Opposite effects of suicidality and lithium on gray matter volumes in bipolar depression

Francesco Benedetti, Daniele Radaelli, Sara Poletti, Clara Locatelli, Andrea Falini, Cristina Colombo, Enrico Smeraldi

Research output: Contribution to journalArticlepeer-review


Background: Mood disorders are associated with the highest increase of attempted and completed suicide. Suicidality in major depressive disorder and in schizophrenia has been associated with reduced gray matter volumes in orbitofrontal cortex. Lithium reduces the suicide risk of patients with bipolar disorder (BD) to the same levels of the general population, and can increase GM volumes. We studied the effect of a positive history of attempted suicide and ongoing lithium treatment on regional GM volumes of patients affected by bipolar depression. Methods: With a correlational design, we studied 57 currently depressed inpatients with bipolar disorder: 19 with and 38 without a positive history of suicide attempts, 39 unmedicated and 18 with ongoing lithium treatment. Total and regional gray matter volumes were assessed using voxel-based morphometry. Results: Total GM volume is inversely correlated with depression severity. A positive history of suicide attempts was associated with higher stress in early life. Suicide attempters showed reduced GM volumes in several brain areas including dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate, superior temporal cortex, parieto-occipital cortex, and basal ganglia. Long term lithium treatment was associated with increased GM volumes in the same areas where suicide was associated with decreased GM. Conclusions: Reduced GM volumes in critical cortical areas of suicidal patients could be a biological correlate of an impaired ability to associate choices and outcomes and to plan goal-directed behaviors based on a lifetime historical perspective, which, coupled with mood-congruent depressive cognitive distortions, could lead to more hopelessness and suicide. Lithium could exert its specific therapeutic effect on suicide by acting in the same areas.

Original languageEnglish
Pages (from-to)139-147
Number of pages9
JournalJournal of Affective Disorders
Issue number1-3
Publication statusPublished - Dec 2011


  • Adverse childhood experiences
  • Bipolar disorder
  • Gray matter
  • Lithium
  • Suicide

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology


Dive into the research topics of 'Opposite effects of suicidality and lithium on gray matter volumes in bipolar depression'. Together they form a unique fingerprint.

Cite this