Psychological and behavioral effects of genetic diagnosis in clinical practice

Individual Impacts Genetic Diagnosis

Individual Impacts of Genetic Diagnosis

The number of inherited disorders and risk factors that can be detected through genetic testing is increasing rapidly, and genetic testing may soon become a common component of routine medical care. Is behavioural medicine ready? For the first time, a sophisticated understanding of gene-environment interactions as manifested in the interactions among an individual's genetic predispositions, behaviour, and environment seems within reach. Rather than diminishing the role of behavioural science, advances in molecular medicine highlight the centrality of behaviour both in disease etiology and in the translation of science into practice.

This paper is systematic review of the literature on the individual impacts of genetic diagnosis in behavioural and psychological terms. It draws from papers on these topics and cites their studies extensively. The upshot is that carrier and predictive testing may have effects on anxiety and depression, but that there is genetic stigmatization. Prenatal testing may lead to increased premature termination of pregnancies.

The subset of psychological issues and processes that are most salient within the clinical genetics context has evolved alongside advances in biotechnology. Prenatal testing and carrier testing were among the first services offered, affording an opportunity for individuals to learn whether they had transmitted an altered gene to their offspring. As these tests provided information about the risk to the fetus, the focus of counseling tended to be on reproductive decision-making. More recently, genetic testing is being applied to detect personal susceptibility to disease, shifting the focus of counseling to personal risk reduction. The hope is that awareness of genetic risk will enhance informed medical decision making by physicians and patients alike. However, there may also be psycho- logical and social risks of genetic testing that should be considered, regardless of the potential medical benefits provided by testing. It is in this consideration of the entire breadth of the potential costs and benefits that psychologists can play a critical role. Both researchers and clinicians can assist patients, families, physicians, and policymakers as they grapple with the complex task of integrating genetic information into their professional practice and everyday lives (Lerman et al., 2002).

Psychological Effects of Carrier Testing

In one of the earliest reports of the impact of carrier testing, investigators studied the implementation of a sickle-cell disease carrier screening program in a community where 23% of the population were gene carriers and about 1% of infants were born with sickle-cell disease. The community's custom of arranging marriages provided the opportunity to offer counseling aimed at avoiding matings between carriers. A 7-year follow-up descriptive evaluation indicated that notification of carrier status resulted in anxiety, embarrassment, and an inferior social status, particularly among women. In fact, 20% of parents reported that they requested that their noncarrier children not marry a carrier, even though such an arrangement would not result in any offspring with the disease. In a related study, carriers and noncarriers did not report differences in self-image. However, noncarriers were found to have more negative attitudes about sickle-cell carrier status than carriers, suggesting the potential for social stigmatization.

A more recent qualitative study examined adults' experiences with carrier testing for four disorders: cystic fibrosis, Tay-Sachs disease, Duchenne muscular dystrophy, and Fragile X syndrome. Results suggested that noncarriers experienced relief and a general sense of well-being toward their future childbearing. However, carriers reported feelings of hopelessness regarding the health of their offspring.

As is evident from this brief review, few studies of carrier testing have used validated tools for assessing psychological outcomes. However, in a prospective study of general-population cystic fibrosis screening in Great Britain, investigators compared carriers and noncarriers in terms of anxiety levels (as measured by the State -- Trait Anxiety Inventory [STAI]). Carriers reported small but statistically significant increases in anxiety immediately following testing. Although most carriers did not report sustained anxiety, those who still intended to have children reported some anxiety at 6-month follow-up. One study also reported on the psychological status of cystic fibrosis mutation carriers. A modified version of the STAI administered after genetic counseling did not reveal differences in anxiety between carriers and a matched control sample of test decliners (Lerman, et al., 2002).

Psychological Effects of Predictive Testing

Huntington's disease. The first longitudinal study of HD testing was initiated in British Columbia in 1986. The results indicated that immediately after learning test results (7 -- 10 days), the in- creased risk group reported decreased scores on the General Well- Being Scale, but little change on measures of distress (General Severity Index from the Symptom Checklist 90) and depressive symptoms (Beck Depression Inventory [BDI]) from baseline. Those who had a decreased risk reported increases on the General Well-Being Scale, along with reductions in the General Severity Index and the BDI. By 6 months posttest, the difference between groups was limited to scores on the General Well-Being Scale, and at the 1-year posttest measurement the groups did not differ significantly on any of the three measures. This study also followed 40 individuals who did not receive risk-altering information. A subset (n =23) of these individuals declined testing, whereas the others (n =17) were told that testing would not be informative for them. By the 1-year follow-up, this group had higher levels of depressive symptoms and lower well- being scores than the increased or decreased risk groups.

