Common and specific cognitive deficits in schizophrenia: relationships to function.

The goals of the present study were to assess the interrelationships among tasks from the MATRICS and CNTRACS batteries, to determine the degree to which tasks from each battery capture unique variance in cognitive dysfunction in schizophrenia, and to determine the ability of tasks from each battery to predict functional outcome. Subjects were 104 schizophrenia patients and 132 healthy control subjects recruited as part of the CNTRACS initiative. All subjects completed four CNTRACS tasks and two tasks from the MATRICS battery: Brief Assessment of Cognition in Schizophrenia Symbol Coding and the Hopkins Verbal Learning Test. Functional outcome was also assessed in the schizophrenia subjects. In both the patient and control groups, we found significant intercorrelations between all higher order cognitive tasks (episodic memory, goal maintenance, processing speed, verbal learning) but minimal relationships with the visual task. For almost all tasks, scores were significantly related to measures of functional outcome, with higher associations between CNTRACS tasks and performance-based measures of function and between one of the MATRICS tasks and self-reported functioning, relative to the other functioning measures. After regressing out variance shared by other tasks, we continued to observe group differences in performance among task residuals, particularly for measures of episodic memory from both batteries, although these residuals did not correlate as robustly with functional outcome as raw test scores. These findings suggest that there exists both shared and specific variance across cognitive tasks related to cognitive and functional impairments in schizophrenia and that measures derived from cognitive neuroscience can predict functional capacity and status in schizophrenia.

The spatial range of contour integration deficits in schizophrenia.

Contour integration (CI) refers to the process that represents spatially separated elements as a unified edge or closed shape. Schizophrenia is a psychiatric disorder characterized by symptoms such as hallucinations, delusions, disorganized thinking, inappropriate affect, and social withdrawal. Persons with schizophrenia are impaired at CI, but the specific mechanisms underlying the deficit are still not clear. Here, we explored the hypothesis that poor patient performance owes to reduced feedback or impaired longer-range lateral connectivity within early visual cortex--functionally similar to that found in 5- to 6-year old children. This hypothesis predicts that as target element spacing increases from .7 to 1.4° of visual angle, patient impairments will become more pronounced. As a test of the prediction, 25 healthy controls and 36 clinically stable, asymptomatic persons with schizophrenia completed a CI task that involved determining whether a subset of Gabor elements formed a leftward or rightward pointing shape. Adjacent shape elements were spaced at either .7 or 1.4° of visual angle. Difficulty in each spacing condition depended on the number of noise elements present. Patients performed worse than controls overall, both groups performed worse with the larger spacing, and the magnitude of the between-group difference was not amplified at the larger spacing. These results show that CI deficits in schizophrenia cannot be explained in terms of a reduced spatial range of integration, at least not when the shape elements are spaced within 1.5°. Later-developing, low-level integrative mechanisms of lateral connectivity and feedback appear not to be differentially impaired in the illness.

Neuropathological associates of multiple cognitive functions in two community-based cohorts of older adults.

Studies of neuropathology-cognition associations are not common and have been limited by small sample sizes, long intervals between autopsy and cognitive testing, and lack of breadth of neuropathology and cognition variables. This study examined domain-specific effects of common neuropathologies on cognition using data (N = 652) from two large cohort studies of older adults. We first identified dimensions of a battery of 17 neuropsychological tests, and regional measures of Alzheimer's disease (AD) neuropathology. We then evaluated how cognitive factors were related to dimensions of AD and additional measures of cerebrovascular and Lewy Body disease, and also examined independent effects of brain weight. All cognitive domains had multiple neuropathology determinants that differed by domain. Neocortical neurofibrillary tangles were the strongest predictors of most domains, while medial temporal tangles showed a weaker relationship with episodic memory. Neuritic plaques had relatively strong effects on multiple domains. Lewy bodies and macroscopic infarcts were associated with all domains, while microscopic infarcts had more limited associations. Brain weight was related to all domains independent of specific neuropathologies. Results show that cognition is complexly determined by multiple disease substrates. Neuropathological variables and brain weight contributed approximately a third to half of the explained variance in different cognitive domains.

