Volume 101, Issue 2 p. 395-403
Original Article
Free Access

Psychologic distress after disclosure of genetic test results regarding hereditary nonpolyposis colorectal carcinoma

A preliminary report

Yoshie Murakami R.N., M.S.N.

Yoshie Murakami R.N., M.S.N.

Psycho-Oncology Division, National Cancer Center Research Institute East, Chiba, Japan

Department of Adult Nursing/Terminal and Long-Term Care Nursing, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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Hitoshi Okamura M.D., Ph.D.

Hitoshi Okamura M.D., Ph.D.

Psycho-Oncology Division, National Cancer Center Research Institute East, Chiba, Japan

Division of Occupational Therapy, Institute of Health Sciences, Faculty of Medicine, Hiroshima University, Hiroshima, Japan

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Kokichi Sugano M.D., Ph.D.

Kokichi Sugano M.D., Ph.D.

Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Tochigi, Japan

Genetic Counseling Clinic, National Cancer Center Hospital, Tokyo, Japan

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Teruhiko Yoshida M.D.

Teruhiko Yoshida M.D.

Genetic Counseling Clinic, National Cancer Center Hospital, Tokyo, Japan

Genetics Division, National Cancer Center Research Institute, Tokyo, Japan

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Keiko Kazuma R.N., Ph.D.

Keiko Kazuma R.N., Ph.D.

Department of Adult Nursing/Terminal and Long-Term Care Nursing, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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Tatsuo Akechi M.D., Ph.D.

Tatsuo Akechi M.D., Ph.D.

Psycho-Oncology Division, National Cancer Center Research Institute East, Chiba, Japan

Psychiatry Division, National Cancer Center Hospital East, Chiba, Japan

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Yosuke Uchitomi M.D., Ph.D.

Corresponding Author

Yosuke Uchitomi M.D., Ph.D.

Psycho-Oncology Division, National Cancer Center Research Institute East, Chiba, Japan

Psychiatry Division, National Cancer Center Hospital East, Chiba, Japan

Fax: (011) 81 471347026

Psycho-Oncology Division, National Cancer Center Research Institute East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan===Search for more papers by this author
First published: 24 May 2004
Citations: 39

Abstract

BACKGROUND

To the authors' knowledge, there have been few studies of the psychologic distress after disclosure of genetic test results for hereditary nonpolyposis colorectal carcinoma (HNPCC). The objectives of this study were to identify the prevalence rates and predictors of psychologic distress and to evaluate the feelings of guilt after disclosure of the test results in Japanese probands and unaffected relatives.

METHODS

Probands and unaffected relatives were interviewed immediately after the first genetic counseling session for HNPCC and again 1 month after disclosure of the genetic test results. The prevalence of major and minor depression, acute stress disorder (ASD), posttraumatic stress disorder (PTSD), and posttraumatic stress symptoms (PTSS) were assessed using the Structured Clinical Interview based on the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition revised (DSM-III-R) or the DSM-IV; feelings of guilt were investigated using a numeric scale and a semistructured interview.

RESULTS

Among 47 participants who completed the baseline interview, 42 participants (89%) completed the 1-month follow-up interview. Although none of the participants met the criteria for major depression, ASD, or PTSD at the follow-up interview, 3 of 42 participants (7%) met the criteria for minor depression and 2 participants (5%) had PTSS. The only predictor of psychologic distress found was the presence of a history of major or minor depression (odds ratio, 19.41; 95% confidence interval, 1.42–264.95; P < 0.05). Five of 42 participants (12%) had feelings of guilt.

CONCLUSIONS

Disclosure of genetic test results for HNPCC may not cause significant psychologic distress in Japanese probands or relatives. However, healthcare providers should not neglect to assess these individuals for psychologic responses, such as minor depression and PTSS. Cancer 2004. © 2004 American Cancer Society.

