Diagnostic exome sequencing in children: A survey of parental understanding, experience and psychological impact.

Clinical exome sequencing (CES) is increasingly being used as an effective diagnostic tool in the field of pediatric genetics. We sought to evaluate the parental experience, understanding and psychological impact of CES by conducting a survey study of English-speaking parents of children who had diagnostic CES. Parents of 192 unique patients participated. The parent's interpretation of the child's result agreed with the clinician's interpretation in 79% of cases, with more frequent discordance when the clinician's interpretation was uncertain. The majority (79%) reported no regret with the decision to have CES. Most (65%) reported complete satisfaction with the genetic counseling experience, and satisfaction was positively associated with years of genetic counselor (GC) experience. The psychological impact of CES was greatest for parents of children with positive results and for parents with anxiety or depression. The results of this study are important for helping clinicians to prepare families for the possible results and variable psychological impact of CES. The frequency of parental misinterpretation of test results indicates the need for additional clarity in the communication of results. Finally, while the majority of patients were satisfied with their genetic counseling, satisfaction was lower for new GCs, suggesting a need for targeted GC training for genomic testing.

Assessing mental capacity for everyday decision-making in the Chinese older population.

1. The abilities to make everyday decisions may be reliably measured in the local elderly population. 2. The Chinese version of the Assessment of Capacity for Everyday Decision-Making is a reliable tool to assess these abilities. 3. Significant proportion of participants with mild dementia was mentally incapable in making decisions on everyday tasks. Global cognitive functioning appeared to be an important prerequisite for intact mental capacity.

Effect of public deliberation on attitudes toward surrogate consent for dementia research.

OBJECTIVE: To assess the informed, deliberative views of the older general public toward a policy of allowing surrogate consent for Alzheimer disease (AD) research. METHODS: A total of 503 persons aged 50+ recruited by random digit dialing were randomly assigned to 1 of 3 groups: deliberation, education, or control. The deliberation group attended an all-day education/peer deliberation session; the education group received written information only. Participants were surveyed at baseline, after deliberation session (or equivalent time), and 1 month after the session, regarding their attitudes toward a policy of allowing surrogate consent for research studies of varying risks and potential benefits (a lumbar puncture study, a drug randomized controlled trial, a vaccine randomized controlled trial, and an early phase gene transfer trial). RESULTS: At baseline, a policy of surrogate consent for AD research was supported by 55%-91%, depending on the scenario. The education group had a transient increase in support for one research scenario after receiving the information materials. In the deliberation group, support for surrogate consent was higher after deliberation for all scenarios (67% to 97%), with much of the increase sustained 1 month after the deliberation session. No changes occurred in the control group. The study's limitations include self-selection of participants due to the demanding nature of attendance at the deliberation sessions. CONCLUSIONS: This sample of the older general public generally supported a policy of surrogate consent for AD research at baseline. Their support increased with democratic deliberation involving informed, in-depth exploration of the relevant scientific and ethical issues.

Neuropsychological performance predicts decision-making abilities in Chinese older persons with mild or very mild dementia.

OBJECTIVE: To explore the relationship of the 4 decision-making abilities (Understanding, Appreciation, Reasoning, and Expressing a Choice) and neuropsychological performance in patients with very mild and mild dementia. METHODS: Chinese subjects were recruited from local social centres and residential hostels for elderly people in Hong Kong. Clinical diagnosis was made by experienced geriatric psychiatrists. A battery of neuropsychological tests that assesses general cognitive abilities, verbal memory, executive function, concept formation, and auditory and visual attention, was administered. Mental capacity to consent to treatment was assessed using the Chinese version of the MacArthur Competence Assessment Tool - Treatment. RESULTS: Fifty participants with very mild or mild dementia were compared with 42 cognitively intact subjects. After controlling for the effects of age and education, stepwise linear regression analysis demonstrated that the 4 decision-making abilities correlated with different neuropsychological test performances, which predicted 45% of the common variance for Understanding, 39% for Appreciation, 20% for Reasoning, and 30% for Expressing a Choice. The Reasoning score was only predicted by the Category Verbal Fluency Test (ß = 0.4, p = 0.01). CONCLUSION: Neuropsychological test performance differentially predicted different decision-making abilities in older patients with mild or very mild dementia.

