2.1 Design

This is an exploratory and qualitative study, using semi-structured interviews.

2.2 Study sample and recruitment

Participants in this study were noncarriers who had undergone predictive testing for HD mutation and were over 18 years old. We recruited participants through Kyoto University Hospital and the Japanese Huntington's Disease Network (JHDN), the only HD support group in Japan. In the former, the clinical geneticist (TW) and the certified genetic counselors (HM and MT) in charge of their predictive testing sessions recruited patients to the study in the follow-up call. In the latter, the support group's secretariat contacted the members and asked them to participate in this study. The researcher (HO), who was in the master's degree program for genetic counselor training course, contacted individuals who were interested in participating in this study and sent them the consent form. After receiving the consent form, HO called the participants to schedule the interview date and confirm the method of the interview.

2.3 Data collection

Before the interviews, the subjects complete a questionnaire about age, sex, marital status, child status, and time of undergoing predictive testing. HO conducted semi-structured one-on-one interviews for about 60–90 min via telephone or video call using Zoom, responding to their requests. The interviews were recorded after obtaining informed consent. The interviews focused on the circumstances and feelings of the participants before the decision to undergo predictive testing for HD, their feelings at receiving the results, and changes in their minds after receiving the results to the present.

2.4 Data analysis

The interview data were transcribed verbatim and evaluated by reflexive thematic analysis (Braun & Clarke, 2006, 2021) using MAXQDA2022 software. We decided to conduct interview with people who have tested negative for HD predictive testing and explore their experiences, feelings, and perceptions through an inductive approach based on the data obtained from the interview. HO repeatedly read the entire interview data and generated initial codes relevant to the psychosocial impact on noncarriers for HD. Next, HO continually compared the codes from analogous or different points of view, generated categories summarizing the codes and themes by comparing the categories and determining relationships under the supervision of AY and MT, who are certified genetic counselors and have extensive experience in qualitative research. Triangulation was conducted with OH, AY, and MT to enhance the certainty of the analysis and avoid interpretation bias.

2.5 Ethical considerations

The study was approved by Kyoto University Graduate School and Faculty of Medicine, Ethics Committee (No. R3492).

Participants gave written informed consent in advance. They were informed that they could cancel their participation in the study at any time, not have to answer questions they did not want to answer, and not suffer disadvantages because of that.

3.1 Study sample

Seven people underwent predictive testing for HD at Kyoto University Hospital between 2015 and 2019, and all got negative results. Five of the seven (71.4%) individuals agreed to participate in the study. From the JHDN, three individuals who met the criteria for the research consented to the study. The attributes of the eight individuals are presented in Table S1. Three individuals were interviewed by phone, and five by video call using Zoom, two of whom turned off the video during the call. The interview time was 61–101 min, 80 min on average.

3.2 Thematic analysis

From the thematic analysis of the psychosocial impact of noncarriers of HD, four themes, 21 categories, and 46 codes were identified (Table S2).

3.3 Theme 1: Diversity of perceptions concerning the test results

3.4 Theme 2: Views on life as a noncarrier

3.5 Theme 3: Changes in feelings toward and relationships with family members

3.6 Theme 4: Sharing information within the family

4.1 The complex psychological condition of being noncarrier

A negative result may bring a psychologically complex state for those who have long-term experience living as a carrier. After receiving negative results, some participants calmly accepted that they were noncarriers, some were surprised and had doubts about the unexpected results, and others felt relieved from the tension because their strained nerves were suddenly relaxed. If noncarriers assumed that they had the HTT mutation and established their identity before genetic testing, they had to reconstruct their identity after learning they were negative for HD (Tillerås et al., 2020). The long time they spend confronting HD and the strong perception of being positive before the test may strengthen their identity as carriers and make it difficult to accept being noncarriers. Furthermore, some participants changed their living environment or had an abortion in anticipation of a positive result and regretted their decisions after receiving the negative result. It has been reported that some individuals who undergo predictive testing for HD may experience intensified emotional responses regardless of the results if they made significant or irreversible life decisions before the test (Tillerås et al., 2020). These decisions include wasteful debt, sterilization (e.g., vasectomy) (Huggins et al., 1992), and abortion (Tillerås et al., 2020). Regret may persist in noncarriers long after receiving the test results. Therefore, people in charge of genetic counseling should consider that noncarriers may be in a complex psychological state and provide them with decision-making support to completely consider the possibility of a negative result before they take the test. It is also important to carefully reflect and follow up on their thoughts and experiences prior to the test, even if the result is negative. In particular, in Japan, most information is already held in the person and communication often occurs without explicit verbalization (Hall & Hall, 1990), and it is important to focus on emotions by observing nonverbal communication to build rapport in genetic counseling (Matsukawa et al., 2022). Therefore, it is necessary to be more cautious and supportive by being attuned to their feelings before and after the test.

