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Previous Volume 361:245-254 July 16, 2009 Number 3 Next

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ABSTRACT

Background The apolipoprotein E (APOE) genotype provides information on the risk of Alzheimer's disease, but the genotyping of patients and their family members has been discouraged. We examined the effect of genotype disclosure in a prospective, randomized, controlled trial.

Methods We randomly assigned 162 asymptomatic adults who had a parent with Alzheimer's disease to receive the results of their own APOE genotyping (disclosure group) or not to receive such results (nondisclosure group). We measured symptoms of anxiety, depression, and test-related distress 6 weeks, 6 months, and 1 year after disclosure or nondisclosure.

Results There were no significant differences between the two groups in changes in time-averaged measures of anxiety (4.5 in the disclosure group and 4.4 in the nondisclosure group, P=0.84), depression (8.8 and 8.7, respectively; P=0.98), or test-related distress (6.9 and 7.5, respectively; P=0.61). Secondary comparisons between the nondisclosure group and a disclosure subgroup of subjects carrying the APOE 4 allele (which is associated with increased risk) also revealed no significant differences. However, the 4-negative subgroup had a significantly lower level of test-related distress than did the 4-positive subgroup (P=0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the 4-positive and 4-negative subgroups. Baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures (P<0.001 for both comparisons).

Conclusions The disclosure of APOE genotyping results to adult children of patients with Alzheimer's disease did not result in significant short-term psychological risks. Test-related distress was reduced among those who learned that they were APOE 4–negative. Persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure. (ClinicalTrials.gov number, NCT00571025 [ClinicalTrials.gov] .)

Source Information

From Boston University School of Medicine (R.C.G., T.B., L.A.F.), Boston University School of Public Health (R.C.G., L.A.C., C.C., L.A.F.), and Harvard Medical School Genetics Training Program (R.C.G.) — all in Boston; the University of Michigan School of Public Health, Ann Arbor (J.S.R.); Weill Cornell Medical College, New York (N.R.R.); Case Western Reserve University School of Medicine, Cleveland (P.J.W., M.B.); Columbia University School of Medicine, New York (S.L.E.); the University of British Columbia, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada (A.D.S.); Indiana University School of Medicine, Indianapolis (K.A.Q.); and Duke University, Durham, NC (R.C.-D.).

Address reprint requests to Dr. Green at Boston University School of Medicine, 715 Albany St., L-320, Boston, MA 02118, or at rcgreen{at}bu.edu.

Full Text of this Article

This article has been cited by other articles:

• (2009). Psychological Effect of Disclosing Genetic Risk for Alzheimer Disease. JWatch General 2009: 2-2 [Full Text]  
• (2009). APOE Genotyping: Nothing to Worry About?. JWatch Psychiatry 2009: 1-1 [Full Text]  
• (2009). All you need to read in the other general journals. BMJ 339: b2918-b2918 [Full Text]  
• Kane, R. A., Kane, R. L. (2009). Effect of Genetic Testing for Risk of Alzheimer's Disease. NEJM 361: 298-299 [Full Text]