Hereditary nonpolyposis colorectal carcinoma (HNPCC), the most common hereditary colon carcinoma syndrome, is an autosomal dominantly inherited disease associated with an increased lifetime risk of a range of cancers. This syndrome has been associated with germline mutations in either one of the five DNA mismatch-repair genes. Mutations in these genes confer a lifetime risk of colon carcinonoma of approximately 80–85%.1, 2

To our knowledge to date, only one study has evaluated the psychologic consequences of undergoing a genetic test for HNPCC.3 In that report, it was found that unaffected individuals who received positive test results exhibited increased anxiety immediately after the disclosure of the test results and that the degrees of anxiety did not change significantly before the first counseling session, 1 month after disclosure, and 12 months after disclosure, irrespective of the test results. Although the results of that study provided information concerning the course of anxiety by including a 1-year follow-up evaluation, anxiety was assessed with a self-rating questionnaire alone, without the use of more accurate methods for the clinical evaluation of psychiatric disorders, and only unaffected relatives were included.

Does the same psychologic distress develop in individuals who receive genetic information that develops in patients who are informed of a cancer diagnosis? Previous studies of hereditary breast carcinoma suggest that negative test results are beneficial psychologically and that receiving a positive result does not appear to increase psychologic distress.4-6 However, because these reports only assessed psychologic distress using various self-rating questionnaires, it is difficult to compare the rates of clinically significant psychologic distress after a primary diagnosis of sporadic cancer (14–38%)7-9 or the prevalence of current posttraumatic stress disorder (PTSD) (2.5–6.0%) among breast carcinoma survivors.10, 11

Similarly, although feelings of guilt are a known, specific psychosocial response among individuals undergoing genetic testing,12, 13 previous reports were based on anectodotal experience.13 Therefore, to our knowledge, no studies to date have investigated the degree or persistence of feelings of guilt in detail after the disclosure of genetic test results.

It has been shown that the psychologic and social effects of genetic testing also are very important in Japan, but the exact nature of psychologic distress is unknown because of a lack of research in this area.14 Moreover, the Japanese word iden, or inheritance in English, carries a negative connotation, because the word is used commonly for the inheritance of unexpected phenotypes.15 Therefore, we hypothesized that the disclosure of genetic information may cause more significant psychologic distress in the Japanese population compared with the Western population.

Our objectives were to identify the prevalence and predictive factors of major and minor depression, acute stress disorder (ASD), PTSD, and posttraumatic stress symptoms (PTSS) after the disclosure of genetic test results for HNPCC in Japanese individuals, both in probands affected with cancer and in unaffected relatives, using a rigorous diagnostic interview at 1 month and 12 months after the disclosure. We also elucidated the presence, levels, and objects of guilty feelings at 1 month and 12 months after the disclosure of test results. The current report provides data that were obtained up to 1 month after the disclosure of genetic test results. The study is ongoing, and the 12-month follow-up data will be provided in a future report.

MATERIALS AND METHODS

Genetic Counseling and Testing Protocol

A weekly outpatient clinic that specialized in familial cancer syndromes and related conditions was established in April 1998 at the National Cancer Center Hospital (NCCH) in Japan, and the study of the genetic counseling and testing protocol was initiated simultaneously. Individuals who fulfilled either the Amsterdam criteria,16 the Japanese clinical criteria,17 or the HNPCC-Variant criteria2 received relevant information regarding the familial cancer syndrome and genetic counseling from physicians and nurses in charge of the genetic counseling clinic. In the course of the counseling, some clients were offered the option of undergoing a test for hMLH1 or hMSH2 gene mutations; if the client's consent was provided, then blood was drawn for the genetic mutation analysis by a combination of sequencing for reverse transcriptase-polymerase chain reaction product and genomic DNA.18 In addition, if probands who had a gene mutation identified in hMLH1/hMSH2 before October 1999 or who had a mutation identified during the study period disclosed the presence of the HNPCC-related mutation to unaffected relatives, then unaffected relatives came of their own will to the outpatient clinic at the NCCH. We asked these unaffected relatives to participate in the same psychologic study as the probands.

After 2 months, the participants were informed of their genetic test results. Probands received either a positive result or an uninformative result; because, even using the best technology available, negative data cannot exclude the presence of undetectable mutations or genomic abnormalities in the hMLH1 or hMSH2 genes. It is also possible that a pathogenic germline mutation resides in the mismatch-repair genes other than hMLH1 and hMSH2. Conversely, genetic diagnoses of unaffected relatives were performed only after the pathogenic germline mutation was identified in the proband. A positive result in an unaffected relative indicated the presence of an HNPCC-related mutation. Surveillance options for these positive, unaffected relatives were considered, and a surveillance schedule was set up. A negative result meant the definitive absence of the known mutation in the relative's family. Relatives who received a definitive negative result were reassured by the physician that their cancer risk was the same as that in the general population. Therefore, unaffected relatives received either a positive result or a definitively negative result.