Latent Profiles of Cognitive Control, Episodic Memory, and Visual Perception Across Psychiatric Disorders Reveal a Dimensional Structure.

Although meta-analyses suggest that schizophrenia (SZ) is associated with a more severe neurocognitive phenotype than mood disorders such as bipolar disorder, considerable between-subject heterogeneity exists in the phenotypic presentation of these deficits across mental illnesses. Indeed, it is unclear whether the processes that underlie cognitive dysfunction in these disorders are unique to each disease or represent a common neurobiological process that varies in severity. Here we used latent profile analysis (LPA) across 3 distinct cognitive domains (cognitive control, episodic memory, and visual integration; using data from the CNTRACS consortium) to identify distinct profiles of patients across psychotic illnesses. LPA was performed on a sample of 223 psychosis patients (59 with Type I bipolar disorder, 88 with SZ, and 76 with schizoaffective disorder). Seventy-three healthy control participants were included for comparison but were not included in sample LPA. Three latent profiles ("Low," "Moderate," and "High" ability) were identified as the underlying covariance across the 3 domains. The 3-profile solution provided highly similar fit to a single continuous factor extracted by confirmatory factor analysis, supporting a unidimensional structure. Diagnostic ratios did not significantly differ between profiles, suggesting that these profiles cross diagnostic boundaries (an exception being the Low ability profile, which had only one bipolar patient). Profile membership predicted Brief Psychiatric Rating Scale and Young Mania Rating Scale symptom severity as well as everyday communication skills independent of diagnosis. Biological, clinical and methodological implications of these findings are discussed.

Construct validity: advances in theory and methodology.

Measures of psychological constructs are validated by testing whether they relate to measures of other constructs as specified by theory. Each test of relations between measures reflects on the validity of both the measures and the theory driving the test. Construct validation concerns the simultaneous process of measure and theory validation. In this article, we review the recent history of validation efforts in clinical psychological science that has led to this perspective, and we review the following recent advances in validation theory and methodology of importance for clinical researchers. These are: the emergence of nonjustificationist philosophy of science; an increasing appreciation for theory and the need for informative tests of construct validity; valid construct representation in experimental psychopathology; the need to avoid representing multidimensional constructs with a single score; and the emergence of effective new statistical tools for the evaluation of convergent and discriminant validity.

Cross-diagnostic analysis of cognitive control in mental illness: Insights from the CNTRACS consortium.

BACKGROUND: In recent years, psychiatry research has increasingly focused on understanding mental illnesses from a cross-diagnostic, dimensional perspective in order to better align their neurocognitive features with underlying neurobiological mechanisms. In this multi-site study, we examined two measures of cognitive control (d-prime context and lapsing rate) during the Dot Probe Expectancy (DPX) version of the AX-Continuous Performance Task in patients with either schizophrenia (SZ), schizoaffective disorder (SZ-A), or Type I bipolar disorder (BD) as well as healthy control (HC) subjects. We hypothesized significantly lower d-prime context and higher lapsing rate in SZ and SZ-A patients and intermediate levels in BD patients relative to HC. METHODS: 72 HC, 84 SZ, 77 SZ-A, and 58 BD patients (ages 18-56) were included in the final study sample. RESULTS: Significant main effects of diagnosis were observed on d-prime context (F(3,279) = 9.59, p < 0.001) and lapsing (F(3,279) = 8.08, p < 0.001). A priori linear contrasts suggesting intermediate dysfunction in BD patients were significant (p < 0.001), although post-hoc tests showed the BD group was only significantly different from HC on d-prime context. Group results for d-prime context remained significant after covarying for lapsing rate. Primary behavioral measures were associated with mania and disorganization symptoms as well as everyday functioning. CONCLUSIONS: These findings suggest a continuum of dysfunction in cognitive control (particularly d-prime context) across diagnostic categories in psychiatric illness. These results further suggest that lapsing and d-prime context, while related, make unique contributions towards explaining deficits in cognitive control in these disorders.

Working Memory Impairment Across Psychotic disorders.

