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

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

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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 1H magnetic resonance spectroscopy (1H 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.

Original languageEnglish (US)
Pages (from-to)73-79
Number of pages7
JournalInternational Clinical Psychopharmacology
Issue number2
StatePublished - Mar 2003

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Pharmacology (medical)


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