Cognitive heterogeneity has been a key barrier to clarifying the neuropathologic underpinnings of schizophrenia. We used an idiographic method for cluster analysis of neuropsychological data from 144 middle-aged and older people with schizophrenia to characterize and group the patterns of relative (within-person) profiles of cognitive strength and weakness. Results indicated a 5-cluster solution as most appropriate, with relatively even distribution across the five clusters in terms of the proportion of patients in each cluster. Cognitive subtyping may be useful in imaging and genetic research on schizophrenia, as well as having practical utility in treatment planning and cognitive rehabilitation.
To explore the neuropsychological correlates of the capacity to consent to research and to appoint a research proxy among persons with Alzheimer’s disease.
Design, Setting, and Participants
Interview study of 77 persons with Alzheimer’s disease recruited through an Alzheimer’s disease research center and a memory disorder clinic.
The capacity to consent to two research scenarios (a drug randomized clinical trial and a neurosurgical clinical trial) and the capacity to appoint a research proxy were determined by five experienced consultation psychiatrists who rendered categorical judgments based on videotaped interviews of the MacArthur Competence Assessment Tool-Clinical Research (MacCAT-CR) and the Capacity to Appoint a Proxy Assessment (CAPA). Mattis Dementia Rating Scale-2 (DRS-2) was used to assess neuropsychological functioning.
The capacity to appoint a proxy and to consent to the drug randomized clinical trial, as determined by a majority or greater opinion of the 5-psychiatrist panel, were predicted by Conceptualization and Initiation/Perseveration subscales whereas the capacity to consent to a neurosurgical randomized clinical trial was predicted by the Memory subscale. Furthermore, the more lenient individual psychiatrists’ judgments were predicted by the Conceptualization subscale whereas the stricter psychiatrists’ judgments were predicted by the Memory subscale.
How experienced psychiatrists view Alzheimer’s patients’ capacity for consenting to research and for appointing a proxy may be related to the patients’ conceptualization and memory functioning. More explicit and standardized guidance on the role of short term memory in capacity determinations may be useful.
decision-making capacity; neuropsychology; Alzheimer’s disease
Efforts to identify differential or core cognitive deficits in schizophrenia have been made for several decades, with limited success. Part of the difficulty in establishing a cognitive profile in schizophrenia is the considerable inter-patient heterogeneity in the level of cognitive impairment associated with this condition. Thus, it may be useful to examine the presence of relative cognitive weaknesses on an intra-patient level. In the present study we examined the rates of significant intra-person differences between crystallized verbal ability versus five other cognitive abilities among 127 persons with schizophrenia or schizoaffective disorder and 127 demographically matched normal comparison (NC) subjects. We found that the rates of significant discrepancies above the NC group base-rates was significantly greater in reference to those discrepancies involving visual memory relative to those associated with auditory memory, working memory, processing speed, and perceptual organization. The findings conflict with prior suggestions that working memory or auditory episodic memory are differential or core deficits in schizophrenia, and highlight the importance of considering visual memory in characterizing the cognitive effects of this condition.
psychosis; neuropsychology; neurocognitive; heterogeneity; idiographic
Context: The nature of executive dysfunction in schizophrenia is nebulous, due to inconsistencies in conceptualizing and operationalizing the construct, and the broader question of whether schizophrenia is best characterized in terms of specific vs generalized cognitive deficits. The current study aimed to determine whether executive functions represent unitary vs diverse constructs in schizophrenia.
Methods: Participants included 145 community-dwelling individuals with schizophrenia. Executive functions were measured with the Delis-Kaplan Executive Functioning System (D-KEFS). We conducted an exploratory factor analysis (EFA) with principal axis factoring, as well as parallel analyses to examine the latent constructs underlying the D-KEFS tasks, a second EFA on weighted residuals of the D-KEFS tasks (after accounting for processing speed measured with the Digit Symbol task), and bivariate correlations to examine relationships between the D-KEFS components and relevant demographic and clinical variables, crystallized verbal knowledge, and functional capacity.
Results: EFA of the D-KEFS tasks yielded 2 factors (cognitive flexibility/timed tests and abstraction). EFA of the processing speed-weighted D-KEFS residuals also yielded 2 factors (cognitive flexibility and abstraction). Cognitive flexibility was negatively correlated with psychopathology. Better abstraction was associated with higher education, shorter illness duration, and better functional capacity. Both factors were positively correlated with crystallized verbal knowledge.
