Depression and Suicidal Ideation After Predictive ... - Springer Link

c 2006) Journal of Genetic Counseling, Vol. 15, No. 5, October 2006 ( DOI: 10.1007/s10897-006-9027-6

Original Research

Depression and Suicidal Ideation After Predictive Testing for Huntington’s Disease: A Two-Year Follow-up Study Maria U. Larsson,1,2,7 Mary A. Luszcz,3 The-Hung Bui,4,5 and Tarja-Brita Robins Wahlin1,2,6 Published Online: 12 September 2006

The present study reports a two-year follow-up of psychological effects of predictive testing for Huntington’s disease. Questionnaires assessing depression, general health, well-being, self injurious behavior, life satisfaction, and lifestyle were completed by 35 carriers and 58 non-carriers before the predictive test, and 2, 6, 12, and 24 months afterwards. Both carriers and non-carriers showed high suicidal ideation before the predictive testing. Depression scores and frequency of suicidal thoughts increased for carriers, compared to non-carriers, over time. There were no differences regarding life satisfaction or life style between carriers and non-carriers. Predictive testing was beneficial in reducing overall ill-health symptoms and increasing well-being for those initially expressing concern about Huntington’s disease. The importance of assessing suicidal ideation and of continuing to provide adequate support is emphasized. KEY WORDS: Huntington’s disease; presymptomatic; psychosocial; longitudinal; predictive testing.

INTRODUCTION

wide range in the age of onset. The duration of HD is approximately 15–20 years and the patient dies of sequelae of the disease (Kremer, 2002). Presymptomatic testing for HD has been available since the mid 1980’s when genetically linked markers for the HD-gene were discovered (Gusella et al., 1983). In 1993 the gene causing HD was identified and it was possible to offer a mutation test with sensitivity and specificity close to 100% (The Huntington’s Disease Collaborative Research Group, 1993). There have been significant concerns about the effects of gaining knowledge about genetic status on the psychological health of those people at risk who undergo predictive testing for HD (Wexler, 1992). The fact that there is no cure and limited symptomatic treatment with no effect on progression of HD, has not resolved the issues regarding the impact of predictive testing on individuals. The majority of evidence to date suggests that predictive testing does not result in profound harmful effects and most studies support the view that carriers and non-carriers only differ in short-term psychological

Huntington’s disease (HD) is an autosomal, dominant, neurodegenerative disorder characterized by a long prodromal period. The clinical manifestations of HD involve motor impairment, psychiatric symptoms, and cognitive decline. A child of a parent who is symptomatic or a non-symptomatic gene carrier is at 50% risk of having inherited the mutated gene. The symptoms of HD often manifest themselves at around 40 years of age but there is a 1

Neurotec Department, Karolinska Institutet,Stockholm, Sweden. Stockholm Gerontology Research Center,Stockholm, Sweden. 3 School of Psychology, Flinders University,Adelaide, Australia. 4 Clinical Genetics Unit, Karolinska University Hospital, Stockholm, Sweden. 5 Department of Molecular Medicine, Karolinska Institutet,Stockholm, Sweden. 6 KC-Kompetenscentrum, Research and Development Center in Elderly Care,Stockholm, Sweden. 7 Correspondence should be directed to Maria U. Larsson, ¨ Stockholm Gerontology Research Center,Gavlegatan 16, 113 30 Stockholm, Sweden; e-mail: [email protected]. 2

361 C 2006 National Society of Genetic Counselors, Inc. 1059-7700/06/1000-0361/0

362 impact (for reviews see Duisterhof et al., 2001; Meiser and Dunn, 2000). However, some points of caution have been raised. There are indications that both carriers and non-carriers have problems coping with, and adjusting to, their new knowledge of their genetic status (Bloch et al., 1992; Huggins et al., 1992; Robins Wahlin et al., 1997). In previous studies the effects of genetic testing for HD have mainly been assessed on psychological health in terms of depression and wellbeing (Codori et al., 1997; Decruyenaere et al., 2003; Tibben et al., 1997; Timman et al., 2004). Less evaluated are suicidal ideation, the effect of psychiatric symptoms, the overt effect on lifestyle and health behavior. Suicide is known to be more prevalent in families affected with HD than in the general population (Farrer, 1986). A worldwide study by Almqvist et al. (1999) reported few cases of catastrophic events e.g. suicide, suicide attempts and hospitalizations due to psychiatric problems after predictive testing. Almqvist et al. (2003) also reported similar results in a 5-year follow-up study. However, suicidal behavior in connection with predictive testing is reported by Robins Wahlin et al. (2000). Their study conducted on the first 34 persons who registered in the predictive testing program in Stockholm, Sweden, showed high suicidal ideation and self-injurious behavior at baseline, before test disclosure, among both carriers and non-carriers (Robins Wahlin et al., 2000). An important issue in relation to suicidal ideation in HD is that psychiatric symptoms have been reported to occur before neurological signs in about 50% of the HD cases (Mattson, 1974). Whether or not this is the case has been an issue in previous studies (Berrios et al., 2002; Close Kirkwood et al., 2002a, 2002b; Witjes-Ane´ et al., 2002). WitjesAne´ et al. (2002) found that presymptomatic carriers complained more about sadness, low self-esteem, aggressive behavior, and compulsions than non-carriers did. A recent double-blind longitudinal follow-up study showed increasing irritability and cynical hostility among presymptomatic carriers compared to non-carriers (Close Kirkwood et al., 2002b). These findings may have implications for the predictive testing and the effects of psychiatric symptoms need to be more thoroughly investigated. The effect of psychiatric symptoms has mainly been assessed in relationship with adverse events after predictive testing. For example, both Lawson et al. (1996) and Almqvist et al. (1999) found that around 40% of those who

