Cortical abnormalities in bipolar disorder investigated with MRI and voxel-based morphometry

Allison C. Nugent, Michael P. Milham, Earle E. Bain, Linda Mah, Dara M. Cannon, Sean Marrett, Carlos A. Zarate, Daniel S. Pine, Joseph L. Price, Wayne C. Drevets

Research output: Contribution to journalArticlepeer-review

173 Scopus citations


Bipolar disorder (BD) has been associated with abnormalities of brain structure. Specifically, in vivo volumetric MRI and/or post mortem studies of BD have reported abnormalities of gray matter (GM) volume in the medial prefrontal cortex (PFC), amygdala, hippocampal subiculum and ventral striatum. These structures share anatomical connections with each other and form part of a "visceromotor" network modulating emotional behavior. Areas of the lateral orbital, superior temporal and posterior cingulate cortices project to this network, but morphometric abnormalities in these areas have not been established in BD. The current study assessed tissue volumes within these areas in BD using MRI and voxel-based morphometry (VBM). MRI images were obtained from 36 BD subjects and 65 healthy controls. To account for possible neurotrophic and neuroprotective effects of psychotropic medications, BD subjects were divided into medicated and unmedicated groups. Images were segmented into tissue compartments, which were examined on a voxel-wise basis to determine the location and extent of morphometric changes. The GM was reduced in the posterior cingulate/retrosplenial cortex and superior temporal gyrus of unmedicated BD subjects relative to medicated BD subjects and in the lateral orbital cortex of medicated BD subjects relative to controls. White matter (WM) was increased in the orbital and posterior cingulate cortices, which most likely reflected alterations in gyral morphology resulting from the reductions in the associated GM. The morphometric abnormalities in the posterior cingulate, superior temporal and lateral orbital cortices in BD support the hypothesis that the extended network of neuroanatomical structures subserving visceromotor regulation contains structural alterations in BD. Additionally, localization of morphometric abnormalities to areas known to exhibit increased metabolism in depression supports the hypothesis that repeated stress and elevated glucocorticoid secretion may result in neuroplastic changes in BD.

Original languageEnglish
Pages (from-to)485-497
Number of pages13
Issue number2
StatePublished - Apr 1 2006


  • Bipolar depression
  • Magnetic resonance imaging
  • Morphometry


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