Long-term outcome of presymptomatic testing in Huntington disease

Our study on long-term outcome of presymptomatic testing for Huntington disease had two aims: the comparison of the psychological well-being and social adjustment of carriers and non-carriers of the mutation, and the identification of psychological determinants to improve care/support of testees. We performed a cross-sectional study of 351 persons who underwent presymptomatic testing. Those who had motor signs were excluded from the comparison of asymptomatic carrier and non-carriers. A structured interview including five self-report scales and the MINI (Mini International Neuropsychiatric Inventory) was proposed to detect a psychopathology or problem with social adjustment.We interviewed 119 testees (53%), 62 non-carriers and 57 carriers after a mean delay of 3.7 years (range: 0.32 to 8.9) after their result. Depression was frequent in asymptomatic carriers (58%). Interestingly, the self reported impact of the test showed that 27% of non-carriers did not cope well with a favourable result, and a significant percentage of non-carriers (24%) were depressed during follow-up. Multivariate analysis showed that only a previous episode of depression was predictive of depression after genetic testing in both carriers and non-carriers of the HD mutation (P<0.0001).Psychological support is necessary for all testees regardless of the result of their presymptomatic test, because psychiatric care is often needed by both carriers and non-carriers.     

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.     

Predictive DNA-testing for Huntington's disease and reproductive decision making: a European collaborative study

This European collaborative study addresses the question whether a predictive test result for Huntington's disease (HD) has an effect on subsequent reproduction by comparing carriers and non-carriers of the Huntington mutation. A unique characteristic of this study is that this evaluation is done in persons at reproductive age who had a predictive test after the identification of the Huntington gene and who were counselled in one of the participating centres. Data were collected for 180 carriers and 271 non-carriers who received a predictive test result in the period 1993-1998 in Aberdeen, Athens, Cardiff, Leiden, Leuven, Paris or Rome. The mean age of the total study group was 31.5 years and for about half of the group the follow-up interval was 3 years or more, with a maximum of 7 years. The collaborative study clearly revealed an overall impact of the predictive test result on subsequent reproduction: 14% of the carriers had one or more subsequent pregnancies vs 28% of the non-carriers. In the total carrier group a prenatal test was carried out in about two thirds of the pregnancies and one child was born after preimplantation genetic diagnosis; artificial insemination by donor, egg cell donation or adoption were not reported. A more refined analysis was performed in the subgroup with a follow-up interval of at least 3 years and who reported 'family planning' as a motive to apply for predictive testing in the pretest period. The complexity of this motive is discussed. In this subgroup with a desire for children in the pretest period the effect of the predictive test result was more pronounced: 69% of the non-carriers had subsequent pregnancies while only 39% of the carriers who mentioned 'family planning' as one of the major reasons to apply for predictive testing had a subsequent pregnancy. Of the carriers with one or more subsequent pregnancies the percentage using prenatal diagnosis was slightly higher than the percentage not using it, although there were clear differences from one centre to another. The latter group's decisions may seem more intriguing but may be partially understood based on stage theories of health behaviour. Last, but not least, whatever option is chosen by a couple at increased risk of transmitting the Huntington mutation, it is of the utmost importance that professionals fully respect this decision and support the couple.     

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.     

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.     

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.     

Areas of intervention for genetic counselling of dementia: cross-cultural comparison between Italians and Americans

OBJECTIVE: Purposes of this study are: (1) to evaluate attitudes, beliefs and experiences towards dementia among relatives of Italian familial cases; (2) to perform a cross-cultural comparison between Italian and American samples; (3) to identify predictors of intentions to undergo hypothetical genetic testing. METHODS: Participants were 134 relatives of patients affected by familial forms of dementia. We administered tests measuring health psychological styles, social variables, illness perceptions, intentions regarding genetic testing, and perceptions of the pros and cons of genetic testing. RESULTS: Respondents had a poor Alzheimer's disease knowledge and a low perceived dementia threat. When compared to Americans, Italians reported greater willingness to undergo genetic testing and perceived a different subset of benefits and risks. The strongest predictors of test intention were decisional balance, homemaker status and two beliefs concerning dementia causes. CONCLUSIONS: Italians had a poor knowledge of the disease and a low awareness of personal risk of developing dementia. As compared to Americans, they expressed higher intentions to undergo genetic testing and they have a different perception of benefits and risks. PRACTICE IMPLICATIONS: Understanding of cultural differences in knowledge, attitudes and perception of the disease is important to design optimal health services and education programs for dementia.     

