June 23, 2000

VU launches search for depression genes

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VU launches search for depression genes

A network of international researchers is set to begin the largest study ever to search for genes that cause major depression.

The study, coordinated by Vanderbilt University's Program in Human Genetics in collaboration with the pharmaceutical company Glaxo Wellcome, could lead to the development of new drugs to prevent or treat the disease.

Major or unipolar depression affects about 12 percent of the population in the Western world at some point in life, making it one of the most common mental illnesses and the leading cause of disability worldwide. Although about 70 percent of patients respond to treatment with antidepressants, up to 75 percent experience recurrent depression within 10 years, and a very high proportion of sufferers remain undiagnosed and untreated.

"Unipolar depression is a devastating illness that destroys the lives of both patients and their families," said Jonathan L. Haines, Ph.D., professor of Molecular Physiology and Biophysics and director of the Program in Human Genetics. "Understanding the genetic basis of unipolar depression will give us new targets to help design new, improved medicines to deal with the condition."

Although some candidate genes for depression have been identified, none have been confirmed. In addition, most studies searching for depression genes have focused on bipolar depression (manic-depressive disorder), which historically was considered to be more of a genetic disease than unipolar depression. There is now strong evidence that points to a genetic predisposition to unipolar depression.

The new study will recruit a minimum of 1200 families in which at least two individuals have been characterized as clinically depressed — a DSM-IV diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders. Clinical histories and DNA data will be collected from eligible families at multiple centers, including:

• Institute of Psychiatry, Social Genetic and Developmental Psychiatry Research Centre, London, UK

• University of Birmingham, Department of Psychiatry, Birmingham, UK

• University of Wales, Department of Psychological Medicine, Cardiff, Wales

• Washington University School of Medicine, Department of Psychiatry, St. Louis, Missouri, USA

• Trinity Centre for Health Sciences, Department of Psychiatry, St. James Hospital, Dublin, Ireland

Four additional sites are anticipated to join the effort in fall 2000.

Investigators at Vanderbilt University will analyze all of the data collected at study centers, looking for links between genetic markers and clinical depression. Spots in the genome that are found to be linked to depression then act as signposts, pointing the way to the actual genes that play a role in the disease.

"Collaboration by this international team of experts, including the genetic epidemiology group of the Program in Human Genetics here at Vanderbilt, will provide an unparalleled opportunity to identify and characterize genes that increase susceptibility to unipolar depression," said Jason H. Moore, Ph.D., assistant professor of Molecular Physiology and Biophysics and the Vanderbilt coordinator for the study.

"The information available from the sequencing of the human genome together with the data we gather from this study will provide an unprecedented level of understanding, which Glaxo Wellcome can feed into its research and development program to help speed up the discovery of new medicines," said Dr. Allen Roses, world-wide director for Genetics at Glaxo Wellcome.