Changes in capacity to consent over time in patients involved in psychiatric research.

BACKGROUND: Informed consent is a key element of ethical clinical research. Patients with serious mental illness may be at risk for impaired consent capacity. Corrective feedback improves within-session comprehension of consent-relevant information, but little is known about the trajectory of patients' comprehension after the initial enrolment session. AIMS: To examine whether within-session gains in understanding after feedback were maintained between study visits and to examine stability of decisional capacity over time. METHOD: This was a longitudinal, within-participants comparison of decisional capacity assessed at baseline, 1 week, 3 months, 12 months and 24 months in 161 people with schizophrenia or bipolar disorder. RESULTS: Within-session gains from corrective feedback generally dissipated over each follow-up interval. Decisional capacity showed a general pattern of stability, but there was significant between-participant heterogeneity. Better neuropsychological performance was associated with better decisional capacity across time points. Positive symptoms of schizophrenia did not predict any aspects of decisional capacity, but general psychopathology, negative symptoms and depression evidenced some modest associations with certain subdomains of decisional capacity. CONCLUSIONS: Informed consent may be most effectively construed as an ongoing dialogue with participants at each study visit.

Meta-analysis of the association between cognitive abilities and everyday functioning in bipolar disorder.

OBJECTIVES: Neurocognitive deficits are common in bipolar disorder and contribute to functional disability. However, the degree to which general and specific cognitive deficits affect everyday functioning in bipolar disorder is unknown. The goal of this meta-analysis was to examine the magnitude of the effect of specific neurocognitive abilities on everyday functioning in bipolar disorder. METHODS: We conducted a comprehensive meta-analysis of studies that reported associations between performance on objective neuropsychological tasks and everyday functioning among individuals with bipolar disorder. From an initial pool of 486 papers, 22 studies met inclusion criteria, comprising a total of 1344 participants. Correlation coefficients were calculated for 11 cognitive domains and four measurement modalities for functioning. We also examined effect moderators, such as sample age, clinical state, and study design. RESULTS: The mean Pearson correlation between neurocognitive ability and functioning was 0.27, and was significant for all cognitive domains and varied little by cognitive domain. Correlations varied by methods of everyday functioning assessment, being lower for clinician and self-report than performance-based tasks and real-world milestones such as employment. None of the moderator analyses were significant. CONCLUSIONS: Overall, the strength of association between cognitive ability and everyday functioning in bipolar disorder is strikingly similar to that seen in schizophrenia, with little evidence for differences across cognitive domains. The strength of association differed to a greater extent according to functional measurement approach.

Evaluation of specific executive functioning skills and the processes underlying executive control in schizophrenia.

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.

Short-term course of neuropsychological abilities in middle-aged and older adults with bipolar disorder.

OBJECTIVES: 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. METHODS: We administered a battery of neurocognitive tests, repeated 1-3 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. RESULTS: 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. CONCLUSIONS: 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.

Verbal fluency impairments among middle-aged and older outpatients with schizophrenia are characterized by deficient switching.

Patients with schizophrenia demonstrate impaired verbal fluency, but no studies have examined the underlying cognitive mechanisms (e.g., clustering and switching) associated with impaired fluency among middle-aged and older, non-institutionalized patients. Using Troyer et al.'s [Troyer, A.K., Moscovitch, M., Winocur, G., 1997. Clustering and switching as two components of verbal fluency: evidence from younger and older healthy adults. Neuropsychology 11 (1), 138-146] conceptual model, we examined clustering and switching on verbal fluency tasks among 163 middle-aged and older outpatients with schizophrenia and 92 age comparable healthy comparison (HC) participants. The patients produced significantly fewer total words than HC participants on both the letter ("F", "A", "S") and Animal fluency conditions. With regard to clustering, patients were similar to HC participants on both FAS and Animal fluency tasks. However, significantly fewer switches between lexical-semantic categories were observed among patients with schizophrenia on both conditions relative to HC participants. A small, but statistically significant association was found between number of switches on the Animal fluency task and severity of negative symptoms. The absence of a difference in mean cluster size between the patient and HC groups suggests intact lexical-semantic stores among middle-aged and older outpatients with schizophrenia. Differences in switching between patients and HC participants may be driven by several cognitive impairments associated with schizophrenia. Further delineation of the cognitive mechanisms of the observed lexical-semantic switching deficits in schizophrenia should be a focus of future research.

