Psychological Effects of Presymptomatic DNA Testing for Huntington's

Disease in the Dutch Program

AAD TIBBEN, PHD, HUGO J. DUIVENVOORDEN, PHD, MARTINUS F. NIERMEIJER, MD,

MARIA VEGTER-VAN DER VLIS, MD, RAYMUND A. C. Roos, MD, AND
FRANS VERHAGE, PHD

This study assessed the 6-month follow-up effects of presymptomatic DNA testing for Huntington's disease
(HD) in 73 individuals at 50% prior risk who were identified either as carriers of the HD gene (N = 29] or as
noncarriers (N = 44). The subject's knowledge of being a gene carrier was expected to induce intrusive
emotions, denial-avoidance behavior, and pessimistic expectancies of the future and adjustment problems.
The Impact of Event Scale, the Beck Hopelessness Scale, and the General Health Questionnaire were used
as standard measures of psychological distress. At the disclosure of the test results, carriers had a strong
increase in pessimistic expectations but showed a decline to baseline levels 6 months later. Noncarriers
reported a steep decline in hopelessness compared with their pretest conditions but had increased scores
after 6 months. Six months after the disclosure of the test results, both gene carriers and noncarriers reported
a significant decrease in unwanted intrusive thoughts about HD. Carriers showed a slight increase in denial-
avoidance behavior, whereas noncarriers showed a clear decrease. Our observations might indicate that
tested individuals found relief from the prior psychological distress and that they were able to acknowledge
the impact of the test result on their future. An unresolved question is how the foreknowledge will affect
carriers as they approach the impending onset of the disease. Longer observation periods (> 6 months after
disclosure) are required to study changes of the impact of DNA test results over time.
Key words: Huntington's disease, intrusion, denial-avoidance, presymptomatic testing, adjustment, follow-
up.

INTRODUCTION modified to approximately 98% (gene carriers) or 2%

Huntington's disease (HD) is a delayed-onset, in-
herited, neurodegenerative disorder that is charac-
terized by involuntary movements, changes in be-
havior and personality, and cognitive impairment
(1). Children of an affected parent are at 50% risk of
being affected in later life by HD. Although the mean
age of onset is 40 years, with a range of 2 to 75 years
(2), at-risk individuals can never be sure of having
escaped HD.
New developments in presymptomatic DNA test-
ing for an increasing number of inheritable disorders
imply that it is now possible to detect the genetic
status in relation to a defined disorder (3). Thus,
individuals at 50% risk for HD might have their risk
From the Clinical Genetics Centre (A.T., M.V.-v.d.V.) and
Department of Neurology (R.A.C.R.) and University Hospital,
Leiden; and Department of Medical Psychology and Psychother-
apy, Erasmus University (A.T., H.J.D., F.V.), and Department of
Clinical Genetics, Erasmus University and University Hospital
Dijkzigt (A.T., M.F.N.), Rotterdam, The Netherlands.
Address reprint requests to: Aad Tibben. Department of Clin-
ical Genetics, Erasmus University, PO Box 1738, 3000 DR Rotter-
dam, The Netherlands.
Received for publication February 26, 1993; revision received
March 18, 1994.
(noncarriers). The recent identification of the HD
gene mutation (4) makes testing also accessible for
those individuals at 50% risk who could previously
not be tested. With the discovery of the gene defect
and the establishment of psychologically guided di-
agnostic programs, fundamental research questions
to be addressed include the basis for the variable
age of onset and duration of the illness and the
nature of the differential onset of phenotypical
symptoms.
The more accurate risk determination might give
at-risk individuals options that could improve the
quality of their lives (5). On the other hand, before
the availability of the presymptomatic test, attitu-
dinal studies showed that an unfavorable result was
expected to lead to major psychological and social
difficulties, including a preoccupation with symp-
toms of the future disease, depression, and suicidal
behavior (6-8). Because the development of DNA
technology has enabled an accurate prediction of
delayed-onset genetic diseases, a number of pro-
spective studies have been carried out on the impact
of testing for HD (9-12).
Before the disclosure of DNA test results, most
test candidates denied or minimized the possible
adverse effects of an unfavorable test result and,
above all, attempted to gain control over their future
(12). Furthermore, female candidates tended to turn