BACKGROUND: Working memory (WM) has been a central focus of cognitive neuroscience research because WM is a resource that is involved in many different cognitive operations. The goal of this study was to evaluate the clinical utility of WM paradigms developed in the basic cognitive neuroscience literature, including methods designed to estimate storage capacity without contamination by lapses of attention. METHODS: A total of 61 people with schizophrenia, 49 with schizoaffective disorder, 47 with bipolar disorder with psychosis, and 59 healthy volunteers were recruited. Participants received multiple WM tasks, including two versions each of a multiple Change Detection paradigm, a visual Change Localization paradigm, and a Running Span task. RESULTS: Healthy volunteers performed better than the combined patient group on the visual Change Localization and running span measures. The multiple Change Detection tasks provided mixed evidence about WM capacity reduction in the patient groups, but a mathematical model of performance suggested that the patient groups differed from controls in their rate of attention lapsing. The 3 patient groups performed similarly on the WM tasks. Capacity estimates from the Change Detection and Localization tasks showed significant correlations with functional capacity and functional outcome. CONCLUSIONS: The patient groups generally performed in a similarly impaired fashion across tasks, suggesting that WM impairment and attention lapsing are general features of psychotic disorders. Capacity estimates from the Change Localization and Detection tasks were related to functional capacity and outcome, suggesting that these methods may be useful in a clinical context.

Self versus informant reports on the specific levels of functioning scale: Relationships to depression and cognition in schizophrenia and schizoaffective disorder.

The goal of the current study was to examine the relationships between insight and both cognitive function and depression in schizophrenia and schizoaffective disorder, and to determine if there were similar relationships across diagnostic categories. We examined discrepancies between self and informant reports of function on the Specific levels of function scale as a metric of insight for interpersonal, social acceptance, work and activities. We examined two samples of individuals with schizophrenia and/or schizoaffective disorder (Ns of 188 and 67 respectively). In Sample 1, cognition was measured using the Dot Probe Expectancy Task. In Sample 2, cognition was measured by averaging several subtests from the MATRICS consensus cognitive battery, as well as additional measures of working memory. In both samples, depression was measured using the Brief Psychiatric Rating Scale. In both samples, we found significant relationships between worse cognition and overestimations of work function, as well as between higher depression levels and underestimation of interpersonal function. These relationships were specific to interpersonal and work function, with significantly stronger correlations with interpersonal and work function compared to the other areas of function. Similar results were found across diagnostic categories. These results have important implications for treatment planning, as they suggest the need to take into account depression and cognitive function when evaluating the patient's self-report of function, and highlight the utility of informant reports in evaluating function and treatment planning. Further, they add to the literature on the similarity across schizophrenia and schizoaffective disorder in a variety of pathological mechanisms.

Explicit and implicit reinforcement learning across the psychosis spectrum.

Motivational and hedonic impairments are core features of a variety of types of psychopathology. An important aspect of motivational function is reinforcement learning (RL), including implicit (i.e., outside of conscious awareness) and explicit (i.e., including explicit representations about potential reward associations) learning, as well as both positive reinforcement (learning about actions that lead to reward) and punishment (learning to avoid actions that lead to loss). Here we present data from paradigms designed to assess both positive and negative components of both implicit and explicit RL, examine performance on each of these tasks among individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis, and examine their relative relationships to specific symptom domains transdiagnostically. None of the diagnostic groups differed significantly from controls on the implicit RL tasks in either bias toward a rewarded response or bias away from a punished response. However, on the explicit RL task, both the individuals with schizophrenia and schizoaffective disorder performed significantly worse than controls, but the individuals with bipolar did not. Worse performance on the explicit RL task, but not the implicit RL task, was related to worse motivation and pleasure symptoms across all diagnostic categories. Performance on explicit RL, but not implicit RL, was related to working memory, which accounted for some of the diagnostic group differences. However, working memory did not account for the relationship of explicit RL to motivation and pleasure symptoms. These findings suggest transdiagnostic relationships across the spectrum of psychotic disorders between motivation and pleasure impairments and explicit RL. (PsycINFO Database Record

The cognitive origins of specific types of schizophrenic speech disturbances.

