Increased anterior cingulate/medial prefrontal cortical glutamate and creatine in bipolar depression

Mark A. Frye, June Watzl, Shida Banakar, Joseph O'Neill, Jim Mintz, Pablo Davanzo, Jeffrey Fischer, Jason W. Chirichigno, Joseph Ventura, Shana Elman, John Tsuang, Irwin Walot, M. Albert Thomas

Research output: Contribution to journalArticlepeer-review

147 Scopus citations


Proton magnetic resonance spectroscopy (1HMRS) is an in vivo brain imaging method that can be used to investigate psychotropic drug mechanism of action. This study evaluated baseline 1HMRS spectra of bipolar depressed patients and whether the level of cerebral metabolites changed after an open trial of lamotrigine, an anti-glutamatergic mood stabilizer. Twenty-three bipolar depressed and 12 control subjects underwent a MRS scan of the anterior cingulate/medial prefrontal cortex. The scan was performed on a GE whole-body 1.5 T MRI scanner using single-voxel PRESS (TE/TR=30/3000 ms, 3 × 3 × 3 cm3 and post-processed offline with LCModel. Baseline CSF-corrected absolute concentrations of glutamate+glutamine ([Glx]), glutamate ([Glu]), and creatine+phosphocreatine ([Cr]) were significantly higher in bipolar depressed subjects vs healthy controls. The non-melancholic subtype had significantly higher baseline [Glx] and [Glu] levels than the melancholic subtype. Remission with lamotrigine was associated with significantly lower post-treatment glutamine ([Gln]) in comparison to non-remission. These data suggest that non-melancholic bipolar depression is characterized by increased glutamate coupled with increased energy expenditure. Lamotrigine appears to reduce glutamine levels associated with treatment remission. Further study is encouraged to determine if these MR spectroscopic markers can delineate drug mechanism of action and subsequent treatment response.

Original languageEnglish (US)
Pages (from-to)2490-2499
Number of pages10
Issue number12
StatePublished - Dec 2007


  • Bipolar
  • Depression
  • Glutamate
  • Lamotrigine
  • MR spectroscopy

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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