Understanding the decision to take the predictive test for Huntington disease.

The predictive test for Huntington disease (HD) has allowed those at risk to determine gene status prior to symptoms. The purpose of this research was to understand the motivation and the anticipated reactions of those requesting the test. Forty persons at 50% risk for HD and 31 companions participated in a structured personal interview as part of the predictive test protocol. Reasons for taking the test centered on the reduction of anxiety and uncertainty associated with being at risk and enhanced planning and decision making. Participants also believed that taking the test would produce more positive than negative outcomes. With a favorable result, most anticipated a reduction of anxiety, a more normal future, and relief knowing their children would be at a very low risk. Most also cited benefits as more likely than consequences with an unfavorable result. Making the most of life, easier planning, and reduced uncertainty were rated as more likely than any of the adverse impacts, including short-term depression and becoming frightened. Almost all participants (95%) said they would rather learn that they have the HD gene than remain at 50% risk. The uncertainty, anxiety, and chronic stress associated with being at risk appears to underlie the motivation of many seeking the predictive test for HD.     

On attitudes and appreciation 6 months after predictive DNA testing for huntington disease in the Dutch program

We have studied the 6-month follow-up attitudes of 63 individuals, after predictive testing for Huntington disease (HD). Reducing uncertainty (81%) and family planning (60%) were the major reasons for taking the test. Twenty-four individuals were diagnosed as having an increased risk (± 98%), and 39 a decreased risk (± 2%). Among those with an increased risk, denial or minimization of the ultimate impact of the increased risk result was observed. Most of them (84%) rated their current life situation, at the very least, as being good. Twenty-one percent of individuals with an increased risk who originally planned to have a family, decided to refrain from having children. Sixty percent of those with increased risk who still wished to have children, would choose to have prenatal testing. In most individuals with increased risk, the test result did not increase the previously expected control over their own future. Half of the partners of persons with increased risk acknowledged the burden of the future disease. Half had no one in whom they could confide. They showed loyalty to the denial and avoidance reactions of their spouses. Half of the individuals with decreased risk denied the impact of the result, as reflected by absence of relief, and emotional numbness. A third of persons with decreased risk experienced involvement with problems of affected relatives. We found that 20% of all participants were discontented with the support given by their general practitioner, who is normally regarded as being the most significant professional for aftercare. Our findings suggest that the perpetuation of psychological defenses, which may temporarily be adequate, may ultimately prevent an individual from taking advantage of being informed. These questions should be further addressed in long-term follow-up studies. © 1993 Wiley-Liss, Inc.     

Presymptomatic DNA-testing for Huntington disease: Pretest attitudes and expectations of applicants and their partners in the Dutch program

We studied the baseline attitudes, prior to testing, of 70 applicants at risk for Huntington disease (HD) and their partners in the Dutch presymptomatic DNA-testing program. Two thirds of the applicants were female; 36% already had children. The main reason (60%) for undertaking the test was for family planning. Other reasons were either to reduce uncertainty (43%) or to obtain certainty (38%). Partners of applicants stated that planning for the future was for them the most important reason (76%). Significantly more at-risk females (42%) than males (16%) anticipated an unfavorable test outcome. Quite remarkably, most applicants and partners denied that a positive result might have adverse effects on either personal mood, quality of life, or marriage. Only a few did not expect that a favorable result would induce relief. The eventual outcome of the test was expected to enable applicants to gain control over their future, whatever the result. Hence, we propose that the applicants form a self-selected group, based on their expectation that they will not be emotionally affected by either result. © 1993 Wiley-Liss, Inc.     

Intended use of predictive testing by those at risk for Huntington disease

Huntington disease (HD) is a late-onset genetic disorder that is incurable and undetectable until the onset of symptoms. A marker for the gene that causes HD was recently discovered that will lead to a predictive test. The purpose of this research was to assess the attitudes, beliefs, and behavioral intentions concerning the impending predictive test by those at risk for HD. Results from a sample of 56 at-risk individuals indicated that a majority (65%) favored using the presymptomatic test and would encourage their adult children to use it as well. Fewer but still a substantial percentage of respondents would use the prenatal test (42%) and would test at-risk minors (35%). Surprisingly, knowledge about predictive testing was quite low and a majority of those least knowledgeable about predictive testing intended to use the test. These findings emphasized the need for outreach and prevention efforts to prepare the at risk and specialized programs of genetic counseling and follow up to accompany predictive testing.     