526 Psychosomatic Medicine 56:526-532 (1994)

0033-3174/94/5606-0526SO3 00/0
Copyright © 1994 by the American Psychosomatic Society
DNA TESTING FOR HUNTINGTON'S DISEASE
their unacceptable feelings against themselves and
believed that their health and future prospects de-
pended on themselves; male candidates turned their
unacceptable feelings to the outer world and tended
to base their future prospects on chance (13).
In previous reports on the effects of presympto-
matic testing, it was observed that carriers of the HD
gene had so far not shown catastrophic reactions (9,
10, 14, 15). The perception of relief in individuals
who were shown to be free from the HD gene has
been overestimated. Feelings of numbness, survi-
vor's guilt, marital disturbances, and divorces have
been observed in noncarriers (15, 16). Partners, rel-
atives, and health care professionals have found
these reactions difficult to appreciate (15).
To evaluate the presymptomatic testing program
more fully, we studied the psychological effects on
subjects who received test results. The main empha-
sis was laid on the psychological adjustment to the
subject being either a gene carrier or a noncarrier.
We used Horowitz's (17, 18) stress response theory,
and our conclusions led us to believe that tested
individuals might experience intrusive emotions
with regard to HD, both before and after the DNA
test, but also consciously attempt to avoid these
emotions. In addition, we expected that gene car-
riers, as a reaction to the test outcome, would dem-
onstrate significantly more pessimistic expectancies
about their future than noncarriers. Here we report
on the psychological effects of the predictive test
outcome on 73 consecutively tested applicants, at 1
week and 6 months after they received the test
results.
METHOD
Participants
Presymptomatic testing for HD has been available at the Clin-
ical Genetics Centre in Leiden, The Netherlands, since October
1987, The inclusion criteria for the testing program was older
than 18 years, absence of major mental illness or the intention to
commit suicide after an unfavorable result, no neurological man-
ifestations of HD, and the ability to give informed consent.
The counseling protocol and DNA linkage analyses have been
presented elsewhere (19). The DNA test is currently informative
in more than 90% of the applicants if sufficient data on affected
and unaffected relatives are available. The reliability is fre-
quently higher than 96%.
This study reports on 73 at-risk individuals who were consec-
utively informed about risk modification. The male/female ratio
was 1:1.7. Two thirds of the tested candidates had a stable rela-
tionship; 36% had at least one child. With respect to educational
level, 60% had had more than lower vocational school. Most male
(88%) and 62% of females subjects were employed. Major reasons
for undertaking the test were relief of uncertainty (80%) and
Psychosomatic Medicine 56:526-532 (1994)
family planning (60%). A more detailed description of the study
sample has been reported elsewhere (12). Twenty-nine individ-
uals received an increased risk result (approximately 98% risk),
which identified them as gene carriers (male/female ratio, 1:2.1);
44 were identified as noncarriers (risk decreased to approximately
2%; male/female ratio, 2:3). The carrier/noncarrier ratio (2:3) was
the same as in similar studies of HD screening (9-11).
The criteria for enrollment in the psychological follow-up
study were the ability to understand the questionnaires and to
give informed consent. The research protocol was approved by
the Medical Ethics Committee of the University Hospital of Lei-
Procedure
At the first counseling session, the test candidates were given
an introduction to the research protocol and asked consent to
participate in a follow-up study on the psychosocial consequences
of the test outcome. The quantitative part of the study involved
completion of psychological tests, including the Impact of Event
Scale (IES), the Beck Hopelessness Scale (BHS), and the General
Health Questionnaire (GHQ). In this article, we report on the
psychological effects of presymptomatic testing for HD over time.
The questionnaires were administered at baseline and at 1 week
and 6 months after disclosure of the DNA test results.
The IES is a reliable, self-reported scale used to measure the
current degree of subjective impact, experienced as a result of a
specific event (18). Horowitz et al. (18) suggested that the 15 items
of the IES should be coupled to the specific stress factor, e.g., HD.
The IES summarizes the influence of HD on two major dimen-
sions, i.e., intrusion into consciousness of unwanted ideas and
feelings and consciously recognized deniaJ-avoidance. The IES
consists of seven items that form an intrusion subscale (range, 0-
35), and eight items that denote a denial-avoidance subscale
(range, 0-40). The IES was chosen for its suitability to assess test
candidates over time and for comparison of the degree of impact
of HD among subgroups (e.g., male/female and gene carrier/
noncarrier).
The BHS consists of 20 true-false statements that focus on
pessimistic expectations concerning oneself and one's future. The
scale was considered appropriate for our population, given such
questions as "I have enough time to accomplish the things I most
want to do" and "The future seems vague and uncertain to me."
A score of 9 or more positive items (range, 0-20) is regarded as a
possible predictor of depression and suicidal behavior (20, 21).
The 60-item GHQ is a reliable estimator of psychopathological
states, such as depression, anxiety, somatic complaints, and social
dysfunction. A score of 12 or more positive items (range, 0-60)
indicates a possibly psychiatric condition (22, 23).
Data Analysis
All data analyses were carried out using the Statistical Package
for the Social Sciences (SPSS-PC, SPSS Inc., Chicago, IL). Pearson
product-moment correlations were calculated for the biographi-
cal variables, i.e., gender (male = 0, female = 1), age, time lag
(years elapsed since the test candidate learned about HD in the
family), the DNA test outcome (carrier = 1; noncarrier = 0), and
the pretest and posttest psychological variables.
To examine the effect of the DNA test outcome, multivariate
analysis of variance (MANOVA) for repeated measurements was
performed on the four psychological measures (intrusion, denial-
527
 A. TIBBEN et al.

