title: Preliminary investigation of miRNA expression in individuals at high familial risk of bipolar disorder.
abstract: Bipolar disorder (BD) is a highly heritable psychiatric disorder characterised by recurrent episodes of mania and depression. Many studies have reported altered gene expression in BD, some of which may be attributable to the dysregulated expression of miRNAs. Studies carried out to date have largely studied medicated patients, so it is possible that observed changes in miRNA expression might be a consequence of clinical illness or of its treatment. We sought to establish whether altered miRNA expression might play a causative role in the development of BD by studying young, unmedicated relatives of individuals with BD, who are at a higher genetic risk of developing BD themselves (high-risk individuals). The expression of 20 miRNAs previously implicated in either BD or schizophrenia was measured by qRT-PCR in whole-blood samples from 34 high-risk and 46 control individuals. Three miRNAs, miR-15b, miR-132 and miR-652 were up-regulated in the high-risk individuals, consistent with previous reports of increased expression of these miRNAs in patients with schizophrenia. Our findings suggest that the altered expression of these miRNAs might represent a mechanism of genetic susceptibility for BD. Moreover, our observation of altered miRNA expression in the blood prior to the onset of illness provides hope that one day blood-based tests may aid in the risk-stratification and treatment of BD.
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. Electronic address: rwalke13@staffmail.ed.ac.uk.
authors.forename: Rosie May
authors.initials: RM
authors.lastname: Walker
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. Electronic address: joanna.rybka1@wp.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Rybka
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. Electronic address: Susan.Anderson@igmm.ed.ac.uk.
authors.forename: Susan Maguire
authors.initials: SM
authors.lastname: Anderson
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. Electronic address: Helen.Torrance@igmm.ed.ac.uk.
authors.forename: Helen Scott
authors.initials: HS
authors.lastname: Torrance
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. Electronic address: R.Boxall@sms.ed.ac.uk.
authors.forename: Ruth
authors.initials: R
authors.lastname: Boxall
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK. Electronic address: Jess.Sussmann@ed.ac.uk.
authors.forename: Jessika Elizabeth
authors.initials: JE
authors.lastname: Sussmann
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK. Electronic address: david.porteous@igmm.ed.ac.uk.
authors.forename: David John
authors.initials: DJ
authors.lastname: Porteous
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK. Electronic address: andrew.mcintosh@ed.ac.uk.
authors.forename: Andrew Mark
authors.initials: AM
authors.lastname: McIntosh
authors.affiliation: Medical Genetics Section, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK. Electronic address: Kathy.Evans@igmm.ed.ac.uk.
authors.forename: Kathryn Louise
authors.initials: KL
authors.lastname: Evans
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D005192:Family Health; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: C547077:MIRN132 microRNA, human; C505361:MIRN15 microRNA, human; C574011:MIRN652 microRNA, human; D035683:MicroRNAs
keywords: Biomarker; Bipolar disorder; GABA; Gene expression; PI3K/Akt; miRNA