Conclusions: Executive functions in schizophrenia could be parsed into 2 partially related but separable subconstructs. Future efforts to elucidate functional outcomes as well as neurobiological underpinnings of schizophrenia may be facilitated by attending to the distinction between cognitive flexibility and abstraction.
cognitive flexibility; abstraction; D-KEFS; factor analysis
The aim of the current study was to investigate the frequency of periodic limb movements in sleep (PLMS) in Parkinson’s disease (PD) and their impact on nocturnal sleep and daytime functioning.
Forty-five PD patients (mean age 68.5±8.7 years; 32 males) underwent one night of polysomnography (PSG). Clinical assessment and questionnaires evaluating sleep disturbance and quality of life (QoL) were completed. Patients were divided into two groups based on their PLMS index (PLMSI): PLMSI ≥15 (PLMS+) and PLMSI <15 (PLMS−).
There were 26 (57.8%) PD patients in the PLMS+ group and 19 (42.2%) patients in the PLMS− group. Subjective assessment revealed an association between PLMS+ status and greater PD symptom severity, more subjective sleep disturbance, and decreased QoL. All patients showed poor sleep, and no significant group differences were detected on PSG measures.
We observed that PLMS occurred frequently in PD and increased with more severe PD. Although PLMS did not affect objective sleep, it was associated with increased sleep complaints and reduced QoL. Overall, our findings support the association between PLMS and PD as well as the clinical relevance of sleep disturbances in PD.
Dopaminergic treatment; Parkinson’s disease; periodic limb movements in sleep; polysomnography; quality of life; sleep disturbance
Schizophrenia is associated with executive dysfunction. Yet, the degree to which executive functions are impaired differentially, or above and beyond underlying basic cognitive processes is less clear. Participants included 145 matched pairs of individuals with schizophrenia (SCs) and normal comparison subjects (NCs). Executive functions were assessed with 10 tasks of the Delis-Kaplan Executive Function System (D-KEFS), in terms of “achievement scores” reflecting overall performance on the task. Five of these tasks (all measuring executive control) were further examined in terms of their basic component (e.g., processing speed) scores and contrast scores (reflecting residual higher order skills adjusted for basic component skills). Group differences were examined via multivariate analysis of variance. SCs had worse performance than NCs on all achievement scores, but the greatest SC-NC difference was that for the Trails Switching task. SCs also had worse performance than NCs on all basic component skills. Of the executive control tasks, only Trails Switching continued to be impaired after accounting for impairments in underlying basic component skills. Much of the impairment in executive functions in schizophrenia may reflect the underlying component skills rather than higher-order functions. However, the results from one task suggest that there might be additional impairment in some aspects of executive control.
Cognition; Executive function; Schizoaffective disorder; Psychotic disorders; Trail Making Test; D-KEFS
Cognitive dysfunction is common in patients with advanced, life-threatening illness and can be attributed to a variety of factors (e.g., advanced age, opiate medication). Such dysfunction likely affects decisional capacity, which is a crucial consideration as the end of life approaches and patients face multiple choices regarding treatment, family, and estate planning. This study examined the prevalence of cognitive impairment and its impact on decision-making abilities among hospice patients with neither a chart diagnosis of a cognitive disorder nor clinically apparent cognitive impairment (e.g., delirium, unresponsiveness).
110 participants receiving hospice services completed a one-hour neuropsychological battery, a measure of decisional capacity, and accompanying interviews.
In general, participants were mildly impaired on measures of verbal learning, verbal memory, and verbal fluency; 54% of the sample was classified as having significant, previously undetected cognitive impairment. These individuals performed significantly worse than the other participants on all neuropsychological and decisional capacity measures, with effect sizes ranging from medium to very large (0.43–2.70). A number of verbal abilities as well as global cognitive functioning significantly predicted decision-making capacity.
Despite an absence of documented or clinically obvious impairment, more than half of the sample had significant cognitive impairments. Assessment of cognition in hospice patients is warranted, including assessment of verbal abilities that may interfere with understanding or reasoning related to treatment decisions. Identification of patients at risk for impaired cognition and decision-making may lead to effective interventions to improve decision-making and honor the wishes of patients and families.
dementia; delirium; hospice; neuropsychology; cognitive impairment; decision-making; palliative care
Subsyndromal symptoms of depression (SSD) in patients with schizophrenia are common and clinically important. While treatment of depression in major depressive disorder may partially ameliorate cognitive deficits, the cognitive effects of antidepressant medications in patients with schizophrenia or schizoaffective disorder and SSD are unknown.
