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Letters to Nature
Nature 386, 824 - 827 (24 April 1997); doi:10.1038/386824a0

Subgenual prefrontal cortex abnormalities in mood disorders

Wayne C. Drevets*§, Joseph L. Price, Joseph R. Simpson Jr, Richard D. Todd*, Theodore Reich*, Michael Vannier§ & Marcus E. Raichle**

*Department of Psychiatry, Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Department of Anatomy and Neurobiology, Department of Genetics, Department of Neurology and Neurological Surgery (Neurology), **McDonnell Center for Studies of Higher Brain Function, Washington University School of Medicine, St Louis, Missouri 63110, USA
§Present addresses: Departments of Psychiatry and Radiology, University of Pittsburgh Medical Center, 3811 O'Hara Street, Pittsburgh, Pennsylvania 15213-2593, USA (W.C.D.); Department of Radiology, University of Iowa, Iowa City, Iowa 52242, USA (M.V.).

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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