Psychologic Study Population

The study participants were consecutive individuals who visited the outpatient clinic for cancer genetics at the NCCH and were offered an option for HNPCC genetic testing. The eligibility criteria for the current study were as follows: probands or unaffected relatives whose family members had been identified as carrying the hMLH1/hMSH2 mutation before or during this psychologic study procedure, and age ≥ 20 years. In addition, individuals were considered ineligible for this study if they were not able to understand the explanation about this research (i.e., dementia) or if they were too ill. Individuals who underwent the genetic testing and those who did not were both eligible. However, the participants included only individuals who underwent genetic testing, because those who did not have genetic testing refused to participate in the psychologic study. This study was approved by the Institutional Review Board of the NCCH, Japan.

Procedure

The study was performed on clients who visited the hospital between October 1999 and September 2002. After the genetic counseling session, an eligible individual was approached by investigators who did not participate in the genetic counseling session for an explanation of the objectives of the psychologic study. If the client agreed to participate in the study and provided written consent, then a baseline interview was conducted immediately after the genetic counseling session or within 1 week. At the time of the baseline interview, none of the participants had received their genetic test results. After the baseline interview, the participants were asked to complete a questionnaire on personality at home and return it by mail. If any answers were missing, then mail or telephone inquiries were made by the investigators. The participants who completed the baseline interview were contacted 1 month after the disclosure of their test results. Those who refused to know their test results were contacted at similar time point. Participants who agreed to undergo the 1-month follow-up interview were assessed for psychologic distress and feelings of guilt. If the individual was unable to come to the hospital, then the follow-up interview was conducted by telephone. Because we are conducting a longitudinal psychologic study with no link between individuals and genetic test results, we analyzed an anonymous data set of psychologic study data linked to genetic test results.

Measures

Major and minor depression at baseline and 1 month after disclosure

To obtain information pertaining to the prevalence of major and minor depression, each participant was interviewed at baseline and 1 month after the disclosure of their genetic test results by a trained nurse (Y.M.) and a psychiatrist (H.O.) using the Structured Clinical Interview based on the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition revised (DSM-III-R)19 (SCID)20 for major depression. In addition, criteria for minor depression were adapted from the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) research criteria.21 The reliability of the interview rating was determined by having a second rater attend a random sample of 30 interviews. The reliability ratings were excellent for the diagnoses of minor depression (κ statistic = 1.0); whereas reliability ratings for the diagnoses of major depression were not conducted, because none of the participants met the diagnostic criteria.

Genetic test-related distress at 1 month after disclosure

A diagnosis of ASD and PTSD were made using the SCID based on the DSM-IV22 at 1 month after the disclosure of test results. PTSD is comprised of three symptoms (reexperience, avoidance, and hyperarousal), and ASD is comprised of four symptoms (dissociative symptoms, reexperience, avoidance, and hyperarousal). Although reliability ratings for the ASD and PTSD diagnoses were not conducted because none of the participants met the diagnostic criteria, the reliability for PTSS was excellent (κ statistic = 1.0).

Feelings of guilt

To assess feelings of guilt, each participant was interviewed 1 month after the disclosure of test results and was asked 1) whether he or she felt guilty about anything in connection with the test results, and 2) if so, with whom the guilt was associated. The level of guilt feelings was assessed using 4 Likert-style items: 1 (not at all), 2 (somewhat), 3 (moderately), and 4 (severe). When participants indicated that they felt guilty, a semistructured question was asked to clarify the reason for the guilt (for example, “would you tell me why you feel guilty?”). Qualitative data were recorded during or immediately after the interview. The reliability of the assessments of the levels of the guilt feelings was excellent (κ statistic = 1.0). The qualitative comments were recorded during or immediately after the interview by one investigator, and the contents of qualitative comments were summarized briefly in a manner that retained the original meaning of the participants' words after consultation with other investigators.