Larsson, Luszcz, Bui, and Robins Wahlin experience an adverse event also had a past psychiatric history. There are indications that affective disorders in HD can be more common in some families (Folstein et al., 1983). For example Folstein et al. (1983) found that affective disorders in offspring were highly associated with the presence of similar symptoms in the HD parent. Based on these findings psychiatric symptoms in relatives should be taken into account. The purpose of the present study was to explore the psychological and psychosocial health of carriers and non-carriers before and after the predictive test. We used data from a 2-year longitudinal follow-up of carriers and non-carriers for HD in Stockholm, Sweden. In addition to depression and well-being, the suicidal ideation and the impact of psychiatric symptoms are emphasized. Further, we also aim to investigate if presymptomatic testing influences the overt lifestyle of the participants. Hence, measures of lifestyle and health behavior factors are also analyzed. Life style and behavior factors addressed are smoking, alcohol consumption, sleeping problems, amount of money spent, and use of prescription medications. To evaluate what may explain the variation in the different outcomes we used predictors such as carrier status, sex, age, parental status, HD as a major problem, psychiatric problems of participants, and psychiatric symptoms among relatives with and without HD.

MATERIAL AND METHODS Procedure Genetic counseling for HD at the Department of Clinical Genetics, Karolinska University Hospital Solna, Stockholm, Sweden, was established in the autumn of 1990. Inclusion criteria for participation in the program were: age over 18 years; a 50% risk of HD; or 25% risk of HD if the parent was dead or if a parent with 50% risk participated in the program. The participants were asked to participate in pre-test and post-test counseling, neurological, and psychiatric examinations to exclude persons who already had signs and symptoms of the disease. The neurological examination followed recommendations from Folstein et al. (1983), and later from Unified Huntington’s Disease Rating Scale (UHDRS; Huntington Study Group, 1996). Persons with manifest symptoms of HD were referred to the Department of Neurology for clinical follow-up. Those

Psychological Aspects of Predictive Testing persons who were diagnosed during the 2-year follow-up (n = 2) were not excluded. The general procedure for the genetic counseling and testing-program has been described in detail elsewhere (Robins Wahlin et al., 2000). The data used in this study was collected at baseline 2–12 weeks before the molecular test and then approximately 2, 6, 12, and 24 months after the genetic test disclosure. The participation consisted of completing a psychosocial questionnaire and an in-depth interview according to the wishes and needs of the participant. Paper and pencil assessments were also part of the genetic counseling screening program for the psychosocial health of the participants. Each assessment session took approximately one hour to complete. Only those persons who gave their formal consent for the psychosocial questionnaires to be used for research were included in the study.

Participants From October 1990 to February 2004, a total of 93 individuals (35 carriers, 58 non-carriers) who received a genetic test result participated. Linkage analysis was performed until 1993 and thereafter all participants were tested using the direct mutation test. The persons tested with the linkage analysis (n = 11) were informed in a personal letter about the direct genetic test. These persons were offered a complementary mutation analysis, which confirmed the linkage determined risk (n = 7). Four persons did not take up the offer of a direct mutation analysis. For the remaining 82 participants only direct mutation analysis were performed. Hence, participants in this study are referred to as carriers or non-carriers. Five participants, two carriers and three noncarriers, did not complete the counseling sessions for the follow-ups (5.4%), three were lost after baseline and two were lost after first follow-up. The remaining 88 persons followed the program. The missing occasion rate in the total group varied from 1.1–12.9% (Table I). No significant differences were found in any of the outcome measures in a series of analyses, where participants with missing data were compared with participants who had completed the entire program. Overall, among the background and demographic variables there were no differences. The single exceptions were that dropout carriers were younger (p = .039) and had more relatives with psychiatric symptoms (p = .026). The study was

363 Table I.

Sample Size at Each Follow-up Assessment Carriers (n = 35)

Non-carriers (n = 58)

Total (n = 93)

