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No Harm Seen in Disclosing Genetic Risk for Alzheimer's Disease

by Rajashri on July 16, 2009 at 8:52 PM
 No Harm Seen in Disclosing Genetic Risk for Alzheimer's Disease

Disclosing genetic risk information to adult children of patients with Alzheimer's disease (AD) who request this information does not result in significant short-term psychological distress, researchers from Boston University School of Medicine (BUSM) have shown.

The report from the REVEAL Study*, which appears in the July 16 issue of the New England Journal of Medicine, is the first randomized trial to disclose to participants whether or not they carried the ε4 variant of the APOE gene, a variant that has been found to increase the risk of developing AD. The study demonstrated that test-related distress was reduced among those who learned that they were APOE ε4 negative, and was only transiently increased among those who learned they were APOE ε4 positive. The study also showed that persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure.


The study comes at a time when gene variants that are associated with risks of common diseases are being rapidly discovered and genetic testing is now being marketed by direct-to-consumer genetics testing companies such as 23andMe, Navigenics and DeCodeMe. Considerable controversy has accompanied the launch of these companies and one area of concern has been the potential for psychological harm if individuals learn they are at increased risk for diseases that have no treatment, such as AD.

The BUSM researchers, along with their collaborators at the University of Michigan, Weill Cornell Medical College and Case Western Reserve University School of Medicine randomly assigned 162 asymptomatic adults who had a parent with Alzheimer's disease to two groups: the disclosure group, who received a risk assessment for their chance to develop AD that included their APOE genotyping results, and the nondisclosure group, who received a risk assessment for AD that excluded their APOE genotyping status. They then measured symptoms of anxiety, depression, and test-related distress six weeks, six months, and one year after disclosure or nondisclosure and found no significant differences between the two groups in measures of anxiety, depression or test-related distress.

Comparisons between the subgroup of participants carrying the APOE ε4 variant and those who did not learn their genotype revealed no significant differences, suggesting that learning about increased risk did not cause psychological harm. However, the ε4 negative subgroup had a significantly lower level of test-related distress than did the ε4 positive subgroup, suggesting a psychological benefit to those who learned they were at lower risk.

"Study participants who learned they were ε4 positive and were therefore at increased risk for Alzheimer's disease showed no more anxiety, depression, or test-related distress than those who did not learn their genotype," said lead author Robert C. Green, MD, MPH, a professor of neurology, genetics and epidemiology at BUSM as well as a fellow in genetics at Harvard Medical School, "but those who learned they were ε4 negative experienced considerable relief."

"It's important to recognize that our participants were carefully screened for pre-existing emotional problems and that trained genetic counselors disclosed the information," adds Green, "so it is not the same thing as simply providing risk information to anyone who asks. Nevertheless, our work supports the notion that learning genetic risk information can be a positive and empowering experience for some people, even when the disease is frightening and the genetic information has no clear medical benefit. "

According to the BUSM researchers, larger studies that follow participants for more than one year will be required to detect uncommon and long-term effects, such as delayed emotional repercussions and injudicious life decisions. These studies are currently underway in new REVEAL Study trials.

Source: Eurekalert
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