb, B. & Whisman, I. Q. (1983) Performance of schizophrenia patients on tests sensitive to left or right frontal, temporal, and parietal function in neurologic patients. Journal of Nervous and Mental Disorders, 171, 435–443.CrossRefGoogle ScholarPubMed
Malmo, H. P. (1974) On frontal lobe functions, psychiatric patient controls. Cortex, 10, 231–237.Google Scholar
Martinot, J.-L., Hardy, P., Feline, A., et al (1990) Left prefrontal glucose hypometabolism in the depressed state, a confirmation. American Journal of Psychiatry, 147, 1313–1317.Google Scholar
Mathew, R. J., Meyer, J. S., Francis, D. J., et al (1980) Cerebral blood flow in depression. American Journal of Psychiatry, 137, 1449–1450.Google ScholarPubMed
Maximillian, V. A., Prohovnik, I. & Risberg, J. (1980) Cerebral hemodynamic responses to mental activation in normo and hypercapnia. Stroke, 11, 342–347.CrossRefGoogle Scholar
Milner, B. (1963a) Some effects of frontal lobectomy in man. In The Frontal Granular Cortex and Behavior (eds Warren, J. M. & Akert, K.), pp. 313–334. New York: McGraw-Hill.Google Scholar
Milner, B. (1963b) Effects of different brain lesions on card sorting. Archives of Neurology, 9, 100–110.Google Scholar
Milner, B. (1971) Interhemispheric differences in the localization of psychological processes in man. British Medical Bulletin, 27, 272–277.Google Scholar
Obrist, W. D., Thompson, H. K., Wang, H. S., et al (1975) Regional cerebral blood flow estimated by xenon 133 inhalation. Stroke, 6, 245–256.Google Scholar
Obrist, W. D., Thompson, H. K., Wang, H. S., & Wilkinson, W. E. (1980) The noninvasive Xe133 method, evaluation of CBF indices. In Cerebral Circulation (eds Bes, A. & Geraud, G.), pp. 119–124. Amsterdam: Elsevier North Holland.Google Scholar
Raese, J. D., Paulman, R. G., Steinberg, J. L., et al (1989) Wisconsin Card Sort activated blood flow in dorsilateral frontal cortex in never medicated and previously medicated schizophrenics and normal controls. Biological Psychiatry, 25, 100A.Google Scholar
Risberg, J., Ali, Z., Wilson, E. M., et al (1975) Regional cerebral blood flow by 133xenon inhalation. Stroke, 6, 142–148.CrossRefGoogle Scholar
Rosenberg, R., Vostrup, S., Andersen, A., et al (1988) Effect of ECT on cerebral blood flow in melancholia assessed with SPECT. Convulsive Therapy, 4, 62–73.Google Scholar
Rubin, P., Holm, S., Friberg, L., et al (1991) Altered modulation of prefrontal and subcortical brain activity in novel diagnosed schizophrenia and schizophreniform disorder: a regional cerebral blood flow study. Archives of General Psychiatry, 48, 987–995.Google Scholar
Sackeim, H. A., Prohovnik, I., Moeller, J. R., et al (1990) Regional cerebral blood flow in mood disorders: comparison of major depressives and normal controls at rest. Archives of General Psychiatry, 47, 60–70.CrossRefGoogle ScholarPubMed
Silfverskiold, P. & Risberg, J. (1989) Regional cerebral blood flow in depression and mania. Archives of General Psychiatry, 46, 253–259.Google Scholar
Tominaga, S., Strandgaard, S., Uemura, K., et al (1976) Cerebrovascular CO2 reactivity in normotensive and hypertensive man. Stroke, 7, 507–510.CrossRefGoogle ScholarPubMed
Utydenhoef, P., Portelange, J., Jacquy, J., et al (1983) Regional cerebral blood flow and lateralized hemispheric dysfunction in depression. British Journal of Psychiatry, 143, 128–132.Google Scholar
Volkow, N. D., Wolf, A. P., Van Gelder, P., et al (1987) Phenomenological correlates of metabolic activity in 18 patients with chronic schizophrenia. American Journal of Psychiatry, 144, 151–158.Google Scholar
Warren, L. R., Butler, R. W., Katholi, C. R., et al (1984) Focal changes in cerebral blood flow produced by monetary incentive during a mental mathematics test in normal and depressed subjects. Brain and Cognition, 3, 71–85.Google Scholar
Weinberger, D. R., Berman, K. F. & Zec, R. F. (1986) Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia, I. Regional cerebral blood flow (rCBF) evidence. Archives of General Psychiatry, 43, 114–125.Google Scholar
Weinberger, D. R., Berman, K. F. & Zec, R. F. (1988) Speculation on the meaning of metabolic hypofrontality in schizophrenia. Schizophrenia Bulletin, 14, 157–168.Google Scholar
Weinberger, D. R., Berman, K. F., Iadarola, M. K., et al (1988a) Prefrontal cortical blood flow and cognitive function in Huntington's disease. Journal of Neurology; Neurosurgery, and Psychiatry, 51, 94–104.Google Scholar
Weinberger, D. R., Berman, K. F., Illowsky, B. P. (1988b) Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia, III. A new cohort and evidence for a monoaminergic mechanism. Archives of General Psychiatry, 45, 609–615.CrossRefGoogle Scholar
Yamamato, M., Meyer, J. S., Sakai, F., et al (1980) Aging and cerebral vasodilator responses to hypercarbia, responses in normal aging and in persons with risk factors for stroke. Archives of Neurology, 37, 489–496.CrossRefGoogle Scholar
Submit a response

eLetters

No eLetters have been published for this article.