Pharmacotherapy for depressed pregnant women: overcoming obstacles to gathering essential data.

Approximately 3% of pregnant women take antidepressant medications. Information on the impact of antidepressants on short- and long-term maternal and offspring outcomes is highly desirable but neglected. The position that the dearth of treatment information is of greater concern than the risks to pregnant subjects involved in medical research is gaining support. Mandating the collection of reproductive outcome data in exposed childbearing women is an overdue step toward societal responsibility to our most vulnerable members.

Surrogate consent for dementia research: a national survey of older Americans.

BACKGROUND: Research in novel therapies for Alzheimer disease (AD) relies on persons with AD as research subjects. Because AD impairs decisional capacity, informed consent often must come from surrogates, usually close family members. But policies for surrogate consent for research remain unsettled after decades of debate. METHODS: We designed a survey module for a random subsample (n = 1,515) of the 2006 wave of the Health and Retirement Study, a biennial survey of a nationally representative sample of Americans aged 51 and older. The participants answered questions regarding one of four randomly assigned surrogate-based research (SBR) scenarios: lumbar puncture study, drug randomized control study, vaccine study, and gene transfer study. Each participant answered three questions: whether our society should allow family surrogate consent, whether one would want to participate in the research, and whether one would allow one's surrogate some or complete leeway to override stated personal preferences. RESULTS: Most respondents stated that our society should allow family surrogate consent for SBR (67.5% to 82.5%, depending on the scenario) and would themselves want to participate in SBR (57.4% to 79.7%). Most would also grant some or complete leeway to their surrogates (54.8% to 66.8%), but this was true mainly of those willing to participate. There was a trend toward lower willingness to participate in SBR among those from ethnic or racial minority groups. CONCLUSIONS: Family surrogate consent-based dementia research is broadly supported by older Americans. Willingness to allow leeway to future surrogates needs to be studied further for its ethical significance for surrogate-based research policy.

Mandated community treatment: beyond outpatient commitment.

Outpatient commitment, although often viewed as merely an extension of inpatient commitment, is only one of a growing array of legal tools used to mandate treatment adherence. The authors describe various forms of mandated community treatment. People with severe and chronic mental disorders often depend on goods and services provided by the social welfare system. Benefits disbursed by representative payees and the provision of subsidized housing have both been used as leverage to ensure treatment adherence. Many discharged patients are arrested for criminal offenses. Favorable disposition of their cases by a mental health court may be tied to participation in treatment. Under outpatient commitment statutes, judges can order committed patients to comply with prescribed treatment. Patients may attempt to maximize their control over treatment in the event of later deterioration by executing an advance directive. The ideological posturing that currently characterizes the field must be replaced by an evidence-based approach.

Thinking carefully about outpatient commitment.

We are witnessing an unprecedented wave of interest in outpatient commitment. In part, enthusiasm for outpatient commitment stems from concerns about highly publicized acts of violence by persons with mental disorders, although this is one of the weaker justifications for new laws. Provision of involuntary outpatient treatment may be an important component of a system of care for persons with schizophrenia, bipolar disorder, and other serious mental illnesses for reasons entirely unrelated to the prevention of headline-grabbing acts of violence. The existing data, all imperfect, tend to favor the efficacy of outpatient commitment as a means of stabilizing patients in the community, and many clinicians who have been involved in the process share this view. Acknowledging limitations in the empirical evidence favoring outpatient commitment, the author reviews key issues for policy makers to address in considering or revising these statutes.

Informed Consent in Early Psychosis Research: National Institute of Mental Health workshop, November 15, 2000.