The goal of this study was to assess the impact of SSD and their treatment on cognition in participants with schizophrenia or schizoaffective disorder aged ≥40 years. Participants were randomly assigned to a flexible dose treatment with citalopram or placebo augmentation of their current medication for 12 weeks. An ANCOVA compared improvement in the cognitive composite scores, and a linear model determined the moderation of cognition on treatment effects based on the Hamilton Depression Rating Scale and the Calgary Depression Rating Scale scores between treatment groups.
There were no differences between the citalopram and placebo groups in changes in cognition. Baseline cognitive status did not moderate antidepressant treatment response.
Although there are other cogent reasons why SSD in schizophrenia warrant direct intervention, treatment does not substantially affect the level of cognitive functioning. Given the effects of cognitive deficits associated with schizophrenia on functional disability, there remains an ongoing need to identify effective means of directly ameliorating them.
Schizophrenia; Citalopram; Cognition; Subsyndromal depression
A review of literature on the neurodevelopmental origins of schizophemia is presented, with particular attention to neurodevelopmental processes in late-onset schizophemia. Definitions of the term “neurodevelopmental” as used in schizophernia literature are first provided. Next, evidence for the developmental origins of the neuropathology in schizophemia is reviewed. This evidence includes studies of the associations between schizophemia and neurodevelopmental brain aberrations, minor physical anomalies, obstetric complications, prenatal viral exposure, childhood neuromotor abnormalities, and pandysmaturation. A brief discussion of the predominant theories about the neurodevelopmental origins of schizophemia is then provided. The concept and nature of “late-onset schizophenia ”is next defined and discussed. Finally, the neurodevelopmental literature is discussed in relation to the phenomenon of late-onset schizophemia. Based on this review, we conclude that there exists a strong likelihood that late-onset schizophrenia involves neurodevelopmental processes.
Psychosis; neurodegeneration; dementia; congnition; aging; developmental disabilities
Aging is not a uniform process. In the general population, there is a paradox of aging: age-associated decline in physical and some cognitive functions stands in contrast to an enhancement of subjective quality of life and psychosocial functioning. This paradox is even more striking in people with schizophrenia. Compared with the overall population, individuals with schizophrenia have accelerated physical aging (with increased and premature medical comorbidity and mortality) but a normal rate of cognitive aging, although with mild cognitive impairment starting from premorbid period and persisting throughout life. Remarkably, psychosocial function improves with age, with diminished psychotic symptoms, reduced psychiatric relapses requiring hospitalization and better self-management. Many older adults with schizophrenia successfully adapt to the illness, with increased use of positive coping techniques, enhanced self-esteem and increased social support. Although complete remission is uncommon, most individuals with schizophrenia experience significant improvement in their quality of well-being. Cohort effect and survivor bias may provide a partial explanation for this phenomenon. However, the improvement also may reflect some brain changes that are beneficial for the course of schizophrenia along with neuroplasticity of aging. The proposed hypothesis has several implications. As significant medical morbidity in schizophrenia takes years to develop, studies of changes in sensitive biomarkers of aging during the course of illness may point to new treatments aimed at normalizing the rate of biological aging in schizophrenia. At the same time, effective psychotherapeutic interventions can affect brain structure and function and produce lasting positive behavioral changes in aging adults with schizophrenia.
psychosis; geriatric; quality of life; psychotherapy; neuropsychological; biomarkers
The role of spirituality in the context of mental health and successful aging is not well understood. In a sample of community-dwelling older women enrolled at the San Diego site of the Women's Health Initiative study, we examined the association between spirituality and a range of variables associated with successful cognitive and emotional aging, including optimism, resilience, depression, and health-related quality of life (HRQoL).
A detailed cross-sectional survey questionnaire on successful aging was completed by 1,973 older women. It included multiple self-reported measures of positive psychological functioning (e.g., resilience, optimism,), as well as depression and HRQoL. Spirituality was measured using a 5-item self report scale constructed using two items from the Brief Multidimensional Measure of Religiosity/Spirituality and three items from Hoge's Intrinsic Religious Motivation Scale
Overall, 40% women reported regular attendance in organized religious practice, and 53% reported engaging in private spiritual practices. Several variables were significantly related to spirituality in bivariate associations; however, using model testing, spirituality was significantly associated only with higher resilience, lower income, lower education, and lower likelihood of being in a marital or committed relationship.