Follow-up

n

%

n

%

n

%

Baseline 2 months 6 months 12 months 24 months

34 31 30 30 29

97.14 88.57 85.71 85.71 82.85

58 55 54 51 53

100.00 94.83 93.10 87.93 91.34

92 86 84 81 82

98.92 92.47 90.32 87.10 88.17

approved by the Ethics Committee of the Karolinska University Hospital, Solna. Instruments The participants completed an extensive psychosocial assessment battery at baseline (before disclosure of the test result) and at each follow-up either by attending the clinic or by correspondence. The Self-Injurious Behavior Scale, Life Satisfaction Index, and Life-Styles Assessment were adopted from the Canadian collaborative study of predictive testing for HD (Fox et al., 1989). At baseline a background questionnaire was administered that comprised questions about education, occupation, psychiatric and suicidal history of participants and relatives. For the variable psychiatric history, participants were asked to state if they themselves had or had previously had psychiatric symptoms to the extent that they had been in contact with a psychiatrist. In a second question they were asked to state if any relatives had psychiatric symptoms and in conjunction also state if these were related to HD. The longitudinal questionnaires will be described in the following and are listed next in the order in which they were administered. Well-being (Robins Wahlin et al., 2000). Participants were asked to estimate their sense of wellbeing during the last three days before their visit by marking a cross on a 150-millimeter- long line on a visual analogue scale. The left side of the line indicated very poor well-being and the right side indicated excellent well-being (score range 0–150). Participants were then asked about the nature of the problem that was of most concern as indicated by the wellbeing cross. This was an open question in which the participants were asked to name the problem. The problem indicated was then coded to either association with being at risk of HD (HD named as a major problem) or association with something else (e.g. economy, studies).

364 The General Health Questionnaire-30 (GHQ-30; Goldberg and Williams, 1988) was used to measure psychological health and well-being. The questions assess depression, anxiety, somatic complaints, and social dysfunction. GHQ-30 is a self-administered screening instrument focusing on alterations in normal psychological function. It assesses variations between psychological sickness and psychological health and focuses on breaks in normal function, rather than upon traits (Goldberg and Williams, 1988). The questionnaire does not capture long-term psychiatric conditions or poor psychological health since it only focuses upon whether a person has experienced more or less of different conditions than usual. Scores were summarized using GHQ-score method (0-0-1-1) across the 30 items with higher scores reflecting more distress (score range 0–30). The categories were ‘0’ = ‘less than usual’ or ‘no more than usual,’ ‘1’ = ‘rather more than usual’ or ‘much more than usual.’ The validity and reliability of this scale are well documented and the threshold for psychological stress is a score above four (Goldberg and Williams, 1988; Tarnopolsky et al., 1979). The Beck Depression Inventory (BDI; Beck et al., 1961) was used to measure intensity of depression. It assesses affective, cognitive, motivational, and vegetative symptoms of depression- and anxietyrelated disorders. BDI is a 21-item questionnaire, and each item consists of four alternative statements that represent gradations of a given symptom rated in severity from 0 to 3. Beck et al. (1961) have defined the 0–9 range as normal, 10–15 as indicating mild depression, 16–20 as indicating moderate depression, and a score above 21 representing severe depression (score range 0–63). The BDI has been found to possess good psychometric properties (Beck, 1987; Beck et al., 1988). The Self-Injurious Behavior Scale (SIBS; Fox et al., 1989). This questionnaire consists of questions which evaluate previous and current levels of suicidal thoughts or attempts, and expected catastrophic reactions if developing symptoms of HD. The second item of SIBS, that also was suitable for longitudinal analysis, assessed the extent of suicidal thoughts by a four-point rating scale (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = very often). For each follow-up the question was stated as ‘since your last visit.’ The Life Satisfaction Index (LSI; Fox et al., 1989) is a rating scale of life-satisfaction in terms of how satisfied participants are with domains of life

Larsson, Luszcz, Bui, and Robins Wahlin experience including leisure time, economy, living standards, work, health, social life, marriage, family life, and total life satisfaction. The items are scored from one (very satisfied) to seven (totally dissatisfied), a higher sum indicating poorer life-satisfaction (score range 0–63). The Life-Styles Assessment (LSA; Fox et al., 1989) deals with the participants’ social and medical background, present situation, and future plans. Five variables from this questionnaire were used. (1) Smoking was defined by the number of cigarettes smoked during a day. (2) Alcohol consumption was measured by the total sum of alcohol including beer, wine or spirits the participant reported drinking during one week. One unit of alcohol was equated as being either one strong beer, one glass of wine or four centiliters of spirits. (3) Sleeping problems and (4) money spent were indicated by a scale ranging from 1–7, a higher number indicating having more sleeping problems or spending more money than usual. (5) The use of prescription medications was the sum of medications used including analgesics, tranquilizers, neuroleptics and antidepressants (range 0–4).

Statistical Analysis Group differences for carriers and non-carriers at baseline were conducted using independent sample t-tests and chi square-tests where appropriate. The statistical package for the social sciences, SPSS 11.5 was used. Multilevel models evaluating change and predictors of change over time were computed using hierarchical linear modeling (HLM) version 5.05 software (Raudenbush et al., 2000). Well-being, GHQ, BDI, LSI, smoking, sleeping problems and money spent, were analyzed as continuous outcomes, prescription medications as count data and suicidal thoughts were analyzed as an ordinal outcome. An alpha level of .05 was used for all statistical tests.

Multilevel Models for Measuring Psychosocial Change Over Time Multilevel models specified for this investigation explore whether individual variation in both intercepts (score at baseline) and slopes (change over time) is related to different predictors. Regarding GHQ, for example, the intercept represents a

Psychological Aspects of Predictive Testing reference individual’s estimated score at baseline with the slope reflecting his/her linear rate of change across follow-up occasions. The multilevel model is comprised of both fixed effects which include the average effect for the intercept and slope as well as random effects representing individual differences from the fixed effects (i.e., person-specific residuals) for the intercept, slope and a within-person residual. Multilevel models are computed at several levels. First, for the Level-1 models, individual growthcurves over time are estimated per individual. These individual intercepts and slopes are then treated as dependent variables for the Level-2 regression equations. The first of the Level-2 models examines the intercepts (scores at baseline) as a function of group membership (e.g., carrier or non-carrier) holding constant the influence of the other predictors. The random effect for this model estimates the variability about the sample mean at baseline. The second Level-2 model examines the slope (rate of change over time) as a function of group membership. The test of significance for the associated random effect evaluates whether individual differences in intraindividual rates of change remain to be explained independent of other predictors included in the model.