Recent research on the early detection and treatment of schizophrenia has generated significant scientific interest along with considerable controversy and debate. Because our ability to alleviate fully the symptoms and deficits of established schizophrenia is limited, the prospect of interrupting disease progression early is compelling. At the same time, in the absence of an infallible marker of disease risk, there are serious questions about the safety, feasibility, and ethics of intervention research on "at-risk" or putatively prodromal individuals. A workshop, Informed Consent in Early Psychosis Research, was convened by the National Institute of Mental Health (NIMH) on November 15, 2000, to review the results of recent research on early detection and intervention in schizophrenia. Beginning with the assumptions that (1) treatment of asymptomatic individuals with antipsychotic medication is not appropriate in research or clinical care, and (2) neither data nor clinical consensus defines optimal intervention for symptomatic at-risk individuals, workshop participants-including clinical researchers, mental health consumers and family members, bioethicists, community health care providers, and NIMH staff-systematically reviewed available data on the potential risks and benefits of alternate approaches to the management of prodromal states. Ethical issues involved in early detection and intervention studies were discussed. Workshop participants summarized information presented during the meeting into informed consent "bullets" that must be communicated to, and understood and appreciated by, potential research participants.

Risk-benefit decision making for treatment of depression during pregnancy.

OBJECTIVE: The Committee on Research on Psychiatric Treatments of the American Psychiatric Association identified treatment of major depression during pregnancy as a priority area for improvement in clinical management. The goal of this article was to assist physicians in optimizing treatment plans for childbearing women. METHOD: The authors' work group developed a decision-making model designed to structure the information delivered to pregnant women in the context of the risk-benefit discussion. Perspectives of forensic and decision-making experts were incorporated. RESULTS: The model directs the psychiatrist to structure the problem through diagnostic formulation and identification of treatment options for depression. Reproductive toxicity in five domains (intrauterine fetal death, physical malformations, growth impairment, behavioral teratogenicity, and neonatal toxicity) is reviewed for the potential somatic treatments. The illness (depression) also is characterized by symptoms of somatic dysregulation that compromise health during pregnancy. The patient actively participates and provides her evaluation of the acceptability of the various treatments and outcomes. Her capacity to participate in this process provides evidence of competence to consent. Included in the decision-making process are the patient's significant others and obstetrical physician. The process is ongoing, with the need for incorporation of additional data as the pregnancy and treatment response progress. CONCLUSIONS: The conceptual model provides structure to a process that is frequently stressful for both patients and psychiatrists. By applying the model, clinicians will ensure that critical aspects of the risk-benefit discussion are included in their care of pregnant women.

The history and current status of competence and informed consent in psychiatric research.

Informed consent to research has recently become a focus of public attention as questions have been raised about the adequacy of information disclosed to potential research subjects and about the competence of psychiatric research subjects to provide valid informed consent to participate in potentially high risk studies. Around the world, policies and position statements have been written to address these concerns and to offer suggestions to protect potentially vulnerable research subjects, such as persons with neuropsychiatric disorders. Relevant literature has demonstrated that a subset of persons with such disorders have significant competence-related deficits, and thus may require specific means of protection with regard to informed consent to research. Recent guidelines offered to improve the informed consent process include review of potential studies for scientific merit and potential risk, assessment of subject competence to consent to research, and the use of proxy decision-makers when subjects are deemed incompetent.

Violent thoughts and violent behavior following hospitalization for mental disorder.

Using a standardized schedule of questions, this study examined (a) the prevalence of self-report of violent thoughts by patients hospitalized for mental disorders compared with nonpatients, (b) the persistence of violent thoughts after discharge, and (c) the relation between patients' violent thoughts while hospitalized and violent acts within 20 weeks after hospital discharge. About 1/3 of the patients reported thoughts of violence while hospitalized, more than twice the proportion found among nonpatients. Reporting violent thoughts in hospital was significantly related to engaging in violent acts within 20 weeks after discharge for non-White patients, patients without major mental disorder but with substance abuse diagnoses, patients with high symptom severity, and patients whose reports of violent thoughts persisted after discharge. Reporting violent thoughts was significantly related to measures of psychopathy, anger, and impulsiveness.