OBJECTIVE: Cognitive impairments associated with schizophrenia might be expected to have a marked impact on the ability to produce coherent speech, yet associations between cognitive performance and speech disorder have typically been weak. Findings on this question may have been limited by measurement methods and by the heterogeneity of speech disorder. This study examined the contributions of impairments in sustained attention and sequencing abilities to schizophrenic speech disorder, measured in terms of communication failures and divided into different types of disorder. METHOD: Samples of natural speech were collected from severely ill inpatients with schizophrenia and nonpsychiatric comparison subjects and rated for frequencies of six types of communication failures: four structural and two nonstructural types. Subjects also completed a battery of cognitive tests assessing several facets of attention and sequencing ability. Hierarchical regression was used to identify cognitive contributors to communication failures. RESULTS: Impaired sustained attention was associated with more frequent structural and nonstructural communication failures. As predicted, impaired sequencing, and in particular conceptual sequencing, also made a substantial contribution to the structural communication failures, but not to the nonstructural ones. These findings held when global level of impairment was controlled statistically. Performance on the tests of attention and sequencing explained 56% of the variance in structural speech disorder. CONCLUSIONS: Schizophrenic speech disorder is heterogeneous in form and in cognitive underpinnings. Impairments in attention and sequencing abilities are highly predictive of communication failures related to language structure.

Integrating the switching, inhibition, and updating model of executive function with the Cattell-Horn-Carroll model.

Executive function is an important concept in neuropsychological and cognitive research, and is often viewed as central to effective clinical assessment of cognition. However, the construct validity of executive function tests is controversial. The switching, inhibition, and updating model is the most empirically supported and replicated factor model of executive function (Miyake et al., 2000). To evaluate the relation between executive function constructs and nonexplicitly executive cognitive constructs, we used confirmatory factor reanalysis guided by the comprehensive Cattell-Horn-Carroll (CHC) model of cognitive abilities. Data from 7 of the best studies supporting the executive function model were reanalyzed, contrasting executive function models and CHC models. Where possible, we examined the effect of specifying executive function factors in addition to the CHC factors. The results suggested that little evidence is available to support updating as a separate factor from general memory factors; that inhibition does not separate from general speed; and that switching is supported as a narrow factor under general speed, but with a more restricted definition than some clinicians and researchers have conceptualized. The replicated executive function factor structure was integrated with the larger body of research on individual difference in cognition, as represented by the CHC model.

Associations between dementia/mild cognitive impairment and cognitive performance and activity levels in youth.

OBJECTIVES: To study the associations between dementia/mild cognitive impairment (MCI) and cognitive performance and activity levels in youth. DESIGN: Retrospective cohort study. SETTING: Research volunteers living throughout the United States. PARTICIPANTS: A total of 396 persons (mean age 75) who were graduates of the same high school in the mid-1940s. MEASUREMENTS: Adolescent intelligence quotient (IQ) scores were gathered from archived student records, and activity levels were determined from yearbooks. A two-stage telephone screening procedure (Modified Telephone Interview for Cognitive Status or Informant Questionnaire on Cognitive Decline in the Elderly followed by Dementia Questionnaire) was used to determine adult cognitive status. Data were analyzed using logistic regression to model the risk of cognitive impairment (dementia/MCI) versus no cognitive impairment as a function of IQ and activity level, adjusting for sex and education. RESULTS: High adolescent IQ and greater activity level were each independently associated with a lower risk for dementia/MCI (odds ratio (OR) for a 1-standard deviation increase in IQ=0.51, 95% confidence interval (CI)=0.32-0.79; OR for a unit increase in activity=0.32, 95% CI=0.12-0.84). No association was found between sex or education and adult cognitive status in this model. CONCLUSION: High IQ and greater activity levels in youth reduce the risk for cognitive impairments in aging. The mechanism(s) underlying these associations are unknown, but intelligence may be a marker for cognitive/neurological "reserve," and involvement in activities may contribute to "reserve." Early neuropathology and ascertainment bias are also possible explanations for the observed associations.

Gender identity and implications for recovery among men and women with schizophrenia.