A prospective study of the trajectories of clinical insight, affective symptoms, and cognitive ability in bipolar disorder.

BACKGROUND: Clinical insight in bipolar disorder is associated with treatment adherence and psychosocial outcome. The short-term dynamics of clinical insight in relationship to symptoms and cognitive abilities are unknown. METHODS: In a prospective observational study, a total of 106 outpatients with bipolar disorder I or II were assessed at baseline, 6 weeks, 12 weeks, and 26 weeks. Participants were administered a comprehensive neuropsychological battery, clinical ratings of manic and depressive symptom severity, and self-reported clinical insight. Lagged correlations and linear mixed-effects models were used to determine the temporal associations between symptoms and insight, as well as the moderating influence of global cognitive abilities. RESULTS: At baseline, insight was modestly correlated with severity of manic symptoms, but not with depressive symptoms or cognitive abilities. Insight and depressive symptoms fluctuated to approximately the same extent over time. Both lagged correlations and mixed effects models with lagged effects indicated that the severity of manic symptoms predicted worse insight at later assessments, whereas the converse was not significant. There were no direct or moderating influences of global cognitive abilities. LIMITATIONS: Our sample size was modest, and included relatively psychiatrically stable outpatients, followed for a six month period. Our results may not generalize to acutely symptomatic patients followed over a longer period. CONCLUSIONS: Clinical insight varies substantially over time within patients with bipolar disorder. Impaired insight in bipolar disorder is more likely to follow than to precede manic symptoms.

Deficits in domains of social cognition in schizophrenia: a meta-analysis of the empirical evidence.

OBJECTIVE: Social cognition is strongly associated with functional outcome in schizophrenia, making it an important target for treatment. Our goal was to examine the average magnitude of differences between schizophrenia patients (SCs) and normal comparison (NCs) patients across multiple domains of social cognition recognized by the recent NIMH consensus statement: theory of mind (ToM), social perception, social knowledge, attributional bias, emotion perception, and emotion processing. METHOD: We conducted a meta-analysis of peer-reviewed studies of social cognition in schizophrenia, published between 1980 and November, 2011. RESULTS: 112 studies reporting results from 3908 SCs and 3570 NCs met our inclusion criteria. SCs performed worse than NCs across all domains, with large effects for social perception (g = 1.04), ToM (g = 0.96), emotion perception (g = 0.89), and emotion processing (g = 0.88). Regression analyses showed that statistically significant heterogeneity in effects within domains was not explained by age, education, or gender. Greater deficits in social and emotion perception were associated with inpatient status, and greater deficits in emotion processing were associated with longer illness duration. CONCLUSIONS: Despite the limitations of existing studies, including lack of standardization or psychometric validation of measures, the evidence for deficits across multiple social cognitive domains in schizophrenia is clear. Future research should examine the role of neurobiological and psychosocial factors in models linking various aspects of deficit in schizophrenia, including social cognition, in order to identify targets for intervention.

Characterizing trajectories of cognitive functioning in older adults with schizophrenia: does method matter?

BACKGROUND: Heterogeneity in clinical outcomes may be caused by factors working at multiple levels, e.g., between groups, between subjects, or within subjects over time. A more nuanced assessment of differences in variation among schizophrenia patients and between patients and healthy comparison subjects can clarify etiology and even facilitate the identification of patient subtypes with common neuropathology and clinical course. METHODS: We compared trajectories (mean duration of 3.5years) of cognitive impairments in a sample of 201 community-dwelling schizophrenia (SCZ) patients (aged 40-100years) with 67 healthy comparison (HC) subjects. We employed growth mixture models to discover subclasses with more homogenous between-subject variation in cognitive trajectories. Post hoc analyses determined factors associated with class membership and class-specific correlates of cognitive trajectories. RESULTS: Three latent classes were indicated: Class 1 (85% HC and 50% SCZ) exhibited relatively high and stable trajectories of cognition, Class 2 (15% HC and 40% SCZ) exhibited lower, modestly declining trajectories, and Class 3 (10% SCZ) exhibited lower, more rapidly declining trajectories. Within the patient group, membership in Classes 2-3 was associated with worse negative symptoms and living in a board and care facility. DISCUSSION: These results bridge the gap between schizophrenia studies demonstrating cognitive decline and those demonstrating stability. Moreover, a finer-grained characterization of heterogeneity in cognitive trajectories has practical implications for interventions and for case management of patients who show accelerated cognitive decline. Such a characterization requires study designs and analyses sensitive to between- and within-patient heterogeneity in outcomes.

