Among the concerns of providers of predictive tests, suicide tops the list. What if knowing one will develop Alzheimer disease in mid-life exacts such an emotional toll on an already anxious and vulnerable person that they decide life has become unbearable? No cases of suicide, or attempted suicide, in recipients of eFAD genetic test results have been reported in the literature, nor were genetic counselors, neurologists, and clinical geneticists interviewed for this series aware of any such cases. But the concern remains. The first reported use of predictive DNA testing drove an eFAD carrier toward suicidal thoughts for a month. Moreover, in an early clinical psychology study that probed prospective test takers' attitudes, two out of 39 people at risk for either EOAD or a related dementia called Pick disease who were interested in taking the test indicated that they might commit suicide, and nine more indicated they had not resolved this question (Tibben et al., 1997). This Dutch study also noted that people who harbor these thoughts tend to forego the test eventually, and that genetic counseling helps them come to the decision regarding testing that is right for them.
As with other questions on predictive eFAD testing, the existing track record with Huntington disease provides some guidance. In the early days of HD testing, too, practitioners were afraid of unleashing intolerable despair. The leading public spokeswoman for HD, Nancy Wexler, eloquently laid out potential pitfalls as early as 1985, when family members could already receive an approximate personal risk prediction based on linkage studies, not DNA sequencing (Wexler, 1985. Genetic jeopardy and the new clairvoyance. In: Bearn, Motulski, Childs (eds) Progress in medical genetics, vol VI. Praeger, New York, pp 277-304). But when Canadian researchers led by Michael Hayden years later gathered data from 100 centers in 21 countries around the world to learn how often predictive HD testing did have catastrophic consequences, they found that it was not very often (Almqvist et al., 1999). Of 4,527 tested people, 44 people had what the researchers called a catastrophic event: five people had taken their lives, 21 more had tried, and 18 were hospitalized for psychiatric reasons. This makes for an overall catastrophic event rate of 0.97 percent, or 2 percent of those who learned that they carried the HD mutation. Of the 4,527 test takers, 119 were lost to follow-up. That is not an unusually high rate for clinical research, but still, it's impossible to know whether they had a higher rate of catastrophic outcomes. Two people who committed suicide had symptoms of HD, as did about half of those who tried or were hospitalized. People who already had a psychiatric history before taking the test, or were unemployed, appeared to be most at risk, raising ethical questions about whether they should have been dissuaded from taking the test, and what level of long-term support is necessary and feasible for them.
Irrespective of predictive testing, the suicide rate among people with symptomatic HD is about seven to 10 times that of the general population in the U.S. The rate reported in the Canadian survey coincides with that but does not exceed it. People with other serious mental and physical illnesses also have higher suicide rates than average. Suicide has been reported in two patients with AD (Rohde et al., 1995); in fact, the first assisted suicide by Jack Kevorkian, in 1990, involved a 54-year-old Oregon women with EOAD.
In a compassionate editorial published alongside the Almqvist et al. analysis, University of Washington neurogeneticist Thomas Bird calls suicide the canary of the genetic testing coal mine. He writes that, overall, the results of the Canadian survey do not suggest that predictive testing ought to be abandoned. Because self-selected test takers, i.e., people who really insist on knowing and who go through the rigors of the counseling protocol, may be more likely to cope well, it is essential that reluctant people never be nudged into testing by more proactive relatives, or tacitly induced by their physicians to take the test. Genetic counselors pay close attention to such dynamics.
Moreover, it is not just the carriers who suffer: among non-carriers, 0.3 percent had a catastrophic event in the Canadian HD survey. Bird notes that in a local study in Washington state, he was sobered to find that a spouse had killed herself after struggling with the illness in her husband and all three of their children. Like many careful practitioners in the field, Bird emphasizes the role of careful counseling prior to any testing. It educates the prospective test-taker about the disease and about potential implications of receiving a positive result. Furthermore, depression should be recognized and treated before a candidate is allowed to proceed with testing. The medical team should make sure that all people tested and their caregivers will receive support in the weeks and months after testing.—Gabrielle Strobel.