Psychological distress in the 5-year period after predictive testing for Huntington's disease

The paper reports on a 5-year longitudinal study on psychological distress after predictive testing for Huntington's disease (HD) and on correlates of post-test distress. Psychometric tests and questionnaires were used. The tested persons were invited to participate in the follow-up study; the uptake rate was 75% (24 carriers, 33 non-carriers). Three time points were included: baseline, 1 year and 5 years post-test. Five years after the test, mean distress scores of both carriers and non-carriers were within the normal range. Carriers did not differ from non-carriers with regard to mean general distress. Compared to non-carriers, however, carriers had significantly less positive feelings (P<0.001) and were more consciously avoiding HD-related situations and thoughts (P<0.01). These findings reflect the carriers' conscious and unconscious attempt to escape from pessimism and to minimise negative consequences of the test result. Psychological distress 5 years post-test was significantly associated with ego-strength (P<0.05 to P<0.001). Except for intrusion and avoidance, distress was also associated with test motivation (P<0.05 to P<0.01). Compared with baseline level, mean depression, general and specific anxiety had significantly decreased 1 year and 5 years post-test (P<0.05 to 0.01). This evolution was independent of the test result. However, based on test motivation, a subgroup of tested persons having long lasting psychological distress could be identified, also irrespective of test result. Persons who asked the test to get rid of the uncertainty, without being able to specify implications for substantial life areas, had more psychological distress before and after the test than those who wanted the test for specific reasons (P<0.001 to P<0.0001). Moreover, the pattern of post-test anxiety differed over time, depending on the test motivation (P<0.05). The findings suggest that pre- and post-test counselling should pay special attention to persons with lower ego-strength and with an unspecified test motivation, because they are at higher risk for long-term psychological distress, independently of the test result.     

Potential impact of a predictive test on the gene frequency of Huntington disease

Fifty-five individuals at 50% risk of inheriting Huntington disease (HD) were given in-depth structured interviews to survey attitudes toward use of a predictive test and to assess the possible impact of such a test on the number of gene carriers born. Three-quarters of the sample said they would take predictive test. Given a positive predictive or prenatal test, the number of individuals choosing to have children is reduced from 80% of the total sample to 42%, or by almost one-half. The large proportion of at risk individuals who say they would use a predictive test underscores the importance of developing guidelines for its administration prior to implementation.     

Interest in genetic testing among first-degree relatives of breast cancer patients

The recent cloning of a breast-ovarian cancer susceptibility gene (BRCA1), and determination of the locus of a related gene (BRCA2), offers potential for clinical genetic testing for breast cancer susceptibility. This study examined interest in and expectations about an impending genetic test among first-degree relatives (FDRs) of breast cancer patients. One hundred five females completed two structured telephone interviews to assess demographics, breast cancer risk factors, psychological factors, and attitudes about genetic testing for breast cancer susceptibility. Overall, 91% of FDRs said that they would want to be tested, 4% said they would not, and 5% were uncertain. The most commonly cited reasons for wanting genetic testing were to learn about one's children's risk, to increase use of cancer screening tests, and to take better care of oneself. Women with less formal education were motivated by childbearing decisions and future planning to a greater degree than were women with education beyond high school. Most women anticipated a negative psychological impact of positive test results, involving increased anxiety (83%), depression (80%), and impaired quality of life (46%). In addition, 72% of women indicated that they would still worry if they tested negative. In multivariate regression analysis, level of baseline depression was the strongest predictor of an anticipated negative impact of genetic testing (Beta =.15; P,.0001). These results suggest that the demand for genetic testing for breast cancer susceptibility may be great, even among women who are not likely to have predisposing mutations. Prior to widespread availability of such testing, it will be critical to develop informed consent protocols to educate individuals about the benefits and limitations of predictive testing for this multifactorial disease. © 1995 Wiley-Liss, Inc.     