Our findings point to a role for spirituality in promoting resilience to stressors, possibly to a greater degree in persons with lower income and education level. Future longitudinal studies are needed to confirm these associations.
Spirituality; religiosity; elderly; successful aging; resilience
Subsyndromal depression (SSD) is several times more common than major depression in older adults, and is associated with significant negative health outcomes. Physical activity can improve depression, yet adherence is often poor. We assessed the feasibility, acceptability, and short-term efficacy and safety of a novel intervention using exergames (entertaining video games that combine game play with exercise) for SSD in older adults.
Community-dwelling older adults (N = 19, age 63–94) with SSD participated in a 12-week pilot study (with follow-up at 20 to 24 weeks) of Nintendo’s Wii Sports, with three 35-minute sessions a week.
86% of enrolled participants completed the 12-week intervention. There was a significant improvement in depressive symptoms, mental health-related quality of life, and cognitive performance, but not physical health-related quality of life. There were no major adverse events, and improvement in depression was maintained at follow-up.
The findings provide preliminary indication of the benefits of exergames in seniors with SSD. Randomized controlled trials of exergames for late-life SSD are warranted.
Physical activity; Aging; Videogames; Depression; Quality of life; Cognition
Limitations of printed, text-based, consent forms have long been documented and may be particularly problematic for persons at risk for impaired decision-making capacity, such as those with schizophrenia. We conducted a randomized controlled comparison of the effectiveness of a multimedia vs routine consent procedure (augmented with a 10-minute control video presentation) as a means of enhancing comprehension among 128 middle-aged and older persons with schizophrenia and 60 healthy comparison subjects. The primary outcome measure was manifest decisional capacity (understanding, appreciation, reasoning, and expression of choice) for participation in a (hypothetical) clinical drug trial, as measured with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and the University of California San Diego (UCSD) Brief Assessment for Capacity to Consent (UBACC). The MacCAT-CR and UBACC were administered by research assistants kept blind to consent condition. Additional assessments included standardized measures of psychopathology and cognitive functioning. Relative to patients in the routine consent condition, schizophrenia patients receiving multimedia consent had significantly better scores on the UBACC and on the MacCAT-CR understanding and expression of choice subscales and were significantly more likely to be categorized as being capable to consent than those in the routine consent condition (as categorized with several previously established criteria). Among the healthy subjects, there were few significant effects of consent condition. These findings suggest that multimedia consent procedures may be a valuable consent aid that should be considered for use when enrolling participants at risk for impaired decisional capacity, particularly for complex and/or high-risk research protocols.
bioethics; mental competency; informed consent; multimedia learning; cognition disorders; schizophrenia
Objective: Providing incentives for research participation is widely practiced but minimally studied. In schizophrenia research, questions about capacity to consent and potential vulnerability may raise concerns when offering incentives for participation. Despite empirical attention focused on consent and decision-making capacity in schizophrenia, the issue of incentives has been essentially ignored. We examined willingness to participate in research, in relation to perceived risks and benefits, among people with schizophrenia and schizoaffective disorder. Method: Forty-six people with schizophrenia or schizoaffective disorder rated perceived risks and benefits of 5 hypothetical research vignettes. They also indicated whether they would be willing to participate at each of 5 incentive levels (including no compensation). Cognition was assessed with Mattis Dementia Rating Scale. Results: Ratings of risk and potential personal benefit were inversely correlated. For all scenarios, significant correlations were found between perceived risk and willingness to participate for greater compensation. Conversely, lower perceived likelihood of benefit was associated with a higher compensation threshold for participation in each scenario. Even at the highest proffered payment level for each scenario, however, a substantial proportion of respondents were not willing to participate. Risk assessment and willingness to participate (at all levels of compensation) were not associated with demographic variables or cognitive status. Conclusions: Determining whether incentives impede voluntarism remains an important task for empirical ethics research. Assessing potential research participants’ understanding and perceptions of risks, benefits, and alternatives to participation will help ensure that informed consent fulfills its mission—embodying the ethical principle of respect for persons.
ethics; informed consent; research participation; incentives; risk perception; voluntarism
To examine whether treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) in patients with Alzheimer's disease (AD) would result in improved cognitive function.
