A New Clue to the Genetics of Bipolar Disorder: Piccolo
Philadelphia, PA, 23 February 2011 - Understanding the genetics of bipolar disorder could lead to new treatments, but identifying specific genetic variations associated with this disorder has been challenging.
A new study in Biological Psychiatry implicates a brain protein called Piccolo in the risk for inheriting bipolar disorder. In the orchestra of neuronal proteins, Piccolo is a member of a protein family that includes another protein called Bassoon. Piccolo is located at the endings of nerve cells, where it contributes to the ability of nerve cells to release their chemical messengers.
Choi and colleagues conducted a creative study to implicate the gene coding for Piccolo (PCLO) in the heritable risk for bipolar disorder.
They compared gene expression patterns in postmortem cortical tissue from people who were diagnosed with bipolar disorder to tissue from people who did not have psychiatric illnesses prior to their death. This analysis identified 45 genes and genetic variations that had significantly altered mRNA levels, and they used this information to narrow the part of the genome that they explored in their genetics study.
They then tested genetic markers (small DNA sequence variations called single nucleotide polymorphisms or SNPs) that are close to the genes that had altered expression levels in the postmortem tissue. A marker for PCLO, SNP rs13438494, emerged as significant in this analysis, suggesting that variation in PCLO contributes to the risk for bipolar disorder.
“We have taken an innovative approach in correlating gene expression with genetic variation data from well-characterized postmortem brains and then combining with a large scale meta-analysis of genome-wide association studies,” explained Dr. Kwang Choi. “If replicated, this study could finally forge a link between gene expression and genome-wide association studies in a complex genetic disorder.”
“This study is an example of how better knowledge of brain biology may help to guide our genetics studies,”added Dr. John Krystal, Editor of Biological Psychiatry.
Notes to Editors:
The article is “Gene Expression and Genetic Variation Data Implicate PCLO in Bipolar Disorder” by Kwang H. Choi, Brandon W. Higgs, Jens R. Wendland, Jonathan Song, Francis J. McMahon, and Maree J. Webster. Choi, Song, and Webster are affiliated with the Stanley Laboratory of Brain Research, Rockville, Maryland. Choi is also with the Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland. Wendland and McMahon are affiliated with the Genetic Basis of Mood and Anxiety Disorders Unit, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. Higgs is from Elashoff Consulting, Redwood City, California. The article appears in Biological Psychiatry, Volume 69, Number 4 (February 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 here.
Full text of the article mentioned above is available upon request. Contact Chris J. Pfister at email@example.com to obtain a copy or to schedule an interview
About Biological Psychiatry
This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length reports of novel results, commentaries, case studies of unusual significance, and correspondence judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise reviews and editorials that focus on topics of current research and interest are also published rapidly.
Biological Psychiatry is ranked 4th out of 117 Psychiatry titles and 13th out of 230 Neurosciences titles in the 2009 ISI Journal Citations Reports® published by Thomson Reuters. The 2009 Impact Factor score for Biological Psychiatry has increased to 8.926.
Elsevier is a global information analytics business that helps scientists and clinicians to find new answers, reshape human knowledge, and tackle the most urgent human crises. For 140 years, we have partnered with the research world to curate and verify scientific knowledge. Today, we’re committed to bringing that rigor to a new generation of platforms. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support, and professional education; including ScienceDirect, Scopus, SciVal, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, 39,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX, a global provider of information-based analytics and decision tools for professional and business customers. www.elsevier.com
Chris J. Pfister
Strategic Marketing Manager - Elsevier