Maurice Bloch

The psychological consequences of predictive testing for Huntington's disease.

Abstract Background. Advances in molecular genetics have led to the development of tests that can predict the risk of inheriting the genes for several adult-onset diseases. However, the psychological consequences of such testing are not well understood. Methods. The 135 participants in the Canadian program of genetic testing to predict the risk of Huntingtons disease were followed prospectively in three groups according to their test results: the increased-risk group (37 participants), the decreased-risk group (58 participants), and the group with no change in risk (the no-change group) (40 participants). All the participants received counseling before and after testing. Standard measures of psychological distress (the General Severity Index of the Symptom Check List 90-R), depression (the Beck Depression Inventory), and well-being (the General Well-Being Scale) were administered before genetic testing and again at intervals of 7 to 10 days, 6 months, and 12 months after the participants received their t...

A Worldwide Assessment of the Frequency of Suicide, Suicide Attempts, or Psychiatric Hospitalization after Predictive Testing for Huntington Disease

Prior to the implementation of predictive-testing programs for Huntington disease (HD), significant concern was raised concerning the likelihood of catastrophic events (CEs), particularly in those persons receiving an increased-risk result. We have investigated the frequency of CEs-that is, suicide, suicide attempt, and psychiatric hospitalization-after an HD predictive-testing result, through questionnaires sent to predictive-testing centers worldwide. A total of 44 persons (0.97%) in a cohort of 4,527 test participants had a CE: 5 successful suicides, 21 suicide attempts, and 18 hospitalizations for psychiatric reasons. All persons committing suicide had signs of HD, whereas 11 (52.4%) of 21 persons attempting suicide and 8 (44.4%) of 18 who had a psychiatric hospitalization were symptomatic. A total of 11 (84.6%) of 13 asymptomatic persons who experienced a CE during the first year after HD predictive testing received an increased-risk result. Factors associated with an increased risk of a CE included (a) a psychiatric history </=5 years prior to testing and (b) unemployed status. The frequency of CEs did not differ between those persons receiving results of predictive testing through linkage analysis in whom there was only changes in direction of risk and those persons receiving definitive results after analysis for the mutation underlying HD. These findings provide insights into the frequency, associated factors, and timing of CEs in a worldwide cohort of persons receiving predictive-testing results and, as such, highlight persons for whom ongoing support may be beneficial.

Silent periods, long-latency reflexes and cortical MEPs in Huntington's desease and at-risk relatives

Short-latency (R1) and long-latency (R2) components of the stretch reflex, the electromyographic silent period (S-X interval) and motor evoked potentials (MEPs) elicited by magnetic stimulation of the cortex were measured in Huntingtons disease (HD), at-risk first degree relatives and a normal control group. R1 and MEPs as well as central motor delay were normal in all 3 groups. R2 was absent in 7/9 patients with HD and 3/13 at-risk subjects. The S-X interval was reduced (less than 84 msec) in 7/9 patients and 5/13 at-risk subjects. Combined studies were abnormal in 88.9% of patients and 54% of at-risk subjects.

FIRST-TRIMESTER PRENATAL DIAGNOSIS FOR HUNTINGTON'S DISEASE WITH DNA PROBES

Polymorphic DNA probes linked to the locus for Huntington disease (HD) were used for prenatal diagnosis of a 10-week fetus at 25% risk for the disease. The fetus proved to have a 48% risk of having inherited the HD mutation which was similar to that for the at-risk parent (50%). On this basis the parents elected to terminate the pregnancy. When appropriate family members are available and DNA studies are informative, prenatal diagnosis of HD with polymorphic DNA probes can determine the at-risk status of the fetus with 96% accuracy.

Risk Reversals in Predictive Testing for Huntington Disease

The first predictive testing for Huntington disease (HD) was based on analysis of linked polymorphic DNA markers to estimate the likelihood of inheriting the mutation for HD. Limits to accuracy included recombination between the DNA markers and the mutation, pedigree structure, and whether DNA samples were available from family members. With direct tests for the HD mutation, we have assessed the accuracy of results obtained by linkage approaches when requested to do so by the test individuals. For six such individuals, there was significant disparity between the tests. Three went from a decreased risk to an increased risk, while in another three the risk was decreased. Knowledge of the potential reasons for these changes in results and impact of these risk reversals on both patients and the counseling team can assist in the development of strategies for the prevention and, where necessary, management of a risk reversal in any predictive testing program.

The Psychological Consequences of Predictive Testing for Huntingtonʼs Disease

BACKGROUND Advances in molecular genetics have led to the development of tests that can predict the risk of inheriting the genes for several adult-onset diseases. However, the psychological consequences of such testing are not well understood. METHODS The 135 participants in the Canadian program of genetic testing to predict the risk of Huntingtons disease were followed prospectively in three groups according to their test results: the increased-risk group (37 participants), the decreased-risk group (58 participants), and the group with no change in risk (the no-change group) (40 participants). All the participants received counseling before and after testing. Standard measures of psychological distress (the General Severity Index of the Symptom Check List 90-R), depression (the Beck Depression Inventory), and well-being (the General Well-Being Scale) were administered before genetic testing and again at intervals of 7 to 10 days, 6 months, and 12 months after the participants received their test results. RESULTS At each follow-up assessment, the decreased-risk group had lower scores for distress than before testing (P < 0.001). The increased-risk group showed no significant change from base line on any follow-up measure, but over the year of study there were small linear declines (P < 0.023) for distress and depression. The no-change group had scores lower than at base line on the index of general well-being at each follow-up (P < or = 0.045). At the 12-month follow-up, both the increased-risk group and the decreased-risk group had lower scores for depression and higher scores for well-being than the no-change group (P < or = 0.049). CONCLUSIONS Predictive testing for Huntingtons disease has potential benefits for the psychological health of persons who receive results that indicate either an increase or a decrease in the risk of inheriting the gene for the disease.