365 Table II.

Demographic Characteristics for Carriers and Noncarriers at Baseline Carriers (n = 35) Characteristic

Gender Men Women Occupationa Unskilled Skilled Academic Marital statusa Partner Single Childrena No children ≥ 1 child HD as a major problema Psychiatric symptoms (Self)a Psychiatric symptoms in relatives with HDa Psychiatric symptoms in relatives without HDa Age Education; years

n

%

Non-carriers (n = 58) n

%

19 16

54.29 45.71

25 33

43.10 56.90

16 8 10

47.06 23.53 29.41

34 11 13

58.62 18.97 22.41

17 16

51.51 48.48

44∗ 14

75.86 24.14

14 20 17∗ 11 23

41.18 58.82 51.52 32.35 71.88

25 33 16 18 37

43.10 56.90 27.59 31.03 64.91

16

48.48

31

54.39

34.88 ± 9.35b 12.18 ± 2.56b

38.29 ± 10.11b 12.48 ± 3.37b

Note. HD: Huntington’s Disease. a Missing values (range 1–3). b M ± SD. ∗ p < .05.

RESULTS

The Final Model

Description of The Data

Each predictor was tested on its own to examine whether it significantly influenced the outcome measures. HD carrier status was included as a predictor in all models. Gender, age, parental status, and psychiatric symptoms among non-HD relatives, were found to be non-significant predictors of the outcome measures. As these predictors were nonsignificant when entered on their own, when entered in combination with other predictors, or when entered as interactions with other predictors, they were excluded from the final multilevel models. The dependent variables LSI, alcohol consumption, smoking, sleeping problems, prescription medications, and amount of money spent did not show any differences between carriers and non-carriers in initial status or in rate of change (Table IV). Therefore no additional predictors were tested for these outcomes. Too few attempted suicides (n = 12) were reported over the two-year period to permit reliable multilevel analyses. Notably, no interaction effects were observed between carrier-status and the various predictors for any of the outcome measures indicating that being a

Table II shows demographic characteristics for carriers and non-carriers at baseline. An independent t-test revealed no significant differences between carriers and non-carriers in age (p = .112) or education (p = .648). There were no significant differences between the groups regarding gender (p = .295), occupation (p = .667), having/not having children (p = .857), psychiatric symptoms (p = .821), psychiatric symptoms in relatives with HD (p = .568) or psychiatric symptoms in relatives without HD (p = .589). However, there was a difference between the groups regarding having a partner at baseline, reflecting the fact that more of the non-carriers reported having a partner (p = .018) and also a reliable difference reflecting the fact that more of the carriers reported HD disease as their major problem at baseline (p = .022). The means, standard deviations and percentages for the psychosocial measures at each follow-up are reported in Table III and the suicidal variables in Table V.

366

Larsson, Luszcz, Bui, and Robins Wahlin

Table III.

The Psychosocial Measures at Each Follow-up by Group

Baseline

Outcome measures Well-being GHQ BDI LSI Smoking Alcohol consumption Sleeping problems Money spent Prescription medications

M SD M SD M SD M SD M SD M SD M SD M SD M SD

2 months

6 months

12 months

24 months

Carriers (n = 34)

Noncarriers (n = 58)

Carriers (n = 31)


Carriers (n = 30)


Carriers (n = 30)


Carriers (n = 29)


85.50 43.43 6.15 6.07 7.09 6.49 22.71 6.42 5.65 8.47 2.67 2.50 2.93 1.92 4.03 0.76 0.15 0.44

93.02 43.00 4.91 6.76 6.00 7.36 23.28 9.10 4.10 8.77 3.36 3.33 2.56 1.79 3.95 0.69 0.32 0.83

77.52 37.69 8.74 9.63 8.71 10.03 26.55 10.49 6.58 9.09 5.04 5.36 2.84 1.86 4.14 0.85 0.39 0.67

101.95 34.69 3.64 7.16 3.98 5.92 24.36 9.27 4.20 8.59 3.25 3.80 2.24 1.60 3.92 0.91 0.20 0.63

79.90 35.34 9.27 9.59 8.77 7.32 25.16 10.24 7.37 11.10 4.23 4.15 2.63 1.71 4.27 1.11 0.27 0.64

105.98 30.32 3.76 6.94 3.93 5.78 24.98 9.55 3.69 7.72 3.50 4.30 2.26 1.70 4.04 0.70 0.28 0.66

98.00 48.33 7.97 8.78 8.43 8.96 26.03 9.23 8.53 11.66 4.76 4.74 2.93 2.00 4.45 1.18 0.41 0.68

98.96 27.31 5.24 8.19 4.69 6.51 25.02 11.16 3.20 6.70 3.22 4.16 2.35 1.66 3.87 0.91 0.25 0.59

