An Exploratory Study Investigating Autonomy in Huntington’s Disease Gene Expansion Carriers

Abstract

Background:

Autonomy describes a psychological state of self-regulation of motivation and action, which is a central characteristic of healthy functioning. In neurodegenerative diseases measures of self-perception have been found to be affected by the disease. However, it has never been investigated whether measures of self-perception, like autonomy, is affected in Huntington’s disease.

Objective:

We investigated whether autonomy is affected in Huntington’s disease and if the degree of autonomy is associated with motor function, neuropsychiatric symptoms, cognitive impairments, and apathy.

Methods:

We included 44 premanifest and motor-manifest Huntington’s disease gene expansion carriers and 19 controls. Autonomy was examined using two self-report questionnaires, the Autonomy-Connectedness Scale-30 and the Index of Autonomous Functioning. All participants were examined according to motor function, cognitive impairments, and neuropsychiatric symptoms, including apathy.

Results:

Statistically significant differences were found between motor-manifest Huntington’s disease gene expansion carriers and premanifest Huntington’s disease gene expansion carriers or controls on two measures of autonomy. Between 25–38% of motor-manifest Huntington’s disease gene expansion carriers scored significantly below the normal level on subscales of autonomy as compared to controls. One autonomy subscale was associated with apathy (r = –0.65), but not with other symptoms of Huntington’s disease.

Conclusion:

This study provides evidence for impaired autonomy in individuals with Huntington’s disease and an association between autonomy and apathy. The results underline the importance of maintaining patient autonomy and involvement in care throughout the disease.

Keywords

Apathy autonomy Huntington’s disease neuropsychiatric symptoms self-perception

INTRODUCTION

Autonomy is a theoretical construct that describes a psychological state of self-regulation of motivation and actions. Generally, autonomy is a central characteristic of healthy functioning and is related to a higher degree of well-being and satisfaction of basic psychological needs [1, 2]. Individuals experiencing a high degree of autonomous behavior perform actions in agreement with their inner values and interests [1]. Conversely, individuals with a low degree of autonomy have a higher risk of developing psychopathology like depression and anxiety.

Multiple approaches to the theoretical definition and conceptualization of autonomy are proposed; however, autonomy as a construct is still not well-defined. In a review on existing psychological theories on the definition of autonomy, Hmel & Pincus [3] described three core aspects of autonomy: autonomy as self-governance, autonomy as separation, and autonomy as vulnerability. Autonomy as self-governance implies self-regulation and self-ruling while being in meaningful relations and interactions with others. The aspect of autonomy as separation implies separation of self from others and the need to act independently. Finally, autonomy as vulnerability implies a cognitive vulnerability associated with the clinical aspects of depression. Although the three core aspects were confirmed in their structural analysis of 15 self-report scales, Hmel & Pincus [3] argued that autonomy as vulnerability did not include the essential element of “agency” and thus, could not constitute a core aspect of autonomy. Irrespectively, autonomy has been linked to depression and also anxiety in several studies [4 –7], but disagreement exists as to the degree and types of autonomy that are predictive of psychiatric illnesses.

Huntington’s disease (HD) is an autosomal dominantly inherited neurodegenerative disease that is characterized by a triad of symptoms, with increasing motor, cognitive, and neuropsychiatric impairments [8, 9]. Among the most prominent symptoms are chorea, dystonia and bradykinesia, psychomotor slowing, executive and social dysfunctions, as well as neuropsychiatric symptoms like depression and anxiety [9 –11]. In time, the daily functioning of individuals with HD will be affected by the motor, cognitive, and neuropsychiatric symptoms, to such a degree where individuals need assistance in basic activities of daily living. These symptoms might cause diminished feelings of competence and inner resources, thereby repressing self-regulated actions and motivations. To our knowledge, no study has examined to which degree the symptoms might affect the self-perception of individuals with HD. Specifically, if these symptoms repress the autonomy of HD gene expansion carriers, to a degree that may decrease their perceived self-regulation. Such studies could contribute with information on a person’s ability to cope with their disease, to preserve social relationships, and to make important life decisions and decisions of care [12, 13].

