Neuronal and Glial Somal Size in the Prefrontal Cortex: A Postmortem Morphometric Study of Schizophrenia and Huntington Disease
Abstract
Background The cortex of patients with schizophrenia exhibits a deficit in neuropil, but the nature and extent of cellular abnormalities remain unclear. To gain further insight into this abnormality, neuronal and glial somal size were analyzed in postmortem brains from 9 patients with schizophrenia, 10 normal (control) patients, and 7 patients with Huntington disease, the latter representing a known neurodegenerative disorder. Methods A 3-dimensional image analyzer was used to measure the perimeters of 10722 neuronal and 19913 glial profiles in Brodmann areas 9 and 17. Neurons and glia were classified by size and layer to assess specific vulnerabilities with respect to cortical architecture and circuitry. Results The schizophrenic prefrontal cortex was characterized by a downward shift in neuronal sizes accompanied by 70% to 140% per layer increases in the density of small neurons. In layer III only, a significant reduction in mean neuronal size was associated with a significant decrease in the density of very large neurons in sublayer Illc. Neither neuronal size in occipital area 17 nor glial size in prefrontal or occipital cortexes were reduced. In cortex with Huntington disease, neuronal degeneration was evidenced by concurrence of reduced neuronal size, decreased density of large neurons, and dramatic elevation in density of large glia. Conclusions Distinct cytometric abnormalities support the hypothesis that neuronal degeneration in the prefrontal cortex is not a promine…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The somal volume of layer 3 DLPFC pyramidal cells is reduced in schizophrenia.
“the somal volume of layer 3 DLPFC pyramidal cells has been found to be reduced (Rajkowska et al., 1998; Pierri et al., 2001)”
From The Computational Anatomy of Psychosis (2013) · cites this paper as Rajkowska et al., 1998
Cites
Hof, P. R., Morrison, J. H., & Cox, K. (1990) · Journal of Comparative Neurology · doi:10.1002/cne.903010105 · Cited by 365 · cited 1× · see citing works
“In patients with Alzheimer disease, large pyramidal neurons have been found to be susceptible to degenerative changes as decreases in the number of large SMI32immunoreactive neurons have been found in layers III and V of prefrontal area 9.(28) As layer III pyramidal cells are one of the major sources of corticocortica…”
Background
Flagged first, then by citations
Cited by
Sorted by citations
Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence
Harrison, P. J., & Weinberger, D. R. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001558 · Cited by 2,020 · see citing works
Neurobiology of emotion perception II: implications for major psychiatric disorders
Phillips, M. L., Drevets, W. C., Rauch, S. L., & Lane, R. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00171-9 · Cited by 1,736 · see citing works
Decreased Dendritic Spine Density on Prefrontal Cortical Pyramidal Neurons in Schizophrenia
Glantz, L. A., & Lewis, D. A. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.1.65 · Cited by 1,636 · see citing works
The neuropathology of schizophrenia
Harrison, P. J. (1999) · Brain · doi:10.1093/brain/122.4.593 · Cited by 1,677 · see citing works
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 · see citing works
Rajkowska, G., Miguel-Hidalgo, J. J., Wei, J., Dilley, G., Pittman, S. D., Meltzer, H. Y., Overholser, J. C., Roth, B. L., & Stockmeier, C. A. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00041-4 · Cited by 1,477 · see citing works
Self-citationThe reduced neuropil hypothesis: a circuit based model of schizophrenia
Selemon, L. D., & Goldman-Rakic, P. S. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00281-9 · Cited by 909 · see citing works
Self-citationThe Computational Anatomy of Psychosis
Adams, R. A., Stephan, K. E., Brown, H. R., Frith, C. D., & Friston, K. J. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00047 · Cited by 850 · see citing works
“It is important to note that DA-R subtypes have opposite effects on synaptic gain: D1R activation stimulates cAMP production and increases the excitability of depolarized neurons, whereas D2R activation inhibits cAMP production and reduces gain (reviewed in Frank, 2005).”
