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

TitleIncreased anterior cingulate/medial prefrontal cortical glutamate and creatine in bipolar depression.
Publication TypeJournal Article
Year of Publication2007
AuthorsFrye, MA, Watzl J, Banakar S, O'Neill J, Mintz J, Davanzo P, Fischer J, Chirichigno JW, Ventura J, Elman S, Tsuang J, Walot I, Thomas AM
JournalNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Date Published2007 Dec
KeywordsAdult, Analysis of Variance, Antidepressive Agents, Bipolar disorder, Creatine, Evaluation Studies as Topic, Female, Glutamic Acid, Gyrus Cinguli, Humans, Magnetic Resonance Spectroscopy, Male, Middle Aged, Prefrontal Cortex, Protons, Triazines

Proton magnetic resonance spectroscopy ((1)HMRS) is an in vivo brain imaging method that can be used to investigate psychotropic drug mechanism of action. This study evaluated baseline (1)HMRS 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 x 3 x 3 cm(3) 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.

Alternate JournalNeuropsychopharmacology