We investigated autonomy (defined as self-governance) in HD gene expansion carriers with an explorative study design. Since autonomy is often perceived as a stable personality trait in adults, it could be hypothesized that autonomy would not decrease with disease progression in HD. However, recent studies have found that the perception of self and identity is negatively affected by dementia [12, 14]. Thus, other neurodegenerative diseases might also affect the feelings of self and identity. The objective of this study was to investigate if the autonomy of individuals with HD were affected, and if there was a difference in degree of autonomy in premanifest and motor-manifest HD gene expansion carriers, using two self-report questionnaires on autonomy. Also, we examined the associations between symptoms of HD and autonomy and investigated if individuals with a low degree of autonomy had a higher risk of experiencing motor disturbances, neuropsychiatric symptoms, cognitive decline, or symptoms of apathy.

MATERIALS AND METHODS

Participants

The participants were 44 HD gene expansion carriers enrolled from the Neurogenetics Clinic, Danish Dementia Research Centre, Rigshospitalet - Blegdamsvej, Copenhagen, Denmark from year 2020-2021. All participants had previously participated in a prospective cohort study on HD at our clinic [15, 16] and were invited to participate in the current study when attending their regular assessment in the clinic. The participants were included based on the following criteria: a Unified Huntington’s Disease Rating Scale-99 total motor score (UHDRS-TMS) ≤55 [17], a Montreal Cognitive Assessment (MoCA) score ≥19 [18], a Mini-Mental State Examination (MMSE) score ≥24 [19], and a CAG repeat length ≥39. Exclusion criteria were other neurological disease, ongoing alcohol- or drug abuse, or a native language other than Danish.

A classification as motor-manifest HD gene expansion carrier was given if the participants had an UHDRS-TMS>5. Contrarily, participants were classified as premanifest HD gene expansion carriers if they presented without substantial motor symptoms and had an UHDRS-TMS ≤5. This cut-off on the UHDRS-TMS scale has previously been applied in the TRACK-HD study [20].

A control group of 19 at-risk individuals who had tested negative for the HD gene expansion (a CAG repeat length <30) was also included. This group was used to match the gene expansion carriers concerning the environmental and psychosocial factors that could have an impact on the results.

All participants had received genetic counselling and were informed of their genetic status prior to and independently from enrolment in this study.

Procedure and instruments

The study was approved by the Ethics Committee of the Capital Region of Denmark (H-17002606) and performed in accordance with the ethical standards of the Helsinki Declaration. Written informed consent was obtained from all participants before enrolment in the study. The participants had one visit in our clinic, where both the regular assessment and the neuropsychological assessment were performed.

Neuropsychological assessment

Participants were examined with a neuropsychological battery on self-perception and autonomy. Self-perception was assessed using a modified version of the Twenty Statements test [21], the Self-identity in Dementia Questionnaire [12], and the Tennessee Self-Concept Scale, Identity Component [22]. Here, we report only on the autonomy scales (please see description in the following).

During the assessment, participants were assessed with instruments on neuropsychiatric symptoms, cognitive status, and symptoms of apathy. The neuropsychiatric symptoms were examined using the Hamilton Depression Scale (HAM-17) [23] and the Symptom Checklist-90 Revised (SCL-90-R) [24]. The HAM-17 is a semi-structured interview on depression and depressive symptoms [23]. It contains 17 items, that are scored on either a 5-point scale (0–4) or a 3-point scale (0–2), where “0” indicates that the symptom is not present, and a higher score indicates increased severity of the symptom. The SCL-90-R is a self-report inventory with 90 items that assesses the status of one’s psychological distress within the previous seven days [24]. Each item reflects one psychological symptom, and the participant must answer on a 5-point Likert scale ranging from 1 “not at all” to 5 “extremely” distressing. The raw scores were converted to T scores, normalized to a sample of nonpsychiatric Danish participants, sorted by gender [25]. Nine symptom dimensions and three global indexes are described by the SCL-90-R. Here, we used the Global Severity Index (GSI) and the dimensions Depression and Anxiety of the SCL-90-R, to describe the neuropsychiatric status of the participants.

