J Psychiatry Neurosci 2012;37(3):185-92
Tomas Hajek, MD, PhD; Michael Bauer, MD; Andrea Pfennig, MD; Jeffrey Cullis, MSc; Jana Ploch, MSc; Claire O’Donovan, MD; Georg Bohner, MD; Randolf Klingebiel, MD; L. Trevor Young, MD, PhD; Glenda M. MacQueen, MD, PhD; Martin Alda, MD
Hajek, Cullis, O’Donovan, Alda — Department of Psychiatry, Dalhousie University, Halifax, NS; Hajek, Alda — Prague Psychiatric Centre, Department of Psychiatry and Medical Psychology, 3rd School of Medicine, Charles University, Prague, Czech Republic; Bauer, Pfennig, Ploch — Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus,Technische Universität Dresden, Dresden, Germany; Bohner, Klingebiel — Department of Neuroradiology, Charité Universitaetsmedizin Berlin, Berlin, Germany; Young — Department of Psychiatry, University of Toronto, Toronto, Ont.; MacQueen— Department of Psychiatry, University of Calgary, Calgary, Alta.
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 crosssectional 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.
Submitted Aug. 5, 2011; Revised Oct. 17, 2011; Accepted Nov. 15, 2011.
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 consult ancy fees from Wyeth, BMS and Novartis. L.T. Young declares having received speaker fees from Eli Lilly and Astra Zeneca. 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 Can adian 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.
Correspondence to: T. Hajek, Department of Psychiatry, Dalhousie University, Queen Elizabeth II Health Sciences Centre, A.J. Lane Bldg., Room 3093, 5909 Veteran’s Memorial Lane, Halifax NS B3H 2E2; firstname.lastname@example.org