Reduced Dendritic Spine Density in Auditory Cortex of Subjects with Schizophrenia
Open accessAbstract
We have previously identified reductions in mean pyramidal cell somal volume in deep layer 3 of BA 41 and 42 and reduced axon terminal density in deep layer 3 of BA 41. In other brain regions demonstrating similar deficits, reduced dendritic spine density has also been identified, leading us to hypothesize that dendritic spine density would also be reduced in BA 41 and 42. Because dendritic spines and their excitatory inputs are regulated in tandem, we further hypothesized that spine density would be correlated with axon terminal density. We used stereologic methods to quantify a marker of dendritic spines, spinophilin-immunoreactive (SP-IR) puncta, in deep layer 3 of BA 41 and 42 of 15 subjects with schizophrenia, each matched to a normal comparison subject. The effect of long-term haloperidol exposure on SP-IR puncta density was evaluated in nonhuman primates. SP-IR puncta density was significantly lower by 27.2% in deep layer 3 of BA 41 in the schizophrenia subjects, and by 22.2% in deep layer 3 of BA 42. In both BA 41 and 42, SP-IR puncta density was correlated with a marker of axon terminal density, but not with pyramidal cell somal volume. SP-IR puncta density did not differ between haloperidol-exposed and control monkeys. Lower SP-IR puncta density in deep layer 3 of BA 41 and 42 of subjects with schizophrenia may reflect concurrent reductions in excitatory afferent input. This may contribute to impairments in auditory sensory processing that are present in subjects with schizophrenia.
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Individuals with schizophrenia show a profound reduction in spine density on pyramidal neurons in the superior temporal gyrus, particularly in the primary auditory cortex.
“At the cellular level, individuals with schizophrenia show a profound reduction in spine density on pyramidal neurons in the superior temporal gyrus, particularly in the primary auditory cortex15.”
From Dendritic spine pathology in neuropsychiatric disorders (2011) · cites this paper as [15]
Layer 3 pyramidal cells in schizophrenia show reduced spine numbers.
“This is an interesting observation in light of the finding of reduction in spine number on layer 3 pyramidal cells in schizophrenia (Glantz and Lewis, 2000; Sweet et al., 2009).”
From Perineuronal nets and schizophrenia: The importance of neuronal coatings (2014) · cites this paper as Sweet et al., 2009
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Formation of dendritic spines in cultured striatal neurons depends on excitatory afferent activity
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Endoplasmic Reticulum Export Site Formation and Function in Dendrites
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Reduced Superior Temporal Gyrus Volume in Young Offspring of Patients With Schizophrenia
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Anatomical Evidence of Impaired Feedforward Auditory Processing in Schizophrenia
Sweet, R. A., Bergen, S. E., Sun, Z., Marcsisin, M. J., Sampson, A. R., & Lewis, D. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.07.033 · Cited by 81 · see citing works
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Rho Family GTPases and Dendrite Plasticity
Negishi, M., & Katoh, H. (2005) · The Neuroscientist · doi:10.1177/1073858404268768 · Cited by 80 · see citing works
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Patterns of regional cortical dysmorphology distinguishing schizophrenia and chronic alcoholism
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Excitatory and inhibitory connections show selectivity in the neocortex
Watts, J., & Thomson, A. M. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.076984 · Cited by 62 · see citing works
Examining neocortical circuits: Some background and facts
Peters, A. (2002) · Journal of Neurocytology · doi:10.1023/a:1024157522651 · Cited by 57 · see citing works
Dopamine receptor signaling molecules are altered in elderly schizophrenic cortex
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Phalloidin-Eosin Followed by Photo-oxidation
Capani, F., Deerinck, T. J., Ellisman, M. H., Bushong, E. A., Bobik, M., & Martone, M. E. (2001) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540104901103 · Cited by 52 · see citing works
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Mathalon, D. H., Sullivan, E. V., Lim, K. O., & Pfefferbaum, A. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.2.148
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Dendritic spine pathology in neuropsychiatric disorders
Penzes, P., Cahill, M. E., Jones, K. A., VanLeeuwen, J.-E., & Woolfrey, K. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2741 · Cited by 1,523 · see citing works
Social cognition in schizophrenia
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The Neurodevelopmental Hypothesis of Schizophrenia, Revisited
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Dendritic spine pathology in schizophrenia
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Self-citationGao, R., & Penzes, P. (2015) · Current Molecular Medicine · doi:10.2174/1566524015666150303003028 · Cited by 516 · see citing works
“Moreover, there is also a profound reduction in spine density on pyramidal neurons in the primary auditory cortex, which could explain why schizophrenics suffer from auditory hallucinations [55].”
