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

Psychopharmacology (Berl). 2007 Dec;195(3):357-67. doi: 10.1007/s00213-007-0906-9. Epub 2007 Aug 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / pathology
  • Drug Administration Schedule
  • Female
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Humans
  • Lithium Compounds / administration & dosage
  • Lithium Compounds / therapeutic use*
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Mental Recall / drug effects*
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / therapeutic use*
  • Verbal Learning / drug effects


  • Lithium Compounds
  • Neuroprotective Agents