Studies of testing for HD have also examined predictors of psychological responses to testing. Another study reported data from carriers and noncarriers approximately 6 months after receiving genetic test results. Precounseling HD-related stress symptoms (based on the Impact of Event Scale [IES]) predicted poorer adjustment. Other studies evaluated participants in an HD testing program using the BDI and the BHS. Baseline distress scores were the best predictor of postcounseling distress, and genetic status was only marginally predictive (Lerman et al., 2002).

Cancer susceptibility. A few large-scale longitudinal studies have begun to yield data on the psychological effects of genetic testing for cancer susceptibility. In a study of members of hereditary breast cancer families, noncarriers of BRCA1 mutations reported significant reductions in depressive symptoms (as defined by the CES -- D scale) and functional impairment (as measured by two scales from the Medical Outcomes Study), compared with carriers and those who chose not to be tested. However, carriers did not show overall increases from baseline to follow-up in measures of depressive symptoms and functional impairment. In another study of BRCA1 testing, carriers reported higher levels of test-related distress (as measured by the IES) than noncarriers approximately 1 -- 2 weeks after learning test results. Similar to this study, carriers did not exhibit increases in anxiety (as defined by scores on the STAI) from baseline to follow-up. In this study, carrier women who had never experienced cancer or cancer-related surgery reported higher levels of test-related distress (Lerman et al., 2002).

Although these studies did not provide evidence for adverse effects of testing, analyses have been conducted to identify sub- groups of individuals that might be more psychologically vulnerable. Other studies classified their hereditary breast cancer family members into low-moderate (two lowest tertiles) and high-stress categories based on their scores on the Intrusion subscale of the IES. The highest levels of depression symptoms 1 month after testing (based on CES -- D scores) were reported by individuals with high stress at baseline who decided not to get tested. In this subgroup, 26% reported symptoms consistent with depression at baseline, and by 1 month, this number had increased to 47%. More recently, a study reported that testing participants who underestimated the emotional impact of testing were more likely to experience distress 6 months after receiving their results (Lerman et al., 2002).

A study addressed the psychological effects of genetic testing for familial adenomatous polyposis, a form of colon cancer first characterized by the formation of hundreds of polyps in adolescence and early adulthood. Investigators surveyed tested children and their parents before and 3 months after testing using the Children's Depression Inventory or the Reynolds Adolescent Depression Scale and Children's Manifest Anxiety Scale. Children's depression levels remained in normal ranges after testing. How- ever, mutation-positive children with affected mothers had significantly higher follow-up depression scores. Further, all children with affected mothers had increased anxiety scores.

Behavioral Outcomes of Predictive Testing

Although initial studies suggest that genetic-testing decisions were motivated by the desire to gain information about surveillance options, little is known about the actual ways in which genetic testing influences behavior. In one longitudinal study, none of the 41 BRCi carriers reported having a prophylactic mastectomy by 1-year follow-up, but 17% were considering it. It is interesting to note that 43% of the eligible carriers reported having had an oophorectomy within the year since learning their test results, with most of the other carriers considering it. There were no differences in reported mammography use between carriers and noncarriers among women over 40 years old (81% of carriers and 73% of noncarriers reported a mammogram within the year). However, younger carriers (aged 25 -- 39) were more likely than younger noncarriers to have reported a mammogram within the year (45% vs. 17%, respectively). A second study of women followed for 1 year after BRCi testing found that only 1 of 29 (3%) unaffected female carriers had a prophylactic mastectomy within 1 year after receiving genetic test results and 13% had a prophylactic oophorectomy. Sixty-eight percent of carriers reported an annual mammogram at the 1-year follow-up, com- pared with 44% of the noncarriers. Women over 40 were more likely to have had an annual mammogram than women between 25 and 39 years old. Of greater concern was the finding that less than 15% of BRCi carriers had the recommended ovarian cancer screening (Lerman et al., 2002).

Salient among these are:-

a) the realisation that both positive and negative results can cause personal and family anguish or dislocation. While anxiety and depression may be expected to follow a result which indicates that one has the condition, there is some evidence to suggest that those 'escaping' it experience a negative reaction through a kind of survivor guilt (some of their loved ones are or will be victims) and through a feeling of 'not belonging' to the descent group they thought was theirs. They also may have in some senses planned their lives as sufferers; by for example choosing not to reproduce.

b) the recognition that some kin groups within which the disorder has been transmitted have their methods of 'deciding' which individuals will be sufferers. Through a process which has been called 'pre-selection' some families appear to identify a member who has inherited the disorder, and proceed to treat that person as 'sick'. Schooling decisions and both intra and extra familial activities may be circumscribed. While pre-selection is not accurate as a means of identifying affected individuals, Kessler postulates that it functions to reduce: multiple uncertainties . . . As if the chance nature of gene transmission is brought under control and the chronic threat of stochastic processes has been defused.

c) the indication that uncertainty (not knowing the ostensibly precise details of personal risk status) may have a distinct cultural or social value (Davison et al. 1994). The idea that knowing about possible futures may actually decrease the quality of a person's life is not easily accommodated within the essentially rationalist or utilitarian philosophy underlying the idea of screening. One aspect of this is the maintenance of 'hope' (often 'against hope'), as articulated by a tested individual receiving results indicative of high risk:

I feel like someone has died. Part of me has died - the hopeful part.

