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.     

To know or not to know: a review of behaviour and suicidal ideation in preclinical Huntington's disease

OBJECTIVE: At present, the problems associated with suicidal ideation and suicide in Huntington's disease (HD), worldwide, are much the same as 2 decades ago. This study seeks to investigate the psychological complications of predictive testing in HD at risk populations. METHODS: The key problems of predictive testing, fear of acquiring carrier status, psychological consequences, autonomy, and rights to know are discussed. RESULTS: This review (1) describes psychological affect and problems of persons facing the decision to test for HD, (2) discusses suicidal ideation, behaviour, and catastrophic events associated with predictive testing, (3) assesses ethical questions raised in the genetic counselling, (4) questions whether counsellors should promote or advocate predictive testing, and finally (5) discusses what professionalism actually is in genetic counselling. CONCLUSION: The need for professional counselling, using a well designed protocol, and the importance of focusing on the suicide risk of participants in predictive testing programs are emphasized. PRACTICE IMPLICATIONS: The counsellor has an obligation to provide adequate information. The professionals should not promote nor advocate presymptomatic DNA-testing. Depression, hopelessness, anxiety, emotional distress, suicidal tendencies, and social dysfunction grading should be considered in predictive testing of HD.     

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.     

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.     

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 myotonic dystrophy type 1

In the Saguenay-Lac-Saint-Jean region (Quebec, Canada), a predictive DNA-testing program for myotonic dystrophy type 1 (DM1) has been available as a clinical service since 1988. From 1 to 12 years (median, 5 years) after receiving predictive testing, a total of 308 participants (44 carriers and 264 non-carriers) answered a questionnaire to determine the psychosocial impact of this genetic testing. The main reasons for wanting to be tested were to learn if children are at risk for DM1 or for reproductive decision making (75%) and to relieve the uncertainty for themselves (17%). The majority of participants (96.1%) remembered correctly their test result. At the time of the survey, the perception of the general well-being, the psychological distress (Psychiatric Symptom Index), and the self-esteem (Rosenberg Self-Esteem Scale) were similar in carriers, in non-carriers, and in the reference (Quebec) population. When participants indicated a change in different aspects of their lives following predictive testing, it was perceived as a change for the better by non-carriers and as a change for the worse by carriers. Nevertheless, for a majority of carriers and of non-carriers, the test result did not bring changes in their lives. All respondents believed that predictive testing should be available for the at-risk population and the vast majority of carrier and of non-carriers would recommend the use of predictive testing to their family members. Predictive testing for individuals at-risk of DM1 can be offered safely within a well-organized clinical and genetic counseling program that includes careful pre-test counseling, pre-test clinical assessment, post-test psychological support, and follow-up for those identified as carriers.     

Evaluation of a counselling protocol for predictive genetic testing for hereditary non-polyposis colorectal cancer

OBJECTIVES—To evaluate the feasibility of a reduced counselling programme for predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC) in terms of counsellees' opinions on the extent and significance of genetic counselling and need for psychological support at different phases of the testing procedure.
DESIGN—Prospective follow up study with pre-test questionnaire assessment of background sociodemographic variables. The protocol comprised a pre-test counselling session, a period for reflection, and a test disclosure session. The outcome variables were studied by post-test questionnaires at one month and one year follow up.
SUBJECTS—Two hundred and seventy one high risk members of 36 families with HNPCC who attended both counselling sessions and completed the questionnaires.
RESULTS—The pre-test counselling was considered fairly or very useful by 89% of respondents and one post-test session was considered sufficient by over 80% of respondents at follow up. Fifty three percent would have used extra psychological support had it been offered with the counselling. On enquiry one year after receiving the test result, only 2% stated that the need for support was at its greatest at that time, while the majority (46%) reported that the need for support had been greatest at the moment of test disclosure.
CONCLUSIONS—A protocol that includes one comprehensive pre-test counselling session and a test disclosure session, supplemented with the option of professional psychological support, seems to be sufficient for both the educational and supportive needs of counsellees. Only a minority expressed a need for post-test follow up sessions, which suggests that, in this disorder, resources can be directed to the beneficial surveillance programmes rather than to extensive psychological support.


Keywords: predictive genetic testing; genetic counselling; HNPCC; hereditary non-polyposis colorectal cancer     

Predicting adaptation to presymptomatic DNA testing for late onset disorders: who will experience distress? Rotterdam Leiden Genetics Workgroup.

