Striatal Brain Volume Predicts Huntington Disease Onset

Reports new study in Biological Psychiatry

Philadelphia, PA, April 26, 2012 – Huntington disease (HD) is an inherited neurodegenerative disorder caused by a defect on chromosome four where, within the Huntingtin gene, a CAG repeat occurs too many times. Most individuals begin experiencing symptoms in their 40s or 50s, but studies have shown that significant brain atrophy occurs several years prior to an official HD diagnosis. As a result, the field has sought a preventive treatment that could be administered prior to the development of actual symptoms that might delay the onset of illness.

Using data from the ongoing PREDICT-HD study and led by Dr. Elizabeth Aylward, author and Associate Director at the Center for Integrative Brain Research, Seattle Children’s Research Institute, researchers examined whether neuroimaging measures can improve the accuracy of prediction of disease onset.

The PREDICT- HD study is an international, multi-site, long-term study of individuals who carry the gene mutation for Huntington disease but entered the study prior to onset of diagnosable motor impairment. Participants underwent structural magnetic resonance imaging (MRI) scans, which allowed for the comparison of individuals who developed HD during the course of the study and those who had not yet been diagnosed with HD.

They found that striatum and white matter volumes in the brain were significantly smaller in individuals diagnosed 1 to 4 years following the initial scan, suggesting that these volumetric measures can assist in determining which individuals are closest to disease onset.

“We believe that the results of this study will be important in designing future clinical trials for individuals who have the Huntington disease gene mutation, but who are not yet showing symptoms. We also believe this group of individuals is well suited for drug intervention studies, as their brain involvement is not as severe as those who have already been diagnosed,” said Dr. Aylward.

“Huntington disease can be considered a model neuropsychiatric disorder, since it is caused by a single gene and has such predictable and well-characterized brain changes. It may guide thinking about other disorders with genetic contribution, such as schizophrenia,” commented Dr. Christopher A. Ross, co-author and Professor of Psychiatry, Neurology and Neuroscience, Johns Hopkins University. “If we could better understand the natural history of brain changes in schizophrenia, for instance, we may be able to identify genetically vulnerable individuals, and intervene therapeutically, not just to treat symptoms, but to alter the biology and course of the disease.”

Dr. John Krystal, Editor of Biological Psychiatry, agreed, noting that “biomarkers of illness progress are critical for all neuropsychiatric disorders.”

For now, these results may enhance the formulas used to calculate age of onset and help aid in the planning of future clinical trials aimed at delaying disease onset.

“Identifying individuals who are close to onset of diagnosable symptoms will allow feasible studies that use onset of symptoms as the primary outcome measure to determine if a drug intervention is effective,” Dr. Aylward added. “Although it would be unreasonable to suggest that all potential clinical trial participants receive MRI scans one to four years prior to taking part in a trial, there are many individuals who have participated in pre-HD observational studies who already have such data available.”

Perhaps more importantly, Dr. Krystal concluded that “the development of good disease staging using MRI in Huntington disease could assist investigators studying novel treatments and affected individuals and family members anxious to learn about disease progress.”

The article is “Striatal Volume Contributes to the Prediction of Onset of Huntington Disease in Incident Cases” by Elizabeth H. Aylward, Dawei Liu, Peggy C. Nopoulos, Christopher A. Ross, Ronald K. Pierson, James A. Mills, Jeffrey D. Long, Jane S. Paulsen, and PREDICT-HD Investigators and Coordinators of the Huntington Study Group (doi: 10.1016/j.biopsych.2011.07.030). The article appears in Biological Psychiatry, Volume 71, Issue 9 (May 1, 2012), published by Elsevier.

 

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Notes for editors
Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact Sean Thompson, public relations coordinator for the PREDICT-HD study, at +1 319 384 4094 or sean-thompson@uiowa.edu.

The authors’ affiliations, and 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.

About Biological Psychiatry
Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 4th out of 126 Psychiatry titles and 15th out of 237 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2010 Impact Factor score for Biological Psychiatry is 8.674.

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Media contact
Rhiannon Bugno
Editorial Office, Biological Psychiatry
+1 214 648 0880
biol.psych@utsouthwestern.edu