MicroRNA Expression Is Down-Regulated and Reorganized in Prefrontal Cortex of Depressed Suicide Subjects
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BACKGROUND: Recent studies suggest that alterations in expression of genes, including those which regulate neural and structural plasticity, may be crucial in the pathogenesis of depression. MicroRNAs (miRNAs) are newly discovered regulators of gene expression that have recently been implicated in a variety of human diseases, including neuropsychiatric diseases. METHODOLOGY/PRINCIPAL FINDINGS: The present study was undertaken to examine whether the miRNA network is altered in the brain of depressed suicide subjects. Expression of miRNAs was measured in prefrontal cortex (Brodmann Area 9) of antidepressant-free depressed suicide (n = 18) and well-matched non-psychiatric control subjects (n = 17) using multiplex RT-PCR plates. We found that overall miRNA expression was significantly and globally down-regulated in prefrontal cortex of depressed suicide subjects. Using individual tests of statistical significance, 21 miRNAs were significantly decreased at p = 0.05 or better. Many of the down-regulated miRNAs were encoded at nearby chromosomal loci, shared motifs within the 5'-seeds, and shared putative mRNA targets, several of which have been implicated in depression. In addition, a set of 29 miRNAs, whose expression was not pairwise correlated in the normal controls, showed a high degree of co-regulation across individuals in the depressed suicide group. CONCLUSIONS/SIGNIFICANCE: The findings show widespread changes in miRNA expression that are likely to participate in pathogenesis of major depression and/or suicide. Further studies are needed to identify whether the miRNA changes lead to altered expression of prefrontal cortex mRNAs, either directly (by acting as miRNA targets) or indirectly (e.g., by affecting transcription factors).
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In the prefrontal cortex BA9 of MDD patients, 21 miRNAs including miR-142-5p, miR-101, miR-137, and miR-301a were downregulated.
“In the prefrontal cortex (BA9) of MDD patients, other 21 miRNAs, including miR-142-5p, miR-101, miR-137, and miR-301a, was downregulated.244”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [244]
The Abstract (Methodology/Principal Findings) identifies the sample as antidepressant-free depressed suicide subjects, not MDD patients generally, and reports 21 significantly decreased miRNAs in BA9. Table 2 lists all four named miRNAs among those decreased. The claim omits the suicide and antidepressant-free qualifiers and thus extends the finding to a broader population. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMiRNA expression levels were also found to be altered in BA10, BA44, anterior cingulate cortex, and other brain regions in MDD.
“MiRNA expression levels were also found to be altered in BA10,244 BA44,245 anterior cingulate cortex (ACC),246 and other brain regions in MDD.247”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [244]
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- Authors
- Smalheiser, N. R., Lugli, G., Rizavi, H. S., Torvik, V. I., Turecki, G., & Dwivedi, Y.
- Affiliations
- University of Illinois Chicago (US)
- University of Illinois Urbana-Champaign (US)
- McGill University (CA)
- Corresponding author
- Dwivedi, Yogesh
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-03-09
- Volume
- 7
- Issue
- 3
- Pages
- e33201
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3302855
- OpenAlex
- W2050613411
- Cited by
- 324
- References
- 58
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 18 · 2023: 19 · 2022: 22 · 2021: 35 · 2020: 24 · 2019: 22 · 2018: 26 · 2017: 30 · 2016: 35 · 2015: 26 · 2014: 20 · 2013: 16 · 2012: 9
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- American Foundation for Suicide Prevention (R21MH081099, MH082802)
- Stanley Medical Research Institute
- Canadian Institutes of Health Research (171859_1, 190734_1)
- National Institute of Mental Health (R21MH081099, R01MH68777, R01MH068777, R01MH082802, MH082802, R21MH091509)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- microRNA expression, depression, suicide, prefrontal cortex, microRNA downregulation, miRNA target genes, chromosomal loci, gene expression regulation
- MeSH terms
- Adult, Depression, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Proteins, Quebec, Suicide, Blotting, Western, Case-Control Studies, RNA-Binding Proteins, Prefrontal Cortex, DNA Primers, Statistics, Nonparametric, Reverse Transcriptase Polymerase Chain Reaction, MicroRNAs, Ribonuclease III, DEAD-box RNA Helicases, Multiplex Polymerase Chain Reaction
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