Brain choline concentrations may not be altered in euthymic bipolar disorder patients chronically treated with either lithium or sodium valproate

Ren H Wu,Sheila J Asghar,Peter H Silverstone,Tina O'Donnell,Michele Ulrich,Christopher C Hanstock

doi:10.1186/1475-2832-3-13

Abstract

BackgroundIt has been suggested that lithium increases choline concentrations, although previous human studies examining this possibility using 1H magnetic resonance spectroscopy (1H MRS) have had mixed results: some found increases while most found no differences.MethodsThe present study utilized 1H MRS, in a 3 T scanner to examine the effects of both lithium and sodium valproate upon choline concentrations in treated euthymic bipolar patients utilizing two different methodologies. In the first part of the study healthy controls (n = 18) were compared with euthymic Bipolar Disorder patients (Type I and Type II) who were taking either lithium (n = 14) or sodium valproate (n = 11), and temporal lobe choline/creatine (Cho/Cr) ratios were determined. In the second part we examined a separate group of euthymic Bipolar Disorder Type I patients taking sodium valproate (n = 9) and compared these to controls (n = 11). Here we measured the absolute concentrations of choline in both temporal and frontal lobes.ResultsThe results from the first part of the study showed that bipolar patients chronically treated with both lithium and sodium valproate had significantly reduced temporal lobe Cho/Cr ratios. In contrast, in the second part of the study, there were no effects of sodium valproate on either absolute choline concentrations or on Cho/Cr ratios in either temporal or frontal lobes.ConclusionsThese findings suggest that measuring Cho/Cr ratios may not accurately reflect brain choline concentrations. In addition, the results do not support previous suggestions that either lithium or valproate increases choline concentrations in bipolar patients.

Highlights

It has been suggested that lithium increases choline concentrations, previous human studies examining this possibility using 1H magnetic resonance spectroscopy (1H MRS) have had mixed results: some found increases while most found no differences
Of note is that choline concentrations increase significantly in rats following electroconvulsive shock [8]. Based upon this data choline has been used to treat mania in a some small pilot studies [9], with one open label study reporting that choline augmentation of lithium treatment helped rapid-cyclers [10]
Patients treated with choline had increased basal ganglia concentrations of choline, suggesting that externally administered choline could alter brain concentrations [11,12]

Summary

Introduction

It has been suggested that lithium increases choline concentrations, previous human studies examining this possibility using 1H magnetic resonance spectroscopy (1H MRS) have had mixed results: some found increases while most found no differences. One suggestion is that it acts via effects on choline metabolism This is based upon findings that lithium can inhibit the membrane transport of choline in both animals [2], and human post-mortem brain tissue [3]. It increases the accumulation of erythrocyte choline in lithium-treated patients [4,5,6,7]. Of note is that choline concentrations increase significantly in rats following electroconvulsive shock [8] Based upon this data choline has been used to treat mania in a some small pilot studies [9], with one open label study reporting that choline augmentation of lithium treatment helped rapid-cyclers [10]. Patients treated with choline had increased basal ganglia concentrations of choline, suggesting that externally administered choline could alter brain concentrations [11,12]

Methods

Results

Conclusion