Effects of mood and subtype on cerebral glucose metabolism in treatment-resistant bipolar disorder

Terence A. Ketter, Tim A. Kimbrell, Mark S. George, Robert T. Dunn, Andrew M. Speer, Brenda E. Benson, Mark W. Willis, Aimee Danielson, Mark A. Frye, Peter Herscovitch, Robert M. Post

Research output: Contribution to journalArticlepeer-review

241 Scopus citations


Background: Functional brain imaging studies in unipolar and secondary depression have generally found decreased prefrontal cortical activity, but in bipolar disorders findings have been more variable. Methods: Forty-three medication-free, treatment-resistant, predominantly rapid-cycling bipolar disorder patients and 43 age- and gender-matched healthy control subjects had cerebral glucose metabolism assessed using positron emission tomography and fluorine-18-deoxyglucose. Results: Depressed bipolar disorder patients compared to control subjects had decreased global, absolute prefrontal and anterior paralimbic cortical, and increased normalized subcortical (ventral striatum, thalamus, right amygdala) metabolism. Degree of depression correlated negatively with absolute prefrontal and paralimbic cortical, and positively with normalized anterior paralimbic subcortical metabolism. Increased normalized cerebello-posterior cortical metabolism was seen in all patient subgroups compared to control subjects, independent of mood state, disorder subtype, or cycle frequency. Conclusions: In bipolar depression, we observed a pattern of prefrontal hypometabolism, consistent with observations in primary unipolar and secondary depression, suggesting this is part of a common neural substrate for depression independent of etiology. In contrast, the cerebello-posterior cortical normalized hypermetabolism seen in all bipolar subgroups (including euthymic) suggests a possible congenital or acquired trait abnormality. The degree to which these findings in treatment-resistant, predominantly rapid-cycling patients pertain to community samples remains to be established.

Original languageEnglish (US)
Article number6844
Pages (from-to)97-109
Number of pages13
JournalBiological psychiatry
Issue number2
StatePublished - 2001


  • Bipolar disorders
  • Cerebral metabolism
  • Depression
  • PET
  • Rapid cycling

ASJC Scopus subject areas

  • Biological Psychiatry


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