Abstract
Background: Neuroprotective effects of lithium (Li) have been well documented in tissue cultures and animal models, whereas human data continue to be limited. Previous studies investigating the association between Li treatment and brain N-acetylaspartate (NAA), a putative neuronal marker, showed mixed results because of methodological heterogeneity. Methods: To investigate the effects of Li on prefrontal cortex NAA levels, we compared patients with bipolar disorder from specialized Li clinics in Berlin and Halifax with at least 2 years of ongoing Li treatment (Li group), patients with lifetime Li exposure of less than 3 months more than 2 years ago (non-Li group) and healthy controls. Participants in both patient groups had at least 10 years of illness and 5 episodes. We measured left prefrontal NAA levels using 1.5-T magnetic resonance spectroscopy. Results: We enrolled 27 participants in the Li, 16 in the non-Li and 21 in the healthy control groups. The non-Li group had lower prefrontal NAA levels than the Li group (t41 = -3.44, corrected p < 0.01) or control participants (t35 = -2.91, corrected p < 0.05), who did not differ from the Li group (t46 = -0.14, p = 0.89). The same pattern of prefrontal NAA differences was replicated in both sites. In addition, there was a negative correlation between prefrontal NAA and duration of illness in the non-Li group (r = -0.60, p = 0.019) but not in the Li group (r = 0.07, p = 0.74). Limitations: Study limitations include the cross-sectional design and exposure to other medications. Conclusion: Whereas patients with bipolar disorder, substantial illness burden and limited lifetime Li exposure had significantly lower prefrontal NAA levels than controls, Li-treated patients with similar illness burden showed prefrontal NAA levels comparable to those of healthy controls. These findings provide indirect support for neuroprotective effects of Li and for negative effects of illness burden on prefrontal NAA levels in patients with bipolar disorder.
| Original language | English |
|---|---|
| Pages (from-to) | 185-192 |
| Number of pages | 8 |
| Journal | Journal of Psychiatry and Neuroscience |
| Volume | 37 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - May 2012 |
| Externally published | Yes |
Bibliographical note
Funding Information:Patients with bipolar disorder, substantial burden of illness and limited lifetime Li exposure had significantly lower pre-frontal NAA levels than controls or Li-treated patients, who showed comparable prefrontal NAA levels to those of healthy controls despite substantial burden of bipolar disorder. Since the groups did not differ in relevant demographic and clinical variables, these results provide indirect in vivo support for neuroprotective effects of Li and for negative effects of illness burden on prefrontal NAA levels in individuals with bipolar disorder once lifetime exposure to Li is limited. Acknowledgements: This study was supported by funding from the Canadian Institutes of Health Research, the Nova Scotia Health Research Foundation and the Dalhousie Clinical Research Scholarship to T. Hajek Competing interests: None declared for J. Cullis, C. O’Donovan, J. Ploch and M. Alda. As above for T. Hajek. M. Bauer declares having received institutional grant support from The Stanley Medical Research Institute and NARSAD; consultancy fees and travel support from AstraZeneca, Lilly, Servier, Janssen-Cilag, Lundbeck, BMS/ Otsuka, Pfizer and GlaxoSmithKline; lecture fees and travel support from AstraZeneca, GlaxoSmithKline, Lundbeck, BMS/Otsuka and Pfizer; and board membership with AstraZeneca, Lilly, Servier, Janssen-Cilag, Lundbeck and BMS/Otsuka. A. Pfennig declares having received grant support from GlaxoSmithKline, and speaker fees from AstraZeneca and Eli Lilly. G. Bohner declares having received consultancy fees from Wyeth, BMS and Novartis. L.T. Young declares having received speaker fees from Eli Lilly and AstraZeneca. G. MacQueen declares having received consultancy and speaker fees from Lilly, AstraZeneca, BMS, Pfizer and Lundbeck; a grant from AstraZeneca; and payment for developing educational presentations for the Canadian Psychiatric Association and Lundbeck. Contributors : M. Bauer, A. Pfennig, R. Klingebiel, L.T. Young and M. Alda designed the study. T. Hajek, M. Bauer, A. Pfennig, J. Ploch, C. O’Donovan, G. Bohner, R. Klingebiel and M. Alda acquired the data. T. Hajek, M. Bauer, J. Cullis, G. MacQueen and M. Alda analyzed the data. T. Hajek wrote the article. All authors reviewed the article and approved its publication.
ASJC Scopus Subject Areas
- Psychiatry and Mental health
- Biological Psychiatry
- Pharmacology (medical)
