Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia
Abstract
Upregulation of the immune response may be involved in the pathogenesis of schizophrenia with changes occurring in both peripheral blood and brain tissue. To date, microarray technology has provided a limited view of specific inflammatory transcripts in brain perhaps due to sensitivity issues. Here we used SOLiD Next Generation Sequencing to quantify neuroimmune mRNA expression levels in the dorsolateral prefrontal cortex of 20 individuals with schizophrenia and their matched controls. We detected 798 differentially regulated transcripts present in people with schizophrenia compared with controls. Ingenuity pathway analysis identified the inflammatory response as a key change. Using quantitative real-time PCR we confirmed the changes in candidate cytokines and immune modulators, including interleukin (IL)-6, IL-8, IL-1β and SERPINA3. The density of major histocompatibility complex-II-positive cells morphologically resembling microglia was significantly increased in schizophrenia and correlated with IL-1β expression. A group of individuals, most of whom had schizophrenia, were found to have increased inflammatory mRNA expression. In summary, we have demonstrated changes in an inflammatory response pathway that are present in ∼40% of people diagnosed with schizophrenia. This suggests that therapies aimed at immune system attenuation in schizophrenia may be of direct benefit in the brain.
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Prior work has identified differential activation of glial and neural-immune processes in brains of patients with psychiatric disorders.
“Previous work has identified differential activation of glial and neural-immune processes in brain from patients with psychiatric disorders (16, 52, 57, 66–69)”
From Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018) · cites this paper as [67]
The group of schizophrenic patients with high levels of neuroinflammation had lower expression of BDNF.
“The group of patients with high levels of neuroinflammation had lower expression of BDNF [120].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [120]
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- Authors
- Fillman, S. G., Cloonan, N., Catts, V. S., Miller, L. C., Wong, J., McCrossin, T., Cairns, M., & Weickert, C. S.
- Affiliations
- Schizophrenia Research Institute (AU)
- The University of Queensland (AU)
- UNSW Sydney (AU)
- Children's Medical Research Institute (AU)
- University of Wollongong (AU)
- The University of Sydney (AU)
- Corresponding author
- Weickert, C S
- Venue
- Molecular Psychiatry
- Published
- 2012-08-07
- Volume
- 18
- Issue
- 2
- Pages
- 206-214
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2045761141
- Cited by
- 609
- References
- 79
- Citations by year
- 2026: 23 · 2025: 29 · 2024: 53 · 2023: 43 · 2022: 48 · 2021: 54 · 2020: 65 · 2019: 37 · 2018: 47 · 2017: 49 · 2016: 53 · 2015: 29 · 2014: 41 · 2013: 31 · 2012: 6
- FWCI
- 10.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Online (University of Wollongong) (submittedVersion)
- Figshare (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R24AA012725)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- schizophrenia, neuroinflammation, dorsolateral prefrontal cortex, inflammatory gene expression, cytokines, interleukin-6, interleukin-8, IL-1β, alpha-1-antichymotrypsin, microglia, MHC class II, immune response, transcriptome
- MeSH terms
- Adolescent, Adult, Aged, Histocompatibility Antigens Class II, Chromosome Mapping, Female, Gene Expression Regulation, HLA-DP Antigens, Humans, Male, Middle Aged, RNA, Messenger, Schizophrenia, Serpins, Chi-Square Distribution, Case-Control Studies, Cytokines, Prefrontal Cortex, Microglia, Young Adult
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