Cognitive symptoms were assessed with the short screening test MoCA [18]. Apathy was examined using the Lille Apathy Rating Scale (LARS) [26], a standardized structured interview on symptoms of apathy. The LARS contains 33 items divided into 9 domains. The first three items are scored on a 5-point Likert scale, while item 4–33 are positively worded questions, that are answered by yes/no answers (binary scale, with an additional NA for non-applicable items). LARS yields a global score and four subscale scores (Intellectual Curiosity, Emotion, Action Initiation, and Self Awareness), where a higher score indicates a higher degree of apathy. The LARS has previously been used for examining apathy in HD [27].

Assessment of autonomy

Autonomy was assessed using two self-report questionnaires: the Autonomy-Connectedness Scale (ACS-30) [28] and the Index of Autonomous Functioning (IAF) [29]. Both scales were translated to Danish agreed upon with the authors of the original scales.

The ACS-30 scale is a self-report questionnaire on autonomy [28]. It was developed as a shorter version of the Autonomy scale [30], with a theoretical background that draws on elements from feminist theory, neo-analytical object relations theory, and attachment theory, and describes autonomy as self-governance [3]. The scale was developed for healthy subjects and has to our knowledge not previously been used in patients with neurological disorders. In the ACS-30, autonomy and connectedness is not seen as opposites on a dimension, but focuses on the subject as autonomous while being connected to others [28].

The ACS-30 consists of 30 questions that participants must answer on a 5-point Likert scale, ranging from 1 (disagree) to 5 (agree). It has a three-factor structure, where autonomy is described through three subscales: Sensitivity to Others (Sensitivity –17 items), Capacity for Managing New Situations (Capacity –6 items), and Self-Awareness (Self-Awareness –7 items). Capacity does not describe elements of self-governance, but was included because the authors found it to be a clinical relevant aspect of autonomy [28]. A higher score on each of the three subscales represents a higher degree of the trait in that subscale.

A difference between the sexes on the Sensitivity subscale, where women scored higher than men, corresponded to a large effect when examined in the original study [28]. The authors argue that this sex difference support the relevance of connectedness as a characteristic of female identity, and thus, underline the idea that connectedness is an inseparable aspect of autonomy.

The ACS-30 has been found to be a reliable instrument with sufficient convergent validity. In the Bekker & van Assen [28] study, Cronbach’s alpha was reported to be 0.83, 0.82 and 0.81 for Sensitivity, Capacity, and Self-Awareness, respectively. Moderate correlation coefficients were found between the three subscales on the ACS-30 and the Occupational Self-Efficacy scale [31], the Symptom Checklist-90 [32], and Becks Depression Inventory [33]. The authors argued that these results represented initial support for the validity of the ACS-30 and that the moderate correlation coefficients indicated that there was no contamination by the clinical measures [28].

The IAF is a self-reported questionnaire on autonomy, that was developed for healthy individuals with a theoretical background in self-determination theory [29]. Self-determination theory places the definition of autonomy within the core aspect of self-governance [2, 3]. According to the self-determination theory, autonomy is described as an inner self-regulation of behavior, where an individual with a high degree of autonomous behavior perceive their actions as congruent with their self, and this is most often associated with positive outcomes like well-being and improved performance [1, 2].

The IAF includes 15 questions, which participants must answer on a 5-point Likert scale, ranging from 1 (not at all true) to 5 (completely true). Like the ACS-30, the IAF was also developed with a three-factor structure and consisted of the three subscales: Authorship/Self-congruence (5 items), Interest-taking (5 items), and Susceptibility to control (5 items). Based on the method from the original study [29], a total score was calculated, as the summed score of Authorship/Self-congruence and Interest-taking, subtracted the score of Susceptibility to control (Total IAF = Author + Interest –Control). A higher total score indicates a higher degree of autonomy.

In the original paper, the IAF was validated through several studies, that placed the IAF in a nomological net, where both convergent and divergent validity were examined with satisfactory results [29]. The IAF had meaningful correlations to measures of personality characteristics, satisfaction, and well-being outcomes, as well as other instruments that examined autonomy, like the Emotional Autonomy scale [34] and the General Causality Orientation Scale [35]. The internal reliability was examined through seven studies, with Cronbach’s alpha levels between 0.81–0.83 for the Total IAF score [29]. Test-retest reliability was examined over a 6-month period and results showed high consistency across time (ICC = 0.86, p < 0.001). The IAF has previously been applied in a sample of patients with multiple sclerosis [36].

