Cited by 513Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

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Emerging principles of altered neural circuitry in schizophrenia

Benes, F·2000·Brain Research Reviews

DOI 10.1016/s0165-0173(99)00041-7

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Abstract

This paper presents an overview of recent microscopic studies that have sought to define how limbic circuitry may be altered in postmortem schizophrenic brain. The discussion is organized around several basic questions regarding the manner in which interconnections within and between the anterior cingulate cortex and hippocampal formation and involving the glutamate, GABA and dopamine systems may contribute to the pathophysiology of this disorder. The answers to these questions are used to derive several conclusions regarding circuitry changes in schizophrenia: 1) Schizophrenia is not a 'typical' degenerative disorder, but rather it is one in which excitotoxicity may contribute to neuronal pathology, whether or not cell death occurs; 2) Three or more neurotransmitter systems may be simultaneously altered within a single microcircuit; 3) Each transmitter system may show circuitry changes in more than one region, but such changes may vary on a region-by-region basis; 4) The pathophysiology of schizophrenia may involve 'mis-wirings' in intrinsic circuits (microcircuitry) within a given region, but significant changes are probably also present at the level of interconnections between two or more regions within a network (macrocircuitry); 5) While some microscopic findings appear to be selectively present in schizophrenia and be related to a susceptibility gene for this disorder, others may also be present in patients with bipolar disorder; 6) Although some of the circuitry changes seen in schizophrenia and bipolar disorder seem to be associated with neuroleptic exposure, most are not and may reflect the influence of non-specific environmental factors such as pre- and/or postnatal stress; 7) Normal postnatal changes at the level of both macro- and microcircuitry within the limbic system may serve as 'triggers' for the onset of schizophrenia during adolescence. Taken together, these emerging principles can provide a framework for future postmortem studies of schizophrenic brain.