Randomized double-blind placebo-controlled trial. Participants were randomized to either therapeutic CPAP for six weeks or placebo CPAP for three weeks followed by therapeutic CPAP for three weeks.
General clinical research center
52 men and women with mild-moderate AD and OSA
Continuous positive airway pressure
A complete neuropsychological test battery was administered before treatment, at three and at six-weeks.
A comparison of subjects randomized to 3 weeks of therapeutic versus placebo CPAP suggested no significant improvements in cognition. A comparison of pre- versus post-treatment neuropsychological test scores after 3 weeks of therapeutic CPAP in both groups showed a significant improvement in cognition. The study was underpowered to make definitive statements about improvements within specific cognitive constructs. However, exploratory post-hoc examination of change scores for individual tests suggested improvements in episodic verbal learning and memory and some aspects of executive functioning such as cognitive flexibility, and mental processing speed.
OSA may aggravate cognitive dysfunction in dementia and thus may be a reversible cause of cognitive loss in AD patients. OSA treatment seems to improve some of the cognitive functioning. Clinicians who care for AD patients should consider implementing CPAP treatment when OSA is present.
dementia; Alzheimer's disease; obstructive sleep apnea; CPAP; cognitive impairment
Application of a neuropsychological perspective to the study of schizophrenia has established a number of important facts about this disorder. Some of the key findings from the existing literature are that, while neurocognitive impairment is present in most, if not all, persons with schizophrenia, there is both substantial interpatient heterogeneity and remarkable within-patient stability of cognitive function over the long-term course of the illness. Such findings have contributed to the firm establishment of neurobiologic models of schizophrenia, and thereby help to reduce the social stigma that was sometimes associated with purely psychogenic models popular during parts of the 20th century. Neuropsychological studies in recent decades have established the primacy of cognitive functions over psychopathologic symptoms as determinants of functional capacity and independence in everyday functioning. Although the cognitive benefits of both conventional and even second generation antipsychotic medications appear marginal at best, recognition of the primacy of cognitive deficits as determinants of functional disability in schizophrenia has catalyzed recent efforts to develop targeted treatments for the cognitive deficits of this disorder. Despite these accomplishments, however, some issues remain to be resolved. Efforts to firmly establish the specific neurocognitive/neuropathologic systems responsible for schizophrenia remain elusive, as do efforts to definitively demonstrate the specific cognitive deficits underlying specific forms of functional impairment. Further progress may be fostered by recent initiatives to integrate neuropsychological studies with experimental neuroscience, perhaps leading to measures of deficits in cognitive processes more clearly associated with specific, identifiable brain systems.
Psychoses; Cognitive; Heterogeneity; Activities of daily living; Historical
There are few longitudinal studies of neurocognition in bipolar disorder, and the short-term course of cognitive deficits in later-life bipolar disorder is unknown.
We administered a battery of neurocognitive tests, repeated one to three years after baseline, to 35 community-dwelling outpatients with bipolar disorder (mean age = 58), and compared their performance on a composite measure of cognitive functioning to that of demographically-matched samples of normal comparison subjects (NCs; n=35) and patients with schizophrenia (n=35). Using regression analyses, we examined group differences in baseline performance, trajectory of change over time, and variability in performance across time. Within the bipolar group, we examined the impact of baseline severity and change in severity of psychiatric symptoms on intra-individual change in neurocognitive performance.
At baseline, the group with bipolar disorder differed in overall neurocognitive functioning from the NCs, but did not differ significantly from the schizophrenia group. The bipolar group did not differ from the NCs or schizophrenia group in the mean trajectory of change between time points, but the bipolar patients showed more intra-individual variability over time than the NCs or schizophrenia group. In the bipolar group, change in neurocognitive function was not related to baseline or change in psychiatric symptom severity.
Middle-aged and older community-dwelling adults with bipolar disorder have greater short-term variability in level of neurocognitive functioning relative to NCs or people with schizophrenia. The developmental course of and risk factors for cognitive deficits in bipolar disorder should be examined in future longitudinal studies.
Bipolar disorder; neuropsychology; memory; aging; schizophrenia; depression
Purpose of review
Although the basic standards of adjudicative competence were specified by the U.S. Supreme Court in 1960, there remain a number of complex conceptual and practical issues in interpreting and applying these standards. In this report we provide a brief overview regarding the general concept of adjudicative competence and its assessment, as well as some highlights of recent empirical studies on this topic.