Attitudes of neurologists, psychiatrists, and psychotherapists towards predictive testing for Huntington''s disease in Germany.

Predictive testing for Huntington's disease (HD) in Germany is performed by genetic counsellors, neurologists, psychiatrists, and psychotherapists. In order to evaluate the attitudes of neurologists, psychiatrists, and psychotherapists in Germany towards predictive testing for HD, a postal questionnaire was sent to this group. Two German Bundesländer were chosen, Baden Württemberg (BW) and Niedersachsen (NS). Of 469 persons interviewed the response rate was 32.6%. The questionnaire consisted of 17 items assessing sociodemographic data, acquaintance with HD patients, lay organisations, attitudes towards genetic counselling, presymptomatic and prenatal DNA testing, and reproduction of persons at risk for HD. More than 70% of the subjects were well informed about predictive DNA testing but knowledge about the details of the test procedure, especially the World Federation of Neurology (WFN) and International Huntington Association (IHA)1 recommendations, was quite low (11.8%). Nevertheless, the majority would recommend predictive testing for HD although they anticipated problems for the probands. The majority of our respondents favoured psychological test and post-test counselling for those tested. Concerning reproduction, most subjects favoured prenatal testing or that persons at risk should refrain from having children. We found that the opinions of practitioners and at risk persons differed with respect to the predictive DNA test and, particularly, to prenatal testing. Therefore the testing procedure could be improved if practitioners were better informed about the DNA test in general and about the attitudes and wishes of their patients.     

Attitudes of persons at risk for Huntington disease toward predictive testing

Attitudes of 69 persons at risk for Huntington disease (HD) were obtained by means of semistructured interviews and questionnaires. About 79% of the individuals said that they would use a presymptomatic predictive test if it were available. All believed that the test should be made available even though there was no cure for HD. Nearly 2/3 of subjects would use the test for prenatal diagnosis, and of these 71% would terminate a pregnancy if the fetus was found to carry the HD gene. Most subjects believed that pretest counseling should be mandatory and many said that testing should be withheld from persons who were psychologically unstable or were threatening self-harm. The data suggest that about 2-6% of persons at risk for HD may have severe psychiatric or suicidal responses to a positive outcome of predictive testing. This underscores the need for adequate pretest counseling and the availability of professional and community resources to deal with the impact of predictive testing on individuals and their relatives.     

22 Years of predictive testing for Huntington's disease: the experience of the UK Huntington's Prediction Consortium

Huntington''s disease (HD) is a progressive neurodegenerative condition. At-risk individuals have accessed predictive testing via direct mutation testing since 1993. The UK Huntington''s Prediction Consortium has collected anonymised data on UK predictive tests, annually, from 1993 to 2014: 9407 predictive tests were performed across 23 UK centres. Where gender was recorded, 4077 participants were male (44.3%) and 5122 were female (55.7%). The median age of participants was 37 years. The most common reason for predictive testing was to reduce uncertainty (70.5%). Of the 8441 predictive tests on individuals at 50% prior risk, 4629 (54.8%) were reported as mutation negative and 3790 (44.9%) were mutation positive, with 22 (0.3%) in the database being uninterpretable. Using a prevalence figure of 12.3 × 10⁻⁵, the cumulative uptake of predictive testing in the 50% at-risk UK population from 1994 to 2014 was estimated at 17.4% (95% CI: 16.9–18.0%). We present the largest study conducted on predictive testing in HD. Our findings indicate that the vast majority of individuals at risk of HD (>80%) have not undergone predictive testing. Future therapies in HD will likely target presymptomatic individuals; therefore, identifying the at-risk population whose gene status is unknown is of significant public health value.     