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Chapter 26. The Limbic Thalamus
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Part 4. Treatment
(2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg33
Chapter 19. Binswanger’s Disease: An Ongoing Controversy
Hurley, R. A., Tomimoto, H., Akiguchi, I., Fisher, R. E., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg21
Chapter 21. Neuropsychiatric Presentation of Multiple Sclerosis
Hurley, R. A., Taber, K. H., Zhang, J., & Hayman, L. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg23
Chapter 3. Ecstasy in the Brain: A Model for Neuroimaging
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Chapter 7. Applications of Xenon Computed Tomography in Clinical Practice: Detection of Hidden Lesions
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Chapter 22. Functional Neuroanatomy of Sleep and Sleep Deprivation
Taber, K. H., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg25
Chapter 11. Blast-Related Traumatic Brain Injury: What Is Known?
Taber, K. H., Warden, D. L., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg13
Chapter 29. An Update on Estrogen: Higher Cognitive Function, Receptor Mapping, Neurotrophic Effects
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Chapter 4. The Future for Diffusion Tensor Imaging in Neuropsychiatry
Taber, K. H., Pierpaoli, C. M., Rose, S., Rugg‐Gunn, F. J., Chalk, J. B., Jones, D. K., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg05
Chapter 20. Normal Pressure Hydrocephalus: Significance of Magnetic Resonance Imaging in a Potentially Treatable Dementia
Hurley, R. A., Bradley, W. G., Latifi, H. T., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg22
Chapter 5. Cortical Inhibition in Alcohol Dependence
Taber, K. H., Hurley, R. A., Abi‐Dargham, A., & Bernice Porjesz, A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg06
Index
(2008) · doi:10.1176/appi.books.9781615377886.index
Part 3. Anatomy and Circuitry
(2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg24
Chapter 2. Functional Magnetic Resonance Imaging: Application to Post-Traumatic Stress Disorder
Taber, K. H., Rauch, S. L., Lanius, R. A., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg03
Chapter 10. Bipolar Disorder: Imaging State Versus Trait
Friedman, J. N. W., Hurley, R. A., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg12
Chapter 13. Traumatic Axonal Injury: Novel Insights Into Evolution and Identification
Hurley, R. A., McGowan, J. C., Arfanakis, K., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg15
Chapter 23. Neural Underpinnings of Fear and Its Modulation: Implications for Anxiety Disorders
Miller, L. A., Taber, K. H., Gabbard, G. O., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg26
Front Matter
(2008) · doi:10.1176/appi.books.9781615377886.fm01
Chapter 24. Rabies and the Cerebellum: New Methods for Tracing Circuits in the Brain
Taber, K. H., Strick, P. L., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg27
Chapter 14. Functional Imaging as a Window to Dementia: Corticobasal Degeneration
Seritan, A. L., Mendez, M. F., Silverman, D. H. S., Hurley, R. A., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg16
Chapter 31. Schizophrenia: What’s Under the Microscope?
Taber, K. H., Lewis, D. A., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg35
Chapter 12. Mild Traumatic Brain Injury: Neuroimaging of Sports-Related Concussion
Mendez, C. V., Hurley, R. A., Lassonde, M. C., Zhang, L., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg14
Chapter 9. Sudden Onset Panic: Epileptic Aura or Panic Disorder?
Hurley, R. A., Fisher, R. E., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg11
Chapter 16. Identification of HIV-Associated Progressive Multifocal Leukoencephalopathy: Magnetic Resonance Imaging and Spectroscopy
Hurley, R. A., Ernst, T., Khalili, K., Valle, L. D., Simone, I. L., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg18
Chapter 28. Functional Anatomy of Central Pain
Taber, K. H., Rashid, A., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg31
Chapter 1. Blood Flow Imaging of the Brain: 50 Years’ Experience
Taber, K. H., BLACK, K. J., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg02
Chapter 25. Conversion Hysteria: Lessons From Functional Imaging
Black, D. N., Seritan, A. L., Taber, K. H., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg28
Chapter 6. Application of Magnetoencephalography to the Study of Autism
Hurley, R. A., Lewine, J. D., Jones, G. M., Orrison, W. W., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg07
Part 1. Imaging Techniques
(2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg01
Chapter 27. Understanding Emotion Regulation in Borderline Personality Disorder: Contributions of Neuroimaging
Johnson, P. A., Hurley, R. A., Benkelfat, C., Herpertz, S. C., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg30
Chapter 30. Predicting Treatment Response in Obsessive-Compulsive Disorder
Hurley, R. A., Saxena, S., Rauch, S. L., Hoehn‐Saric, R., & Taber, K. H. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg34
Chapter 15. Metachromatic Leukodystrophy: A Model for the Study of Psychosis
Black, D. N., Taber, K. H., & Hurley, R. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615377886.lg17

Authors: Benes, F.
Affiliations: Harvard University (US)
Corresponding author: Benes, F
ORCID: Benes, F
Venue: Brain Research Reviews
Publisher: Elsevier BV
Published: 2000-03
Volume: 31
Issue: 2-3
Pages: 251-269
ISSN: 0165-0173 (ISSN-L)
DOI: 10.1016/s0165-0173(99)00041-7
OpenAlex: W2066213630
Cited by: 513
References: 161
Citations by year: 2026: 1 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 7 · 2017: 7 · 2016: 10 · 2015: 20 · 2014: 8 · 2013: 14 · 2012: 15
FWCI: 28.14
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Brain Research Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Mental Health (MH-42261, MH00423, MH31152)
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, limbic system, neural circuits, anterior cingulate cortex, hippocampal formation, glutamatergic system, GABA system, dopaminergic system, excitotoxicity, microcircuitry, bipolar disorder, prenatal stress, postnatal development, schizophrenia pathophysiology, postmortem brain
MeSH terms: Animals, Humans, Limbic System, Neural Pathways, Schizophrenia

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Emerging principles of altered neural circuitry in schizophrenia

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