Most adjudicative competence assessments are conducted by psychiatrists or psychologists. There are no universal certification requirements, but some states are moving toward required certification of forensic expertise for those conducting such assessments. Recent data indicate inconsistencies in application of the existing standards even among forensic experts, but the recent publication of consensus guidelines may foster improvements in this arena. There are also ongoing efforts to develop and validate structured instruments to aid competency evaluations. Telemedicine-based competency interviews may facilitate evaluation by those with specific expertise for evaluation of complex cases. There is also interest in empirical development of educational methods to enhance adjudicative competence.
Adjudicative competence may be difficult to measure accurately, but the assessments and tools available are advancing. More research is needed on methods of enhancing decisional capacity among those with impaired competence.
Competence; ethics; informed consent
The frequency, pattern, and correlates of neurocognitive impairment in older patients with bipolar disorder have received little study. We examined neurocognitive abilities in middle-aged and older adults with bipolar disorder to groups with schizophrenia or normal subjects, as well as the relation of neurocognition to clinical characteristics.
We administered a battery of neurocognitive and clinical measures to older (45–85 years) outpatients with bipolar disorder (n=67), schizophrenia (n=150), and normal comparison subjects (n=85). Within the bipolar group, we assessed the association between neurocognitive performance and psychiatric symptoms, quality of life, and medication status.
The group with bipolar disorder differed on nearly all neuropsychological tests compared to normal subjects, with medium effect sizes. Bipolar patients as impaired as those with schizophrenia on half of the tests administered, and performed better on the remaining tests, with small effect sizes. Neurocognitive deficits in bipolar disorder group related to lower quality of life, but not to psychiatric symptom severity or duration of illness.
Samples were outpatients with mild-moderate symptoms, and findings may not generalize to acutely ill populations. We lacked data on illness history to examine the cumulative impact of psychopathology.
Among clinically stable middle-aged and older outpatients, bipolar disorder was associated with substantial neurocognitive impairment, with a pattern that was somewhat distinct from that found in schizophrenia. Deficits in the bipolar group were not related to severity or duration of psychiatric symptoms, but were related to quality of life. Bipolar disorder often involve disabling and enduring cognitive impairments in older outpatients.
Bipolar disorder; neuropsychology; memory; aging; schizophrenia; depression
Despite the availability of structured decision-making capacity assessment tools, insufficient guidance exists for applying their results. Investigators often use cutpoints on these instruments to identify potential subjects in need of further assessment or education. Yet, information is lacking regarding the effects of different cutpoints on the proportion and characteristics of individuals categorized as possessing adequate or impaired decisional abilities for consent to research. To demonstrate the potential impact of different standards, we informed 91 individuals, aged 50 or older with a diagnosis of schizophrenia or schizoaffective disorder, about a hypothetical clinical trial, and assessed their decisional abilities with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). Three published MacCAT-CR-based standards were applied to participants’ scores to examine the rates and correlates of categorical determinations of adequate performance. The three standards ranged in stringency: the most stringent incorporated cutpoints on all three of the major MacCAT-CR subscales (Understanding, Appreciation, and Reasoning); the other two standards required threshold performance only on the Understanding subscale. The most stringent standard resulted in a 57% rate of impaired performance; the intermediate standard, 19%; and the least stringent standard, 8%. Nearly half of the participants (n=45) were classified as having performed adequately by the least stringent standard yet inadequately by the most stringent. The majority of these 45 were impaired on the Appreciation subscale (n=9), Reasoning (n=15), or both (n=18). Cognitive functioning was correlated with performance status for the more stringent standards. These findings underscore the need for refinement of capacity assessment procedures and for improvements in the use of capacity assessment tools for screening purposes and to assist in categorical capacity determinations.