Statistical analyses

Group comparisons between the motor-manifest HD gene expansion carriers, the premanifest HD gene expansion carriers, and controls on the demographic variables and the basic clinical variables were performed using one-way analysis of variance (ANOVA) or the Kruskal Wallis test when the assumption of homogeneity of variances was not met. Post hoc comparisons were performed using Dunnett’s t-test or pairwise comparisons. The same method was used for group comparisons of the autonomy performance scores.

Correlation analyses were applied to test the level of significance of the associations between variables with Pearson’s r or Spearman’s rho (for skewed distributions). To examine the associations between the basic clinical variables and autonomy in participants with a very low degree of autonomy, we calculated a 10th percentile cut-off score on the ACS-30 subscales and the Total IAF score based on the scores of the controls. The association analyses were performed in the group of motor-manifest HD gene expansion carriers with a low degree of autonomy or the entire group of motor-manifest HD gene expansion carriers depending on the number classified as below the 10th percentile cut-off score. The basic clinical information that was examined included the neuropsychiatric scale scores (the HAM-17 and the SCL-90-R GSI, Depression, and Anxiety), a motor score (the UHDRS-TMS), an apathy score (the global LARS), and a cognitive screening test (the MoCA).

For all analyses the Bonferroni-Holm correction was used to adjust the level of significance when multiple comparisons were performed. The alpha level for significance was p < 0.05 (two-tailed significance).

RESULTS

Table 1 shows the demographic data and basic clinical information (the HAM-17, the SCL-90-R GSI, Depression, and Anxiety, the UHDRS-TMS, the global LARS, and the MoCA) on the HD gene expansion carriers and the controls. No significant difference in educational level or on the HAM-17 scale were found. The motor-manifest HD gene expansion carriers differed significantly from the other groups on almost all other measures (except for the educational level, the HAM-17 score, and age for the controls). The premanifest HD gene expansion carriers were significantly younger than the controls but did not differ significantly from controls on any other measure.

Table 1

Demographic data and basic clinical information on the HD gene expansion carriers and the controls. Results are presented as mean (SD), unless otherwise noted

	HD gene expansion carriers		Controls
	Premanifest HD	Motor-Manifest HD
N	20	24	19
Sex (M/F)	11/9	17/7^*	7/12
Age	39.1 (9.3)^*	54.3 (11.7) ^†	52.7 (12.3)
Educational Level	14.4 (1.7)	13.6 (1.9)	14.7 (1.9)
UHDRS-TMS	1.7 (1.3)	23.6 (13.5)^*†	1.6 (1.7)
HAM-17	2.5 (1.9)	3.4 (2.8)	3.0 (2.5)
SCL-90-R GSI	40.0 (8.0)	51.5 (9.3) ^*†	41.8 (10.5)
SCL-90-R Depression	42.9 (7.1)	50.9 (7.7) ^*†	43.5 (8.1)
SCL-90-R Anxiety	40.9 (7.0)	51.4 (9.2) ^*†	42.0 (7.1)
MoCA	28.5 (1.8)	26.1 (2.6)^*†	28.4 (2.0)
Global LARS	–26.7 (4.4)	–23.2 (5.8)^*†	–27.4 (2.5)

^*Statistically significant difference from the controls (p < 0.05). ^‡Statistically significant difference from the premanifest HD gene expansion carriers (p < 0.05). F, female; GSI, Global Severity Index; HAM-17, Hamilton Depression Scale; HD, Huntington’s Disease; LARS, Lille Apathy Rating Scale; M, Male; MoCA, Montreal Cognitive Assessment; N, number of participants; SCL-90-R, Symptom Checklist-90 Revised; SD, standard deviation; TMS, Total Motor Score; UHDRS, Unified Huntington’s Disease Rating Scale.