Long-term impact of Huntington disease linkage testing

We performed a long-term follow-up of Huntington disease (HD) predictive testing (an average of 6 years post-test) for 16 of 20 people who received informative linkage test results. Although no pre-test or baseline psychological differences were noted between those with an increased versus a decreased risk of HD, the long-term impact was dramatically different in these two groups. The low-risk group reported less uncertainty, anxiety or worry, fear, and worry about children's risk, whereas the high-risk group reported either the same or increased concern in these areas. Those at low risk also acknowledged an increased sense of control and self-esteem, whereas those at high risk reported decreases or no changes. One high-risk individual reported chronic depression that had occurred since the testing. Additionally, those at low risk reported greater reliance and faith in spiritual or religious beliefs than those at high risk. The emotional impact of HD genetic testing justifies the continued utilization of pre- and post-test counseling protocols. Pre-test counseling should include discussion of the known risks and benefits of predictive testing, with special emphasis on the participant's expectations for future change and improvement. Although the psychological impact appears mostly favorable for those with decreased risk, there is risk for a decline in psychological well-being over time for those with an increased risk for HD. Am J. Med. Genet. 70:365–370, 1997. © 1997 Wiley-Liss, Inc.     

Psychological distress in applicants for predictive DNA testing for autosomal dominant, heritable, late onset disorders. The Rotterdam/Leiden Genetics Workgroup.

In a comparative study on the effects of predictive DNA testing for late onset disorders, pre-test psychological distress was assessed in people at risk for Huntington's disease (HD, n = 41), cerebral haemorrhage (HCHWA-D, n = 9), breast and ovarian cancer (HBOC, n = 24), and polyposis coli (FAP, n = 45). Partners, if available, also participated in the study. Distress was measured with the subscales Intrusion and Avoidance of the Impact of Event Scale. People at risk for the neurodegenerative disorders reported more avoidance than those at risk for the cancer syndromes. People at risk for FAP and partners of those at risk for HBOC reported less intrusion than the others at risk and the other partners. Subjects who were more distressed reported more experiences with the disease in close relatives, the disease having a great impact on their lives, having considerations against predictive testing, expecting that being identified as a gene carrier would have adverse effects, and expecting relief after being identified as a non-carrier. Test candidates who expected an increase of personal problems showed higher avoidance, whereas those who could better anticipate future life as a carrier had higher intrusion levels. Generally, subjects with high distress levels are of more concern to the healthcare professional than those with low distress levels. However, high distress may reflect worrying as a mental preparation for the test result, whereas low distress may indicate denial-avoidance behaviour and poor anticipation of the test outcome. In pre-test counselling sessions, this should be acknowledged and addressed.     

Psychosocial impact of predictive testing for Huntington disease on support persons

Although a support person is required by many centers during the predictive testing protocol for Huntington disease (HD), little is known about the psychosocial impact of predictive testing on persons serving in this role. Eighteen adults who were support persons during predictive HD testing in one HD testing center completed a semi-structured interview to describe their experiences. Participants also completed the Impact of Events Scale (IES) to assess perceptions of emotional distress regarding predictive testing and the State Anxiety Scale of the State Trait Anxiety Inventory (STAI) to assess anxiety regarding the interview. State anxiety scores were similar to normative values for working adults. Although support persons for individuals with a positive gene test scored higher on all measures of the IES than those who were support persons for persons with negative gene mutation results, these differences were not statistically significant. Support persons identified aspects of the protocol that did not fit their needs, perceived the testing process as extending into subsequent caregiving responsibilities when the test was positive, and were uninformed regarding specific caregiving issues for family members with the gene mutation. The impact of the testing experience appeared to be most intense for those support persons who were at-risk offspring of probands. Findings suggest that individual assessment of support person needs may allow more focused counseling of support persons during predictive genetic HD testing. Collaboration with health care providers may facilitate symptom management following testing.     

Reluctance to undergo predictive testing: The case of Huntington Disease

The development of a presymptomatic test for Huntington Disease (HD) has enabled some persons at risk to determine whether or not they are gene carriers. The purpose of this study was to explore the reasons why those at risk choose not to be tested in a situation where testing is available and most of the test-associated costs are covered by state funding. Subjects were also asked their levels of knowledge about testing, attitudes towards aspects of the testing protocols, and intentions towards testing once the gene for HD is found. Sixty-six individuals at risk for HD who had chosen not to be tested completed a mailed questionnaire. The most important reasons for not being tested were increased risk to children if one was found to be a gene carrier, absence of an effective cure, potential loss of health insurance, financial costs of testing, and the inability to “unndo” the knowledge. Individuals comprising this sample were quite knowledgeable about predictive testing. Most supported the availability of testing despite the lack of a cure, the need for special counseling prior to testing, and the idea that testing should be a voluntary decision. Most said they would take the test if a treatment was available, if the mechanics of the test were simplified, or if the test was 100% accurate. The risk to relatives, lack of treatment or cure, fear of losing one's health insurance, and the accuracy of the information to be gained from testing are important factors in the decision not to be tested. © 1993 Wiley-Liss, Inc.     