Research ethics; decision-making capacity; competency; clinical trials; schizophrenia; neuropsychology
Prior empirical studies suggest that cognitive impairment is the strongest predictor of capacity to consent to research among persons with schizophrenia. Yet, despite the frequency and importance of cognitive deficits and impaired decisional capacity in schizophrenia, the scope of neuropsychological testing in most published reports in this area has been relatively narrow. In the present study of 70 people with schizophrenia aged 40 to 70 years we evaluated decisional capacity with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). Participants were also evaluated with standardized rating scales of psychopathology and level of insight and with a comprehensive neuropsychological test battery that permitted evaluation of 7 specific cognitive abilities. Results showed that the strongest correlates of capacity (particularly, understanding and appreciation of disclosed information) were cognitive test scores, but there was little evidence of differential relationships between individual cognitive abilities and specific dimensions of capacity. Understanding was also correlated with severity of negative symptoms and of general psychopathology, but not with age, education, severity of positive or depressive symptoms, or level of insight. Understanding improved over successive presentations of consent-relevant information. The results suggest that age and diagnosis should not be viewed as determinants of decisional capacity; investigators should be alert to the presence of cognitive deficits, as well as negative symptoms. Also, an interactive dialogue between patient and investigator with repeated presentation of information is likely to aid understanding of disclosed information among patients with schizophrenia.
neurocognition; informed consent; psychoses; bioethics; competence
Research protocols frequently necessitate procedures or design elements that differ from those used in routine clinical care. An example is the inclusion of a placebo arm in many randomized clinical trials. Because there are risks to taking a placebo when one has a chronic disorder such as schizophrenia, ascertaining how well people with severe mental illness understand placebos is an important task for empirical research ethics. We investigated whether schizophrenia patients' understanding of placebo controls could be improved with a brief educational intervention. We randomized 49 middle-aged and older patients with schizophrenia or schizoaffective disorder to receive either (1) a routine explanation of placebos in the context of consent for a hypothetical double-blind placebo-controlled clinical trial, or (2) the consent for the hypothetical trial plus a brief educational module explaining placebos in more depth. Understanding of placebos was assessed with a 12-item questionnaire, and we examined demographic, clinical, neurocognitive, and decision-making correlates of understanding of placebos. Those participants who received the intervention obtained higher scores on the placebo post-test compared to those who received the standard information alone. Performance on the placebo post-test was positively correlated with measures of decisional capacity and neurocognitive abilities and negatively correlated with severity of negative symptoms, but it showed no relationship with positive or general symptoms. Some participants interpreted the common phrase “sugar pill” as relating somehow to diabetes. We conclude that the level of understanding of important research design–related information is not static but may be influenced by how investigators approach the consent process.
research ethics; decision making; informed consent; research designs; clinical trials
Empirical studies of ethical issues, which have increased in number and scope in recent years, may themselves raise both practical and ethical issues. One example of such an issue is the question of who may be legitimately enrolled in studies of decision-making capacity; must all participants in studies of consent capacity have capacity to consent? This question may pose a “Catch-22”: For example, if some of the participants in a study of consent capacity are deemed by a particular standard to be incapable of consent. In weighing the risks and benefits of studies of consent capacity, how should reviewers consider the context of actual versus hypothetical trials for which the participant's consent is being sought? Here, we explore these “meta-consent” issues by describing the dimensions of the issue and potential solutions, centering around the concept of “active assent” (requiring expressed understanding of the purpose of the study and its voluntary nature, as well as expression of a choice to participate).
decision-making capacity; research ethics; informed consent; bioethics; clinical trials
The capacity of individuals with schizophrenia to make decisions related to research participation or clinical treatment has received increasing empirical attention. A number of studies have compared patients with schizophrenia to nonpsychiatric comparison subjects (NPCs) on structured measures of decision-making capacity. In this review, we evaluated the magnitude of the difference between schizophrenia and NPC groups reported across these studies, as well as the influence of sample characteristics on observed effect sizes. We also computed the effect sizes of group differences in psychopathology and cognitive deficits. Twelve studies met the search criteria; a majority of them reported data using the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) or for Treatment (MacCAT-T). The mean effect size (evaluated in terms of Cohen's d) for group differences on the Understanding subscale of the MacCAT instruments was 0.88 (SD = 0.40); it was twice as high among inpatient samples as among outpatients. Similar differences were observed in terms of Appreciation and Reasoning subscales, but the effect sizes for Expression of Choice were small (mean d = 0.29, SD = 0.24). Notably, these observed effect sizes were generally smaller than those for differences between schizophrenia and NPC groups in psychopathology (mean d = 2.06, SD = 1.03) and cognition (mean d = 1.01, SD = 0.61). The published studies demonstrate a substantial heterogeneity in decision-making capacity among people with schizophrenia, as well as among NPCs, suggesting that the presence of schizophrenia does not necessarily mean the patient has impairment in capacity.
schizophrenia; decisional capacity; competence; consent; cognition; psychosis