avoidance, hopelessness, and general health) with the factors: TABLE 2. Pearson Product-Moment Intercorrelations of
DNA test outcome (carrier/noncarrier), gender, measurement Pretest Psychological Variables, Age, Time Lag, and DNA Test
(baseline, 3 months = 1 week after disclosure, 9 months = 6 Outcome for 73 Individuals, Tested for HD
months after disclosure of the DNA test results), and their inter- 2 3 4 5 6 7
actions.
The three measurements can be decomposed into the orthon- Age .42*** .06 .00 .02 .14 .12
ormalized polynomial contrasts. Both linear trend and quadratic Time lag .01 -.03 - .15 .02 -.24
trends were examined. First of all, we investigated whether there lES-lntrusion .73*** .41** , 62 *** .16
were multivariately significant effects (p < .05, two-tailed) in lES-Denial/Avoidance .31** .44*** .07
DNA test outcome, gender, and their interactions. Subsequently, BHS .46*** .05
we tested univariately whether the linear or the quadratic trend CHQ .12
(or both) were significant. A p value < .05 (two-tailed) was DNA test outcome (0 = noncarrier; 1 = carrier)
considered significant.
p<.001.

RESULTS
lies than younger ones. Although noncarriers had a
Descriptive Analyses longer awareness of HD, DNA test outcome and time
lag were not correlated.
Table 1 presents means and standard deviations The stress dimensions of the IES, intrusion and
for age and time lag and for the psychological vari- denial-avoidance, were significantly intercorre-
ables at baseline (the first counseling session) in lated. Both dimensions were independent of age,
carriers and noncarriers. Noncarriers had a signifi- time lag, and the DNA test result. The significant
cantly longer awareness of HD in their families than correlations of the pretest scores on both the GHQ
did carriers (time lag). To account for this difference, and the BHS, with the IES scales support the validity
we entered time lag as a covariate into the MANO- of the IES as a measure of psychological distress.
VAs. The male/female ratio did not differ signifi-
cantly between both groups (chi-square, Yates cor-
rected, = .36; p = .54).
Prospective gene carriers were not significantly Analysis of Repeated Measures
different from noncarriers in intrusion, denial-
avoidance, hopelessness, and general health at base- Repeated-measures MANOVA (Table 3) yielded a
line. univariately significant effect of measurement on
Intercorrelations of the baseline psychological the level of intrusion in both carriers and noncar-
variables, age and time lag, and the DNA test out- riers (F(l,69) = 9.76, p < .01). Shortly after the test
come are presented in Table 2. The factor gender candidates had been informed of the DNA test re-
did not significantly correlate with any of these sults, the same level of intrusive thoughts and feel-
variables and was therefore not included in the ings with regard to HD were reported as in the
