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January 25, 2005
Informed Consent in Schizophrenia
Wirshing DA, Sergi MJ, Mintz J.
Wirshing DA, Wirshing WC, Marder SR, Liberman RP, Mintz J.
The topic of informed consent can be difficult when conducting research, particularly when mental illness is involved. The process often involves explaining complex and technical procedures to an audience who otherwise would not have knowledge of such. A skilled clinician must know how to address concerns and explain difficult concepts in language appropriate to the patient/subject. Legal requirements often add more risks than might otherwise be discussed and so it can be difficult to convey the seriousness of such risks. True informed consent is a legal definition that is usually considered to have occurred if the patient is able to have the ability to express a choice, understand the risks/benefits/alternatives to proposed treatment, appreciate the significance of the choice have or forego treatment, and to come to their decision in a rational manner.
Psychiatric patients often are considered to have difficulties in the latter part of the consent process. There are some who maintain that those with delusions or hallucinations are unable to come to rational decisions. Those who work more closely with patients who have those symptoms may disagree, but nevertheless the bias is often present. While psychiatry patients are often considered to have extra difficulties in understanding consents, it is the case that patients from a broad spectrum of disease have similar problems in understanding the complexities of modern medicine. In one survey, it was found that 60% of cancer patients could not describe even one benefit or risk as little as one day after signing a consent form for chemotherapy.
In article 1, the authors describe an experimental videotape that they made to assist in teaching patients prior to going through an informed consent process. It included explanations regarding their rights and carefully explained the process of obtaining an informed consent. Additionally, it gave examples of how patients can be active participants in the consent process, and ways that they can take the information they’ve been given to make a good decision for them. They compared patients with schizophrenia to patients with other medical disorders and to healthy university students. Patients were randomly assigned either to watch the experimental videotape or to watch a similar tape that was written with an identical tone but was an historical piece about human subject research.
The groups started with different levels of pretest knowledge. The VA medical patients scored the highest on the pretest and the schizophrenia patients the lowest. However, all groups showed a significant learning when given the experimental tape versus the historical tape. The university students had the highest gains on the post-test, but all groups showed some benefit. Schizophrenia patients who demonstrated problems with conceptual organization type of thinking tended to score the worst on the pre/post test. However, other symptoms such as hallucinations or delusions did not have any correlation with their ability on the pre or post test. It should be noted though, that the most psychotic people were generally screened out from participating in this research as they would be unlikely research candidates for other studies. However, the population studied is generally the population that will enroll in a long term study and therefore this tape may have some utility with that group of individuals.
Article 2 describes research in which they determined whether patients with schizophrenia had the ability to understand the concepts involved in informed consent. They looked at patients who were being enrolled in other studies at the VA as they were going through the consent process. Patients were given a quiz in which the main concepts of informed consent were tested. If they did not answer all questions correctly the first time, they took the quiz again until they got all the answers correct. Only after answering the questions correctly could they sign the informed consent. One week later the test was readministered and again they had to answer all questions correctly in order to participate in research. It was seen that 37% of the subjects needed 3 or more trials to pass the test completely. Again, it was conceptual disorganization, more than hallucinations or delusions, that correlated with ability to perform on the test.
Overall, these studies demonstrate that the ability to perform thorough informed consenting is challengign for physician and patient alike. There is evidence that particular symptoms, namely conceptual disorganization, make consent more difficult for schizophrenia patients than healthy people. However, symptoms such as hallucinations or delusions do not seem to impact strongly a patient's ability to understand risks and benefits and to make rational decisions regarding their treatment, particuarly if given adequate support during the consenting process.
January 23, 2005
Risks in "at-risk" research
Prodromal interventions for schizophrenia vulnerability: the risks of being "at risk".
Corcoran C, Malaspina D, Hercher L.
Researchers have been trying to identify and treat teenagers and young adults who may be clinically at risk or “prodromal” for showing psychotic symptoms. This “prodromal” research (prodromal means early symptoms and signs of an illness that precede the beginning of the acute, fully developed illness) is trying to help avoid the damage that can occur once the illness begins especially since the longer the duration of untreated psychosis the worse the long term prognosis. But, this type of prodromal research has many controversies, ethical concerns and risks associated with it which are summarized in this article a leading schizophrenia researcher as follows:
Defining “at-risk”: Corcoran and colleagues point out that it is more complicated to identify those who are “at risk” for an illness than those who already show symptoms. While there are many studies that have been done to identify “at risk” factors, current standards for identifying those who are “At-Risk Mental State Prodromal” were developed in 1996 by a group of Australian researchers (Yung, McGorry and colleagues) and are seen in individuals fitting into one of three categories:
The three groups together are estimated to have about a 40% likelihood of developing psychosis by 12 months and a 50% likelihood of developing psychosis within the next 24 months. But the authors of this paper point out that it is important to keep in mind that not all measures of vulnerability are the same. A baby of two parents with schizophrenia has a 50% chance of developing the disease, which is the same statistical risk as a 17-year-old boy who is currently experiencing attenuated psychotic symptoms. But, the teenager is immediately at risk while the baby is not. This raises the ethical question of how useful is a preventive intervention that interrupts a time that could have been one of relative health and normalcy as compared to an intervention that actually addresses the immediate threat of a disease.