4.2 Noncarriers' “Survivors' guilt”

Noncarriers for HD may feel survivor's guilt beyond intimate family members. They also may express a sense of mission or responsibility. It has been reported that noncarriers are more likely to have survivor's guilt toward their siblings who were untested, positive, or affected (Tillerås et al., 2020). However, in this study, one of the participants felt guilt toward unspecified or unrelated carriers of HD, even though they had no relatives who had been diagnosed with HD. In addition, although some participants expressed sympathy for relatives who had developed HD without knowing the possibility of future onset, surprisingly, none of them talked about guilt toward siblings who had not been tested or tested positive. Instead, the noncarriers expressed a sense of responsibility to support their siblings and live a meaningful future life and a desire to help others. Survivor's guilt was originally considered to be the guilt felt by the survivors of events related to death, such as natural disasters or war. However, it has been extended to those situations that do not necessarily link to death, such as carriers and noncarriers of hereditary diseases within a family (Domen, 2009). Moreover, survivor's guilt may lead to adopting new values (Watanabe, 2009) or guiding people toward altruistic action (Domen, 2009). Up until now, survivor's guilt emphasized “guilt as being a noncarrier,” but our study suggests that noncarriers of HD may embrace altruistic behavior as a member of their family and society by examining the consequences or meaning of their negative results. It implies that empathy for unspecified others, stemming from the Japanese collectivist mindset (Hall & Hall, 1990), makes noncarriers feel that they are part of a group related to HD and have a responsibility to help the group. Moreover, for those with whom they have a closer and stronger connection, such as siblings, noncarriers may think of and help their siblings who are at risk, positive, or HD patients as if they were their own concerns. Although survivor's guilt is considered the main issue for noncarriers of HD, genetic counselors need to understand that noncarriers may feel survivor's guilt even when they have no affected relatives. It is also important to keep in mind that a sense of mission and responsibility may manifest as they live future lives with their siblings who are positive or at risk. Some noncarriers of HD feel pressure to do something special in their lives as they redefine themselves (Winnberg et al., 2018), so being a noncarrier might become a psychological burden. We must consider what kinds of thoughts and feelings are evoked by being a noncarrier and whether they feel burdened through dialogue in Japanese genetic counseling. Once they have found out they are noncarriers, it is important to reconsider their current feelings, situation, and the impact on the future both subjectively and objectively.

4.3 Feelings of the spouses of HD patients toward their children

Our results suggest that children who are at risk may be unconsciously pressured by the spouses of HD patients to undergo genetic testing. One of the noncarriers was relieved from the pressure given by the spouse of an affected parent, who expected her results to be negative and recommended her undergo predictive testing. It has been reported that the spouses of affected parents shared a common understanding that the decision to undergo predictive testing for HD was a matter for the children to decide for themselves, although they feared the possibility of their children developing HD (Lowit & van Teijlingen, 2005). This study cannot directly clarify the feelings of the spouses of affected parents. However, the interviews indicated that their expectations and fears may unintentionally cause unexpected psychological burdens for some potential carriers, even if the parents respected their children's decisions. At-risk individuals for HD may prioritize their family's wishes over their own when considering undergoing predictive testing for HD (Klitzman et al., 2007), and genetic counselors should provide decision-making support and empower at-risk individuals for HD to consider undergoing predictive testing autonomously. It was also found that noncarriers shared their negative results with the spouses of affected patients, who were worried before testing, because they wanted to reassure them. The spouses of the affected patients have concerns about their children being at risk while fulfilling their role as caregivers (Williams et al., 2009). In Japan, it has been reported that some neurologists are reluctant to conduct genetic testing for the definitive or exclusive diagnosis of HD because it is difficult for them to inform patients of the positive results and provide psychological support to them and their families (Yoshida et al., 2013). In other words, it is inferred that the spouses of the affected parents for HD are less likely to receive or connect with genetic counseling. All HD patients and their families should be able to access information related to supporting them equally but the facilities conducting predictive genetic testing and genetic counseling are limited in Japan (Shibata et al., 2022). It is expected that many caregivers of HD patients may not have access to genetic counseling, and quite a few of them may be troubled by their situation. Therefore, it is necessary to establish a support system for the spouses who are not at risk from the stage when the individuals are suspected of potentially having HD.

4.4 Challenges sharing information with siblings

Even when the result is negative, some may struggle to share their carrier status with their siblings. It was found that the negative individuals with siblings who were not informed of being at risk for HD had concerns about their sibling's perception of the possibility of developing HD in the future and assumed that they did not want to know about that. The noncarriers also assumed that their untested siblings were unlikely to test negative, potentially making them hesitate to share information with their siblings. The reasons for sharing the predictive testing results with their family members included a sense of responsibility to inform them and to relieve them from anxiety (Stuttgen et al., 2020). Conversely, the reasons for not sharing included guilt from the negative result and hesitation toward the family members who had adverse perceptions toward the predictive test for HD (Stuttgen et al., 2020). The noncarriers felt relief about their results, and it was suggested that they originally hoped for a negative result before testing. However, despite receiving desirable results, some noncarriers had difficulty sharing this information with their siblings. Therefore, people in charge of genetic counseling must know the challenges associated with sharing information as noncarriers and support them. Furthermore, it is expected that the challenges of sharing information will persist for many years and we need to consider the timing and method for follow-up, including the possibility of contacting them again in a few years if necessary.

4.5 Limitations of the study and prospects

Although the number of participants in this study may seem small, we deem that the sample size was sufficient to provide new insights unique to the Japanese noncarriers for HD, because the prevalence of HD in Japan is one-tenth of that in the West. It was appropriate to complete such a thematic analysis to handle very sensitive information from the participants through interviewing. We could maximize the number of individuals who participated in the study or five out of seven (71.4%) individuals who underwent predictive testing for HD and got negative results at Kyoto University Hospital between 2015 and 2019. It is difficult to generalize the results of this study because the sampling was based mainly on subjects who underwent predictive testing at Kyoto University Hospital. In addition, there was a possibility of bias as many of the participants were female, and many of the participants' fathers had developed HD. Three participants had undergone predictive testing for HD more than 5 years before the interviews, which could lead to a recall bias. In future studies, it is necessary to broaden the diversity of the subjects whose results are negative. Additionally, studies targeting individuals at risk for HD and those who have tested positive for HD are also needed.