Chronic treatment with lithium, but not sodium valproate, increases cortical N-acetyl-aspartate concentrations in euthymic bipolar patients.

Previous studies have found that treatment with lithium over a 4-week period may increase the concentration of N-acetyl-aspartate (NAA) in both bipolar patients and controls. In view of other findings indicating that NAA concentrations may be a good marker for neuronal viability and/or functioning, it has been further suggested that some of the long term benefits of lithium may therefore be due to actions to improve these neuronal properties. The aim of the present study was to utilize H magnetic resonance spectroscopy ( H MRS) to further examine the effects of both lithium and sodium valproate upon NAA concentrations in treated euthymic bipolar patients. In the first part of the study, healthy controls (n =18) were compared with euthymic bipolar patients (type I and type II) who were taking either lithium (n =14) or sodium valproate (n =11), and NAA : creatine ratios were determined. In the second part, we examined a separate group of euthymic bipolar disorder patients taking sodium valproate (n =9) and compared these to age- and sex-matched healthy controls (n =11), and we quantified the exact concentrations of NAA using an external solution. The results from the first part of the study showed that bipolar patients chronically treated with lithium had a significant increase in NAA concentrations but, in contrast, there were no significant increases in the sodium valproate-treated patients compared to controls. The second part of the study also found no effects of sodium valproate on NAA concentrations. These findings are the first to compare NAA concentrations in euthymic bipolar patients being treated with lithium or sodium valproate. The results support suggestions that longer-term administration of lithium to bipolar patients may increase NAA concentrations. However, the study suggests that chronic administration of sodium valproate to patients does not lead to similar changes in NAA concentrations. These findings suggest that sodium valproate and lithium may not share a common mechanism of action in bipolar disorder involving neurotrophic or neuroprotective effects.

Chronic treatment with both lithium and sodium valproate may normalize phosphoinositol cycle activity in bipolar patients.

BACKGROUND: It has been proposed that lithium may be clinically effective due to its actions on the phosphoinositol second messenger system (PI-cycle). Studies have also suggested that untreated manic patients may have raised myo-inositol and phosphomonoester (PME) concentrations and also that unmedicated euthymic bipolar patients may have lowered PME concentrations. The objective of the present study was to test the hypothesis that chronic treatment with either lithium or sodium valproate in patients with bipolar mood disorder leads to a normalization in the activity of the PI-cycle. METHODS: This study had two parts each with different MRS methodology. The first part compared healthy controls (n = 19) with euthymic bipolar patients who were taking either lithium (n = 16) or sodium valproate (n = 11) using both (1)H-MRS and (31)P-MRS. In the second part we examined a separate group of euthymic bipolar disorder patients taking sodium valproate (n = 9) and compared these with age and sex-matched healthy controls (n = 11) using (1)H-MRS. RESULTS: Both studies showed that there were no differences in either myo-inositol or phosphomonoester (PME) concentrations between controls and patients taking either medication. CONCLUSIONS: These findings examine two key components of the PI-cycle in treated euthymic bipolar (myo-inositol and PME concentrations). The results from this study are consistent with the suggestion that chronic treatment with either lithium or sodium valproate in bipolar patients may normalize PI-cycle functioning.

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

BACKGROUND: It 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. METHODS: The 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. RESULTS: The 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. CONCLUSIONS: These 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.