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Subgenual prefrontal cortex abnormalities in mood disorders


Pathological disturbances of mood may follow a 'bipolar' course, in which normal moods alternate with both depression and mania, or a 'unipolar' course, in which only depression occurs1–3. Both bipolar and unipolar disorders can be heritable illnesses associated with neurochemical, neuroendocrine and autonomic abnormalities. The neurobiological basis for these abnormalities has not been established2,3. Using positron emission tomographic (PET) images of cerebral blood flow and rate of glucose metabolism to measure brain activity, we have now localized an area of abnormally decreased activity in the pre-frontal cortex ventral to the genu of the corpus callosum in both familial bipolar depressives and familial unipolar depressives. This decrement in activity was at least partly explained by a corresponding reduction in cortical volume4, as magnetic resonance imaging (MRI) demonstrated reductions in the mean grey matter volume in the same area of 39 and 48% in the bipolar and unipolar samples, respectively. This region has previously been implicated in the mediation of emotional and autonomic responses to socially significant or provocative stimuli, and in the modulation of the neurotransmitter systems targeted by antidepressant drugs3,5–10.

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  1. 1

    Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) (American Psychiatric Association, Washington, DC, 1987).

  2. 2

    Goodwin, F. K. & Jamison, K. R. Manic-depressive Illness (Oxford University Press, New York, 1990).

    Google Scholar 

  3. 3

    Drevets, W. C. & Todd, R. D. in Adult Psychiatry (ed. Guze, S. B.) 99–142 (Mosby, St Louis, 1997).

    Google Scholar 

  4. 4

    Mazziotta, J. C., Phelps, M. E., Plummer, D. & Kuhl, D. E. Quantitation in positron emission computed tomography: 5. Physical-anatomical effects. J. Comput. Assist. Tomogr. 5, 734–743 (1981).

    CAS  Article  Google Scholar 

  5. 5

    Carmichael, S. T. & Price, J. L. Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys. J. Comp. Neurol. 363, 615–641 (1995).

    CAS  Article  Google Scholar 

  6. 6

    Neafsey, E. J., Terreberry, R. R., Hurley, K. M., Ruit, K. G. & Frysztak, R. J. in Neurobiology of Cingulate Cortex and Limbic Thalamus (eds Vogt, B. A. & Gabriel, M.) 206–223 (Birkhauser, Boston, 1993).

    Book  Google Scholar 

  7. 7

    Sesack, S. R., Deutch, A. Y., Roth, R. H. & Bunney, B. S. Topographic organization of the efferent projections of the medial prefrontal cortex in the rat: an anterograde tract-tracing study using Phaseolus vulgaris leucoagglutinin. J. Comp. Neurol. 290, 213–242 (1989).

    CAS  Article  Google Scholar 

  8. 8

    Damasio, A. R., Tranel, D. & Damasio, H. Individuals with sociopathic behavior caused by frontal damage fail to respond automatically to social stimuli. Behav. Brain Res. 41, 81–94 (1990).

    CAS  Article  Google Scholar 

  9. 9

    Bechara, A., Tranel, D., Damasio, H. & Damasio, A. R. Failure to respond autonomically to anticipated future outcomes following damage to the prefrontal cortex. Cerebr. Corf. 6, 215–225 (1996).

    CAS  Article  Google Scholar 

  10. 10

    Damasio, A. R. Descarte's Error: Emotion, Reason, and the Human Brain. (Grosset/Putnam, New York, 1994; Picador MacMillan, London, 1995).

    Google Scholar 

  11. 11

    Drevets, W. C. et al. A functional anatomical study of unipolar depression. J. Neurosci. 12, 3628–3641 (1992).

    CAS  Article  Google Scholar 

  12. 12

    Winokur, G. The development and validity of familial subtypes in primary unipolar depression. Pharmacopsychiatry 15, 142–146 (1982).

    CAS  Article  Google Scholar 

  13. 13

    Baxter, L. R. et al. Cerebral metabolic rates for glucose in mood disorders. Arch. Gen. Psychiat. 42, 441–447 (1985).

    Article  Google Scholar 

  14. 14

    Baxter, L. R. et al. Reduction of prefrontal cortex glucose metabolism common to three types of depression. Arch. Gen. Psychiat. 46, 243–250 (1989).