Psychological aspects of pre-symptomatic testing for Machado-Joseph disease and familial amyloid polyneuropathy type I

Machado-Joseph disease [MJD, also spinocerebellar ataxia type 3 (SCA3)] and familial amyloid polyneuropathy type I (FAP-I or ATTR V30M) are neurodegenerative disorders, inherited in an autosomal dominant fashion, which have a high prevalence in Portugal, probably due to a founder effect. MJD and FAP-I are late-onset diseases, with symptoms emerging usually during adulthood. CGPP, which is the national reference centre for these disorders, has a genetic lab that offers diagnostic, pre-symptomatic and prenatal testing and an outpatient clinic to counsel and follow relatives at risk for hereditary ataxias, FAP-I and Huntington disease (HD). The present work is a review of our 10-year experience with psychological counselling of individuals at risk for MJD and FAP-I. Persons at risk for FAP-I may show a better response to pre-symptomatic testing than those who are at risk for MJD and HD because of the availability of liver transplantation, which may improve their health and life expectancy. Psychological well-being and specific distress of MJD and FAP-I test applicants, before undergoing genetic testing (baseline level) and 3 to 6 months after disclosure of test results, have shown a low level of change, both in identified carriers and non-carriers. A major goal of psychological characterization of at-risk individuals for MJD and FAP-I is to determine the factors that influence the uptake of genetic testing.     

Carrier testing of children for two X linked diseases in a family based setting: a retrospective long term psychosocial evaluation

The question of whether genetic carrier testing should be performed on children has been the subject of much debate. However, one important element has been lacking from this debate. There has been practically no knowledge of how those tested in childhood have experienced carrier testing. Twenty three subjects in families affected by Duchenne muscular dystrophy and 23 in families affected by haemophilia A, all of whom had been tested during childhood for carriership in the Department of Medical Genetics, University of Helsinki, from 1984 to 1988, participated in our study. We investigated long term psychosocial consequences of carrier testing in childhood. A questionnaire relating to sociodemographic background and life situation was used, together with assessment of health related quality of life (HRQOL) using the RAND 36 item Health Survey 1.0 (RAND). RAND results showed that the emotional, social, and physical well being of the young female subjects was not statistically different from those of control female subjects at a similar age. We also found no statistically significant differences in means in any RAND dimension (p<0.146) between carriers, non-carriers, and a group in which carrier status was uncertain. However, two out of seven carriers reported that they were worried and three that they were slightly worried about the test result. Four out of 22 young female subjects in the uncertain group reported being worried and 11 reported being slightly worried.


Keywords: carrier testing in childhood; health related quality of life; psychosocial consequences; RAND     

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.     

Areas of intervention for genetic counselling of dementia: Cross-cultural comparison between Italians and Americans

ObjectivePurposes of this study are: (1) to evaluate attitudes, beliefs and experiences towards dementia among relatives of Italian familial cases; (2) to perform a cross-cultural comparison between Italian and American samples; (3) to identify predictors of intentions to undergo hypothetical genetic testing.MethodsParticipants were 134 relatives of patients affected by familial forms of dementia. We administered tests measuring health psychological styles, social variables, illness perceptions, intentions regarding genetic testing, and perceptions of the pros and cons of genetic testing.ResultsRespondents had a poor Alzheimer's disease knowledge and a low perceived dementia threat. When compared to Americans, Italians reported greater willingness to undergo genetic testing and perceived a different subset of benefits and risks. The strongest predictors of test intention were decisional balance, homemaker status and two beliefs concerning dementia causes.ConclusionsItalians had a poor knowledge of the disease and a low awareness of personal risk of developing dementia. As compared to Americans, they expressed higher intentions to undergo genetic testing and they have a different perception of benefits and risks.Practice ImplicationsUnderstanding of cultural differences in knowledge, attitudes and perception of the disease is important to design optimal health services and education programs for dementia.     

