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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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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