BackgroundThe 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
Self-citationCurley, A. A., Arion, D., Volk, D. W., Asafu-Adjei, J. K., Sampson, A. R., Fish, K. N., & Lewis, D. A. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.11010052 · Cited by 283 · see citing works
Self-citationPrenatal interaction of mutant DISC1 and immune activation produces adult psychopathology
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Social Cognition in Schizophrenia
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Extracellular matrix abnormalities in schizophrenia
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Glutamatergic Synaptic Dysregulation in Schizophrenia: Therapeutic Implications
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Translating Glutamate: From Pathophysiology to Treatment
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Chung, D. W., Fish, K. N., & Lewis, D. A. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2016.16010025 · Cited by 148 · see citing works
“25 μm z-step) in layer 2 or 4 from each section were selected using a previously published method for systematic random sampling(24).”
MethodSelf-citationAyhan, Y., Abazyan, B., Nomura, J., Kim, R., Ladenheim, B., Krasnova, I. N., Sawa, A., Margolis, R. L., Cadet, J. L., Mori, S., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2009.144 · Cited by 148 · see citing works
Developmental vulnerability of synapses and circuits associated with neuropsychiatric disorders
Penzes, P., Buonanno, A., Passafaro, M., Sala, C., & Sweet, R. A. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12261 · Cited by 125 · see citing works
Self-citationSynaptic Actin Dysregulation, a Convergent Mechanism of Mental Disorders?
Yan, Z., Kim, E., Datta, D., Lewis, D. A., & Soderling, S. H. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2360-16.2016 · Cited by 120 · see citing works
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Perineuronal nets and schizophrenia: The importance of neuronal coatings
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The role of the primary auditory cortex in the neural mechanism of auditory verbal hallucinations
Kompus, K., Falkenberg, L. E., Bless, J. J., Johnsen, E., Kroken, R. A., Kråkvik, B., Larøi, F., Løberg, E.-M., Vedul-Kjelsås, E., Westerhausen, R., et al. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00144 · Cited by 91 · see citing works
Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia
Pietersen, C. Y., Mauney, S. A., Kim, S. S., Lim, M. P., Rooney, R. J., Goldstein, J. M., Petryshen, T. L., Seidman, L. J., Shenton, M. E., McCarley, R. W., et al. (2014) · Journal of Neurogenetics · doi:10.3109/01677063.2014.882918 · Cited by 87 · see citing works
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Electrophysiological assessment of auditory stimulus-specific plasticity in schizophrenia
Mears, R. P., & Spencer, K. M. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.12.016 · Cited by 64 · see citing works
Khanal, P., & Hotulainen, P. (2021) · Cells · doi:10.3390/cells10092392 · Cited by 60 · see citing works
Kalirin loss results in cortical morphological alterations
Xie, Z., Cahill, M. E., & Penzes, P. (2010) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2009.09.006 · Cited by 56 · see citing works
- Authors
- Sweet, R. A., Henteleff, R. A., Zhang, W., Sampson, A. R., & Lewis, D. A.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Sweet, Robert A
- Venue
- Neuropsychopharmacology
- Published
- 2008-05-07
- Volume
- 34
- Issue
- 2
- Pages
- 374-389
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC2775717
- OpenAlex
- W1989278867
- Cited by
- 290
- References
- 119
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 9 · 2023: 16 · 2022: 14 · 2021: 20 · 2020: 12 · 2019: 23 · 2018: 17 · 2017: 16 · 2016: 21 · 2015: 24 · 2014: 13 · 2013: 15 · 2012: 17
- FWCI
- 14.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- University of Pittsburgh
- National Institutes of Health (071533)
- U.S. Public Health Service
- VISN 4 Mental Illness Research, Education, and Clinical Center
- VA Pittsburgh Healthcare System
- National Institute of Mental Health (MH071533, 071533, MH-045156, R01MH071533, P50MH045156)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- dendritic spine density, schizophrenia, auditory cortex, spinophilin, haloperidol, auditory sensory processing, stereology
- MeSH terms
- Neurabins, Adult, Animals, Auditory Cortex, Female, Haloperidol, Humans, Macaca fascicularis, Male, Microfilament Proteins, Middle Aged, Nerve Tissue Proteins, Photomicrography, Psychotic Disorders, Schizophrenia, Antipsychotic Agents, Multivariate Analysis, Presynaptic Terminals, Pyramidal Cells, Microscopy, Confocal, Dendritic Spines
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.
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