Illness duration and total brain gray matter in bipolar disorder: Evidence for neurodegeneration?

Benicio N. Frey, Giovana B. Zunta-Soares, Sheila C. Caetano, Mark A. Nicoletti, John P. Hatch, Paolo Brambilla, Alan G. Mallinger, Jair C. Soares

Research output: Contribution to journalArticlepeer-review


Previous studies have suggested that bipolar disorder (BD) is associated with alterations in neuronal plasticity, but the effects of the progression of illness on brain anatomy have been poorly investigated. We studied the correlation between length of illness, age, age at onset, and the number of previous episodes and total brain, total gray, and total white matter volumes in BD, unipolar (UP) and healthy control (HC) subjects. Thirty-six BD, 31 UP and 55 HCs underwent a 1.5 T brain magnetic resonance imaging scan, and gray and white matter volumes were manually traced blinded to the subjects' diagnosis. Partial correlation analysis showed that length of illness was inversely correlated with total gray matter volume after adjusting for total intracranial volume in BD (rp = - 0.51; p = 0.003) but not in UP subjects (rp = - 0.23; p = 0.21). Age at illness onset and the number of previous episodes were not significantly correlated with gray matter volumes in BD or UP subjects. No significant correlation with total white matter volume was observed. These results suggest that the progression of illness may be associated with abnormal cellular plasticity. Prospective longitudinal studies are necessary to elucidate the long-term effects of illness progression on brain structure in major mood disorders.

Original languageEnglish
Pages (from-to)717-722
Number of pages6
JournalEuropean Neuropsychopharmacology
Issue number10
Publication statusPublished - Oct 2008


  • Bipolar disorder
  • Brain imaging
  • Gray matter
  • Major depressive disorder
  • Pathophysiology

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Neurology
  • Pharmacology
  • Psychology(all)


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