The first comparative study on predicting post-test distress (conceptualised by intrusion and avoidance, measured with the Impact of Event Scale) after presymptomatic genetic testing for Huntington's disease (HD, n=25), cancer syndromes (familial adenomatous polyposis (FAP, n=23)), and hereditary breast and ovarian cancer (HBOC, n=10) is reported. The variables with the highest predictive potential of post-test distress are presented. Participants who were depressed before the test were more distressed after testing, but we found that those who were anxious before the test were less distressed, that is, had less intrusive thoughts post-test. Other factors associated with a higher level of post-test intrusion were gender (being a woman), having children, and pre-test intrusion. Religion and being at risk for HBOC were associated with less post-test intrusion. Participants who showed avoidance behaviour before the test and those who had many people available for support showed more avoidance behaviour post-test. The test result did not additionally contribute to post-test distress. The prima facie simple notion that the test result, as such, determines the distress experienced seems to be a misrepresentation of the complex reality.     

Perception of predictive testing for Huntington's disease by young women: preferring uncertainty to certainty?

Opinions on the implications of predictive testing for Huntington's disease were evaluated in a group of 169 women (aged 21-35 years) with interest in psychosocial issues, but with no special pre-existing knowledge or training in genetics. Predictive testing for Huntington's disease (HD) is considered to be a test case for predictive testing for other late onset diseases, monogenic as well as multifactorial disorders. In the hypothetical situation of having a 50% risk for developing HD, about half of the group expressed interest in a predictive test. As to the question of giving results of predictive tests to third parties, the group would be very reluctant to inform the employer or the insurer, but not their own family. Prenatal testing for late onset diseases was considered acceptable by half of the women; only one quarter of the total group would terminate a pregnancy of a child that might develop a late onset disease. The assessment of attitudes towards predictive testing was carried out within the context of a global evaluation of perceived advantages and disadvantages of genetic counselling. The attitudes towards predictive testing were systematically associated with perceiving 'having more certainty about the future' as an advantage of genetic counselling and with rejecting 'knowing everything in advance' as a disadvantage.     

Considerations in using linkage analysis as a presymptomatic test for Huntington''s disease.

The polymorphic locus D4S10 that is genetically linked to the locus for Huntington's disease (HD) has made possible a presymptomatic test for those at risk. Because the symptoms of this progressively debilitating and fatal illness are not usually manifest until adulthood, the outcome of the test will influence major decisions about career, marriage, and procreation. Several differential diagnoses must be considered before using the test if HD is not confirmed in at least one family member. Review of a large number of pedigrees has shown that 40% of persons at risk do not have appropriate family structure for a linkage test. Furthermore, uncooperative or inaccessible relatives may make this test infeasible for many others who wish to be tested. Linkage phase, which must be known in the affected parent for an informative test, can be determined using one or more of 12 probe-enzyme combinations for D4S10. Although the polymorphism information content (PIC) value for any one RFLP is less than 40%, the PIC value for the haplotype of the two G8 HindIII, pK083 EcoRI, and R7 BglII RFLPs is greater than 88%. We have developed a scheme to incorporate linkage data and age at onset information adjusted for censored observations, sex of affected parent, and familial correlation for age at onset, using the computer program MLINK for calculation of risk of having HD. Simulated experiments showed that proper age at onset adjustment is crucial to the calculation of the probability of risk. A formal presymptomatic testing protocol, including pre- and post-test counselling, psychological testing, and paternity testing is recommended. Many of these considerations are illustrated in several actual test cases.     

Psychological consequences of predictive genetic testing: a systematic review

The aim of this systematic literature review is to describe the psychological consequences of predictive genetic testing. Five databases were searched for studies using standardised outcome measures and statistical comparison of groups. Studies were selected and coded by two independent researchers. From 899 abstracts, 15 papers, describing 11 data sets, met the selection criteria for the review. The studies were of predictive genetic testing for Huntington's disease, hereditary breast and ovarian cancer, familial adenomatous polyposis and spinocerebellar ataxia. One involved children; the rest were of adults. None of the 15 papers reported increased distress (general and situational distress, anxiety and depression) in carriers or non-carriers at any point during the 12 months after testing. Both carriers and non-carriers showed decreased distress after testing; this was greater and more rapid amongst non-carriers. Test result (ie being a carrier or non-carrier) was rarely predictive of distress more than one month after testing (predictive in two of 14 analyses). Pre-test emotional state was predictive of subsequent distress in 14 of 27 analyses. There is a lack of informative studies in this field. The studies reviewed suggest that those undergoing predictive genetic testing do not experience adverse psychological consequences. However, the studies are of self-selected populations who have agreed to participate in psychological studies and have been followed up for no more than three years. Most research has been of testing for Huntington's Disease and included follow-up of no more than one year. The results suggest that testing protocols should include a pre-test assessment of emotional state so that post-test counselling can be targeted at those more distressed before testing. None of the studies experimentally manipulated the amount or type of counselling provided. The relationship between counselling and emotional outcome is therefore unclear and awaits empirical study.     

