Choline, myo-inositol and mood in bipolar disorder: a proton magnetic resonance spectroscopic imaging study of the anterior cingulate cortex.
OBJECTIVE
Alterations in choline and myo-inositol metabolism have been noted in bipolar disorder, and the therapeutic efficacy of lithium in mania may be related to these effects. We wished to determine the relationship between anterior cingulate cortex choline and myo-inositol levels, assessed using proton magnetic resonance spectroscopic imaging (MRSI), and mood state in subjects with bipolar disorder.


METHODS
Serial assessments of anterior cingulate cortex choline and myo-inositol metabolism were performed in nine subjects with bipolar disorder, taking either lithium or valproate, and 14 controls. Each bipolar subject was examined between one and four times (3.1 +/- 1.3). On the occasion of each examination, standardized ratings of both depression and mania were recorded.


RESULTS
In the left cingulate cortex, the bipolar subjects' depression ratings correlated positively with MRSI measures of Cho/Cr-PCr. In the right cingulate cortex, the Cho/Cr-PCr ratio was significantly higher in subjects with bipolar disorder compared with control subjects. In addition, bipolar subjects not taking antidepressants had a significantly higher right cingulate cortex Cho/Cr-PCr ratio compared with patients taking antidepressants or controls. No clinical or drug-related changes were observed for the Ino/Cr-PCr ratio.


CONCLUSIONS
The results of this study suggest that bipolar disorder is associated with alterations in the metabolism of cytosolic, choline-containing compounds in the anterior cingulate cortex. As this resonance arises primarily from phosphocholine and glycerophosphocholine, both of which are metabolites of phosphatidylcholine, these results are consistent with impaired intraneuronal signaling mechanisms.
Brain Imaging Center, McLean Hospital, Belmont, MA, USA. const@mclean.harvard.edu
C M
CM
Moore
J L
JL
Breeze
S A
SA
Gruber
S M
SM
Babb
B B
BB
Frederick
R A
RA
Villafuerte
A L
AL
Stoll
J
J
Hennen
D A
DA
Yurgelun-Todd
B M
BM
Cohen
P F
PF
Renshaw
D000328:Adult; D000339:Affect / Q000187:drug effects / Q000502:physiology*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D001931:Brain Mapping; D002794:Choline / Q000378:metabolism*; D004292:Dominance, Cerebral / Q000187:drug effects / Q000502:physiology; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D007294:Inositol / Q000378:metabolism*; D016651:Lithium Carbonate / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010725:Phosphocreatine / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D014635:Valproic Acid / Q000627:therapeutic use
D010725:Phosphocreatine; D016651:Lithium Carbonate; D007294:Inositol; D014635:Valproic Acid; D002794:Choline