table. Age and time lag were, not surprisingly, re- pretest condition. Six months later, the level of in-
lated. We expected that older participants had a trusive thoughts had decreased (Figure 1).
significantly longer awareness of HD in their fami- There was a significant, linear DNA test outcome
by measurement interaction for the level of denial-
avoidance behavior (Figure 2). Soon after gene car-
TABLE 1. Means and Standard Deviations of Psychological riers had been informed of the result, they had a
and Biographical Variables
level of denial-avoidance similar to their baseline
Gene
Noncarriers scores. Six months later, they showed a slight in-
Carriers
Variable N = 29 N = ( crease in denial-avoidance behavior. Noncarriers
showed a strong decrease in denial-avoidance be-
Mean SD Mean SD havior, a trend that continued until 6 months after
Age 31.3 9.8 32.6 10.1 0.55 disclosure of the test results. A nearly significant
Time lag (in years) 6.6 6.1 10.3 7.7 2.11* linear trend for a DNA test outcome by gender by
Pretest
lES-intrusion 15.4 6.1 13.8 4.1 -1.33
measurement interaction (F(l,69) = 3.17, p = .08)
lES-denial/avoidance 14.3 5.9 14.8 4.7 -0.45 was found in denial-avoidance: female subjects and
BHS 4.9 4.0 4.5 3.3 -0.42 male noncarriers showed a linear decline in denial-
CHQ 11.8 13.5 8.7 10.9 -1.05 avoidance behavior or remained at the same level
* p < .05; for all t values: df = 71. for the ensuing 6 months, whereas male carriers

528 Psychosomatic Medicine 56:526-532 (1994)

DNA TESTING FOR HUNTINCTON'S DISEASE

TABLE 3. MANOVAs (Repeated Measures) With Time Lag as a Covariate on the Psychological Variables With the Factors DNA
Test Outcome (Carrier/Noncarrier), Measurement (Baseline/1 Week After Disclosure/6 Months After Disclosure), and Gender0

MANOVA
Gender by DNA by DNA by Gender
Measurement
Measurement Measurement by Measurement
lES-lntrusion
Multivariate' .13** .00 .01 .03
Univariate linear trend 9.76** .20 .82 1.94
Univariate quadratic trend .06 .02 .01 .05
lES-Denial/Avoidance
Multivariate .02 .02 .13" .05
Univariate linear trend 1.04 .50 9.53** 3.17
Univariate quadratic trend .71 .65 .08 .05
BHS
Multivariate .00 .01 .10* .04
Univariate linear trend .07 .00 .52 .27
Univariate quadratic trend .30 .70 6.72* 2.94
CHQ
Multivariate .01 .04 .02 .05
Univariate linear trend .43 3.01 1.08 1.64
Univariate quadratic trend .15 .02 .11 1.19
a
All entries are F(1,69) values.
b
Pillais multivariate test.
*p<.05.
**p<.01.

m!"• .••'•: * .

13,•.•!•;

0 1 2 4 5 I 9 10
baseline closure nonths follow-up

'Gene-carriers ~l~ Non-carriers

disclosure of test results after 3 months disclosure of test results after 3 months
lower scores indicate less intrusive feelings about HD lower scores indicate less denial-avoidance behavior
Fig. 1. Mean scores of carriers and noncarriers on the intrusion Fig. 2. Mean scores of carriers and noncarriers on the denial-
subscale of the IES. avoidance subscale of the IES.