Table 2 presents the scores on the ACS-30 and the IAF as divided by groups. The premanifest and motor-manifest HD gene expansion carriers differed significantly on the Total IAF score (the motor-manifest participant scored significantly lower than the premanifest HD gene expansion carriers). The motor-manifest HD gene expansion carriers had significantly lower scores than the controls on the ACS-30 Capacity subscale, whereas the premanifest group did not differ significantly from the controls on any measure of autonomy.

Table 2

Scores on the ACS-30 and the IAF for all HD gene expansion carriers and the controls. Scores are reported as mean (SD)

	HD Gene Expansion Carriers		Controls
	Premanifest HD	Motor-Manifest HD
N	20	24	19
ACS-30
ACS-30 Sensitivity	54.9 (8.7)	56.8 (7.5)	57.1 (5.4)
ACS-30 Capacity	21.0 (5.6)	19.4 (5.7)^*	23.2 (3.9)
ACS-30 Self-Awareness	27.0 (5.3)	25.1 (5.6)	26.8 (3.1)
IAF
Total Score	28.3 (3.5)	24.5 (6.5)^†	26.5 (4.5)

^*Statistically significant difference from the controls (p < 0.05). ^‡Statistically significant difference from the premanifest HD gene expansion carriers (p < 0.05). ACS-30, Autonomy-Connectedness Scale; HD, Huntington’s disease; IAF, Index of Autonomous Functioning; N, number of participants.

The motor-manifest participants were classified as below the 10th percentile cut-off or not on the ACS-30 subscales and the Total IAF score. Table 3 shows the number and percentages of motor-manifest HD gene expansion carriers classified as having a low degree of autonomy when using the 10th percentile cut-off (a less conservative cut-off) compared to the 5th percentile cut-off which corresponds to the normally used 2 SD below the mean. Six motor-manifest HD gene expansion carriers (25%) scored below the 10th percentile the ACS-30 Sensitivity subscale. These individuals had a low degree of sensitivity to others and a low degree of autonomy. When examining if ACS-30 Sensitivity was associated with scores on the basic clinical variables, no significant correlations were found. Eight persons (33%) of the motor-manifest HD gene expansion carrier group, scored below the 10th percentile on the ACS-30 Capacity subscale, suggesting a low degree of capacity for managing new situations and therefore a low degree of autonomy. A significant negative correlation between the global LARS score and the ACS-30 Capacity score was found in the entire group of motor-manifest HD gene expansion carriers (r = –0.65, p = 0.001), indicating that participants with a high capacity for managing new situations have a low degree of apathy. On the ACS-30 Self-Awareness subscale, 9 motor-manifest HD gene expansion carriers (38%) scored below the 10th percentile, suggesting a low degree of self-awareness and a low degree of autonomy. No significant correlations were found between the ACS-30 Self-Awareness subscale and the basic clinical variables in this group. For the Total IAF score, only two motor-manifest HD gene expansion carriers scored below the 10th percentile, and consequently, no association analyses were applied. There were no significantly correlated association between the basic clinical variables and the Total IAF score when examined in the entire group of the motor-manifest HD gene expansion carriers.

Table 3

Frequency of the motor-manifest HD gene expansion carriers classified as below the cut-off when using the 10th percentile and 5th percentile cut-off scores

	Cut-off
	10th percentile	5th percentile
IAF
Total	2 (8 %)	2 (8 %)
ACS-30
Sensitivity	6 (25 %)	1 (4 %)
Capacity	8 (33 %)	6 (25 %)
Self-Awareness	9 (38 %)	8 (33 %)

Frequency is reported as N (%). ACS-30, Autonomy-Connectedness Scale; HD, Huntington’s disease; IAF, Index of Autonomous Functioning; N, number of participants.

Figure 1 illustrates the distribution of scores on the Total IAF, the ACS-30 Capacity subscale, and the Global LARS in the three groups. As can be seen the motor-manifest HD gene expansion carriers had a higher dispersion of scores on all measures. Although the scores differ significantly from the premanifest HD gene expansion carriers on the Total IAF, the controls on the ACS-30 Capacity subscale, and both groups on the Global LARS, there was an overlap between the scores of the three groups.