Neuropsychological characteristics of Huntington''s disease carriers: a double blind study.

A cohort of 33 people at risk for Huntington's disease (HD), applying for genetic testing, were tested with a battery of neuropsychological tests covering attentional, visuospatial, learning, memory, and planning functions. A psychiatric rating scale, SCL-90R, was also applied, mainly as a control, since cognitive dysfunction could be ascribed to functional disorders as well as neurodegenerative processes. Self-rating did not indicate any psychiatric symptoms in carriers or non-carriers. However, significantly inferior cognitive functioning in the gene carriers was disclosed by the neuropsychological tests. Primarily, attentional, learning, and planning functions were affected. It is concluded that premorbid cognitive decline occurs in HD.     

Genetic testing for a BRCA1 mutation: prophylactic surgery and screening behavior in women 2 years post testing

Mutations in the BRCA1 gene are associated with an increased risk of breast and ovarian cancer in carrier women. An understanding of behavioral responses to BRCA1 mutation testing by mutation carriers and non-carriers is important to guide the clinical application of this new technology. This study examined the utilization of genetic testing for a BRCA1 mutation in high-risk individuals and the response of tested women with respect to interventions for early cancer detection and prevention. This study assessed the utilization of genetic testing for both men and women in a large kindred and the behavioral responses by women with respect to use of health care interventions during the 2 years following testing. Participants were offered BRCA1 mutation testing. Surveillance behaviors related to breast and ovarian cancer were assessed by computer-assisted telephone interviews at baseline (prior to genetic counseling and testing), 1-2 weeks, 4-6 months, 1 and 2 years after the provision of test results. Mutation carriers, non-carriers, and individuals of unknown mutation status were compared to determine the impact of test results. Utilization of genetic testing for both men and women are reported and, for women, mammography, breast self-exam, clinical breast exam, mastectomy, oophorectomy, transvaginal ultrasound, and CA125 screening were assessed. Of those fully informed of the opportunity for testing, 55% of the women and 52% of the men pursued genetic testing. With respect to mammography for women 40 years and older, 82% of mutation carriers obtained a mammogram in each year following testing compared to 72% of non-carrier women the first year and 67% the second year. This mammography utilization represents a significant increase over baseline for both mutation carriers and non-carriers. Younger carrier women also significantly increased their mammography utilization from baseline. Overall, 29% of the carrier women did not obtain a single mammogram by 2 years post-testing. At 2 years, 83% of the carrier women and 74% of the non-carriers reported adherence to recommendations for breast self-exam and over 80% of carrier women had obtained a clinical breast examination each year following testing. None of the carrier women had obtained a prophylactic mastectomy by 2 years after testing, although 11% were considering this procedure. Of carrier women 25 years of age and older who had at least one intact ovary at the time of testing, 46% of carriers had obtained an oophorectomy 2 years after testing, including 78% of women 40 years of age and older. The majority of carrier women (73%) had discussed their genetic test results with a medical doctor or health care provider. Our results indicate utilization of genetic testing by a majority of high-risk individuals who received information about testing. Both carriers and non-carriers increased their utilization of mammography and breast self-exam following testing. Oophorectomy was obtained by a large proportion of carrier women in contrast to mastectomy which was not utilized within the first 2 years following testing.     