Suicide risk in Huntington''s disease.

In order to evaluate the relevance of suicide risk in families affected by Huntington's disease (HD), 2793 subjects registered with the National Huntington's Disease Research Roster were studied. Suicide was the reported cause of death in 205 subjects (7.3%). This group included affected and possibly affected subjects, subjects at 50% and 25% risk, possibly at risk subjects, and normal relatives. In all categories suicide was more frequent than in the general US population. The data suggest that suicide is quite frequent in some families with HD. This increased suicide risk must be carefully considered in planning genetic counselling for predictive testing in HD.     

Psychological functioning before predictive testing for Huntington's disease: the role of the parental disease, risk perception, and subjective proximity of the disease

BACKGROUND: Psychometric testing of participants in predictive DNA testing for Huntington's disease (HD) has shown that 15% of the subjects at risk for HD had at least mild depression or a high score for general anxiety or both in the pre-test period. The main aim of the study was the delineation of variables associated with pre-test distress of applicants for predictive testing for HD. Based on theoretical considerations, four specific hypotheses were tested regarding the role of (1) the test participant's age at the (perceived) parental onset of HD, (2) the affected parent's sex, (3) the perception of the risk for HD, and (4) the subjective proximity of the disease. Secondly, these four variables were used in multiple regression analyses to select the best predictors of pre- and post-test psychological functioning (one year after the test). Increasing the understanding of pre- and post-test distress is important for developing better counselling and support strategies for test applicants. METHODS: Data were collected by means of clinical interviews and psychometric questionnaires during the pre- and post-test (one year after the test) counselling sessions for predictive testing for HD. RESULTS: We found significant associations of the participant's age at the parental onset, the subjective proximity of the disease onset, and the perceived risk with pre-test psychometric measures of psychological functioning. Multiple regression analyses showed that the best predictors of pre-test functioning were the perceived proximity of the disease onset and its interaction with risk perception. Regarding post-test functioning, none of the proposed variables had a unique contribution beyond that accounted for by pre-test psychological functioning. CONCLUSIONS: Test participants who are close to the perceived age of onset of HD and who have a pessimistic risk perception should be given special attention during pre-test counselling because of their possible negative affective condition at that time. Pre-test psychological measures were the best predictors of post-test distress, irrespective of the test result. Suggestions for future longitudinal research are formulated. This kind of research should enable clinical geneticists and mental health professionals to refine the pre- and post-test counselling strategies for predictive DNA testing, not only for HD, but also for other incurable late onset disorders.     

Self-selection in predictive testing for Huntington's disease

Several studies have reported favorable psychological reactions to predictive testing for Huntington's disease (HD). However, few atrisk persons have been tested, and there is evidence that some at-risk people avoid testing because they fear being unable to cope with the information. Favorable psychological reactions may result from self-selection of persons who believe they are better-equipped to handle “bad news.” We surveyed 32 at-risk persons who had considered, but not chosen, testing and 66 persons who had been previously tested. Twelve persons decided not to be tested (No group); 20 persons postponed testing until some later date (Maybe group). Of the two untested groups, a significantly greater number of the No group had not been tested because they anticipated problems associated with their emotional reactions. The persons in the Tested group had less often anticipated problems with their emotional reactions; and among the minority who had anticipated some problems, most did not question their ability to cope. We conclude that the Tested persons are psychologically selected for favorable responses to genetic testing. Surveys of health professionals suggest that a sizable minority would disclose genetic disease risk whether or not people want it. Thus, people who would not choose to be tested might be persuaded to do so, or have results thrust upon them. We should be wary about assuming that the generally favorable reactions to HD testing will continue when testing becomes more widespread, as is likely to happen with simplification of the technology and acceptance of these tests by the medical community. © 1994 Wiley-Liss, Inc.     