Sociodemographic and clinical variables

We evaluated sociodemographic and clinical variables on potential predictive factors for psychologic distress. Data concerning age, gender, marital status, employment status, education level, religion, household size, cancer status, and number of first-degree and second-degree relatives affected with HNPCC-related cancer were obtained by a semistructured interview. We evaluated the participant's history of major and minor depressive disorders and life-time PTSD using the SCID. The Eysenck Personality Questionnaire-Revised (EPQR)23 is a 48-item self-rating scale that measures 4 personality subscales (extraversion, neuroticism, psychoticism, and lie). The validity and reliability of the Japanese version of the EPQR have been confirmed.24

Statistical Analysis

Descriptive statistics were used to characterize the participants in terms of their genetic test results, the prevalence of psychologic distress, and feelings of guilt. To identify the psychologic effect of genetic test result disclosure, we compared the prevalence of major or minor depression at baseline and at the 1-month follow-up interview using the McNemar test. Psychologic distress was dichotomized on the basis of the SCID (present if the participant met the criteria for major or minor depression, ASD, PTSD, or PTSS at the 1-month follow-up interview; absent if no psychiatric diagnosis was made). We used the Student t test, the Fisher exact probability test or chi-square test, and the Mann–Whitney U test to compare sociodemographic, medical, and psychologic factors between participants with or without psychologic distress at the 1-month follow-up interview. To explore possible predictive factors of psychologic distress at the follow-up interview, baseline variables, personality measured by the EPQR, and genetic test results were included in the preliminary univariate analysis. Because minor depression and PTSS were diagnosed in both probands and unaffected relatives, and because the number of participants who met the criteria for psychologic distress was small, we did not distinguish between probands and relatives in the univariate analysis. To identify the final predictive factors, variables with P values < 0.05 in the univariate analysis were entered into a logistic regression model. All reported P values are two-tailed. The statistical software package SPSS 11.0J for Windows was used to perform all the data analyses (SPSS Japan Institute Inc., Tokyo, Japan). Qualitative data with regard to feelings of guilt were summarized briefly, preserving the original meaning of each participants' words.

RESULTS

Characteristics of the Study Sample

Fifty-nine individuals visited the outpatient clinic at NCCH for genetic counseling regarding HNPCC during the study's entry period, as shown in Figure 1. Of the 51 eligible individuals, 47 participants completed the baseline interview, and 4 individuals refused to participate in the psychologic study. The four who refused to participate included all three individuals who also rejected the genetic testing protocol; all these individuals were men who were probands.

Details are in the caption following the image

Flow diagram showing study the procedure.

Among 47 participants who completed the baseline interview, 42 participants (89%) completed the 1-month follow-up interview, as shown in Table 1. Two of those 42 participants (5%) completed the follow-up interview by telephone, because they lived far from the hospital. Of the 5 participants who completed the baseline interview but did not complete the 1-month follow-up interview, 3 participants said that they were “too busy,” and 2 participants decided not to receive the genetic test results and did not wish to continue participating in the psychologic study. The baseline variables and personality-measured EPQR scores of participants who completed the 1-month follow-up interview did not differ from the variables and scores of participants who dropped out. Thus, the study population was comprised of 42 participants who completed both the baseline and follow-up interviews. All 42 participants received the genetic test.

