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Miller School Genetics Researchers Publish New Psychiatric Findings

12/19/2008

Despite major strides in determining the genetic influences of many complex diseases, it’s been extremely difficult to make significant progress when it comes to psychiatric disorders, which is why the published findings of a team of investigators from the Miami Institute for Human Genomics at the University of Miami Miller School of Medicine, their collaborators at Duke University and the National Institute of Mental Health are so significant.

The researchers, led by Stephan Züchner, M.D., associate professor of human genetics and neurology and director of the Center for Human Molecular Genomics at the Miller School have identified genetic variations that may increase susceptibility for not only obsessive compulsive disorder (OCD), but also for associated conditions, such as trichotillomania.  These disorders are all characterized by persistent intrusive thoughts (obsessions), repetitive actions (compulsions), and often anxiety.  Trichotillomania specifically is characterized by an urge to pull one’s hair excessively.

“This represents an interesting shift in our thinking about the genetics that underlie psychiatric disorders and may indicate that some disorders may share common genetic influences,” says Michael Cuccaro, Ph.D., associate professor of human genetics and director of the Patient and Family Ascertainment Section in the Center for Genomic Medicine at the Miller School, amd co-investigator in the study.

A 2007 study published in Nature reported increased OCD-like behavior of mice with deficient levels of postsynaptic SAP90/PSD95-associated protein 3 (Sapap3).  With colleagues from the National Institute of Mental Health and Duke University, Miami Institute of Human Genomics  researchers examined the human equivalent of this gene (SAPAP3) for correlations with OCD spectrum behavior in humans.  In the study, the researchers looked at 170 people with either OCD, trichotillomania (obsessive hair pulling), or a combination of both and 170 controls.

“We detected seven novel missense variants we believe interact with other genes and/or environmental factors to increase an individual’s susceptibility to developing OCD spectrum behavior,” explains Züchner.  The findings were published online December 19 and will appear in the January   issue of Molecular Psychiatry.

There are only a few candidate risk genes for psychiatric diseases and disorders in general and even fewer for OCD spectrum disorders.  The identification of risk-conferring genes for psychiatric disorders using classic genetic association studies has been largely unsuccessful.  This finding supports the burgeoning hypothesis in the field of genetic research that rare variants are a major source for human disease risk.

“These findings can give people who suffer from these types of behaviors a sense of hope,” said Züchner.  “This is the first step toward understanding the mechanism behind the disorder and it helps us to one day move toward new treatments.”

Co-investigators at Duke University Medical Center include Allison E. Ashley-Koch. Ph.D., from the Duke Center for Human Genetics, David Steffens, M.D., and Ranga Krishnan, M.B., CH.B.,  from the Department of Psychiatry.  Co-Investigators from the National Institute of Mental Health include Jens R. Wendland, M.D., Guoping Feng, Ph.D.,  and Dennis L. Murphy, M.D..