False Positives: In prodromal studies there is also a risk of false positives, i.e. many people who are identified to be “at-risk” do not go on to experience psychosis, at least not within the 2-year time frame that has been studied so far. This raises the risk of over-treatment for those who are unfortunate to fall in this false positive group. In any case, the use of antipsychotic medication for those who have not developed psychotic symptoms is controversial and the research is inconclusive about whether it is effective and safe. Some studies have suggested that newer medications like Risperdal and Zyprexa can be effective prodromally, although side effects have been prominent in these studies. Yet, it appears that antipsychotic medications are already being prescribed prodromally in the community and so the authors argue that there is a need for many more controlled studies to measure the effectiveness of such prescribing practices on preventing the onset of psychosis.
Stigma: There is also the risk that prodromal research subjects may experience stigma due to being “labeled” at risk for psychosis which can impact their sense of self, relationships with friends and family and possibly their choices in terms of education, employment, or other life plans. It could also impact the extent to which such plans and aspirations are supported by other family members. Interviews with parents of patients at prodromal clinics have shown that their concerns about stigma are strongly dependent on the behavior and symptoms of the patient prior to interaction with the clinic.
However, the authors point out that the stakes change if patients are younger or less symptomatic. In such a group that is not immediately at risk or impaired, the idea of being vulnerable for psychosis could leave false positive individuals with a lasting sense of being fragile or damaged. In some families this knowledge of risk could be productive, allowing them to protect the at risk person from stress and help redefine behavioral problems as due to the illness rather than character flaws. But in other families, the protective impulse might mean that the family stops encouraging growth and progress in the person identified as being “at-risk”. As a result, the authors suggest that it is important for family education be a part of prodromal research programs, especially since sometimes people forget that there is difference between being “at risk” and already having an illness.
Confidentiality: Confidentiality is an important tool for protecting the at-risk population from insurance discrimination and other forms of stigma. There are new laws involving the Health Insurance Portability and Accountability Act of 1996 and a Certificate of Confidentiality, issued by the Department of Health and Human Services, which protect privacy but yet they have no jurisdiction over what research subjects themselves disclose. The authors point out that it is important to evaluate what information is available to third parties, either directly or by implication. Relevant third parties can be insurance companies, as well as employers, schools, religious organizations and other community groups. It is not safe to assume that all people or institutions will appreciate the difference between a risk assessment and a diagnosis. As such, public education becomes important especially since these same issues have been debated in medicine for studies of insulin treatment for children at risk of Type 1 diabetes, women with a family history of breast cancer who pursue genetic testing and in pre-symptomatic testing for Huntington’s disease.
Autonomy or Self-rule: The right to make your own decisions or autonomy involves going through the informed consent process in research. The authors point out that in the prodromal period, patients are on the edge of competence – with respect to their age and mental status. Intervention at such an early stage suggests that these patients will be helped in terms of their future symptoms, but since they’re younger they would be less able to participate in the decision-making process. The authors suggest that there is no easy formula for balancing the obligation of families and doctors to protect vulnerable individuals while giving them some latitude for self-determination. But, there is a burden on the researcher or clinician to provide a high standard of informed consent since there are many who stand to gain from research in schizophrenia: families, particularly in light of familial predisposition; pharmaceutical companies with treatments to market; society at large in what can be learned about the disease. Nonetheless, the authors make it clear that these benefits cannot be earned at the expense of a vulnerable population.