Table 1. Characteristics of the Study Participants at the Baseline Evaluation and Predictors of Psychologic Distress at 1 Month After Disclosure (n = 42 participants)
Characteristic No. with psychologic distress (%)a P valueb
Presence (n = 5) Absence (n = 37)
Age (yrs)
 Mean ± SD 46 ± 7 48 ± 13 0.69c
 Range 35–51 21–69
 Median 50 50
Male gender 2 (40) 18 (49) 1.00
Marital status: married 5 (100) 30 (81) 0.57
Children (yes) 5 (100) 28 (76) 0.57
Employed (yes) 3 (60) 29 (78) 0.58
Education level: ≥ college 4 (80) 21 (57) 0.63
Religion (present) 2 (40) 5 (14) 0.19
Household size: living alone 0 (0) 4 (10) 1.00
Disease status: affected 4 (80) 23 (62) 0.64
More than 2 first-degree relatives affected with HNPCC-related cancerd 4 (80) 13 (35) 0.14
More than 2 second-degree relatives affected with HNPCC-related cancerd 2 (40) 24 (65) 0.35
Criteria
 Amsterdam 2 (40) 15 (41) 0.89
 Japanese: A 0 (0) 2 (5)
 Japanese: B 2 (40) 10 (27)
 HNPCC variant 1 (20) 10 (27)
Current major depression (present) 0 (0) 0 (0) 0.00
Current minor depression (present) 1 (20) 10 (27) 0.23
History of major or minor depression (present) 4 (80) 5 (14) 0.005
Life-time PTSD (present) 0 (0) 0 (0) 0.00
Mean scores of EPQR (mean ± SD)
 Psychoticism 4.2 ± 2.6 3.4 ± 1.5 0.24 (63.0d)
 Extraversion 5.8 ± 4.0 6.8 ± 3.2 0.57 (78.0d)
 Neuroticism 6.8 ± 2.3 4.4 ± 2.5 0.06 (41.5d)
 Lie 5.8 ± 2.6 5.1 ± 3.1 0.61 (79.5d)
Genetic testing results
 Positive 4 (80) 7 (19) 0.013e
 Uninformative 1 (20) 20 (54)
 Negative 0 (0) 10 (29)
  • SD: standard deviation; HNPCC: hereditary nonpolyposis colorectal carcinoma; PTSD: posttraumatic stress disorder; EPQR: Eysenck Personality Questionnaire-Revised.
  • a Minor depression and posttraumatic stress.
  • b All P values were determined with the Fisher exact probability test unless noted otherwise.
  • c Student t test = 0.41 (40 degrees of freedom).
  • d Mann–Whitney U test.
  • e Chi-square test (8.649; 2 degrees of freedom).

Genetic Test Results

Six of 27 probands (22%) received positive test results, and 21 of 27 probands (78%) received uninformative test results. Five of 15 relatives (33%) received positive test results, and 10 of 15 relatives (67%) received negative test results.

Prevalence of psychologic distress at 1 month after disclosure

None of the probands or relatives met the criteria for major depression at the time of the 1-month follow-up interview. Three of 42 participants (7%) met the criteria for minor depression 1 month after disclosure. All three participants with minor depression were probands. The prevalence of minor depression among the 27 probands was 11% (3 of 27 probands). Two of 42 participants (5%) met the criteria for minor depression at the baseline interview; of these 2 participants, only 1 proband who had received a positive test result also was diagnosed with minor depression at the follow-up interview. Among the 40 participants who were not diagnosed with minor depression at the baseline interview, 2 participants (1 of whom received a positive test result and one of whom received an uninformative test result) were diagnosed with minor depression at the follow-up interview. The prevalence rates of minor depression at baseline and 1-month follow-up interviews were 5% (2 of 42 participants) and 7% (3 of 42 participants), respectively; there was no significant change between the 2 interviews (P = 0.38).

None of the 42 participants met the criteria for ASD or PTSD at the time of the 1-month follow-up interview. PTSS was seen in 2 participants (5%), both of whom had received positive test results. One of the participants was an affected proband who exhibited reexperience and hyperarousal symptoms. The other participant was an unaffected relative who exhibited reexperience symptoms. These two participants did not fulfill the criteria for minor depression at the 1-month follow-up interview.

Predictive factors for psychologic distress

The presence of a history of major or minor depression and positive genetic test results were associated significantly with psychologic distress according to the univariate analysis (Table 1). A logistic regression analysis that included these two factors as independent variables showed that a history of major or minor depression was a significant predictor of psychologic distress, whereas genetic test results were not found to be a significant predictor (Table 2).

Table 2. Predictive Factors for Psychologic Distress at 1 Month after Disclosure: Logistic Regression Analysis of Psychologic Distress (n = 42 participants)a
Variable β SE OR 95% CI P value
History of major or minor depression
 Presence 2.97 1.33 19.41 1.42–264.95 0.03
 Absence (reference)
Genetic testing results
 Positive 9.35 47.18 1.75 0.00–1.64 0.84
 Uninformative 7.73 47.18 1.14 0.00–3.30 0.87
 Negative (reference)
  • SE: standard error; OR: odds ratio; 95% CI: 95% confidence interval.
  • a Psychologic distress was defined as minor depression and posttraumatic stress symptoms.