85.66 36.01 6.28 7.61 7.52 7.19 25.21 7.79 5.45 9.22 4.29 5.54 2.25 1.56 3.87 0.90 0.38 0.68

112.26 29.40 3.60 6.55 3.77 4.93 24.42 9.42 3.04 6.66 3.62 4.64 2.40 1.70 4.06 1.02 0.23 0.58

Note. GHQ: General Health Questionnaire, BDI: Beck Depression Inventory, LSI: Life Satisfaction Index. Score range: Well-being = 0– 150; GHQ = 0–30; BDI = 0–63; LSI = 0–63; Smoking = cigarettes/day; Alcohol consumption = drinks/week; Sleeping problems 1–7; Money spent 1–7; Prescription medications = 1–4.

carrier in combination with any of the predictors did not have an effect on intercept or slope. In addition to consulting significance tests for each individual predictor, the deviance statistic (see Table IV) was used to assess whether model fit was improved for the five models including all final predictors in comparison to a baseline model including only retest as a predictor. The models with all final predictors represented a better fit to the data than the model including retest only; Wellbeing χ2 (8) = 38.1, p < .001; GHQ χ2 (8) = 35.1, p < .001; Beck χ2 (8) = 38.9, p < .001; Suicidal thoughts χ2 (8) = 49.21; p < .001. The results of the multilevel analysis are represented in Table IV. The predictors were coded categorically into two groups where 0 = not belonging to the group and 1 = belonging to the group (e.g noncarriers = 0, carriers = 1). The intercept (γ 00 ) for each psychosocial measure represents the score at baseline, before test-disclosure, for a person with a value of zero for all predictors. The estimated score for example for carriers at baseline is γ 00 + γ 01 . The slopes represent the amount of change for each subsequent testing occasion. For example the first slope (γ 10 ) represents the average change for each follow-up for

a person belonging to the group with zero for all predictors. The second slope (γ 11 ) represents the difference between carriers and non-carriers in the average rate of linear change per additional follow-up. The results of the final models for each outcome measure are presented below.

Well-Being HD as a major problem (γ 02 ) and psychiatric symptoms (γ 03 ) had an effect on well-being at baseline. Concerning the change over the two-year period, only those reporting HD as their major problem (γ 12 ) significantly increased their well-being over time. Having HD relatives with psychiatric symptoms (γ 04 ) indicated a tendency (p = .087) to report a lower well-being at baseline and similarly approached significance (p = .069) for reporting increased well-being over time (γ 14 ). The random coefficients were significant, indicating that there remain individual differences at baseline and in change over time to be explained, i.e. variance that was not explained by the predictors in the model (see variance components, Table IV).

779.24

σ2 e

σ2 0 σ2 1 Deviancea Devianceb

−0.26 0.43 −1.15∗ 0.38 0.42

−1.68 −2.63 8.75∗∗∗ −0.34 4.19#

γ 10 γ 11 γ 12 γ 13 γ 14

18.83

−0.19 0.86∗ −0.68 −0.18 −0.01

1.29 1.69 3.24∗ 4.18∗ 2.69∗

BDI

1.30

−0.04 0.16∗ −0.03 0.02 −0.07

1.23∗∗∗ −0.08 0.34 0.54∗ 0.19

Suicidal thoughts

397.09∗∗∗ 18.23∗∗∗ 26.12∗∗∗ 1.26∗∗∗ 14.96∗ 0.77∗ 0.99∗∗ 1.02∗∗∗ 4146.36 (6)c 2802.60 (6)c 2652.80 (6)c 944.60 (6)c 4108.22∗∗∗ (14)c 2767.53∗∗∗ (14)c 2613.90∗∗∗ (14)c 895.38∗∗∗ (14)c

31.05

1.77# 2.69# 3.07∗ 3.50∗ 1.30

114.05∗∗∗ −5.23 −25.84∗∗ −18.04∗ −11.59#

γ 00 γ 01 γ 02 γ 03 γ 04

GHQ

47.48∗∗∗ (Fixed) — 2899.01 (2)c

40.28

0.28 0.03 — — —

24.06∗∗∗ 0.42 — — —

LSI

76.36∗∗∗ 1.26∗∗∗ — 2659.39 (4)c

11.27

−0.33 0.24 — — —

4.30∗∗∗ 2.43 — — —

Smoking

Multilevel Prediction Models for Psychosocial Measures

8.78∗∗∗ 0.43∗∗∗ — 2145.49 (4)c

3.90

0.00 0.19 — — —

3.35∗∗∗ 0.50 — — —

Alcohol consumption

0.44

0.00 0.00 — — —

3.95∗∗∗ 0.22 — — —

Money spent

1.18∗∗ 0.13∗∗ (Fixed) 0.10# — — 1534.73 (2)c 979.23 (4)c

1.14

−0.08 −0.06 — — —

1.83∗∗ 0.41 — — —

Sleeping problems

5.87∗∗∗ (Fixed) — 994.48 (2)c

1.25

0.00 0.04 — — —

0.26∗∗∗ 0.02 — — —

Prescription medications

Note. Dashes indicate that the predictor/model was not estimated. GHQ: General Health Questionnaire, BDI: Beck Depression Inventory, LSI: Life satisfaction Index, HD: Huntington’s disease. Score range: Well-being = 0–150; GHQ = 0–30; BDI = 0–63; Suicidal thoughts 1–4; LSI = 0–63; Sleeping problems 1–7; Money spent 1–7; Prescription medications = 1–4. Level 1: estimates individual changes across occasions. Level 2: estimates between-group differences in change. a model with retest as only predictor. b model with retest and level 2 predictors. c number of model parameters estimated. ∗ p < .05; ∗∗ p < .01; ∗∗∗ p < .001; # p < .10.

