The DOI matches its Crossref record; 208 of the 211 references it cites were found in a registry or an index.
Neuropathological and neuromorphometric abnormalities in bipolar disorder: View from the medial prefrontal cortical network
Abstract
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.
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“There is evidence of vmPFC gray matter loss in mood disorders7,115,116, which implies dendritic atrophy.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [116]
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From inflammation to sickness and depression: when the immune system subjugates the brain
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Cognitive and emotional influences in anterior cingulate cortex
Bush, G., Luu, P., & Posner, M. I. (2000) · Trends in Cognitive Sciences · doi:10.1016/s1364-6613(00)01483-2 · Cited by 6,259
Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression
Miller, A. H., Maletic, V., & Raison, C. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.029 · Cited by 3,848
Thayer, J. F., Åhs, F., Fredrikson, M., Sollers, J. J., & Wager, T. D. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.11.009 · Cited by 3,224
Subgenual prefrontal cortex abnormalities in mood disorders
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Self-citationNeurocircuitry of Mood Disorders
Price, J. L., & Drevets, W. C. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.104 · Cited by 1,606
Self-citationThe Orbitofrontal Cortex and Reward
Rolls, E. T. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.3.284 · Cited by 1,595
Glial reduction in the subgenual prefrontal cortex in mood disorders
Öngür, D., Drevets, W. C., & Price, J. L. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.13290 · Cited by 1,525
Self-citationGuidotti, A., Auta, J., Davis, J. M., Gerevini, V. D. G., Dwivedi, Y., Grayson, D. R., Impagnatiello, F., Pandey, G. N., Pesold, C., Sharma, R. P., et al. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.11.1061 · Cited by 1,222
Structural Brain Changes in Aging: Courses, Causes and Cognitive Consequences
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Stress weakens prefrontal networks: molecular insults to higher cognition
Arnsten, A. F. T. (2015) · Nature Neuroscience · doi:10.1038/nn.4087 · Cited by 752
The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders
Réus, G. Z., Fries, G. R., Stertz, L., Badawy, M., Passos, I. C., Barichello, T., Kapczinski, F., & Quevedo, J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.018 · Cited by 594
Steullet, P., Cabungcal, J.-H., Coyle, J., Didriksen, M., Gill, K., Grace, A. A., Hensch, T. K., LaMantia, A.-S., Lindemann, L., Maynard, T. M., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.47 · Cited by 360
The Emerging Neurobiology of Bipolar Disorder
Harrison, P. J., Geddes, J. R., & Tunbridge, E. M. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2017.10.006 · Cited by 246
Cotrena, C., Branco, L. D., Shansis, F. M., & Fonseca, R. P. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.11.007 · Cited by 227
Metadata
- Authors
- Savitz, J. B., Price, J. L., & Drevets, W. C.
- Affiliations
- Laureate Institute for Brain Research (US)
- Washington University in St. Louis (US)
- Corresponding author
- Savitz, Jonathan B.
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 42
- Pages
- 132-147
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W1968616230
- Cited by
- 145
- References
- 211
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 4 · 2023: 3 · 2022: 9 · 2021: 29 · 2020: 11 · 2019: 9 · 2018: 8 · 2017: 13 · 2016: 18 · 2015: 21 · 2014: 6
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- bipolar disorder, medial prefrontal cortex, neuropathology, neurodevelopmental disorders, neurodegeneration, neuron size, glial cell density, dendritic atrophy, GABAergic interneurons, gene expression, stress response, chronic disease
- MeSH terms
- Animals, Bipolar Disorder, Humans, Neural Pathways, Neuroglia, Neurons, Prefrontal Cortex
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