Psychosomatic Medicine 56:526-532 (1994) 529


showed a linear increase over the course of the 6-
month follow-up.
We found a significant quadratic DNA test out-
come by measurement interaction for the level of
pessimism (BHS). The unfavorable test result im-
mediately affected the expectancies with respect to
the future (BHS) in both carriers and noncarriers
(Figure 3). At disclosure of the test results, carriers
showed a strong increase in pessimistic expectations
but a decline to almost baseline levels after 6
months. Noncarriers reported a strong decline in
hopelessness in comparison with their pretest con-
ditions, but their scores had increased after 6
months. Nearly significant tests for trends showed
DNA test outcome by gender by measurement inter-
actions; female subjects accounted most for the
quadratic effect on hopelessness.
With general health (GHQ) as the dependent vari-
able, no significant changes at all were observed,
either between or within groups. However, the tests
for trend did indicate an almost significant, overall
linear decline in general health for female subjects
and a linear increase for male candidates (F(l,69) =
3.01, p = .08).
DISCUSSION
In this study, we examined the effects of the
results of presymptomatic DNA testing for HD. Like
others, we found similar biographical and psycho-
logical profiles at baseline in prospective gene car-
riers and noncarriers (9,11). The general observation
that more individuals received a lowered than a
raised risk may be due in part to their age distribu-
tion (24). As age increases, there is a reduction in
the probability of HD developing, and in the cohort
of gene carriers, some cases already have manifested
HD. In addition, a process of self-selection may result
in at-risk individuals who correctly perceive that
they are free of the subtle abnormalities that became
evident in their affected siblings. These people may
thus be encouraged to undergo testing in the expec-
tation of a favorable result. Some presymptomatic
carriers may be less likely to seek testing because
early cognitive and/or personality changes have, in
fact, made them less worried about the possibility
of inheriting the disease.
The results of the current study support previous
reports on presymptomatic testing that carriers have
so far not shown catastrophic reactions (9-11). Al-
though no real norms are available for comparison,
the posttest levels of scores on the IES are broadly
similar to the results obtained elsewhere for individ-
530
A. TIBBEN et al.
' " • - ' • • • ; : / . > > ^ • • • }
• . . ... .-.••«... ..*» V-=V"-,1.»
• '£&" '• . '*•" '• •!
mf^}0;
0 1 2 3 4 5 6 7 8 9 10
baseline enclosure follow-up after 6
months
"— Gene-carriers "+~ Non-carriers
disclosure of test results after 3 months
lower scores indicate less hopelessness
Fig. 3. Mean scores of carriers and noncarriers on the BHS.
uals who had recently experienced a serious trau-
matic injury (25). When we consider the significant
change in intrusion over time (Figure 1) in gene
carriers and noncarriers, we may conclude that both
groups showed a decrease in involuntary feelings
and thoughts about HD, over the course of the 6-
month follow-up after hearing the test results. More-
over, an unfavorable DNA test result did not signif-
icantly induce a long-term increase in pessimistic
expectancies of the future in identified gene carriers
(Figure 3), nor did it increase denial-avoidance be-
havior. These findings suggest that test candidates
found relief from their prior burdens, and partici-
pants indeed stated in the follow-up interviews that
they had found relief from uncertainty, no matter
what the result was (15). Moreover, the DNA test
outcome did not affect the psychological well-being
in carriers of the HD gene, as measured with the
GHQ, which corroborated the current experience in
other studies (9-11). This might indicate that our
participants were able to cope adequately with the
result in the initial 6 months. However, it should be
noted that, in both groups, the baseline scores on
the GHQ, which were only slightly below the cutoff
score of 12, had not changed significantly. This sug-
gests that a number of participants may be at risk
for potentially psychiatric symptoms.
Therefore, a decrease in intrusion and pessimism
and/or increase in denial-avoidance behavior may
Psychosomatic Medicine 56:526-532 (1994)
DNA TESTING FOR HUNTINGTON'S DISEASE
also indicate that carriers did not acknowledge the
full impact but denied or minimized the test result.
The carriers' coping behavior might indeed indicate
a (temporary) postponement of their coming to terms
with the test result and its consequences. Adequate
as this may be in the short run, it has yet to be
determined whether long-term absence of a process
of working through does or does not eventually lead
to psychological maladjustment.
The tested individuals in the current study had
no early signs of the disease (movement disorders)
when they applied for the test. However, in some
cases, if manifest choreic movements are preceded
by early, yet unrecognizable, affective and/or cog-
