GABAergic mechanisms of hippocampal hyperactivity in schizophrenia
Open accessAbstract
Schizophrenia is associated with abnormalities of hippocampal structure and function. Neuroimaging studies have shown that the hippocampus is hyperactive in schizophrenia. Here we explore GABAergic mechanisms of this hippocampal hyperactivity. The initial evidence for GABAergic abnormalities of the hippocampus in schizophrenia came from post-mortem studies of interneuron number, protein expression, and gene expression. These studies revealed marked decreases in gene and protein expression of somatostatin-positive and parvalbumin-positive interneurons, and indicated reduced interneuron numbers. Animal studies of decreased parvalbumin and NMDA-receptor function have shown that selective abnormalities of hippocampal interneurons mimic some of the cognitive deficits and clinical features of schizophrenia. The post-mortem and animal studies are consistent with the neuroimaging finding of increased hippocampal activity in schizophrenia, which can explain some of the psychotic symptoms and cognitive deficits. Taken together, these findings may guide the development of biomarkers and the development of new treatments for psychosis.
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The high frequency of interneuron pathologies in the hippocampus and adjacent cortical areas, such as in schizophrenia and bipolar disorder, may partly reflect extended developmental vulnerability.
“The preponderance of interneuron pathologies in the hippocampus and adjacent cortical areas, such as the interneuron pathologies observed in schizophrenia and BPD, might be, at least in part, a reflection of this extended developmental vulnerability [1, 9, 122, 140-142].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [140]
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Venables, P. H. (1992) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1992.tb22841.x · Cited by 57 · see citing works
NORDAHL, T. E. (1996) · Neuropsychopharmacology · doi:10.1016/s0893-133x(96)00098-x · Cited by 53 · see citing works
Neuroimaging Biomarkers for Early Drug Development in Schizophrenia
Tregellas, J. R. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.08.025 · Cited by 51 · see citing works
Regional cerenral blood flow in patients with schizophrenia: relevance to symptom structures
Kawasaki, Y., Maeda, Y., Sakai, N., Higashima, M., Yamaguchi, N., Koshino, Y., Hisada, K., Suzuki, M., & Matsuda, H. (1996) · Psychiatry Research Neuroimaging · doi:10.1016/0925-4927(96)02685-6 · Cited by 46 · see citing works
Epilepsy, psychosis and schizophrenia
Stevens, J. R. (1988) · Schizophrenia Research · doi:10.1016/0920-9964(88)90044-8 · Cited by 45 · see citing works
Neurostereology: Unbiased Stereology Of Neural Systems
Mouton, P. R. (2014) · Cited by 22 · see citing works
Neuroimaging of Psychotic Disorders
Heckers, S., Woodward, N. D., & Öngür, D. (2013) · Oxford University Press eBooks · doi:10.1093/med/9780199934959.003.0020 · Cited by 2 · see citing works
Self-citation
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Parvalbumin interneuron vulnerability and brain disorders
Ruden, J. B., Dugan, L. L., & Konradi, C. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-020-0778-9 · Cited by 194 · see citing works
Self-citationLong-Lasting Rescue of Network and Cognitive Dysfunction in a Genetic Schizophrenia Model
Mukherjee, A., Carvalho, F., Eliez, S., & Caroni, P. (2019) · Cell · doi:10.1016/j.cell.2019.07.023 · Cited by 169 · see citing works
Structural Brain Abnormalities in Youth With Psychosis Spectrum Symptoms
Satterthwaite, T. D., Wolf, D. H., Calkins, M. E., Vandekar, S. N., Erus, G., Ruparel, K., Roalf, D. R., Linn, K. A., Elliott, M. A., Moore, T. M., et al. (2016) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2015.3463 · Cited by 132 · see citing works
Neural and neuronal discoordination in schizophrenia: from ensembles through networks to symptoms
Krajcovic, B., Fajnerova, I., Horacek, J., Kelemen, E., Kubik, S., Svoboda, J., & Stuchlik, A. (2019) · Acta Physiologica · doi:10.1111/apha.13282 · Cited by 29 · see citing works
Schwarz, K., Moessnang, C., Schweiger, J. I., Harneit, A., Schneider, M., Chen, J., Cao, H., Schwarz, E., Witt, S. H., Rietschel, M., et al. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.07.016 · Cited by 18 · see citing works
- Authors
- Heckers, S., & Konradi, C.
- Affiliations
- Vanderbilt University (US)
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 167
- Issue
- 1-3
- Pages
- 4-11
- ISSN
- 0920-9964 (ISSN-L)
- PMC
- PMC4402105
- OpenAlex
- W2045716255
- Cited by
- 277
- References
- 100
- Citations by year
- 2026: 20 · 2025: 19 · 2024: 28 · 2023: 25 · 2022: 19 · 2021: 30 · 2020: 30 · 2019: 25 · 2018: 26 · 2017: 17 · 2016: 27 · 2015: 11
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Schizophrenia Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01mh070560-16)
- National Institute of Mental Health (R01-MH070560)
- 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
- schizophrenia, hippocampal hyperactivity
- MeSH terms
- Animals, gamma-Aminobutyric Acid, Hippocampus, Humans, Neurons, Schizophrenia
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 ›
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