MicroRNA Expression in the Prefrontal Cortex of Individuals with Schizophrenia and Schizoaffective Disorder

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2007 Mar 1

PMID 17326821

Citations 259

Authors

Diana O Perkins

Clark D Jeffries

L Fredrik Jarskog

J Michael Thomson

Keith Woods

Martin A Newman

Joel S Parker

Jianping Jin

Scott M Hammond

Affiliations

Soon will be listed here.

Abstract

Background: microRNAs (miRNAs) are small, noncoding RNA molecules that are now thought to regulate the expression of many mRNAs. They have been implicated in the etiology of a variety of complex diseases, including Tourette's syndrome, Fragile x syndrome, and several types of cancer.

Results: We hypothesized that schizophrenia might be associated with altered miRNA profiles. To investigate this possibility we compared the expression of 264 human miRNAs from postmortem prefrontal cortex tissue of individuals with schizophrenia (n = 13) or schizoaffective disorder (n = 2) to tissue of 21 psychiatrically unaffected individuals using a custom miRNA microarray. Allowing a 5% false discovery rate, we found that 16 miRNAs were differentially expressed in prefrontal cortex of patient subjects, with 15 expressed at lower levels (fold change 0.63 to 0.89) and 1 at a higher level (fold change 1.77) than in the psychiatrically unaffected comparison subjects. The expression levels of 12 selected miRNAs were also determined by quantitative RT-PCR in our lab. For the eight miRNAs distinguished by being expressed at lower microarray levels in schizophrenia samples versus comparison samples, seven were also expressed at lower levels with quantitative RT-PCR.

Conclusion: This study is the first to find altered miRNA profiles in postmortem prefrontal cortex from schizophrenia patients.

Citing Articles

miRNA-Based Diagnosis of Schizophrenia Using Machine Learning.

Heda V, Dogra S, Kouznetsova V, Kumar A, Kesari S, Tsigelny I Int J Mol Sci. 2025; 26(5).

PMID: 40076899 PMC: 11900116. DOI: 10.3390/ijms26052280.

MicroRNA Expression Profile in Acute Ischemic Stroke.

Mainali S, Nepal G, Shumilov K, Webb A, Fadda P, Mirebrahimi D Int J Mol Sci. 2025; 26(2).

PMID: 39859461 PMC: 11765720. DOI: 10.3390/ijms26020747.

Epigenetic Control in Schizophrenia.

DAddario C, Di Bartolomeo M Subcell Biochem. 2025; 108():191-215.

PMID: 39820863 DOI: 10.1007/978-3-031-75980-2_5.

Comprehensive profiling of small RNAs and their changes and linkages to mRNAs in schizophrenia and bipolar disorder.

Nersisyan S, Loher P, Nazeraj I, Shao Z, Fullard J, Voloudakis G bioRxiv. 2025; .

PMID: 39763727 PMC: 11703252. DOI: 10.1101/2024.12.24.630254.

Role of miRNA Gene Variants (miR-22 and miR-155) as the Factors Affecting Susceptibility to Panic Disorder.

Yegin Z, Sarisoy G, Uzun A, Koc H Clin Psychopharmacol Neurosci. 2024; 22(4):655-661.

PMID: 39420612 PMC: 11494425. DOI: 10.9758/cpn.24.1201.

References

Abelson J, Kwan K, ORoak B, Baek D, Stillman A, Morgan T . Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science. 2005; 310(5746):317-20. DOI: 10.1126/science.1116502. View

Sullivan P . The genetics of schizophrenia. PLoS Med. 2005; 2(7):e212. PMC: 1181880. DOI: 10.1371/journal.pmed.0020212. View

Bentwich I . Prediction and validation of microRNAs and their targets. FEBS Lett. 2005; 579(26):5904-10. DOI: 10.1016/j.febslet.2005.09.040. View