Fig. 1

Dispersion of scores for the motor-manifest HD gene expansion carriers, the premanifest HD gene expansion carriers, and the controls on the Total IAF, the ACS-30 Capacity, and the Global LARS. Error bars represents min. and max. scores.

A significant correlation between the ACS-30 Self-Awareness subscale and the Total IAF score was found for the motor-manifest HD gene expansion carriers (rho = 0.48, p = 0.019). The other ACS-30 subscales did not correlate significantly with the Total IAF score.

DISCUSSION

This study was the first study to investigate if the perception of autonomy is affected in HD. By using an exploratory study design, we examined the degree of autonomy (defined as self-governance) in premanifest and motor-manifest HD gene expansion carriers. Further, we investigated the possible associations between autonomy and basic clinical measures like motor function (the UHDRS-TMS score), neuropsychiatric symptoms (the SCL-90-R and the HAM-17 scores), cognitive status (the MoCA score), and apathy (the LARS score).

Among the motor-manifest HD gene expansion carriers, 25–38% of the participants scored substantially lower than the normal level on the ACS-30 subscales, as compared to controls. No significant associations were found between a low degree of autonomy and motor performance or neuropsychiatric and cognitive screening test, so autonomy did not seem to be associated with symptoms or progression of disease in HD. Only apathy was a relevant focus for these individuals, as a significant association was found between the ACS-30 Capacity subscale and the global LARS score. This important result demonstrates that a theoretically relevant association exists between low initiation and motivation, and low self-regulation, and it contributes importantly to the evidence on apathy, specifically when considering that apathetic symptoms are frequently reported in individuals with HD [37]. Interestingly, only the ACS-30 Capacity subscale was significantly associated with apathy on the LARS, the only subscale that did not describe elements of autonomy as self-governance. Instead, the ACS-30 Capacity subscale include aspects of interest in new situations, the ability to enjoy new activities, and to be adventurous. This might be more associated with the classical aspects of apathy, with diminished motivation and activity, and a lack of interest and initiative, while other aspects of autonomy like the understanding of oneself and the regulation of attitudes and opinions may not be associated with apathy to the same degree.

It should be noted that these results are not merely illustrating that HD gene expansion carriers are affected by growing up in a family with HD, since the control participants were also family members, but with a negative gene test. The results illustrate that a moderate number of HD gene expansion carriers have a substantially lower degree of autonomy, when compared to healthy family members, irrespective of environmental and psychosocial factors.

The motor-manifest HD gene expansion carriers had a significantly lower degree of autonomy compared to premanifest HD gene expansion carriers on the Total IAF, which indicates that the symptoms of HD do affect the degree of autonomy. Individuals with more advanced HD might have more diminished feelings of autonomy, and thereby more diminished feelings of self-regulation and competence as proposed by Ryan & Deci [1, 2]. The motor-manifest HD gene expansion carriers had a significantly lower capacity for managing new situations and thus autonomy on the ACS-30, when compared to controls. These results are in line with the results by Addis & Tippett [13] and Caddell & Clare [12], who reported that the perception of self and identity was negatively affected by dementia. Thus, neurodegenerative diseases can affect the individual’s self-perception and the neurodegeneration of HD seem to similarly affect the self-perception of the individual with the disease. However, as seen in Fig. 1, there was a large overlap between the autonomy scores in the three groups, which oppositely suggests that the disease progression is not associated with autonomy. This suggestion was further supported by the lack of correlation between the UHDRS-TMS and the Total IAF or the ACS-30 subscales for the motor-manifest HD gene expansion carriers. Thus, the lower degree of autonomy in the motor-manifest participants might be driven by other factors than disease progression. Interestingly, the premanifest HD gene expansion carriers did not score differently on any measure of autonomy when compared to controls. Thus, autonomy does not seem to be affected in the early stages of disease, unlike other symptoms of HD, e.g., social cognition [38]. Irrespectively, the present results showed that the self-perception of autonomy in individuals with motor-manifest HD was affected to some degree. These important results should be considered when caring for individuals in more advanced stages of HD, as diminished perception of autonomy could affect the individual’s ability to cope with their disease, to interact with family, friends, or professionals, or to make important decisions on care. This underlines the importance of supporting perception of autonomy throughout the disease course, e.g. by promoting a person’s normal life and control in care [39].

