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ORIGINAL ARTICLES |
From the Departments of Psychiatry (H.A.H., A.B.) and Psychology (T.J.S., A.W.S., S.S.I., A.B.), the University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
Address correspondence and reprint requests to Heidi A. Hamann, PhD, Department of Psychology, Washington State University, PO Box 644820, Pullman, WA 99164-4820. E-mail: hamann{at}wsu.edu
| ABSTRACT |
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Methods: Participants were 84 women enrolled in a larger project focused on genetic testing decisions. Semistructured diagnostic interviews were used to identify instances of threshold and subthreshold PTSD.
Results: Results indicated that 16.7% of the women reported current threshold or subthreshold PTSD related to personal or family cancer history. An additional 26.2% reported past-only cancer-related threshold or subthreshold PTSD. Of the 65 women who received BRCA1/2 results and completed the test-related PTSD module, only 7.7% reported threshold or subthreshold PTSD related to the genetic testing process. However, when rates were examined based on carrier status, 25.0% of BRCA1/2 carriers reported test-related threshold or subthreshold PTSD compared with only 10.0% of variants and 2.3% of noncarriers.
Conclusions: Results from this study suggest that both personal and family cancer diagnoses can be significant stressors for a subset of high-risk women. Rates of threshold and subthreshold PTSD related to genetic testing appear to be less common, although carriers may be at higher risk for significant posttraumatic symptoms.
Key Words: genetic testing posttraumatic stress cancer structured clinical interview BRCA1/2
Abbreviations: CI = confidence interval; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; GAD = generalized anxiety disorder; MDD = major depressive disorder; PTSD = posttraumatic stress disorder; SCID = Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; SPSS = Statistical Package for the Social Sciences.
| INTRODUCTION |
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The importance of genetic tests for cancer risk assessment is well illustrated by the nature and extent of heritable risk for breast and ovarian cancer. Of the more than 200,000 cases of breast cancer and 25,000 cases of ovarian cancer diagnosed annually in the United States (1), an estimated 5% to 10% are associated with mutations in inherited genes (2,3). Two such genes, BRCA1 and BRCA2, were identified in 1994 and 1995, respectively (4,5). A woman who inherits a mutation in BRCA1 or BRCA2 carries an elevated lifetime risk for breast cancer (55% to 85%) and ovarian cancer (16% to 60%; 69).
Having genetic information available as part of an overall risk assessment should permit an unprecedented level of precision and sensitivity in these assessments. At the same time, the availability of tests for BRCA1 and BRCA2 (ie, BRCA1/2) has been accompanied by concern about the psychological impact of having a family cancer history and learning one's mutation status. It is not yet clear whether potential increases in distress among high-risk and tested individuals are associated with higher rates of psychiatric disorders. Some studies have obtained self-report measurements of depressive and anxious symptoms, finding moderately elevated levels of distress among people at high risk for cancer (eg, 10,11). However, estimates of psychiatric disorders elicited from self-report measures may not be consistent with those derived from semistructured interviews (1214). In one recent study that compared assessment methods among women at increased risk for cancer, rates of diagnoses for depressive and anxiety disorders were lower than those suggested from clinical cutoff scores on self-report measures (15). Specifically, although 23% of the women in this study scored in the "clinically distressed" range of the Hopkins Symptom Checklist (HSCL-25), semistructured interviewing revealed that only 1% reported symptoms consistent with current major depression, and even fewer would have been diagnosed with generalized anxiety disorder (GAD) (15). Further, studies of individuals who are undergoing BRCA1/2 genetic testing have not shown significant levels of general distress after result notification. Studies using self-report measures of anxious or depressive symptoms found that when compared with their pretest levels, neither carriers nor noncarriers reported significant increases in general psychological distress after testing (16,17).
There is some evidence that cancer- or test-specific (rather than general) stress reactions are more prevalent in high-risk and tested populations. People who undergo BRCA1/2 testing may already experience distress because of their personal or family cancer history; they could also have significant reactions to the receipt of potentially life-altering genetic information. Instead of global distress, they may experience intrusive thoughts about test- or cancer-related events, heightened motivation to avoid reminders, and increased arousal when reminded. Personal and family cancer history are associated with increased levels of stress responses after screening tests such as mammograms (18,19). These findings may also apply to people who have personal or family cancer histories and face predictive genetic tests.
