Lithium-induced gray matter volume increase as a neural correlate of treatment response in bipolar disorder: A longitudinal brain imaging study

In Kyoon Lyoo, Stephen R. Dager, Jieun E. Kim, Sujung J. Yoon, Seth D. Friedman, David L. Dunner, Perry F. Renshaw

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181 Scopus citations


Preclinical studies suggest that lithium may exert neurotrophic effects that counteract pathological processes in the brain of patients with bipolar disorder (BD). To describe and compare the course and magnitude of gray matter volume changes in patients with BD who are treated with lithium or valproic acid (VPA) compared to healthy comparison subjects, and to assess clinical relationships to gray matter volume changes induced by lithium in patients with BD, we conducted longitudinal brain imaging and clinical evaluations of treatment response in 22 mood-stabilizing and antipsychotic medications-naive patients with BD who were randomly assigned to either lithium or VPA treatment after baseline assessment. Fourteen healthy comparison subjects did not take any psychotropic medications during follow-up. Longitudinal data analyses of 93 serial magnetic resonance images revealed lithium-induced increases in gray matter volume, which peaked at week 10-12 and were maintained through 16 weeks of treatment. This increase was associated with positive clinical response. In contrast, VPA-treated patients with BD or healthy comparison subjects did not show gray matter volume changes over time. Results suggest that lithium induces sustained increases in cerebral gray matter volume in patients with BD and that these changes are related to the therapeutic efficacy of lithium.

Original languageEnglish
Pages (from-to)1743-1750
Number of pages8
Issue number8
StatePublished - Jul 2010

Bibliographical note

Funding Information:
This study received financial support from the National Alliance for Schizophrenia and Depression (Independent Investigator Awards, Dr Lyoo and Dr Renshaw), the National Institute of Mental Health (RO1 MH58681, Dr Renshaw), the Poitras Foundation (Dr Renshaw), the Korean Ministry of Science and Technology (2009K001272, Dr Lyoo), and the National Research Foundation of Korea (2009-0074584, Dr Kim and 2009-0066915, Dr Yoon). We thank all study participants; the whole international collaborative team, including James Anderson, Sujin Bae, Carolyn Bea, Chris Budech, Marie Domsalla, Denise Echelard, Charlotte Haws, Jaeuk Hwang, Kyehyen Kim, and Gerald Ortiz for technical assistance.


  • Bipolar disorder
  • Clinical response
  • Gray matter
  • Lithium
  • Magnetic resonance imaging
  • Valproic acid


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