Fixed effects Initial status (Baseline): Intercept Carriers HD as a major problem Psychiatric symptoms Psychiatric symptoms in relatives with HD Rate of change: Retest Carriers HD as a major problem Psychiatric symptoms Psychiatric symptoms in relatives with HD Variance components Level-1 Level-2 Initial status Rate of change Goodness-of-fit

Well-being

Table IV.

Psychological Aspects of Predictive Testing 367

368


Fig. 1. Individual GHQ change trajectories for carriers and non-carriers. Bold lines reflect average scores. GHQ: General Health Questionnaire. Retest occasion; 0 = baseline, 1 = two months, 2 = six months, 3 = twelve months, 4 = twenty-four months.

General Health Questionnaire Figure 1 shows the different starting points for carriers and non-carriers and the linear change over time. The significant between-group differences for HD as a major problem (γ 02 ) and for psychiatric symptoms (γ 03 ) are at, or slightly above, the GHQ threshold score for breaks in normal psychological function (>4). Over time, only those who had reported HD as a major problem (γ 12 ) significantly improved by lowering their score 1.15 at each followup. The results at baseline for carriers (γ 01 ) approach conventional levels of significance (p = .069). Significant random effects indicate that individual variation in the initial status and rate of change remains to be explained.

Beck Depression Inventory The BDI did not reveal average scores above the threshold for depression (>9). There were no significant differences between carriers and non-carriers

at baseline but over time carriers reported significantly increasing scores (γ 11 ). Those who learned that they were carriers scored 0.86 higher on the BDI for each additional follow-up. Those who regarded HD as their major problem (γ 02 ), those with psychiatric symptoms (γ 03 ) and psychiatric symptoms in relatives with HD (γ 04 ) showed heightened scores at baseline. The significant random effect coefficients indicate that there are still individual differences to be explained in both initial status and in the rate of change. Figure 2 plots the trajectories for carriers and non-carriers over the two-year follow-up period.

Suicidal Thoughts At baseline, those with a psychiatric history (γ 03 ) reported having suicidal thoughts more often but there was no significant change over time for this group. Carriers (γ 11 ) reported thinking about suicide more often over time. Also here the significant random effects for baseline and the change over time indicate remaining individual variance to be explained.

Psychological Aspects of Predictive Testing

369

Fig. 2. Individual BDI change trajectories for carriers and non-carriers. Bold lines reflect average scores. BDI: Beck Depression Inventory. Retest occasion; 0 = baseline, 1 = two months, 2 = six months, 3 = twelve months, 4 = twenty-four months.

For descriptive purposes, we also considered the mean values of other suicidal variables that were not computed using multilevel analysis. A high percentage in both groups considered suicide as a possible solution if developing symptoms of HD at baseline (See Table V). Furthermore, over 30% of the carriers declared that they expected to consider suicide when they got to a middle or advanced stage of HD. After two years, 52% of the carriers expected to consider suicide.

DISCUSSION The aim of the present study was to assess the psychological health over a two-year period of time for persons who underwent predictive testing for HD. Specifically we aimed to evaluate whether different characteristics of the individuals explained the variation in the psychological and behavioral outcome measures at baseline and over two years. Our results showed that across a series of predictors those that had an effect at baseline were HD as a

major problem, psychiatric symptoms, and psychiatric symptoms in relatives with HD. Differences between carriers and non-carriers at baseline were relatively small and non-significant. Carrier-status and HD as a major problem turned out to be important predictors over time.

Psychological Well-Being and Health Behaviors There was a trend towards higher GHQ and BDI scores, and lower well-being for carriers compared to non-carriers at baseline. Trends seen in these measures, especially GHQ, are consistent with previous research indicating that asymptomatic carriers report lower psychological health (Close ´ ´ Ane Kirkwood et al., 2002b; Witjeset al., 2002). Average depression levels were below the cut-off scores for depression for both groups at baseline and over time. In contrast carriers scored above the threshold for psychological stress (GHQ) at baseline and, while this pattern held over the two-year period, rate of change did not differ significantly for

370


Table V.

