Cited by 882Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

Molecular Characterization of Schizophrenia Viewed by Microarray Analysis of Gene Expression in Prefrontal Cortex

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Mirnics, Károly, Middleton, Frank A., Marquez, Adriana, Lewis, David A., Levitt, Pat·2000·Neuron

Abstract

Microarray expression profiling of prefrontal cortex from matched pairs of schizophrenic and control subjects and hierarchical data analysis revealed that transcripts encoding proteins involved in the regulation of presynaptic function (PSYN) were decreased in all subjects with schizophrenia. Genes of the PSYN group showed a different combination of decreased expression across subjects. Over 250 other gene groups did not show altered expression. Selected PSYN microarray observations were verified by in situ hybridization. Two of the most consistently changed transcripts in the PSYN functional gene group, N-ethylmaleimide sensitive factor and synapsin II, were decreased in ten of ten and nine of ten subjects with schizophrenia, respectively. The combined data suggest that subjects with schizophrenia share a common abnormality in presynaptic function. We set forth a predictive, testable model.

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Crossref · 10.1016/s0896-6273(00)00085-4

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  • The degree of correlation between pathways across disorders is higher than expected by chance, indicating that polygenic overlap is nonrandom at a molecular or pathway level.

    “Our observation that the degree of correlation between pathways across disorders is higher than expected by chance builds on the observation of shared genetics between these disorders4 and, importantly, indicates that polygenic overlap is nonrandom at a molecular or pathway level.”

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Authors
Mirnics, K., Middleton, F. A., Marquez, A., Lewis, D. A., & Levitt, P.
Affiliations
University of Pittsburgh (US)
Corresponding author
Mirnics, Károly
Venue
Neuron
Publisher
Elsevier BV
Published
2000-10
Volume
28
Issue
1
Pages
53-67
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2032208151
Cited by
882
References
105
Citations by year
2026: 5 · 2025: 1 · 2024: 3 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 10 · 2019: 13 · 2018: 16 · 2017: 14 · 2016: 19 · 2015: 32 · 2014: 19 · 2013: 29 · 2012: 37
FWCI
48.20
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (T32 MH18273, MH 45156, T32MH018273, P50MH045156)
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, prefrontal cortex, gene expression profiling, presynaptic function, N-ethylmaleimide-sensitive factor, synapsin II, transcriptome
MeSH terms
Animals, Carrier Proteins, Female, Humans, Macaca fascicularis, Male, Middle Aged, Synaptic Transmission, RNA, Messenger, Schizophrenia, Synapses, Antipsychotic Agents, Genetic Variation, Gene Expression, Confounding Factors, Epidemiologic, Synapsins, Prefrontal Cortex, In Situ Hybridization, Presynaptic Terminals, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Vesicular Transport Proteins, N-Ethylmaleimide-Sensitive Proteins

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