Increased anterior cingulate/medial prefrontal cortical glutamate and creatine in bipolar depression.
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.
Frye
Mark A
MA
UCLA Department of Psychiatry and Biobehavioral Sciences, Los Angeles, CA 55905, USA. mfrye@mayo.edu
Watzl
June
J
Banakar
Shida
S
O'Neill
Joseph
J
Mintz
Jim
J
Davanzo
Pablo
P
Fischer
Jeffrey
J
Chirichigno
Jason W
JW
Ventura
Joseph
J
Elman
Shana
S
Tsuang
John
J
Walot
Irwin
I
Thomas
M Albert
MA
D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D003401:Creatine / Q000378:metabolism*; D005069:Evaluation Studies as Topic; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D000077213:Lamotrigine; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011522:Protons; D014227:Triazines / Q000494:pharmacology / Q000627:therapeutic use
D000928:Antidepressive Agents; D011522:Protons; D014227:Triazines; D018698:Glutamic Acid; D003401:Creatine; D000077213:Lamotrigine