Number and Percentages of Suicidal Thoughts and Tendencies Baseline

Suicide attemptsa It is likely that I will attempt suicide if I begin developing symptoms of HDa It is likely that I will attempt suicide when I get to a middle/ advanced stages of HDa

6 months

12 months

24 months

NonNonCarriers carriers Carriers carriers Carriers (n = 34) (n = 58) (n = 31) (n = 55) (n = 30)

Noncarriers Carriers (n = 54) (n = 30)

Noncarriers Carriers (n = 51) (n = 29)


n % n % n

16 48.48 4 12.12 5

29 50.88 5 8.77 11

7 22.58 0 0.00 10

5 9.62 0 0.00

5 9.80 0 0.00

4 7.55 0 0.00

%

15.15

19.64

35.71

35.71

39.29

46.15

n

10

15

10

11

10

13

%

30.30

26.79

35.71

39.29

40.00

52.00

Variable Suicidal thoughtsa

2 months

1 1.85 0 0.00

6 20.69 1b 3.57 10

5 17.24 0 0.00 11

8 27.59 2 6.90 12

Note. HD: Huntington’s Disease. a Missing values (range 1–5). b Completed suicide.

carriers and non-carriers. The LSI did not show any baseline differences or long-term change for carriers and non-carriers. This indicates that the participants do not come from poor environments and are fairly satisfied with their lives and living arrangements, before and after test-disclosure. We also evaluated if the genetic test outcome affected behavior patterns, but found no differences between carriers and non-carriers for alcohol consumption, smoking, use of prescription medications, sleeping problems or economic behavior at baseline or over time. These results, together with the non-differences in the LSI, indicate that predictive testing outcome has little effect on the overt life style of the participants. However, over two years important distinctions did emerge in the more psychological outcome measures regarding depression and suicidal thoughts, both of which increased for carriers, relative to noncarriers. The increasing depression scores for carriers indicate that the predictive test outcome does have an impact, although its magnitude is small. In addition, average GHQ scores remaining above the threshold for normal psychological function for carriers is a sign of an ongoing psychological strain. These results are consistent with a recent study that found negative long-term psychological effects for carriers (Timman et al., 2004). They are also important in the light of a high prevalence of major depression among carriers one year after predictive testing (Codori et al., 2004).

Suicidal Ideation Suicidal thoughts are not well covered in previous research on psychological consequences of predictive testing for HD despite the known suicidal ideation in this population (Farrer, 1986). Our results revealed that a large number of the participants, 50% of the total group, had or had previously had thoughts about committing suicide. However, further analysis of the frequency of the suicidal thoughts indicated that both groups ‘rarely’ had or had previously had thoughts about committing suicide before the predictive testing. Over time carriers’ thoughts about suicide increased to ‘sometimes’ while the frequency of non-carriers’ thoughts decreased. It is possible that suicidal thoughts are a reliable indicator of psychological health and reflect hopelessness, a relationship previously shown to be strong (Beck et al., 1993). This inference is validated by earlier research illustrating that hopelessness is higher among carriers than non-carriers (Codori et al., 1997; Timman et al., 2004). Nine participants reported previous suicide attempts at baseline. This attempted suicide rate of 10.0% for the total sample did not differ between carriers and non-carriers. These results confirm previous findings by Robins Wahlin et al. (2000) who reported a similarly high attempted suicide rate for the first 34 participants entering the present program. A survey of a normal population in Stockholm, Sweden, aged 20–67 years (n = 8800) revealed an

Psychological Aspects of Predictive Testing attempted suicidal rate of 3.5% (Ramberg and Wasserman, 2000). The attempted suicide rate in our total group, that ranged between 19–59 years of age and came from the same area, is almost three times higher. Further, in our sample there were two suicide attempts after 24 months, both carriers, and one completed homicide-suicide involving a parent and child after six months, both carriers. A world-wide study reported a low rate of suicide after predictive testing (Almqvist et al., 1999). This is in agreement with our findings. However, the worldwide study did not assess suicidal thoughts and the high suicidal ideation at baseline and the gradual increase in suicidal thoughts among carriers cannot be overlooked since the long-term effect of predictive testing is not known. A noteworthy baseline result is that from 15% to 30% of both groups thought of suicide as a possible response to developing symptoms of HD. On follow-up occasions a considerable increase of suicidal thoughts was recorded for carriers. Specifically, 30% of the carriers declared that they regard suicide as possible when getting to middle or advanced stages of HD and after two years’ follow-up 52% of carriers declared the same intentions.

Psychiatric Symptoms We hypothesized that psychiatric symptoms might have an effect on adjustment after predictive testing but this was not confirmed. Participants’ psychiatric symptoms had an effect on baseline scores for BDI, GHQ, Well-being, and suicidal thoughts. These heightened scores may in part be due to the predictive testing situation, but it is more likely that the psychiatric symptoms themselves are responsible for this relationship. Bloch et al. (1992) emphasized that persons with a prolonged adverse psychological response in the past could be a more vulnerable group. Our results do not confirm that psychiatric history affects the coping since there was no effect of psychiatric symptoms in lowering health. It is however worth noting that Almqvist et al. (1999) found that 38.5% of those experiencing an adverse event after predictive testing had a past psychiatric history. The presence of psychiatric symptoms in HD is well documented (Crauford and Snowden, 2002; Mattson, 1974), but less is known about whether these symptoms are a presymptomatic marker of HD. Our results did not indicate that psychiatric symptoms were over-represented in the carrier