BackgroundMirnics, K., Middleton, F. A., Marquez, A., Lewis, D. A., & Levitt, P. (2000) · Neuron · doi:10.1016/s0896-6273(00)00085-4 · Cited by 882 · see citing works
White Matter Changes in Schizophrenia: Evidence for Myelin-Related Dysfunction
Davis, K. L., Stewart, D. G., Friedman, J. I., Buchsbaum, M., Harvey, P. D., Hof, P. R., Buxbaum, J., & Haroutunian, V. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.5.443 · Cited by 793 · see citing works
Uranova, N. A., Vostrikov, V. M., Orlovskaya, D. D., & Rachmanova, V. I. (2004) · Schizophrenia Research · doi:10.1016/s0920-9964(03)00181-6 · Cited by 659 · see citing works
Cotter, D. (2002) · Cerebral Cortex · doi:10.1093/cercor/12.4.386 · Cited by 634 · see citing works
Dendritic spine pathology in schizophrenia
Glausier, J. R., & Lewis, D. A. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.04.044 · Cited by 581 · see citing works
Krystal, J. H., D'Souza, D. C., Mathalon, D., Perry, E., Belger, A., & Hoffman, R. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1582-z · Cited by 530 · see citing works
Electron microscopy of oligodendroglia in severe mental illness
Uranova, N., Orlovskaya, D., Vikhreva, O., Zimina, I., Kolomeets, N., Vostrikov, V., & Rachmanova, V. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00528-7 · Cited by 495 · see citing works
Hashimoto, T., Bazmi, H. H., Mirnics, K., Wu, Q., Sampson, A. R., & Lewis, D. A. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.07081223 · Cited by 457 · see citing works
Hof, P. R., Haroutunian, V., Friedrich, V. L., Byne, W., Buitron, C., Perl, D. P., & Davis, K. L. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00237-3 · Cited by 433 · see citing works
A petavoxel fragment of human cerebral cortex reconstructed at nanoscale resolution
Shapson-Coe, A., Januszewski, M., Berger, D. R., Pope, A., Wu, Y., Blakely, T., Schalek, R. L., Li, P. H., Wang, S., Maitin-Shepard, J., et al. (2024) · Science · doi:10.1126/science.adk4858 · Cited by 361 · see citing works
Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review
Trépanier, M. O., Hopperton, K. E., Mizrahi, R., Mechawar, N., & Bazinet, R. P. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.90 · Cited by 360 · see citing works
Benes, F. M., Vincent, S. L., & Todtenkopf, M. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01084-8 · Cited by 327 · see citing works
The glutamate hypothesis of schizophrenia: evidence from human brain tissue studies
Hu, W., MacDonald, M. L., Elswick, D. E., & Sweet, R. A. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12547 · Cited by 286 · see citing works
Reduced Dendritic Spine Density in Auditory Cortex of Subjects with Schizophrenia
Sweet, R. A., Henteleff, R. A., Zhang, W., Sampson, A. R., & Lewis, D. A. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2008.67 · Cited by 290 · see citing works
Sanfilipo, M., Lafargue, T., Rusinek, H., Arena, L., Loneragan, C., Lautin, A., Feiner, D., Rotrosen, J., & Wolkin, A. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.5.471 · Cited by 281 · see citing works
Fornito, A., Yucel, M., Dean, B., Wood, S. J., & Pantelis, C. (2009) · Schizophrenia Bulletin · doi:10.1093/schbul/sbn025 · Cited by 259 · see citing works
Fatemi, S. H., Earle, J., Kanodia, R., Kist, D., Emamian, E. S., Patterson, P. H., Shi, L., & Sidwell, R. (2002) · Cellular and Molecular Neurobiology · doi:10.1023/a:1015337611258 · Cited by 261 · see citing works
Kolluri, N., Sun, Z., Sampson, A. R., & Lewis, D. A. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.6.1200 · Cited by 241 · see citing works