Feelings of guilt at 1 month after the disclosure of genetic test results

Of the 42 probands and relatives, 5 participants (12%) experienced a sense of guilt (Table 3). All five participants were female and had a college education level. Of the 6 probands who received a positive result, 2 probands (33%) felt severe guilt toward their children. Among the 5 unaffected relatives who received positive results, only 1 mother (20%) had feelings of guilt in relation to her children. Three of the other unaffected relatives were not married and had no children. The other unaffected relative was a mother, but she did not feel guilty in relation to anyone. The two unaffected relatives who received definitive negative test results experienced a sense of survivor guilt toward a family member with cancer: a cousin and a younger sister. The cousin already had undergone colorectal surgery 3 times; whereas the younger sister, age 20 years, had been diagnosed with colon carcinoma and had undergone surgery.

Table 3. Feelings of Guilt in Family Members Resulting from the Disclosure of Genetic Test Results
Genetic test results Psychologic distressa Objects of guilt feelings Scoreb Comment
Proband
 Positive Minor depression Children 4 One of my sons already has leukemia; maybe another of my Children might also have the mutation.
 Positive Reexperience and avoidance Children 4 I seriously worry about their future.
Relatives
 Positive Reexperience Children 4 My daughter has already inherited my weak eyesight; maybe I have passed something else on to my son and daughter.
 Negative None Cousin 3 I feel sorry that she was born; I think that she is suffering from the cancer.
 Negative None Sister 2 I cannot tell her I underwent genetic testing and received a negative test result.
  • a Minor depression and posttraumatic stress symptoms.
  • b Scoring: 1 = not at all; 2 = somewhat; 3 = moderately; 4 = severe.

DISCUSSION

To our knowledge, the current study is the first prospective study to investigate psychologic distress using the SCID after the disclosure of HNPCC genetic test results in Japanese probands and unaffected relatives. None of the participants met the criteria for major depression, ASD, or PTSD after the disclosure of their test results. These findings differ distinctly from the prevalence of major depression associated with receiving a primary diagnosis of sporadic cancer (14–38%)7-9 or the prevalence of current PTSD (2.5–6.0%) or lifetime PTSD (4.0– 5.0%) in survivors of breast carcinoma.10, 11 Genetic tests for probands generally are highly specific but quite insensitive, and the negative test results in probands essentially means uninformative results for the family and an inability to pursue any further genetic diagnosis among relatives. Thus, the limitations of genetic test results may contribute to the lower impact of psychologic distress. Furthermore, epidemiologic studies have demonstrated that the prevalence of depression in Asian countries is much lower than in Western countries.25 Our finding of a low prevalence may suggest cultural differences. However, previous studies have reported prevalence rates for major depression of 3.7% among Japanese patients who were newly diagnosed with head and neck carcinoma26 and 4.7% among Japanese patients with nonsmall cell lung carcinoma,27 and a 3% prevalence of cancer-related PTSD was reported in Japanese patients who were survivors of breast carcinoma for ≥ 3 years.28 In our study population, these prevalence rates were lower compared with the Japanese cancer patients in those previous reports, although the disease sites varied in those studies. Therefore, the disclosure of genetic test results may not cause significant psychologic distress in Japanese individuals, either in probands or relatives. Moreover, in the current study, genetic counseling may have affected the levels of psychologic distress because the baseline assessment was scheduled immediately after the genetic counseling and all participants underwent genetic counseling before the genetic test and at the time their test results were disclosed. However, this effect was expected, because genetic counseling usually is provided along with genetic testing.

However, the prevalence rate of minor depression was 7%, which was higher than the rate reported 1 month after surgery in patients with nonsmall cell lung carcinoma (4%).29 Furthermore, only probands met the criteria for minor depression (11%). Probands who receive a positive genetic test result may experience increased concerns regarding their children's risk of developing cancer4; and probands' concerns may not be relieved upon receiving an uninformative result, because the possibility of HNPCC in their family has not been eliminated. The results of the current study suggest that disclosure of the genetic test results may have a negative impact on probands, regardless of their genetic test results. Because it has been reported that minor depression is associated with significant functional impairment,30 careful follow-up and adequate psychologic assessment is needed for probands who undergo HNPCC testing.

PTSS was noted in 2 participants (5%) who received positive results. Previous studies that used self-rating questionnaires demonstrated that test-related distress does not increase after the disclosure of genetic test results, even if the results are positive.5, 6 Although the current study showed that positive genetic test results may affect individuals to a certain degree, it was difficult to reach a conclusion because of the limited number of participants. Higher numbers of subthreshold PTSD symptoms were associated with greater impairment, comorbidity, and suicidal ideation.31 Thus, future studies on genetic testing should not ignore the presence of PTSS, which may result from the disclosure of genetic test results.