Association between older age and more successful aging: critical role of resilience and depression.

OBJECTIVE: There is growing public health interest in understanding and promoting successful aging. While there has been some exciting empirical work on objective measures of physical health, relatively little published research combines physical, cognitive, and psychological assessments in large, randomly selected, community-based samples to assess self-rated successful aging. METHOD: In the Successful AGing Evaluation (SAGE) study, the authors used a structured multicohort design to assess successful aging in 1,006 community-dwelling adults in San Diego County, ages 50-99 years, with oversampling of people over 80. A modified version of random-digit dialing was used to recruit subjects. Evaluations included a 25-minute telephone interview followed by a comprehensive mail-in survey of physical, cognitive, and psychological domains, including positive psychological traits and self-rated successful aging, scaled from 1 (lowest) to 10 (highest). RESULTS: The mean age of the respondents was 77.3 years. Their mean self-rating of successful aging was 8.2, and older age was associated with a higher rating, despite worsening physical and cognitive functioning. The best multiple regression model achieved, using all the potential correlates, accounted for 30% of the variance in the score for self-rated successful aging and included resilience, depression, physical functioning, and age (entering the regression model in that order). CONCLUSIONS: Resilience and depression had significant associations with self-rated successful aging, with effects comparable in size to that for physical health. While no causality can be inferred from cross-sectional data, increasing resilience and reducing depression might have effects on successful aging as strong as that of reducing physical disability, suggesting an important role for psychiatry in promoting successful aging.

Dimensions of executive functioning in schizophrenia and their relationship with processing speed.

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.

Do people with schizophrenia have differential impairment in episodic memory and/or working memory relative to other cognitive abilities?

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. Thus, it may be useful to examine the presence of relative cognitive weaknesses on an intra-person 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.

Development and Pilot Testing of a Novel Compensatory Cognitive Training Intervention for People with Psychosis.

The cognitive deficits of schizophrenia have a profound impact on everyday functioning and level of community integration for affected individuals. Cognitive training (CT) interventions may help improve these impairments. We developed and pilot tested a 12-week, group based CT intervention that focused on compensatory strategies and habit learning. Participants were randomly assigned to CT plus standard pharmacotherapy or standard pharmacotherapy (SP) alone and were assessed at baseline, three months (i.e., post-intervention), and at six months. Effect sizes were calculated comparing change in the CT group with change in the SP group. CT had medium to large positive effects on attention, learning, memory, executive functioning, functional capacity, negative symptoms, and subjective quality of life. Most effects became stronger at follow-up, but the effect on negative symptoms was not maintained. Immediately post-treatment, compared with SP subjects, CT participants reported fewer cognitive problems and greater use of cognitive strategies; many of these effects were maintained, but were generally weaker, at six-month follow-up. The initial effect sizes for this compensatory CT intervention suggest that it holds promise for improving cognitive performance, functional capacity, negative symptoms, and quality of life. It is proposed that CT emphasizing habit learning may result in long term changes in ability to function independently in the community.

The association of specific neuropsychological deficits with capacity to consent to research or treatment.

Informed consent is key to ethical clinical research and treatment, but partially rests on the ability of individual patients or research participants to use disclosed information to make a meaningful choice. Although the construct of decisional capacity emerged from legal and philosophical traditions, several investigators have begun examining the relationship of specific neuropsychological abilities to decisional capacity. This line of research may foster development of better consent procedures, as well as aid in refining the construct of decisional capacity toward a form that better reflects the underlying neurocognitive processes. We conducted a systematic search of the published literature and thereby identified and reviewed 16 published reports of empirical studies that examined the relationship between specific neuropsychological abilities and capacity to consent to research or treatment. Significant relationships between neuropsychological scores and decisional capacity were present across all the reviewed studies. The degree to which specific neuropsychological abilities have particular relevance to decisional capacity remains uncertain, but the existing studies provide a solid basis for a priori hypotheses for future investigations. These ongoing efforts represent an important conceptual and empirical bridge between bioethical, legal, and neuropsychological approaches to understanding meaningful decision-making processes.