Micro-RNA's contribute to risk for panic disorder

(Press-News.org) Philadelphia, PA, 24 March 2011 - Studies in twin pairs suggest that 40% of the risk for panic disorder is heritable, yet the manner in which genes contribute to the risk for panic disorder is far from clear. To date, variations in a growing number of genes have been implicated in the risk for panic disorder, but the magnitude of the impact of each individual gene is relatively small. The pattern of these implicated genes raises the question of whether there might be molecular "switches" that control the function of groups of genes in a coordinated fashion, which would help to explain the observed findings related to the genetics of panic disorder. A new study published in the current issue of Biological Psychiatry now implicates one type of molecular switch, microRNAs (miRNAs), in panic disorder. Ribonucleic acid (RNA) is the immediate product of DNA. The most commonly discussed products of RNA are proteins, hence the common dictum "DNA makes RNA and RNA makes protein." However, miRNAs are small bits of RNA that bind to DNA and control the expression of various genes. There are a large number of miRNAs that have diverse effects on gene expression. Through case-control studies in three different populations, from Spain, Finland and Estonia, Muiños-Gimeno, Espinosa-Parrilla and colleagues found that at least four miRNAs (miR-22, miR-138-2, miR-148a and miR-488) may be involved in the pathophysiology of panic disorder. Their subsequent functional studies revealed that miR-138-2, miR-148a and miR-488 repress several candidate genes for panic disorder including GABRA6, CCKBR and POMC, respectively, and that miR-22 regulates four other candidate genes: BDNF, HTR2C, MAOA and RGS2. Their analysis also implicated miR-22 and miR-488 in the regulation of anxiety related pathways in the brain. "These data provide important new evidence that variation in genes coding for miRNAs may coordinate the involvement of a number of risk genes and thereby contribute to the development of panic disorder," commented Dr. John Krystal, Editor of Biological Psychiatry.

### Notes to Editors: The article is "Human microRNAs miR-22, miR-138-2, miR-148a, and miR-488 Are Associated with Panic Disorder and Regulate Several Anxiety Candidate Genes and Related Pathways" by Margarita Muiños-Gimeno, Yolanda Espinosa-Parrilla, Monica Guidi, Birgit Kagerbauer, Tessa Sipilä, Eduard Maron, Kristi Pettai, Laura Kananen, Ricard Navinés, Rocío Martín-Santos, Mònica Gratacòs, Andres Metspalu, Iiris Hovatta, and Xavier Estivill. Muiños-Gimeno, Espinosa-Parrilla, Guidi, Kagerbauer, Gratacòs, and Estivill are affiliated with the Genes and Disease Program, Centre for Genomic Regulation (CRG), Public Health and Epidemiology Network Biomedical Research Center (CIBERESP), Barcelona, Catalonia, Spain. Muiños-Gimeno, Espinosa-Parrilla, Guidi, and Estivill are also from the Experimental and Health Sciences Department, Pompeu Fabra University, Barcelona, Catalonia, Spain. Espinosa-Parrilla is also with Institut de Biologia Evolutiva-UPF-CSIC, Barcelona, Catalonia, Spain. Navinés and Martín-Santos are both affiliated with Neuropsychopharmacology Programme, IMIM-Hospital Mar, Barcelona, Catalonia, Spain, and Psychiatry Service, Neurosciences Institute, Hospital Clinic, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. Sipilä, Kananen, and Hovatta are affiliated with the Research Program of Molecular Neurology and Department of Medical Genetics, University of Helsinki, Helsinki, Finland. Sipilä and Hovatta are also with the Department of Mental Health and Substance Abuse Services, National Institute for Health, Welfare, Helsinki, Finland. Maron and Metspalu are affiliated with the Estonian Genome Center, University of Tartu, Tartu, Estonia. Maron is also affiliated with Department of Psychiatry, University of Tartu, Tartu, Estonia, and Department of Neuropsychopharmacology and Molecular Imaging, Imperial College London, London, United Kingdom. Metspalu is also affiliated with the Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. Pettai and Metspalu are with the Estonian Biocentre, Tartu, Estonia.

The article appears in Biological Psychiatry, Volume 69, Number 6 (March 15, 2011), published by Elsevier.

The authors' disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D. is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available at http://journals.elsevierhealth.com/webfiles/images/journals/bps/Biological-Psychiatry-Editorial-Disclosures-7-22-10.pdf.

Full text of the article mentioned above is available upon request. Contact Chris J. Pfister at c.pfister@elsevier.com to obtain a copy or to schedule an interview.

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