Risks for true positives: Early intervention may pose some hazards for true positives as well, i.e. those who are in fact truly at risk (vs. false positives). The extent to which a treatment is a risk for true positives is directly related to two variables: current quality of life and the length of the interval between intervention and the onset of disease. But as much as early intervention looks promising, there are no guarantees that medical care is going to change the outcome for schizophrenia. Families are faced with many important questions prior to enrolling in prodromal interventions. Given that in some instances a bad result may be inevitable, and that the problem is perhaps years down the road, would a family prefer to have prior knowledge of the event? Or would they prefer to have the intervening years of relative normalcy? The authors point out that there has been limited interest in pre-symptomatic genetic testing for Huntington’s’ disease and breast cancer genetic research. This suggests that people put a high value on preserving their ability to be hopeful. While concern with insurance discrimination may have resulted in the avoidance of testing for these diseases, it also seems that when push came to shove, many people simply did not want to know their genetic risk status for these diseases. It is yet to be determined what lies ahead for schizophrenia.
Conclusions: Exploring the ethical and social implications of early intervention in schizophrenia gives us a chance to consider what measures might be taken that minimize risks without stopping improvements in treatment. It is important to keep in mind that despite the risks, current prodromal populations receiving treatment are symptomatic and well defined. But in considering people for early intervention, there is an important question of protecting any period of normalcy that the at-risk individual might have had prior to diagnosis or prior to the onset of symptoms that interfere with functioning and quality of life. Overall, decisions by doctors, patients and family members can be facilitated by being sensitive to all the ethics and risks involved, along with gaining accurate and balanced information on the proposed therapies that may impact the course of schizophrenia.
Support: This work was supported by RO1 MH59114: MH01699 K24 and by the G. Harold and Leila Mathers Charitable Foundation.
January 12, 2005
Risk from short birth intervals
Association between short birth intervals and schizophrenia in the offspring.
Smits L, Pedersen C, Mortensen P, van Os J.
Background: Conceiving immediately after delivering a baby has been found to increase risk for premature births, maturity problems and birth defects in the child. Some have hypothesized that this increased risk may be due to incomplete restoring of nutrients such as folic acid, vitamins B6 and B12 in the mother at the time of conception. These nutrients usually take up to 1 year to return to recommended levels. Since there may be a link between prenatal deficiencies of these nutrients and schizophrenia, this study looked at the relationship between the length of the preceding birth interval and the risk of schizophrenia in the offspring.
Method: This was a Danish study that collected information from a huge number of individuals - over 1.4 million Danish-born individuals and their families - and linked it to data from the Danish Psychiatric Central Register which contained data on all admissions to Danish psychiatric inpatient facilities over a certain time period. Using this database, they calculated birth order, size of family and birth interval to nearest older and younger sibling and did various other analyses.
Results: From their group, they found that a total of 5095 persons were diagnosed with schizophrenia. They found that schizophrenia risk changed depending on the birth interval. Those born after long birth intervals (27 months and longer) had the lowest chance of having schizophrenia, while those with moderately short birth intervals (15 to 20 months) showed highest rates. Contrary to what you would expect, they found that there was less risk in those born after very short birth intervals (<15 months) or after intermediate birth intervals (21 to 26 months). All these associations were independent of history of mental illness in a parent or sibling, season of birth, parental age, birth order, level of urbanization at birth, or calendar year.
Interpretation and Limitations: This study suggests that there is a link between birth spacing and the risk of schizophrenia in the child. Individuals born after birth intervals of up to 26 months, and predominantly those born within 15 to 20 months after their preceding sibling, had higher risks of developing schizophrenia than those born after birth intervals of 45 months or more. However, they had an interesting finding where the shortest interval did not result in the greatest risk, as you’d expect if the hypothesis is true about incomplete restoration of maternal nutrients of B-vitamins such as folic acid and vitamin B6. The authors try to explain this contradiction by suggesting that the shortest birth intervals may have occurred in non-lactating women who tend to have more favorable folic acid levels than lactating women. But this is just a hypothesis and needs to be researched further. Also, while this study focused on those with at least one older sibling, they also looked at data from first-born individuals and found that the highest rates associated with short birth interval was about the same as being an only child.
There are several limitations to this study. Since the authors did not have information on duration of pregnancy, they used birth intervals as estimation for inter-pregnancy interval – which might result in overrepresentations of things like premature births in the shortest birth intervals. Since prematurity may also be a risk factor for schizophrenia, this may have biased the results. Also, this study did not look at the effects of some other hypothesized environmental risk factors of schizophrenia possibly associated with birth interval such as maternal stress during pregnancy, later infections or others such as smoking, socio-economic status, planned pregnancy etc. Additionally, since this was a Danish study, their sample may not be representative of other countries with different levels of nutritional problems in the population.
Support: This study was supported by the Stanley Medical Research Institute, the Maastricht Care and Prevention Research Institute (CAPHRI) and the European Graduate School for Neuroscience (EURON) and the National Centre for Register-based Research is funded by the Danish National Research Foundation.