The concept of gender considers masculinity and femininity as a cultural construct that varies along a continuum. Subjectively perceived, gender may affect the experience of illness among persons with schizophrenia and may have an impact on treatment and recovery. This study evaluated gender identity, according to the Bem Sex Role Inventory, among 90 men and women with schizophrenia and schizoaffective disorders. The findings indicate that persons with schizophrenia experience their gender identity in ways that vary from culturally normative standards. Both men and women scored lower on traditional masculine descriptive measures compared with persons without schizophrenia. This finding has important implications for recovery.

Subjective experience of recovery from schizophrenia-related disorders and atypical antipsychotics.

AIMS: This article investigates the subjective experience of the process of improvement and recovery from the point of view of persons diagnosed (according to research diagnostic criteria) with schizophrenia and schizo-affective disorders. METHODS: A community study of persons using psychiatric services was conducted for a sample of ninety subjects taking atypical antipsychotic medications. Sociodemographic data and clinical ratings were collected to complement the qualitatively developed Subjective Experience of Medication Interview (SEMI), which elicits narrative data on everyday activities, medication and treatment, management of symptoms, expectations concerning recovery, stigma, and quality of life. RESULTS: Recovery was observed through: (1) relatively low ratings of psychiatrically observed symptomatology through BPRS scores; (2) the subjective sense among the majority (77.4%) of participants that taking medication plays a critical role in managing symptoms and avoiding hospitalization; and (3) the subjective sense articulated by the vast majority (80%) that they would recover from their illness and that the quality of their lives would improve (70.6%). CONCLUSION: The overall quality of improvement and recovery is best characterized as an incremental, yet definitively discernable, subjective process.

Evaluation of a model of attention with confirmatory factor analysis.

Structural equation modeling (specifically, analysis of moment structures; J. L. Arbuckle, 1996) was used to evaluate the goodness of fit of a model of components of attention (A. F. Mirsky, B. J. Anthony, C. C. Duncan, M. B. Aheam, & S. G. Kellam, 1991) to neuropsychological test data from 2 samples. One sample consisted of psychiatrically normal persons with and without sleep-disordered breathing, and the other sample consisted of the adults studied by A. F. Mirsky et al. (1991), who gave rise to this model. That sample included psychiatric patients as well as normals. An exploratory data reduction procedure, principal-components analysis, suggested that attention might be conceptualized as composed of 4 independent elements or components: focus-execute, sustain, shift, and encode. Neither the proposed orthogonal model nor a model permitting correlated factors adequately fit either data set, suggesting that these 4 attention constructs are as yet not clearly validated in the measures used to assess them.

Comparison of inpatients with major mental illness who do and do not consent to low-risk research.

The generalizability of research data depends on the degree to which the studied sample represents the larger population of interest. By influencing the likelihood of research participation, socio-demographic and clinical factors could bias a sample. To evaluate this, we retrospectively identified 155 consecutive admissions over an 18-month period to a general acute male psychiatry inpatient unit in a Veterans Affairs Hospital on which all competent patients were offered the opportunity to participate in low-risk clinical research. Male inpatients who did (N=70) and did not consent (N=85) were compared on 17 variables. Patients who consented to research were somewhat younger (M(difference)=4.6 year) and were significantly more likely to carry a diagnosis of schizophrenia. The groups did not differ in financial resources, living situation or alcohol/drug abuse. We conclude that at least in this setting, general socio-demographic and clinical variables were not major influences on sample selection.

Executive Functions in Persons with Sleep Apnea.

Seventeen patients with sleep apnea syndrome [SAS, Respiratory Disturbance Index (RDI) = 12-85] were compared with 16 normal controls (RDI < 7) on neuropsychological tests of executive functions, a domain in which SAS patients have been suggested to have deficits. SAS patients demonstrated greater deficits in the retrieval of information from semantic memory (Controlled Oral Word Association task) and in shifting responses in the face of error (Wisconsin Card Sort Test), but differences in working memory were not observed. Eliciting deficits in cognitive executive functions in SAS may require more sensitive measures than are typically used in neuropsychiatric research.

Temporal stability and moderating effects of age and sex on CNTRaCS task performance.

