Oral choline decreases brain purine levels in lithium-treated subjects with rapid-cycling bipolar disorder: a double-blind trial using proton and lithium magnetic resonance spectroscopy.
OBJECTIVE
Oral choline administration has been reported to increase brain phosphatidylcholine levels. As phospholipid synthesis for maintaining membrane integrity in mammalian brain cells consumes approximately 10-15% of the total adenosine triphosphate (ATP) pool, an increased availability of brain choline may lead to an increase in ATP consumption. Given reports of genetic studies, which suggest mitochondrial dysfunction, and phosphorus (31P) magnetic resonance spectroscopy (MRS) studies, which report dysfunction in high-energy phosphate metabolism in patients with bipolar disorder, the current study is designed to evaluate the role of oral choline supplementation in modifying high-energy phosphate metabolism in subjects with bipolar disorder.


METHODS
Eight lithium-treated patients with DSM-IV bipolar disorder, rapid cycling type were randomly assigned to 50 mg/kg/day of choline bitartrate or placebo for 12 weeks. Brain purine, choline and lithium levels were assessed using 1H- and 7Li-MRS. Patients received four to six MRS scans, at baseline and weeks 2, 3, 5, 8, 10 and 12 of treatment (n = 40 scans). Patients were assessed using the Clinical Global Impression Scale (CGIS), the Young Mania Rating Scale (YRMS) and the Hamilton Depression Rating Scale (HDRS) at each MRS scan.


RESULTS
There were no significant differences in change-from-baseline measures of CGIS, YMRS, and HDRS, brain choline/creatine ratios, and brain lithium levels over a 12-week assessment period between the choline and placebo groups or within each group. However, the choline treatment group showed a significant decrease in purine metabolite ratios from baseline (purine/n-acetyl aspartate: coef = -0.08, z = -2.17, df = 22, p = 0.030; purine/choline: coef = -0.12, z = -1.97, df = 22, p = 0.049) compared to the placebo group, controlling for brain lithium level changes. Brain lithium level change was not a significant predictor of purine ratios.


CONCLUSIONS
The current study reports that oral choline supplementation resulted in a significant decrease in brain purine levels over a 12-week treatment period in lithium-treated patients with DSM-IV bipolar disorder, rapid-cycling type, which may be related to the anti-manic effects of adjuvant choline. This result is consistent with mitochondrial dysfunction in bipolar disorder inadequately meeting the demand for increased ATP production as exogenous oral choline administration increases membrane phospholipid synthesis.
Lyoo
In Kyoon
IK
Brain Imaging Center, McLean Hospital, Belmont, MA, USA. inkylyoo@yahoo.com
Demopulos
Christina M
CM
Hirashima
Fuyuki
F
Ahn
Kyung Heup
KH
Renshaw
Perry F
PF
D000284:Administration, Oral; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002794:Choline / Q000008:administration & dosage* / Q000627:therapeutic use; D003401:Creatine / Q000378:metabolism; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D006801:Humans; D008094:Lithium / Q000493:pharmacokinetics / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011522:Protons; D011687:Purines / Q000378:metabolism*; D012720:Severity of Illness Index
D014150:Antipsychotic Agents; D011522:Protons; D011687:Purines; D008094:Lithium; D003401:Creatine; D002794:Choline; C030985:purine