Vo N, Klein M, Varlamova O, Keller D, Yamamoto T, Goodman R . A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proc Natl Acad Sci U S A. 2005; 102(45):16426-31. PMC: 1283476. DOI: 10.1073/pnas.0508448102. View

Shcherbata H, Hatfield S, Ward E, Reynolds S, Fischer K, Ruohola-Baker H . The MicroRNA pathway plays a regulatory role in stem cell division. Cell Cycle. 2005; 5(2):172-5. DOI: 10.4161/cc.5.2.2343. View

Schratt G, Tuebing F, Nigh E, Kane C, Sabatini M, Kiebler M . A brain-specific microRNA regulates dendritic spine development. Nature. 2006; 439(7074):283-9. DOI: 10.1038/nature04367. View

Sethupathy P, Corda B, Hatzigeorgiou A . TarBase: A comprehensive database of experimentally supported animal microRNA targets. RNA. 2005; 12(2):192-7. PMC: 1370898. DOI: 10.1261/rna.2239606. View

Nelson P, Baldwin D, Kloosterman W, Kauppinen S, Plasterk R, Mourelatos Z . RAKE and LNA-ISH reveal microRNA expression and localization in archival human brain. RNA. 2005; 12(2):187-91. PMC: 1370897. DOI: 10.1261/rna.2258506. View

Chen J, Mandel E, Thomson J, Wu Q, Callis T, Hammond S . The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet. 2005; 38(2):228-33. PMC: 2538576. DOI: 10.1038/ng1725. View

10.

Shi Y, Ethell I . Integrins control dendritic spine plasticity in hippocampal neurons through NMDA receptor and Ca2+/calmodulin-dependent protein kinase II-mediated actin reorganization. J Neurosci. 2006; 26(6):1813-22. PMC: 6793632. DOI: 10.1523/JNEUROSCI.4091-05.2006. View

11.

Tada T, Sheng M . Molecular mechanisms of dendritic spine morphogenesis. Curr Opin Neurobiol. 2005; 16(1):95-101. DOI: 10.1016/j.conb.2005.12.001. View

12.

Hammond S . MicroRNA therapeutics: a new niche for antisense nucleic acids. Trends Mol Med. 2006; 12(3):99-101. DOI: 10.1016/j.molmed.2006.01.004. View

13.

Debbane M, Glaser B, David M, Feinstein C, Eliez S . Psychotic symptoms in children and adolescents with 22q11.2 deletion syndrome: Neuropsychological and behavioral implications. Schizophr Res. 2006; 84(2-3):187-93. DOI: 10.1016/j.schres.2006.01.019. View

14.

Thomson J, Newman M, Parker J, Morin-Kensicki E, Wright T, Hammond S . Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev. 2006; 20(16):2202-7. PMC: 1553203. DOI: 10.1101/gad.1444406. View

15.

Tusher V, Tibshirani R, Chu G . Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A. 2001; 98(9):5116-21. PMC: 33173. DOI: 10.1073/pnas.091062498. View

16.

Troyanskaya O, Cantor M, Sherlock G, Brown P, Hastie T, Tibshirani R . Missing value estimation methods for DNA microarrays. Bioinformatics. 2001; 17(6):520-5. DOI: 10.1093/bioinformatics/17.6.520. View

17.

Li C, Hung Wong W . Model-based analysis of oligonucleotide arrays: model validation, design issues and standard error application. Genome Biol. 2001; 2(8):RESEARCH0032. PMC: 55329. DOI: 10.1186/gb-2001-2-8-research0032. View

18.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

19.

Kent W, Sugnet C, Furey T, Roskin K, Pringle T, Zahler A . The human genome browser at UCSC. Genome Res. 2002; 12(6):996-1006. PMC: 186604. DOI: 10.1101/gr.229102. View

20.

Caudy A, Myers M, Hannon G, Hammond S . Fragile X-related protein and VIG associate with the RNA interference machinery. Genes Dev. 2002; 16(19):2491-6. PMC: 187452. DOI: 10.1101/gad.1025202. View