American Journal of Medical Genetics (Neuropsychiatric Genetics) 54174-184 (1994) ~ ~~ Psychological Costs and Benefits of Predictive Testing for Huntington’s Disease Ann-Marie Codori and Jason Brandt Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland The impact of predictive genetic testing for Huntington’s disease (HD)was assessed in 68 persons at high (n = 17) or low risk (n = 51) for the disease at one to six years following dis- closure of test results. There was consensus in both groups that knowledge of HD genetic status was beneficial. A majority of persons felt relief from wondering and uncertainty. High-risk persons identified greater family closeness and financial security. For low-risk persons, the knowledge that their children were spared offered great consolation. Neg- ative effects in high-risk persons were psy- chological burden (worry, guilt). Even for low-risk subjects, there was a period of ad- justment and, in some, disappointment that low risk had not alleviated problems unre- lated to HD. Although the majority of mar- riages were unaffected by testing, some per- sons in both groups reported that their marriages sustained positive or negative im- pact. Despite mixed consequences, most did not regret being tested. The benefits of testing appear to outweigh its drawbacks, at least among this self-selected group of research participants. We also must conclude,however, that predictive genetic testing will result in negative as well as positive consequences, re- gardless of test outcome. o 1994 Wiley-Liss, Inc. KEY WORDS Huntington’s disease, predic- tive testing, psycholopcal re- actions INTRODUCTION In 1983, a genetic marker for Huntington’s disease (HD) was discovered [Gusella et al., 19831. Since then, Received for publication October 13, 1993; revision received December 17, 1993. Address reprint requests to Ann-Marie Codori, Ph.D., De- partment of Psychiatry and Behavioral Sciences, Meyer 218, The Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD 0 1994 Wiley-Liss, Inc. 21287-7218. some people at risk for HD have grappled with a new technological possibility: whether or not to be tested for the marker. HD is a currently incurable progressive disease of the brain that causes a choreiform movement disorder, dementia, and affective disturbances. It is in- herited by autosomal dominant transmission and, thus, occurs in roughly half of the offspring of affected per- sons. The gene is completely penetrant, so that all who inherit it develop the disease, assuming they survive to the time of symptom onset. After symptoms begin (usu- ally around age 401, death occurs within about 15 years [Folstein, 1989; Harper, 1991; Wexler, 19791. It is now known that a mutation on chromosome4 [HD Collabora- tive Research Group, 19931, an “unstable trinucleotide repeat,” is responsible for virtually all cases of HD. From 1983until early 1993, however, the locus ofthe HD gene had been isolated only to a 2 million base-pair segment of the tip of the short arm of chromosome-4 [Gusella et al., 19833. Nonetheless, DNA “markers” from this region allowed predictive genetic testing for at-risk persons. The potential psychological costs and benefits of pre- dictive genetic testing for HD have been debated since the discovery of the first marker, years before any at-risk persons actually received test results. Ethicists, geneti- cists, and mental health professionalscould foresee such problems as depression, suicide, family turmoil, divorce, and survivor guilt [Brandt, in press; Farrer, 1987;Kess- ler, 1987a, bl, as well as insurance and employment discrimination among those found to have the marker, On the positive sid.e, some argued that the genetic infor- mation would allow people to plan for the future and avoid passing on the gene for HD, and could decrease anxiety associated with being at risk [Bates, 1981; Craufurd and Harris, 19861. Although surveys showed that some at-risk persons said they might become de- pressed and have suicidal thoughts if they were found to have the marker [Kessler et al., 1987;Meissen and Ber- chek, 19871, the dominant viewpoint among those who actually were tested was that the test would be more beneficial than harmful [Codori et al., 1994; Tibben et al., 1993al. Wexler [1979,19921 has argued that people who want to know their genetic status in order to plan for the future may be allowing the threat of HD to present a roadblock to a satisfying life. As an alternative to ge-