    CAS  Article  Google Scholar 

  15. 15

    Buchsbaum, M. S. et al. Frontal cortex and basal ganglia metabolic rates assessed by positron emission tomography with [18F]2-deoxyglucose in affective illness. J. Affect. Dis. 10, 137–152 (1986).

    CAS  Article  Google Scholar 

  16. 16

    Cohen, R. M. et al. Evidence for common alterations in cerebral glucose metabolism in major affective disorders and schizophrenia. Nauropsychopharmacology 2, 241–254 (1989).

    CAS  Article  Google Scholar 

  17. 17

    Dolan, R. J. et al. Dorsolateral prefrontal cortex dysfunction in the major psychoses: symptom or disease specificity? J. Neurol. Neurosurg. Psychiat. 56, 1290–1294 (1993).

    CAS  Article  Google Scholar 

  18. 18

    Drevets, W. C. & Botteron, K. in Adult Psychiatry (ed. Guze, S. B.) 53–82 (Mosby, St Louis, 1996).

    Google Scholar 

  19. 19

    Drevets, W. C. & Raichle, M. E. Reciprocal suppression of regional cerebral blood flow during emotional versus higher cognitive processes: implications for interactions between emotion and cognition. Cognit. Emot. (in the press).

  20. 20

    Drevets, W. C., Spitznagel, E. L., MacLeod, A. K. & Raichle, M. E. Discriminatory capability of PET measurements of regional blood flow in familial pure depressive disease. Abstr. Soc. Neurosci. 18, 1596 (1992).

    Google Scholar 

  21. 21

    Young, R. C., Biggs, J. T., Ziegler, V. E. & Meyer, D. A. A rating scale for mania: reliability, validity and sensitivity. Brit. J. Psychiat. 133, 429–435 (1978).

    CAS  Article  Google Scholar 

  22. 22

    DiRocco, R. J., Kageyama, G. H. & Wong-Riley, M. T. The relationship between CNS metabolism and cytoarchitecture: a review of 14C-deoxyglucose studies with correlation to cytochrome oxidase histochemistry. Comp. Med. Imag. Graph. 13, 81–92 (1989).

    CAS  Article  Google Scholar 

  23. 23

    Pearlson, G. D. et al. Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder. Biol. Psychiat. 41, 1–14 (1997).

    CAS  Article  Google Scholar 

  24. 24

    Hamilton, M. A rating scale for depression. J. Neurol. Neurosurg. Psychiat. 23, 56–62 (1960).

    CAS  Article  Google Scholar 

  25. 25

    Raichle, M. E., Martin, W. R. W., Herscovitch, P., Mintun, M. A. & Markham, J. Brain blood flow measured with intravenous 218O. II. Implementation and validation. J. Nucl. Med. 24, 790–798 (1983).

    CAS  PubMed  Google Scholar 

  26. 26

    Fox, P. T. & Mintun, M. A. Noninvasive functional brain mapping by change distribution analysis of averaged PET images of H215O tissue activity. J. Nucl. Med. 30, 141–149 (1989).

    CAS  PubMed  Google Scholar 

  27. 27

    Phelps, M. E. et al. Tomographic measurements of local cerebral glucose metabolic rate in humans with [F-18]2-fluoro-2-deoxy-D-glucose: validation of method. Ann. Neurol. 6, 371–388 (1979).

    CAS  Article  Google Scholar 

  28. 28

    Talairach, J. & Tournoux, P. in Co-Planar Stereotaxic Atlas of the Human Brain 1–122 (Theime, Stuttgart, 1988).

    Google Scholar 

  29. 29

    Fox, P. T., Perlmutter, J. S. & Raichle, M. E. A stereotactic method of anatomical localization for positron emission tomography. J. Comput. Assist. Tomogr. 9, 141–153 (1985).

    CAS  Article  Google Scholar 

  30. 30

    Carmichael, S. T. & Price, J. L. Architectonic subdivision of the orbital and medial prefrontal cortex in the macaque monkey. J. Comp. Neurol. 346, 366–402 (1994).

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Drevets, W., Price, J., Simpson, J. et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 386, 824–827 (1997).

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