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Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study

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Abstract

Rationale

The majority of volumetric magnetic resonance imaging (MRI) studies of the hippocampus in patients with bipolar disorder (BD) show no differences in hippocampal volume between patients and healthy controls. Significant variability, however, exists in the medication status of patients included in these studies. In particular, treatment with lithium may exert long-term effects on hippocampal volume, influencing cognitive outcomes in BD patients.

Objectives

To our knowledge, no longitudinal volumetric study has been performed in patients with BD, which would allow for an examination of whether lithium therapy used to treat BD can exert a long-term effect on hippocampal volume.

Materials and methods

We examined the effects of lithium on hippocampal volumes and recollective memory performance over a period of 2 to 4 years in 12 patients with BD who had never received pharmacotherapy before lithium initiation.

Results

We found bilateral increases in volume of the hippocampus over time. We also found some evidence of improvement in verbal memory performance over the 4-year measurement period as assessed by the California Verbal Learning Test.

Conclusions

Consistent with preclinical literature supporting the neuroprotective effects of lithium, long-term treatment is associated with preservation of recollective memory function and increased hippocampal size in vivo.

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Acknowledgements

We are grateful to the patients and their families for their assistance. We thank Cathy Preete and Benjamin Doxtdator for their assistance in preparation of this manuscript and Laura Garrick, Helen Begin, Cindy D’Amico, Scott Simons, and Tana Pati for assistance with patient scheduling and testing. We are also grateful to Geoff Hall and Andrea Milne for assistance in running the brain imaging protocol and to Marcella Rincon Castro and Anthony Nazarov for assistance in the imaging analysis. This study was supported by Canadian Institutes of Health Research and Ontario Mental Health Foundation grants to G. MacQueen. None of the authors have any possible conflicts of interest, financial or otherwise, related directly or indirectly to this work. Furthermore, this study was performed in compliance with the current laws of Canada.

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  1. Department of Psychiatry and Behavioural Neurosciences, McMaster University, 100 West 5th Street, Hamilton, ON, L8N 3K7, Canada

    Kaan Yucel, Margaret C. McKinnon, Valerie H. Taylor, Kathryn Macdonald & Glenda M. MacQueen

  2. Department of Psychiatry, McGill University, PINE 1033 Avenue West, Montreal, QC, H3A 1A1, Canada

    Martin Alda

  3. Department of Psychiatry, University of British Columbia, 2255 Westbrook Mall, Vancouver, BC, V6T 2A1, Canada

    L. Trevor Young

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  1. Kaan Yucel
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  2. Margaret C. McKinnon
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  4. Kathryn Macdonald
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  5. Martin Alda
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  7. Glenda M. MacQueen
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Correspondence to Glenda M. MacQueen.

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Yucel, K., McKinnon, M.C., Taylor, V.H. et al. Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study. Psychopharmacology 195, 357–367 (2007). https://doi.org/10.1007/s00213-007-0906-9

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