Lithium prevents grey matter atrophy in patients with bipolar disorder: an international multicenter study

Psychol Med. 2021 May;51(7):1201-1210. doi: 10.1017/S0033291719004112. Epub 2020 Jan 27.


Background: Lithium (Li) is the gold standard treatment for bipolar disorder (BD). However, its mechanisms of action remain unknown but include neurotrophic effects. We here investigated the influence of Li on cortical and local grey matter (GM) volumes in a large international sample of patients with BD and healthy controls (HC).

Methods: We analyzed high-resolution T1-weighted structural magnetic resonance imaging scans of 271 patients with BD type I (120 undergoing Li) and 316 HC. Cortical and local GM volumes were compared using voxel-wise approaches with voxel-based morphometry and SIENAX using FSL. We used multiple linear regression models to test the influence of Li on cortical and local GM volumes, taking into account potential confounding factors such as a history of alcohol misuse.

Results: Patients taking Li had greater cortical GM volume than patients without. Patients undergoing Li had greater regional GM volumes in the right middle frontal gyrus, the right anterior cingulate gyrus, and the left fusiform gyrus in comparison with patients not taking Li.

Conclusions: Our results in a large multicentric sample support the hypothesis that Li could exert neurotrophic and neuroprotective effects limiting pathological GM atrophy in key brain regions associated with BD.

Keywords: Bipolar disorder; MRI; grey matter volume; lithium.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimanic Agents / therapeutic use*
  • Atrophy / prevention & control*
  • Bipolar Disorder / drug therapy*
  • Case-Control Studies
  • Female
  • Gray Matter / pathology*
  • Gyrus Cinguli / pathology
  • Hippocampus / pathology
  • Humans
  • Lithium Compounds / therapeutic use*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Temporal Lobe / pathology


  • Antimanic Agents
  • Lithium Compounds