Vostrikov, V. M., Uranova, N. A., & Orlovskaya, D. D. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2007.04.014 · Cited by 233 · see citing works
Pennington, K., Beasley, C. L., Dicker, P., Fagan, A., English, J., Pariante, C. M., Wait, R., Dunn, M. J., & Cotter, D. R. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002098 · Cited by 227 · see citing works
Hill, J. J., Hashimoto, T., & Lewis, D. A. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001792 · Cited by 228 · see citing works
Arion, D., Corradi, J. P., Tang, S., Datta, D., Boothe, F., He, A., Cacace, A. M., Zaczek, R., Albright, C. F., Tseng, G., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.171 · Cited by 177 · see citing works
The role of oligodendrocyte pathology in schizophrenia
Uranova, N. A., Vostrikov, V. M., Vikhreva, O. V., Zimina, I. S., Kolomeets, N. S., & Orlovskaya, D. D. (2007) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145707007626 · Cited by 176 · see citing works
Zikopoulos, B., & Barbas, H. (2007) · Reviews in the Neurosciences · doi:10.1515/revneuro.2007.18.6.417 · Cited by 156 · see citing works
Modeling psychiatric disorders at the cellular and network levels
Brennand, K. J., Simone, A., Tran, N., & Gage, F. H. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.20 · Cited by 119 · see citing works
Neuron density and serotonin receptor binding in prefrontal cortex in suicide
Underwood, M. D., Kassir, S. A., Bakalian, M. J., Galfalvy, H., Mann, J. J., & Arango, V. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711000691 · Cited by 100 · see citing works
Xing, G.-Q., Russell, S., Webster, M. J., & Post, R. M. (2004) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145703004000 · Cited by 91 · see citing works
The neuroanatomy of schizophrenia: circuitry and neurotransmitter systems
Fallon, J. H., Opole, I. O., & Potkin, S. G. (2003) · Clinical Neuroscience Research · doi:10.1016/s1566-2772(03)00022-7 · Cited by 53 · see citing works
Higher and deeper: Bringing layer fMRI to association cortex
Finn, E. S., Huber, L., & Bandettini, P. A. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101930 · Cited by 47 · see citing works
Poland, R. E., Cloak, C., Lutchmansingh, P. J., McCracken, J. T., Chang, L., & Ernst, T. (1999) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(98)00043-0 · Cited by 37 · see citing works
Williams, M. R., Chaudhry, R., Perera, S., Pearce, R. K. B., Hirsch, S. R., Ansorge, O., Thom, M., & Maier, M. (2013) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-012-0325-8 · Cited by 31 · see citing works
Kim, E., Camacho, J., Combs, Z., Ariza, J., Lechpammer, M., Noctor, S. C., & Martínez-Cerdeño, V. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.01.021 · Cited by 17 · see citing works
- Authors
- Rajkowska, G., Selemon, L. D., & Goldman-Rakic, P. S.
- ORCID
- Selemon, Lynn D.
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 1998-03-01
- Volume
- 55
- Issue
- 3
- Pages
- 215
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2121999864
- Cited by
- 537
- References
- 1
- Citations by year
- 2026: 13 · 2025: 8 · 2024: 12 · 2023: 8 · 2022: 17 · 2021: 14 · 2020: 14 · 2019: 9 · 2018: 12 · 2017: 18 · 2016: 18 · 2015: 22 · 2014: 20 · 2013: 16 · 2012: 20
- FWCI
- 21.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (44866)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- schizophrenia, Huntington's disease, prefrontal cortex, cortical layers, neuronal density, cortical architecture, postmortem brain
- MeSH terms
- Adult, Aged, Cell Count, Female, Humans, Huntington Disease, Male, Middle Aged, Neuroglia, Neurons, Occipital Lobe, Schizophrenia, Prefrontal Cortex, Cell Size
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
