Choline, myo-inositol and mood in bipolar disorder: a proton magnetic resonance spectroscopic imaging study of the anterior cingulate cortex

Objectives: Alterations in choline and myo-inositol metabolism have been no ted in bipolar disorder, and the therapeutic efficacy of lithium in mania m ay be related to these effects. We wished to determine the relationship bet ween anterior cingulate cortex choline and mfo-inositol levels, assessed us ing proton magnetic resonance spectroscopic imaging (MRSI), and mood state in subjects with bipolar disorder. Methods: Serial assessments of anterior cingulate cortex choline and myo-in ositol metabolism were performed in nine subjects with bipolar disorder, ta king 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 record ed. Results: In the left cingulate cortex; the bipolar subjects' depression rat ings correlated positively with MRSI measures of Cho/Cr-PCr. In the right c ingulate 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 cingul ate cortex Cho/Cr-PCr ratio compared with patients taking antidepressants o r controls. No clinical or drug-related changes were observed for the Ino/C r-PCr ratio. Conclusions: The results of this study suggest that bipolar disorder is ass ociated with alterations in the metabolism of cytosolic, choline-containing compounds in the anterior cingulate cortex. As this resonance arises prima rily from phosphocholine and glycerophosphocholine, both of which are metab olites of phosphatidylcholine, these results are consistent with impaired i ntraneuronal signaling mechanisms.