nitive changes, subtle neuropsychological correlates
might interfere with coping behavior or with psy-
chological and social adjustment (26). Further fol-
low-up on the coping behavior of identified carriers,
with their inevitable fate that they will become
clinically symptomatic, is essential.
Noncarriers not only reported relief from uncer-
tainty in the follow-up counseling interviews but
also (survivor's) guilt feelings and depressive reac-
tions, and one third sublimated their guilt feelings
by exaggerated attention for at-risk, or affected, rel-
atives (15, 16). This might explain the increase in
pessimistic feelings 6 months after the disclosure of
the test results. They tended to become overly in-
volved in the personal lives of affected or at-risk
relatives, which was also reflected in their strong
decline in denial-avoidance behavior (Figure 2).
We conclude that 6 months may be too short a
period to reach a point of adequate psychological
adjustment. This supports our earlier suggestion that
tested individuals may need years, rather than 6
months, to adapt to their new genetic status and that
this applies to both identified HD carriers and non-
carriers. The need for adaptation in the latter group
has previously been indicated (27) and is substanti-
ated by the present findings.
The observed, nearly significant, trends with re-
gard to sex differences on general health, pessimism,
and denial-avoidance behavior suggest that further
studies on predictive testing should take into ac-
count that female and male subjects may cope dif-
ferently. Bloch et al. (5) suggested that men may
have a greater tendency to deny their feelings,
whereas women may be more involved in the repro-
ductive process, in childbearing, and in rearing chil-
dren than men. Also, female subjects discussed the
test procedure and test result more often with their
partners than did male candidates (15). Further-
more, with regard to their health and future pros-
Psychosomatic Medicine 56:526-532 (1994)
pects, female subjects relied on themselves, whereas
male candidates relied on chance.
Finally, carriers had a significantly shorter aware-
ness than noncarriers of HD in the family (time lag).
However, time lag was not related to any of the pre-
and posttest psychological variables. This finding
does not support the observations of Tyler et al. (28)
who suggested that people who only recently
learned about their being at risk should be advised
to postpone DNA testing, at least for 1 year, to
comprehend fully the implications of either result.
A number of test candidates in our study applied for
the test within the first year after they had learned
about HD in their family. They may not have had
the opportunity to accommodate slowly to the full
implications of HD in their lives, like others who
grew up in the knowledge of HD. They may have
underestimated the impact of testing and its out-
come when they, perhaps impulsively, applied for
the test. It should be examined further how these
newly at-risk individuals adjust in the long run.
In clinical practice, the relief with regard to the
absence of early untoward reactions in identified
carriers should not distract the attention from the
sometimes appalling impact of unfavorable test re-
sults. Although such denial can temporarily be ad-
equate for the identified carrier, it can also lead to
underdiagnosis and undertreatment from profes-
sional caregivers. On the other hand, the absence of
relief in noncarriers is an indication that this also
must be recognized by clinicians. Noncarriers often
need support to accept their relief and change their
previous life expectations. Intrusion, denial-avoid-
ance behavior, and hopelessness are important in-
dications that can be used by the clinician in genetic
counseling and follow-up support.
Caution must be taken in the generalization of
our results. First, the tested group was perhaps self-
selected and not representative of the population at
risk for HD (11, 15, 28). Generally, test candidates
were higher educated than the general population
and appeared to have a healthy level of functioning
(5, 15). Second, a 6-month follow-up period does not
provide deep insight into the long-term psychologi-
cal adjustment of tested individuals. Third, the re-
sults, to some extent, may be an artifact of the
extended psychological support received by the par-
ticipants in the study.
In conclusion, our findings indicated that, irre-
spective of the test results, the effects of the results
of presymptomatic testing for HD might be present
for a period longer than 6 months. An important and
unresolved question is how the foreknowledge will
affect carriers as they approach the impending onset
531

of the disease. Longer observation periods (> 6
months after disclosure) are required to study
changes of the impact of DNA testing for HD over
time.
This study was supported by the Prinses Beatrix
Fonds grants 88-2801 and 89-2984. We thank Drs.
G. C. Beverstock and B. Bonke/or criticaJJy reviewing
the manuscript.
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