Population screening for cystic fibrosis: knowledge and emotional consequences 18 months later

We assessed cystic fibrosis (CF) knowledge and emotional consequences of CF population testing 18 months after screening was offered. Questionnaires were sent to 593 individuals and 353 responded (59.5%). All respondents had sound knowledge of CF disease, although carriers were more likely to correctly state the pattern of CF inheritance and CF carrier rate in Australia. Eleven of 47 carriers falsely believed they were only very likely to be carriers, while nearly a third of test-negative individuals falsely believed they were definitely not carriers. Imprecise recall of the meaning of results may be due to memory loss over time, simplification of result meaning and minimization of risk. The Health Orientation Scale (HOS) was used to assess emotional consequences of CF carrier testing 18 months after testing. Both carriers and test-negative individuals thought most carriers would experience more negative feelings than most non-carriers. Carriers experienced less positive feelings about their test result compared to non-carriers. Interestingly, the carriers' own feelings about their result were more positive compared to how they thought most carriers would feel. These results suggest that carriers experience minimal adverse psychological effects, although a negative social stigma may be attached to carrying the CF gene mutation.     

Psychological impact of news of genetic risk for Huntington disease.

A one-year longitudinal study was conducted investigating the psychological effects of the news of genetic testing for the Huntington disease (HD) gene. Participants were assessed at baseline (before obtaining news of test results) and at three, six, and 12 months after test results on stress-specific symptom measures. Among carriers of the HD gene, a considerable number (55%) showed evidence of neurological impairment at baseline, indicative of HD. Also noteworthy, these individuals had significantly higher psychological symptom scores at baseline than carriers without neurological impairment or noncarriers. Despite this, these individuals were no more aware of their carrier status at baseline than carriers without HD symptoms or noncarriers. Furthermore, the psychological symptom levels of HD carriers with neurological impairment remained elevated across the follow-up assessments. Results for noncarriers and carriers without HD neurological symptoms were consistent with the findings of previous studies indicating that news of genetic testing for the HD gene had limited detrimental impact. The clinical implications of the results are discussed.     

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.     

Psychological impact of news of genetic risk for Huntington disease

A one‐year longitudinal study was conducted investigating the psychological effects of the news of genetic testing for the Huntington disease (HD) gene. Participants were assessed at baseline (before obtaining news of test results) and at three, six, and 12 months after test results on stress‐specific symptom measures. Among carriers of the HD gene, a considerable number (55%) showed evidence of neurological impairment at baseline, indicative of HD. Also noteworthy, these individuals had significantly higher psychological symptom scores at baseline than carriers without neurological impairment or noncarriers. Despite this, these individuals were no more aware of their carrier status at baseline than carriers without HD symptoms or noncarriers. Furthermore, the psychological symptom levels of HD carriers with neurological impairment remained elevated across the follow‐up assessments. Results for noncarriers and carriers without HD neurological symptoms were consistent with the findings of previous studies indicating that news of genetic testing for the HD gene had limited detrimental impact. The clinical implications of the results are discussed. © 2001 Wiley‐Liss, Inc.     

Predictive testing for Huntington's disease: I. Predictors of uptake in South Wales

In Wales, predictive testing for Huntington's disease (HD) has not been offered proactively to families and uptake of testing is low in comparison to other centres. Little is known of those not requesting testing, particularly those not in direct contact with the genetics service. This study examined differences between a cohort of 22 test applicants and a random group of 32 'non-requesters', drawn from the South Wales HD register. Respondents were interviewed by means of a semi-structured schedule in their own homes. The study groups differed significantly on a number of variables including: knowledge of the availability of testing; perceived attitudes of family members and significant others to testing; length of knowledge and perceived stressfulness of being at risk; and perceived ability to cope with an unfavourable result. Overall, knowledge of testing procedures was poor and at-risk individuals' understanding of genetic terminology was at odds with scientific distinctions. Discussion focuses on the organisational and psychological factors associated with lack of knowledge of the availability of testing and the interpretation of reported coping capacities.     

Psychological costs and benefits of predictive testing for Huntington's disease

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 disclosure 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. Negative effects in high-risk persons were psychological burden (worry, guilt). Even for low-risk subjects, there was a period of adjustment and, in some, disappointment that low risk had not alleviated problems unrelated to HD. Although the majority of marriages were unaffected by testing, some persons in both groups reported that their marriages sustained positive or negative impact. 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, regardless of test outcome. © 1994 Wiley-Liss, Inc.