Research in schizophrenia has increasingly focused on incorporating measures from cognitive neuroscience, but little is known about their psychometric characteristics. Here, we extend prior research by reporting on temporal stability, as well as age and sex effects, for cognitive neuroscience paradigms optimized as part of the Cognitive Neuroscience Test Reliability and Clinical applications for Schizophrenia consortium. Ninety-nine outpatients with schizophrenia and 131 healthy controls performed 5 tasks assessing 4 constructs at 3 sessions. The constructs were (1) Goal maintenance (Dot Probe Expectancy [DPX] and AX continuous performance tasks [AX-CPT]); (2) Episodic memory (Relational and Item-Specific Encoding and Retrieval task [RiSE]); (3) Visual integration (Jittered Orientation Visual Integration task [JOVI]); and (4) Perceptual gain control (Contrast-Contrast Effect Task [CCE]). Patients performed worse than controls on all but the CCE, and the magnitude of these group differences was stable across sessions, with no sex differences observed. Improvements over sessions were seen for the AX-CPT, the DPX, and the JOVI though practice effects for the AX-CPT and the DPX were primarily present in older participants. For the AX-CPT and the JOVI, practice effects were larger for T1 to T2 than for T2 to T3. Age was associated with poor associative recognition on the RiSE and accuracy on the JOVI. Test-rest reliability ranged from poor for the JOVI threshold score to adequate to good for the DPX, AX-CPT, and JOVI accuracy measures, with RiSE and CCE measures in the moderate range. These results suggest that group differences in DPX, AX-CPT, RiSE, and JOVI are robust and consistent across repeated testing.

Optimization of a goal maintenance task for use in clinical applications.

BACKGROUND: We sought to develop a Dot Pattern Expectancy task (DPX) to assess goal maintenance for use in clinical trials. Altering the standard task created 5 versions of the DPX to compare-a standard version and 4 others. Alterations in the interstimulus interval (ISI) length and the strength of a learned prepotent response distinguished the different tasks. These adjustments were designed to decrease administration time and/or improve reliability of the data. METHODS: We determined participant eligibility in an initial session (the first of 3) using clinical interviewing tools. The initial session also included a demographic assessment and assessments of community functioning and symptom severity. All versions of the DPX were administered, across 3 sessions. Specific deficits on the context processing compared with difficulty control condition were evaluated using mixed-effects logistic regression within a hierarchical linear model. RESULTS: We analyzed the data from 136 control participants and 138 participants with schizophrenia. Relative to a difficulty control condition, patients performed worse than controls on context processing conditions that required goal maintenance. ISI did not predict errors. Stronger prepotency was associated with increased errors in the difficulty control relative to context processing condition for controls, which improved the interpretability of findings for patients. Reliability was acceptable for a version of the task with a 10-minute running time. CONCLUSIONS: The best compromise between task duration and interpretability occurred on a version with a short ISI and a strong prepotency.

Optimization and validation of a visual integration test for schizophrenia research.

The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative highlighted a contour integration test as a promising index of visual integration impairment because of its well-established psychometric properties; its prior validation in healthy adults, patients, and nonhuman primates; and its potential sensitivity to treatment effects. In this multisite study, our goals were to validate the task on the largest subject sample to date, clarify the task conditions and number of trials that best discriminate patients from controls, and determine whether this discrimination can occur in standard clinical trial settings. For our task, subjects briefly observed a field of disconnected, oriented elements and attempted to decide whether a subset of those elements formed a leftward- or rightward-pointing shape. Difficulty depended on the amount of orientational jitter that was added to the shape's elements. Two versions of this Jittered Orientation Visual Integration task (JOVI) were examined. Study 1 did not reveal between-group differences in threshold (ie, the jitter magnitude needed to reach a performance level of ∼80%), but this likely owed to the wide sampling distribution of jitter levels and resulting floor/ceiling effects in many conditions. Study 2 incorporated a narrower range of difficulty levels and revealed lower thresholds (worse performance) among patients (p < .001). This group difference remained even when only the first half of the trials was analyzed (p = .001). Thus, the JOVI-2 provides a brief, sensitive measure of visual integration deficits in schizophrenia. Neural implications and potential future applications of the JOVI are discussed.