Studies using self-report measures of cancer-related distress indicate that a significant percentage of cancer patients report high levels of psychological intrusion and avoidance (eg, 20,21). Even among people without a personal cancer history, having a close relative with cancer and caregiving for this affected family member can be associated with increased levels of intrusion and avoidance (eg, 19,22,23). Studies of risk- or test-related stress among women who have learned their carrier status have found higher levels of specific distress among carriers (16,24,25). In particular, levels of test-related distress among unaffected BRCA1 carriers were comparable to levels of cancer-related distress in one study of three patients 10 weeks after cancer diagnosis (16,26).
High levels of cancer- or test-specific distress may be consistent with posttraumatic stress disorder (PTSD), a diagnosable disorder manifested by evidence of three symptom clusters (intrusion, avoidance, and hyperarousal) after an experienced or witnessed trauma (27). A few studies have used symptom cluster endorsements from self-report measures to estimate posttraumatic reactions in cancer patients, reporting rates of likely PTSD from 6% to 19% and rates of "subthreshold" PTSD (eg, fulfilling two of the three main symptom clusters) from 5% to 13% (2830). Among women referencing their experiences with a family member's cancer, about 4% endorse symptoms consistent with a PTSD diagnosis, and another 7% report subthreshold PTSD symptoms (23). However, semistructured interviews may more accurately assess rates of PTSD within a given population (ie, 31,32). In studies using semistructured interviews with cancer patients, rates of current PTSD have ranged from 0% to 32%, and rates of lifetime (past) cancer-related PTSD have ranged from 3% to 35% (eg, 3237). Reports of cancer-related posttraumatic stress have not been limited to patients; in one study utilizing semistructured interviews (38), 25% of mothers endorsed PTSD in relation to their child's cancer.
For women who have looked into BRCA1/2 testing, received genetic test results, or are otherwise at heightened risk for cancer, there is little information about rates of threshold or subthreshold PTSD based on semistructured diagnostic interviews. These women often have significant histories of family cancer, and posttraumatic symptoms may occur in response to one's own cancer experience or the experience of watching a close relative battle cancer. Based on their study of high-risk women, Lindberg and Wellisch (23) noted that having a close relative with cancer may be as stressful as experiencing cancer oneself. This suggests the importance of not only evaluating posttraumatic symptoms among women with a personal cancer history but also among unaffected women with a family history of cancer. In addition, some women may perceive genetic testing as a significant stressor and report PTSD symptoms related to this experience. The two goals of the current study were to investigate rates of threshold and subthreshold cancer-related PTSD among high-risk women and test-related PTSD among the subset who learned their genetic status. High-risk women differentiate distress related to genetic testing from distress related to cancer history (39). This suggests the importance of evaluating cancer- and test-related PTSD through independent assessments.
| METHOD |
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After attending an initial genetic counseling session, 75 women elected and completed testing for BRCA1/2 mutations. Nine participants decided against genetic testing. Tested participants learned of their genetic status and personal cancer risk during an in-person, follow-up counseling session. At that time, the women were also provided with information about surveillance procedures and family cancer risks. Among the 75 women who learned their results, 13 (17.3%) were mutation carriers and 51 (68.0%) were mutation noncarriers. Another 11 women (14.7%) had "variant" genetic results (BRCA1/2 polymorphisms of unknown significance).
Procedure
Study participants were recruited from the Cancer Genetics Program at the University of Pittsburgh Cancer Institute and Magee-Women's Hospital. Those who expressed interest in the study were contacted by a research nurse who explained the study and determined eligibility. Data from the present study were gathered 3 to 6 months after result notification for those who were tested and approximately 6 months after study initiation for those who decided against testing. During this session, participants completed sections of a semistructured clinical interview. Participants were reimbursed $25 for each session and were not required to pay for any genetic testing associated with the study.
Measures
Modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID; 40) were administered to participants during the session. All interviews were conducted by clinical psychologists or trained doctoral candidates in clinical psychology. The SCID is a semistructured clinical interview designed to identify psychiatric disorders based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; 27). One of the modules focuses on symptoms related to a diagnosis of PTSD. During the first administration of the PTSD module at the session, participants referenced their own cancer diagnosis (if applicable) or the cancer diagnosis of a relative. In this cancer-related PTSD module, participants were asked about both current (within the last month) and past (anytime since cancer diagnosis) symptoms. The PTSD module was administered again during the session to individuals who had learned their genetic carrier status. During this second administration, women were asked to reference the genetic testing process and report on test-related PTSD symptoms in the interval since genetic testing (approximately 36 months).