The presence of a history of major or minor depression emerged as the only significant predictor of psychologic distress. Individuals who are vulnerable to psychologic distress may have difficulty adapting to stressful events.32 Therefore, the presence of a history of depression should be determined during the first counseling session, and individuals who have a history of major or minor depression should be recommended for careful follow-up.

In the current study, 12% of participants felt a sense of guilt at the follow-up interview. Previous studies have documented two types of guilty feelings that may appear after the disclosure of genetic test results: One is associated with the transmission of a genetic disease to a child,33 and the other is termed “survivor guilt”.12 The current study data revealed the presence of both types of guilt. Three mothers felt guilty toward their children, regardless of the fact that their children had not yet undergone genetic testing, and it was not known whether the children had inherited the mutation. This finding indicates that the identification of genetic predispositions in women with children may be stressful to mothers. In addition, two relatives who received negative test results experienced survivor guilt toward a family member who had been diagnosed with cancer. The guilt experienced by those two relatives was not stronger than that of the mothers, most likely because of no relation to vertical transmission. However, among 5 unaffected relatives who received positive test results, only 1 mother (20%) had feelings of guilt toward her children. Of the remaining relatives, three were not yet married and had no children. Therefore, they may not yet realize feelings of guilt regarding the transmission of an inherited mutation. The other relative was a mother, but she did not felt guilty toward anyone and felt that identifying a gene mutation was informative for members of her family who had not yet undergone genetic testing. The current results suggest that potential feelings of guilt should be examined in individuals undergoing genetic testing, regardless of their test results. Furthermore, whether these feelings of guilt continue for long periods and affect daily activities should be determined.

Because of the Japanese preference for connectedness,34 we hypothesized that the disclosure of genetic information that indicated the transmission of a genetic disease to siblings may cause significant psychologic distress in a Japanese population. However, the prevalence of major depression and PTSD in our study population was lower compared with Western or Japanese cancer patients. The findings of the current study indicated that Japanese probands and relatives did not experience severe psychologic distress, in opposition to our hypothesis. With regard to feelings of guilt, it may be necessary to conduct a cross-cultural and longitudinal study in the future.

To our knowledge, the current study is the first report assessing psychologic distress using the SCID, but it has several limitations. First, the study was conducted at a single institution, and the results were not representative of the population of Japan. In addition, the sample size was relatively small. Second, the study population was comprised of individuals in self-selected volunteers to receive the genetic counseling. This may have led to an underestimation of the extent of adverse effects. Third, the follow-up interview was conducted by telephone for two individuals because they lived far from the hospital. Fourth, although we analyzed an anonymous data set of psychologic study data linked to genetic test results, the authors/experimenters who participated in our study protocol were not blind to the study's hypotheses. Fifth, we only focused on identification of depression and PTSD. In the future study, it may be necessary to assess anxiety after the disclosure of genetic test results. Sixth, genetic counseling and testing were offered to participants free of charge. Thus, the participation rates observed in the current study may overestimate that of the general population participating in genetic testing in a clinical setting. Finally, the study is ongoing, and the preliminary results shown are between the baseline interview and the 1-month follow-up interview.

We conclude that major depression, ASD, and PTSD were not detected by the SCID in Japanese individuals after the disclosure of genetic test results. However, a few individuals met the criteria for minor depression and PTSS after disclosure of the results, regardless of the nature of the test results. These results indicate that the possibility of developing psychologic distress should be taken into account when conducting genetic counseling and disclosing genetic test results, especially in individuals who have a history of major or minor depression. Moreover, feelings of guilt were exhibited in both probands and relatives, irrespective of their test results. Thus, healthcare providers should not neglect the need to assess the psychologic responses of these individuals. We plan to determine whether long-term psychologic distress occurs after the disclosure of genetic test results by conducting a 1-year follow-up interview of these same individuals.

Acknowledgements

The authors are grateful to the patients and family members who gave their time so willingly and to the physicians in Colorectal Surgery Division, National Cancer Center Hospital (Drs. Y. Moriya, S. Fujita, T. Akasu, and T. Kodama) for enrolling their patients in this study. The authors also thank Y. Sugihara and R. Katayama for their research assistance.