Experiences of predictive testing in young people at risk of Huntington's disease,familial cardiomyopathy or hereditary breast and ovarian cancer

While debate has focused on whether testing of minors for late onset genetic disorders should be carried out if there is no medical benefit, less is known about the impact on young people (<25 years) who have had predictive testing often many years before the likely onset of symptoms. We looked at the experiences of young people who had had predictive testing for a range of conditions with variable ages at onset and options for screening and treatment. A consecutive series of 61 young people who had a predictive test aged 15–25 years at the Clinical Genetic Service, Manchester, for HD, HBOC (BrCa 1 or 2) or FCM (Hypertrophic Cardiomyopathy or Dilated Cardiomyopathy), were invited to participate. Thirty-six (36/61; 59%) agreed to participate (10 HD, 16 HBOC and 10 FCM) and telephone interviews were audiotaped, transcribed and analysed using Interpretative Phenomenological Analysis. None of the participants expressed regret at having the test at a young age. Participants saw the value of pretest counselling not in facilitating a decision, but rather as a source of information and support. Differences emerged among the three groups in parent/family involvement in the decision to be tested. Parents in FCM families were a strong influence in favour of testing, in HBOC the decision was autonomous but usually congruent with the views of parents, whereas in HD the decision was autonomous and sometimes went against the opinions of parents/grandparents. Participants from all three groups proposed more tailoring of predictive test counselling to the needs of young people.     

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.     

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.     

Predictive testing for hereditary breast and ovarian cancer: a psychological framework for pre-test counselling

Since the identification of two breast-ovarian cancer susceptibility genes (BRCA1/2), predictive testing for hereditary breast/ovarian cancer (HBOC) has been available. Given the complexity and uncertainties of HBOC and the potential impact of predictive testing on psychological well-being, we offer the test applicants a combination of information-oriented and psychological counselling. In this paper, we describe the multidisciplinary approach for predictive testing for HBOC as a clinical service in Leuven, hereby focusing on psychological and decision counselling practice. Attention is paid to the theoretical framework used for pre-test psychological counselling in Leuven. We discuss three important interacting dimensions of psychological counselling: individual emotional support, decision counselling and support of the family communication process. Decision counselling consists of an evaluation of the cognitive and the emotional processing of the information given and strategies and resources for coping. This serves as a starting point to facilitate free informed decision making. Scenario development is used as a decision aid.     

Predictive testing for Huntington's disease: relationship with partners after testing

This study focuses on the partner relationship of tested persons, 5 years after their predictive test result for Huntington's disease (HD). We describe changes in marital status, quality of the relationship, and perceived changes in the relationship. Twenty-six carriers, 14 of their partners, 33 non-carriers, and 17 of their partners participated in the study. Qualitative and quantitative methods were used. For the majority of tested persons (about 70%), the marital status was unchanged 5 years post test. Overall, carriers rated the quality of the relationship higher than their partners did and they perceived more positive changes. Qualitative data show that a test result leading to changed roles may induce significant marital distress. Another consequence of the test may be the changes in dynamics in asymptomatic carrier couples. A pre-test discussion of the possible impact of the test result on the relationship should result in a better preparation for and more understanding of the reactions after testing. Counselling after testing should stimulate an open communication between partners with consideration of needs and anxieties of both partners.     

Psychological consequences and predictors of adverse events in the first 5 years after predictive testing for Huntington's disease

The promise of genetic medicine is to provide information, based on genotype, to persons not yet sick about their risk of future illness. However, little is known of the long-term psychological effects for asymptomatic persons learning their risk of having a serious disease. Predictive genetic testing for Huntington's disease (HD) has been offered for the longest time for any disease. In the present study, the psychological consequences of predictive testing were assessed prospectively in individuals at risk for HD during seven visits over 5 years. Questionnaires of standard measures of psychological distress (the General Severity Index of the Symptom Check List-90-Revised), depression (the Beck Depression Inventory), and general well-being (the General Well-Being Scale) were administered to the participants. A significant reduction in psychological distress was observed for both result groups throughout 2 years (p < 0.001) and at 5 years (p = 0.002). Despite the overall improvement of the psychological well-being, 6.9% (14 of 202) of the participants experienced an adverse event during the first 2 years after predictive testing that was clinically significant. The frequency of all defined adverse events in the participants was 21.8%, with higher frequency in the increased risk group (p = 0.03) and most occurring within 12 months of receiving results.