Based on DSM-IV criteria, participants needed to meet or exceed threshold symptom levels in three areas (intrusion, avoidance, hyperarousal) for at least 1 month to receive a diagnosis of PTSD. As used in previous studies (eg, 23,4143), a designation of "subthreshold PTSD" described women who met threshold in any two out of the three symptom clusters (ie, intrusion, avoidance, hyperarousal). Among women in the current study who qualified for "subthreshold PTSD," the majority of cases (85.7%) fulfilled criteria for the intrusion and hyperarousal symptom clusters but did not meet threshold for levels of avoidance. In a subset of analyses, women who had threshold or subthreshold diagnoses of PTSD were combined into a "PTSD symptom" group. This procedure is similar to that used by Dougall et al. (43) in their study of individuals in motor vehicle accidents. Individuals who did not fulfill criteria for threshold or subthreshold PTSD were referenced as a "PTSD absent" group.
Although the PTSD assessments related to cancer and genetic testing were of primary interest in this study, we also used SCID modules that address current diagnoses (ie, within the last month) of depressive and more general anxiety disorders. Specifically, we used the appropriate SCID modules to assess symptoms of major depressive disorder (MDD), dysthymic disorder (ie, dysthymia), and GAD. We also used the SCID to measure current PTSD related to traumatic events other than cancer or genetic testing (ie, PTSD-Other).
Data Analysis
Statistical Package for the Social Sciences 11.5 (SPSS) was used to analyze study data. Descriptive statistics were used to characterize the participants based on demographic information and endorsements of posttraumatic symptoms. Chi-square statistics were used to test relationships between two categorical variables (eg, PTSD designation and personal cancer status), whereas analysis of variance (ANOVA) techniques were used to examine relationships in cases with one categorical variable (eg, PTSD designation) and one continuous variable (eg, age). In some cases, post hoc power analyses were reported based on estimates of medium and large effect sizes for the appropriate tests (ANOVA: medium = 0.25, large = 0.40;
2: medium = 0.30, large = 0.50; 44). All power analyses were calculated with the post hoc specifications of the G*Power program (45).
| RESULTS |
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In the following analyses, women who met criteria for threshold or subthreshold PTSD were combined into one symptom group at each temporal endorsement. Three groups were compared: (1) women who endorsed cancer-related threshold or subthreshold PTSD within the past month (Current PTSD Symptoms; n = 14), (2) women who endorsed cancer-related threshold or subthreshold PTSD in the past only (Past-only PTSD Symptoms; n = 22), and (3) women who never evidenced PTSD related to cancer (PTSD Absent; n = 48). There were no significant differences between the three groups in age, F(2,81) = 1.34, p = .27; post hoc analyses of this ANOVA comparison indicated that the power (1-ß) to detect a medium degree of association was 0.51, whereas the power to detect a large association was 0.91. Based on a
2 analysis, there were also no significant differences between PTSD symptom groupings and time since cancer diagnosis,
2 (2, N = 68) = 0.71, p = .70 (power ranged from 0.59 [to detect medium effect] to 0.97 [large effect]). Finally, no significant differences were noted among the PTSD symptom groups based on references to personal or family cancer experience,
2 (2, N = 84) = 0.34, p = .85 (power ranged from 0.69 [to detect medium effect] to 0.98 [large effect]).
When women who were tested (n = 75) were compared with those who were not tested (n = 9), there were similar percentages of cancer-related Current PTSD Symptoms (Tested: 17.3% versus Not Tested: 11.1%) and Past-only PTSD Symptoms (Tested: 25.3% versus Not Tested: 33.3%) in each group. However, since there were multiple cells with less than 5 participants, no statistical tests were performed to evaluate the relationship between test status and cancer-related PTSD symptom groups (46).
