Global grey matter volume in adult bipolar patients with and without lithium treatment: A meta-analysis

J Affect Disord. 2018 Jan 1;225:599-606. doi: 10.1016/j.jad.2017.08.078. Epub 2017 Aug 30.


Objective: The goal of this meta-analysis was to quantitatively summarize the evidence available on the differences in grey matter volume between lithium-treated and lithium-free bipolar patients.

Methods: A systematic search was conducted in Cochrane Central, Embase, MEDLINE, and PsycINFO databases for original peer-reviewed journal articles that reported on global grey matter volume in lithium-medicated and lithium-free bipolar patients. Standard mean difference and Hedges' g were used to calculate effect size in a random-effects model. Risk of publication bias was assessed using Egger's test and quality of evidence was assessed using standard criteria.

Results: There were 15 studies with a total of 854 patients (368 lithium-medicated, 486 lithium-free) included in the meta-analysis. Global grey matter volume was significantly larger in lithium-treated bipolar patients compared to lithium-free patients (SMD: 0.17, 95% CI: 0.01-0.33; z = 2.11, p = 0.035). Additionally, there was a difference in global grey matter volume between groups in studies that employed semi-automated segmentation methods (SMD: 0.66, 95% CI: 0.01-1.31; z = 1.99, p = 0.047), but no significant difference in studies that used fully-automated segmentation. No publication bias was detected (bias coefficient = - 0.65, p = 0.46).

Limitations: Variability in imaging methods and lack of high-quality evidence limits the interpretation of the findings.

Conclusions: Results suggest that lithium-treated patients have a greater global grey matter volume than those who were lithium-free. Further study of the relationship between lithium and grey matter volume may elucidate the therapeutic potential of lithium in conditions characterized by abnormal changes in brain structure.

Keywords: Bipolar disorder; Lithium; Meta-analysis; Neuroimaging.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Adult
  • Bipolar Disorder / drug therapy*
  • Diffusion Magnetic Resonance Imaging
  • Gray Matter / drug effects
  • Gray Matter / pathology*
  • Humans
  • Lithium / therapeutic use*
  • Organ Size
  • Prefrontal Cortex / pathology


  • Lithium