371 group and we found no interaction between carriers and psychiatric symptoms either. In addition to psychiatric symptoms in participants, we also considered psychiatric symptoms in their relatives with HD. This variable showed an effect on depression baseline scores, trends toward lower well-being at baseline with improvement over time. On the other hand, psychiatric symptoms in relatives without HD did not come out significant for any outcome measure. These effects might be interpreted as evidence of the psychosocial impact of interacting with a close relative with HD who demonstrates psychiatric symptoms. Awareness of the Situation–HD as a Major Problem An important predictor was HD as the major problem identified in conjunction with the rating of well-being. Concern about HD predicted poorer general health and well-being and higher depression before test disclosure. These persons were apparently more stressed in the predictive testing situation. However, the trend over time was one of improvement. Despite initial concerns about HD, psychological health improved significantly, as evidenced by a reduction in GHQ and an increase in well-being for all participants. This indicates that these participants actually benefited from the predictive test regardless of the test outcome. One of the major reasons for atrisk individuals going through predictive testing has been found to be that knowing a predictive test outcome relieves uncertainty (Bloch et al., 1989; Codori and Brandt, 1994; Robins Wahlin et al., 2000). Previous research has also found that test-motivation is strongly related to psychological well-being after predictive testing (Decruyenaere et al., 2003). Possibly the individuals who indicate HD as their major problem also have stronger motives for knowing their genetic status. This knowledge enables them to work through the process, adapt to the known genetic status, and thereby improve their psychological health. It has been argued that individuals taking part in predictive testing are a self-selected group with good coping resources (Bloch et al., 1989; Codori et al., 1994). The predictor, HD as the major problem, could be an indication of a more conscious and active reflection on their situation and therefore classifying their genetic status may promote their psychological health. This confirms the importance of avoiding denial in complex situations such as predictive testing.

372 Strength and Limitations of the Study A main strength of the present study is the longitudinal assessment with multiple follow-up occasions and the multilevel method technique used for analyzing the data. Most longitudinal studies on HD have used more conventional analyses, for example repeated measures analysis of variance. These techniques cause loss of information when incomplete cases have to be excluded. To our knowledge only three earlier studies on predictive testing for HD have used or partly used multilevel modeling technique in their analysis (Almqvist et al., 2003; Codori et al., 1997; Timman et al., 2004). Timman et al. (2004), shed light upon methodological issues in published longitudinal studies on predictive testing and concluded that many studies could have yielded improved results if more suitable statistics had been used. They also put emphasis upon dropouts which can influence findings if they have different characteristics than those who are retained. Another main strength of our study, in relation to this, is that only three participants did not return for any of the follow-ups. This is a very small dropout rate and together with the multilevel modeling analysis the influence of dropouts is reduced. Although the present results are informative, several limitations should be acknowledged. Foremost among these is the fact that sample sizes were relatively small followed by a loss in power to detect differences. Obviously, this affects the probability of identifying true differences among the groups. Second, carriers showed increased scores for BDI over time but the GHQ did not detect the same pattern in spite of the fact that the two measures are known to be correlated (Goldberg and Williams, 1988). This non-difference in GHQ might be explained by the fact of the GHQ-scoring method used in this study, where we don’t distinguish between ‘rather more than usual’ and ‘much more than usual.’ This might fail to capture the full range of increase in different symptoms. As a consequence a suggestion for future research is that the instruments used in the assessments should be considered carefully since it is possible that some have more power to detect individual reactions in this specific situation. Our results demonstrated that there is a subtle but gradual increase in depression-scores and suicidal thoughts among carriers indicative of the importance of the instruments’ specificity and sensitivity. Third, a possible bias in the present study is that we did not exclude two participants who were diagnosed with HD

Larsson, Luszcz, Bui, and Robins Wahlin during follow-up, one at six months and another at the last follow-up. On the other hand, to have retained these participants can be considered as a more representative sample in the sense that there will always be individuals attending genetic counseling who are borderline clinical diagnosis. CONCLUSION In summary, the findings in the present study with a sample of Swedish participants at risk of HD showed that the high suicidal tendencies reported by Robins Wahlin et al. (2000) remain in this enlarged sample. The outcome of the predictive test did not affect the health behaviors or satisfaction with life, rather the effect for carriers seems to be on an emotional level characterized by increasing depression and suicidal thoughts. Also, carriers reporting lower psychological health before test disclosure and scores above the threshold for psychological distress over the whole two-year period are a novel finding that needs to be replicated in a larger sample. Accordingly, more research is needed to determine the time of onset of psychological or psychiatric symptoms due to HD. The effect of HD as a major problem clearly shows the importance of at risk individuals’ awareness of the situation and the importance of assisting individuals to avoid denial. In terms of monitoring adaptation to predictive testing, this study also demonstrated that suicidal ideation is an important variable to assess. This variable most likely captures negative feelings and hopelessness. Therefore, suicidal ideation measures could be useful in identifying those individuals in need of support and counseling even after a longer time period from predictive testing. ACKNOWLEDGMENTS This ongoing research would not have been possible without the co-operation and commitment of the study members. The authors are grateful to the persons who so generously gave their time for this study. The research was supported by fellowships from Alzheimer Foundation, Sweden, and the Swedish Association of Persons with Neurological Disabilities (NHR) to Maria U Larsson and by grants from the Swedish Research Council, the Swedish Association of Persons with Neurological Disabilities (NHR), and Alzheimer Foundation, Sweden, to Tarja-Brita Robins Wahlin. We are indebted to

Psychological Aspects of Predictive Testing David Turner and Ove Almkvist for valuable comments on the manuscript. ˚ ¨ Part of this work was presented at Vardst amman 2005, Stockholm, Sweden, and at the World Congress on Huntington’s disease, Manchester, England, 2005.

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