PTSD Related to Genetic Testing
The second PTSD module focused on participant responses to the genetic testing experience. Among the 75 women who received their genetic test result, 65 of them (12 carriers; 43 noncarriers; 10 variants) completed the PTSD module related to genetic testing and are included in the following analyses. The other 10 women were excluded because of missing or incomplete SCID data related to genetic testing. Of the 65 participants, 5 of them (7.7%) presented with threshold (n = 2; 3.1%; CI 0% to 7.5%) or subthreshold (n = 3; 4.6%; CI 0% to 9.8%) PTSD at some interval in the 3 to 6 months since genetic testing. Comparisons indicated that the PTSD Absent group (M = 46.1 years) was significantly older than those who endorsed threshold or subthreshold PTSD symptoms related to testing (M = 36.2 years), F(1,63) = 5.47, p < .05. When rates of PTSD were examined based on carrier status, 25.0% of the carriers endorsed threshold (n = 2) or subthreshold (n = 1) PTSD related to genetic testing. Smaller percentages of subthreshold PTSD were noted among noncarriers (2.3%; n = 1) and variants (10.0%; n = 1). Rates of threshold or subthreshold test-related PTSD were generally comparable among women with (7.9%; n = 3) or without (7.4%; n = 2) a personal history of cancer, although small cell sizes (n < 5) precluded statistical tests of this relationship (46). Four of the 5 women who reported test-related PTSD symptoms had also endorsed threshold or subthreshold cancer-related PTSD at some point in time.
Other Psychiatric Morbidity
In addition to assessing PTSD related to cancer and genetic testing, interview data from the 84 participants were used to estimate rates of current MDD, dysthymia, GAD, and PTSD related to a stressor other than cancer or genetic testing (ie, PTSD-Other). In general, rates of MDD (n = 8; 9.5%; CI 3.2% to 15.8%) were similar to those found by Coyne and colleagues (14) in their assessment of a breast cancer waiting room sample. Two women met criteria for dysthymia (2.4%; CI 0% to 5.7%), 3 women endorsed symptoms consistent with GAD (3.6%; CI 0% to 7.4%), and another 3 women met threshold criteria for PTSD-Other (3.6%; CI 0% to 7.4%).
Comorbidity of PTSD symptoms with depression or other anxiety disorders was also investigated. Of the 14 women who presented with current threshold or subthreshold PTSD related to cancer, 4 of them (28.6%) also fulfilled criteria for current diagnoses of MDD, dysthymia, or GAD, whereas 1 woman (7.1%) endorsed PTSD-Other. Among the 5 women who endorsed threshold or subthreshold PTSD related to genetic testing, 3 of them (60%) also fulfilled diagnostic criteria for MDD, dysthymia, or GAD, and 1 other woman (20%) met threshold for PTSD-Other.
| DISCUSSION |
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In the present analysis, rates of cancer-related PTSD were generally consistent with those in other studies of adult cancer patients and relatives of cancer patients. Specifically, the cancer-related assessment indicated that about 17% of participants endorsed current threshold (5%) or subthreshold (12%) PTSD, whereas another 26% reported past-only symptoms consistent with threshold (8%) or subthreshold (18%) PTSD. Overall rates among women with a personal cancer history and unaffected individuals who referenced a family member's cancer were relatively similar, although due to limited power to detect a medium or smaller effect, this finding should be interpreted with caution. These data are consistent with Lindberg and Wellisch's (23) assertion that high-risk individuals may experience significant distress from several sources, including a personal cancer diagnosis and diagnoses among close family members. They are also consistent with results from a number of studies suggesting that there is a broad psychological impact of having a relative with cancer (19,4750).
Rates of current depressive disorders and other anxiety disorders were relatively low in our sample, but there was some evidence of comorbidity between these disorders and cancer-related PTSD symptoms. For example, over one fourth of participants who endorsed current threshold or subthreshold PTSD related to cancer also fulfilled criteria for MDD, dysthymia, or GAD. However, based on the fact that almost three fourths of those with current cancer-related threshold or subthreshold PTSD would have been missed by the interviews for more general disorders, it appears that assessing for PTSD in clinical settings may provide useful information about cancer-related distress. Furthermore, there was little overlap of cancer-related PTSD symptoms with PTSD related to other traumas, suggesting that cancer is a distinguishable stressor that uniquely affects a subset of individuals.