Five year study of prenatal testing for Huntington''s disease: demand, attitudes, and psychological assessment.

Adult predictive and prenatal testing programmes for Huntington's disease (HD) in Canada have been available since 1986. However, the demand for prenatal testing and the reasons why some people choose not to have the prenatal test for this late onset disorder have not been well documented. In addition, the knowledge and attitudes of adult predictive testing candidates and their partners about prenatal testing are not well known nor are the psychological effects of prenatal testing well understood. As of September 1991, 425 subjects had entered the Canadian Collaborative Study of Predictive Testing and, of these, 47 subjects or their partners had become pregnant. Of this group, 14 (30%) couples requested prenatal testing, 24 (51%) couples did not want prenatal testing, and nine (19%) at risk subjects had already received a decreased risk through adult predictive testing and, therefore, were not eligible for the prenatal test. Of the 14 couples who initially requested prenatal testing, seven withdrew. Thus, demand for the prenatal test by eligible candidates was 7/38 or 18%, which is much lower than the 32 to 65% expected based on early survey data. The most frequently cited reason for declining prenatal testing was the hope that a cure would be found in time for their children. While the majority of adult predictive testing candidates (71%) in our study had accurate information about definitive prenatal testing, many (63%) did not have a correct understanding of exclusion prenatal testing. Although no serious adverse events such as suicide planning or admission to psychiatric hospital have occurred, a particular need for careful counselling was identified for those at risk candidates and their partners who have one prenatal test and feel compelled to use the test again in future pregnancies. Even though prenatal testing for HD is not requested as often originally expected, it still remains a desired option for some at risk persons and their partners.     

Prediction of psychological functioning one year after the predictive test for Huntington''s disease and impact of the test result on reproductive decision making.

For people at risk for Huntington's disease, the anxiety and uncertainty about the future may be very burdensome and may be an obstacle to personal decision making about important life issues, for example, procreation. For some at risk persons, this situation is the reason for requesting predictive DNA testing. The aim of this paper is two-fold. First, we want to evaluate whether knowing one's carrier status reduces anxiety and uncertainty and whether it facilitates decision making about procreation. Second, we endeavour to identify pretest predictors of psychological adaptation one year after the predictive test (psychometric evaluation of general anxiety, depression level, and ego strength). The impact of the predictive test result was assessed in 53 subjects tested, using pre- and post-test psychometric measurement and self-report data of follow up interviews. Mean anxiety and depression levels were significantly decreased one year after a good test result; there was no significant change in the case of a bad test result. The mean personality profile, including ego strength, remained unchanged one year after the test. The study further shows that the test result had a definite impact on reproductive decision making. Stepwise multiple regression analyses were used to select the best predictors of the subject's post-test reactions. The results indicate that a careful evaluation of pretest ego strength, depression level, and coping strategies may be helpful in predicting post-test reactions, independently of the carrier status. Test result (carrier/ non-carrier), gender, and age did not significantly contribute to the prediction. About one third of the variance of post-test anxiety and depression level and more than half of the variance of ego strength was explained, implying that other psychological or social aspects should also be taken into account when predicting individual post-test reactions.     

Attitudes toward presymptomatic testing in Huntington disease

One hundred thirty-one individuals at 50% risk of inheriting Huntington disease (HD) responded to a survey to study their attitudes toward taking a genetic test based on the identification of a genetically linked DNA polymorphism. Ninety-six percent of the respondents believe that presymptomatic testing should be available, and 66% say they will use it themselves. Fewer married individuals, in comparison to those single, separated, and divorced, intend to take the test. Many respondents (40%) said their primary reason for wanting to be tested is to end the uncertainty in their lives. Results suggest that there will be self-selection in test use, with many individuals who believe they will be depressed or possibly suicidal with a positive test result deciding not to be tested or unsure about testing. However, 15% of those who want to be tested acknowledge that they may be at risk for suicide if they are probable gene carriers. Only 12% of all respondents say they will be likely to use prenatal testing, suggesting that initial demand may be low in New England. Implementation of presymptomatic testing challenges health care providers to develop strategies to care for otherwise healthy persons who will be given a diagnosis years before the onset of illness.