Lithium and valproate protect against dextro-amphetamine induced brain choline concentration changes in bipolar disorder patients

Abstract

Background: Lithium may affect brain choline concentrations, and this effect has been proposed to potentially explain its clinical efficacy. Since dextro-amphetamine is a useful human model of mania, we were interested in determining firstly whether dextro-amphetamine would alter brain choline concentrations, and secondly to determine if lithium would protect against any such changes in bipolar patients. In addition, we wanted to determine if valproate would also have any effects upon choline levels.

Methods: Healthy controls (n=18) were compared with euthymic Bipolar Disorder patients (Type I and Type II) who were taking lithium (n=14) or valproate (n=11). We utilized (1)H-magnetic resonance spectroscopy ((1)H-MRS) in a 3.0T scanner to examine brain choline/phosphocholine+creatine (Cho/Cr) ratios. Changes in this ratio were measured to determine any changes in choline concentrations in the temporal lobe.

Results: The results showed that administration of dextro-amphetamine decreased the Cho/Cr ratios. In contrast, in both the lithium-treated and valproate-treated patients this decrease was not seen; this attenuation in the change in Cho/Cr ratio changes was statistically significant. It should be noted that Cho/Cr ratios were significantly higher at baseline in the controls compared to both groups of patients, which may have influenced the results.

Conclusions: These findings are the first to examine the effects of dextro-amphetamine on brain choline concentrations. They show that while in controls dextro-amphetamine decreases choline concentrations, lithium and valproate both appear to protect against this effect in bipolar patients. However, as brain ratios were measured rather than the absolute concentration of choline, and these ratios were lowered in patients at baseline, these results must be regarded as preliminary and require replication in future studies.