Neuropathological and neuromorphometric abnormalities in bipolar disorder: View from the medial prefrontal cortical network

Jonathan B. Savitz, Joseph L. Price, Wayne C. Drevets

Research output: Contribution to journalReview articlepeer-review

86 Scopus citations


The question of whether BD is primarily a developmental disorder or a progressive, neurodegenerative disorder remains unresolved. Here, we review the morphometric postmortem and neuroimaging literature relevant to the neuropathology of bipolar disorder (BD). We focus on the medial prefrontal cortex (mPFC) network, a key system in the regulation of emotional, behavioral, endocrine, and innate immunological responses to stress. We draw four main conclusions: the mPFC is characterized by (1) a decrease in volume, (2) reductions in neuronal size, and/or changes in neuronal density, (3) reductions in glial cell density, and (4) changes in gene expression. These data suggest the presence of dendritic atrophy of neurons and the loss of oligodendroglial cells in BD, although some data additionally suggest a reduction in the cell counts of specific subpopulations of GABAergic interneurons. Based on the weight of the postmortem and neuroimaging literature discussed herein, we favor a complex hypothesis that BD primarily constitutes a developmental disorder, but that additional, progressive, histopathological processes also are associated with recurrent or chronic illness. Conceivably BD may be best conceptualized as a progressive neurodevelopmental disorder.

Original languageEnglish
Pages (from-to)132-147
Number of pages16
JournalNeuroscience and Biobehavioral Reviews
StatePublished - May 2014


  • Bipolar disorder
  • Depression
  • Developmental
  • Gene expression
  • Magnetic resonance imaging
  • Medial prefrontal cortex
  • Neuron
  • Neuropathology
  • Oligodendrocyte
  • Postmortem


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