The present study found generally low rates of threshold and subthreshold PTSD related to undergoing genetic testing. These data support contentions that genetic testing is not associated with high overall rates of adverse effects (51) and may, in fact, be less stressful than experiences of personal and family cancer (39). Based on the relatively low percentage of significant posttraumatic symptoms in this study and reports of overall decreases in posttest distress from other studies (eg, 16), it is possible that the majority of tested individuals experience at least some degree of relief and stress reduction after testing (52). However, this potential relief may not be uniform across different test results; despite the low overall percentages, BRCA1/2 carriers were disproportionately represented among those who reported threshold or subthreshold PTSD. Although the small numbers make it difficult to interpret these findings, they are consistent with data showing higher levels of test-specific distress among carriers than noncarriers (16). The results may indicate that carriers are more susceptible to test-related posttraumatic symptoms than are noncarriers and people with variant results.
Similar to studies showing higher levels of posttraumatic symptoms among younger cancer patients (eg, 53), we also found that younger women were more likely to endorse threshold or subthreshold PTSD related to testing. Research has shown that younger women diagnosed with cancer may report emotional difficulties and note increased concerns about partner communication, sexuality, body image, and fertility (5456). Therefore, it is possible that younger women who undergo genetic testing for cancer may perceive the consequences as more distressing and exhibit more symptoms of posttraumatic syndromes.
Finally, results indicated that 80% of the women who reported test-related (threshold or subthreshold) PTSD also endorsed significant cancer-related symptoms. In addition, 60% fulfilled diagnostic criteria for MDD, dysthymia, or GAD, and another 20% met threshold for PTSD-Other. Although it is difficult to make conclusions with such a small subgroup, these findings support the notion that individuals who have strong responses to past cancer experiences and/or have significant concurrent distress may be primed to perceive an event related to cancer risk (genetic testing) as highly significant or traumatic (57,58). It highlights an important point by Gurevich and colleagues (18) that a distressing experience with cancer could be more likely to trigger stress responses to certain cancer-related cues, such as genetic testing. In addition to carrier status, perceptions about the severity of cancer and its consequences may be related to this process.
As noted above, interpretation of the study data was limited by relatively small numbers of cases in certain cells. As a result, we were unable to conduct some analyses and group comparisons. Although care was taken in the administration of the SCID to discriminate temporal issues, results are also limited by the use of retrospective reports to estimate past posttraumatic symptoms. In addition, interpretation of the test-related PTSD rates may be affected by the relatively short timeframe (36 months posttesting) that was referenced by participants. A subset of individuals experiences "delayed-onset" PTSD (59,60). Depending on the timing, delayed symptoms among our study participants may not have been detected at the time of assessment. Finally, the study population was racially homogenous (Caucasian) and generally well educated; these factors limit the generalizability of the findings. Other research has suggested that lower education may be related to more PTSD symptoms (eg, 6163). This raises the possibility that rates of PTSD in our sample might actually underestimate distress associated with cancer and testing in populations with more educational diversity. Since data on genetic testing responses have primarily focused on mostly Caucasian participants with higher socioeconomic status, research evaluating potential differences across socioeconomic, ethnic, and minority status is a critical gap in our knowledge about these issues (64).
By focusing on rates of PTSD among women tested for BRCA1/2 mutations or otherwise considered at high risk for cancer, the present study adds to the growing literature on psychological issues related to genetic testing. Overall, differences in rates of cancer- and test-related PTSD symptoms support the assertion that genetic testing should be studied as part of larger context that includes personal and family cancer diagnoses (39,51). More research is needed to further examine posttraumatic responses related to cancer history and genetic testing. Specifically, studies focusing more closely on the timing and specific predictors of cancer- and test-related posttraumatic symptoms could help explain the nature of these responses (58). Such results could then inform the use of targeted clinical interventions for PTSD within these populations. Potentially, preventive interventions could focus on individuals seeking testing who may be at higher risk for posttraumatic responses, and empirically supported treatments for PTSD could be applied for the smaller subgroup of individuals experiencing significant posttraumatic symptoms (65,66).
The authors gratefully acknowledge the contributions of Dana Farengo-Clark, MS, Darcy Thull, MS, Wendy Rubinstein, MD, PhD, Julie Lindner Erlichman, MS, Laura Rittmeyer Jenkins, MS, and Michele Elder, RN in the completion of this project.
| NOTES |
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S.S.I. is now a Postdoctoral Scholar at the University of California, San Francisco.
DOI:10.1097/01.psy.0000181273.74398.d7
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