The key response to what are usually seen as 'psychological problems' by those involved in the development of clinical services has been to stress the importance of counselling and support for those offered predictive testing or their families. Research into, and debates about, the role of counselling have mainly focused on the choice to be tested for carrier or 'sufferer' status, and the relative merits of the termination of affected pregnancies following prenatal genetic diagnosis. Any widespread introduction of predictive testing for adult onset diseases will pose additional ethical dilemmas.

Thus, rather than being a field in which people receive information providing a basis for test on freely-determined action, the reality is that 'whatever counsellors might wish those consulting them or referred to them to think, most people perceive the encounter as one with a high-status medical expert, whose advice has to be taken seriously' (Davison et al., 1994).

Petersen offers individual narratives on the experiences of those affected by genetic testing. The data highlighted a number of broad themes revealed by earlier research on illness narratives: experiences of disruption and uncertainty following the onset of illness, individuals' search for a diagnosis, and their effort to achieve acceptance, independence, and some sense of normality. They also revealed some particular challenges confronting individuals posed by the inheritable nature of their condition. Although people's experiences were diverse, having been shaped by factors such as the nature of their condition, its symptoms and treatment, and prior experience of illness, they tended to involve some recurrent themes. One of these was the quest for information, beginning with diagnosis. A pregnancy or a series of episodes of undiagnosed symptoms such as constant tiredness or bleeding trauma, sometimes following surgery, often led the individual to search for an explanation for their illness. Some respondents said that they came to learn about the nature of their condition after a series of misdiagnoses or non-diagnoses and efforts to seek treatments outside the conventional medical system. The experience of a respondent who has haemochromatosis is not untypical:

'The diagnosis was made after continuous complaints by me. I couldn't seem to recover my health and strength and fitness after I had surgery for cancer, and follow up chemotherapy. People to whom I complained, medical people said I had to be patient to wait to get over this chemotherapy. And, no, I felt I was over the chemotherapy, still very tired, very lethargic, sore joints, etc., all the symptoms that go with iron overload, but undiagnosed. And in answer to my frustrations and request to my local GP, another series of blood samples and [he] sent them off for analysis and they called me up telling me that everything was fine and I just had to get on with it. It was only later, after further complaints to the doctor that the respondent was finally presented with a diagnosis of haemochromatosis.'

This medical 'merry go round', whereby patients undergo a lengthy and sometimes fruitless search for a diagnosis and treatment, has been reported to be common among those with chronic illnesses. In other words, respondents recounted a period of uncertainty preceding diagnosis. Once diagnosed, some individuals told of further episodes of uncertainty and disruption, in relation to the management of the illness and future plans.

Respondents described, often in great detail, how the unpredictability of their symptoms and treatment regimes had impacted on and sometimes radically changed their life plans and the way they lived their lives. A woman in her early 30s with cystic fibrosis (P11) who had undergone a lung transplant had decided against having children despite her desire to do so 'due to the fact of what the drugs would do after my transplant.' She had reconciled herself to her childlessness, and in response to a question about how her genetic condition had affected the planning of her life, said:

'I guess it doesn't really I mean my transplant's my life now. I've got new lungs now and they are going to stay as good as what they were the day I was transplanted for how long I will look after them.' Some individuals explained the difficulty they and/or their families had in coming to terms with the fact of their illness and with dealing with episodic illness.

A diagnosis may be met with denial. A Greek woman in her 30s who has thalassamia recounted how difficult it was for her and her family to accept her diagnosis. Her parents told her when she was very young that she had 'a milder form of thalassamia'; however, after a period of hospitalisation for tonsillitis, it was discovered that she had 'a very low haemoglobin' which led to a genetic diagnosis, confirming that 'it was more severe than they first initially thought.' After the haematologist 'explained the genetic side of it' and 'that both parents must have had this genetic condition for me to get it so severe', she told her parents, but they denied that they had the condition (Petersen, 2006).

As she explained it, 'it was "no, I haven't got it," my dad said, "there's no way, there's no way I've got it." In this case, the respondent believed her parents' reticence in talking about the condition was because 'they feel it's a slight on their character. They feel embarrassed, they feel ashamed, they feel upset that they've had a child with a genetic disorder'. Genetic conditions may be stigmatising, and involve feelings of shame and embarrassment; however, not all respondents reported such strong responses from family members. Experiences of social exclusion, however, were commonly reported.