While this study showed that autonomy was associated with apathy, it did not illustrate a significant association between autonomy and psychiatric symptoms, as was found by Bekker & van Assen [28]. This was somewhat surprising since it could be hypothesized that a low degree of autonomy could help identify people at risk for neuropsychiatric symptoms. There are several differences between the studies, but methodological differences in instruments used for examining psychiatric symptoms seem most important. While Bekker & van Assen [28] used the original SCL-90 scale, we used the revised version, where scores were normalized to a Danish sample. Moreover, this negative finding could also be caused by the relatively low number of participants in the present study. It would be interesting to investigate if an association between autonomy and psychiatric symptoms in HD could be replicated in a larger cohort.

Since we used an exploratory design, two different quantitative measures for autonomy were applied. Both the ACS-30 and the IAF defined autonomy as in the core aspect of self-governance, where actions are regulated by the self, while being in meaningful interactions with others [3]. The fact that the scales measure the same construct was supported by the significant correlation between the ACS-30 Self-Awareness subscale and the Total IAF. However, since no other subscale of the ACS-30 was significantly associated with the Total IAF, the two instruments also measure different characteristics of autonomy. Interestingly, the characterization of autonomy used in the ACS-30 seemed to be more sensitive to the changes in individuals with HD, as a higher frequency of participants with a substantially lower autonomy was found than on the IAF scale. One explanation could be that the ACS-30 includes items on the ability to understand and feel with others (the Sensitivity subscale), which may tap abilities of theory of mind, often affected in HD [38], as well as the abilities to handle new situations (the Capacity subscale), which is associated with apathy often found in HD [37]. The IAF includes items concerning the ability to understand oneself and one’s actions, which has not previously been investigated in HD.

One substantial limitation of the present study is the low number of participants included. As this was an exploratory study, we did not include a power analysis. Therefore, it remains unknown whether the missing difference on two of the ACS-30 subscales are genuine or an artefact caused by the low number of participants. However, the results should be seen as an attempt to explore the possible neurodegenerative effect on the self-perception of autonomy by HD and not a final measure of effect. Another limitation concerns the use of self-report measures in studies of HD, as individuals with HD might have decreased insight into their symptoms, proposedly more frequently in more severe stages of disease [40, 41]. The autonomy scales used in the present study were both rated on a 5-point Likert scale, where diminished insight might inhibit ratings in the lowest or highest ends of the scale, thereby increasing the probability of answering in the middle of the scale. It cannot be ruled out that the missing difference between the groups on the two ACS-30 subscales might have been affected by this. Moreover, as autonomy is a phenomenological construct, investigation of autonomy using quantitative rating scales should not stand alone, but in this study, we investigated autonomy with this method in an attempt to incapsulate this complex phenomenon and to explore if the perception of autonomy in individuals with HD was affected.

In conclusion, this study is the first to investigate changes in the perception of self and autonomy in HD gene expansion carriers. Using quantitative scales previously applied in other diseases we found that 25–38% of the motor-manifest HD gene expansion carriers had a degree of autonomy that was substantially lower than the level of gene negative family controls, and these individuals might be at risk of having apathetic symptoms as well. Contrarily, the autonomy of the premanifest HD gene expansion carriers were not affected by the disease, as they did not differ significantly from the controls. The current results should be interpreted in the light of the conceptualization of autonomy as self-governance. While self-governance has gained theoretical foothold specifically in newer studies, other conceptualizations of autonomy exist and might have generated different results. As an example, autonomy defined as vulnerability has been associated with depression in previous studies [6, 7]. Nevertheless, the current results illustrate that changes in autonomy can occur in HD and underline the importance of maintaining patient autonomy and involvement when caring for individuals with HD.

Footnotes

ACKNOWLEDGMENTS

The authors would like to thank all participants for their time and contributions to this study.

The study was financially supported by the Danish Huntington’s Disease Association Research Fund, the Research Board at Rigshospitalet, the Novo Nordisk Foundation, the Søren Segel & Johanne Wiibro Segel’s Research Fund, and the A.P. Møller Foundation for the Advancement of Medical Science.

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

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