Christopher R. Bowie

Predicting schizophrenia patients' real-world behavior with specific neuropsychological and functional capacity measures.

BACKGROUND Significant neuropsychological (NP) and functional deficits are found in most schizophrenia patients. Previous studies have left questions as to whether global NP impairment or discrete domains affect functional outcomes, and none have addressed distinctions within and between ability and performance domains. This study examined the different predictive relationships between NP domains, functional competence, social competence, symptoms, and real-world behavior in domains of work skills, interpersonal relationships, and community activities. METHODS Two hundred twenty-two schizophrenic outpatients were tested with an NP battery and performance-based measures of functional and social competence and rated for positive, negative, and depressive symptoms. Case managers generated ratings of three functional disability domains. RESULTS Four cognitive factors were derived from factor analysis. Path analyses revealed both direct and mediated effects of NP on real-world outcomes. All NP domains predicted functional competence, but only processing speed and attention/working memory predicted social competence. Both competence measures mediated the effects of NP on community activities and work skills, but only social competence predicted interpersonal behaviors. The attention/working memory domain was directly related to work skills, executive functions had a direct effect on interpersonal behaviors, and processing speed had direct effects on all three real-world behaviors. Symptoms were directly related to outcomes, with fewer relationships with competence. CONCLUSIONS Differential predictors of functional competence and performance were found from discrete NP domains. Separating competence and performance provides a more precise perspective on correlates of disability. Changes in specific NP or functional skills might improve specific outcomes, rather than promoting global functional improvement.

Administration and interpretation of the Trail Making Test.

Measurement of cognitive functions is an increasingly important goal for clinicians and researchers. Many neuropsychological test batteries are comprehensive and require specialized training to administer and interpret. The Trail Making Test is an accessible neuropsychological instrument that provides the examiner with information on a wide range of cognitive skills and can be completed in 5–10 min. Its background, psychometric properties, administration procedures and interpretive guidelines are provided in this protocol.

The expert consensus guideline series

Abstract Over the past decade, many new epilepsy treatments have been approved in the United States, promising better quality of life for many with epilepsy. However, clinicians must now choose among a growing number of treatment options and possible combinations. Randomized clinical trials (RCTs) form the basis for evidence-based decision making about best treatment options, but they rarely compare active therapies, making decisions difficult. When medical literature is lacking, expert opinion is helpful, but may contain potential biases. The expert consensus method is a new approach for statistically analyzing pooled opinion to minimize biases inherent in other systems of summarizing expert opinion. We used this method to analyze expert opinion on treatment of three epilepsy syndromes (idiopathic generalized epilepsy, symptomatic localization-related epilepsy, and symptomatic generalized epilepsy) and status epilepticus. For all three syndromes, the experts recommended the same general treatment strategy. As a first step, they recommend monotherapy. If this fails, a second monotherapy should be tried. Following this, the experts are split between additional trials of monotherapy and a combination of two therapies. If this fails, most agree the next step should be additional trials of two therapies, with less agreement as to the next best step after this. One exception to these recommendations is that the experts recommend an evaluation for epilepsy surgery after the third failed step for symptomatic localization-related epilepsies. The results of the expert survey were used to develop user-friendly treatment guidelines concerning overall treatment strategies and choice of specific medications for different syndromes and for status epilepticus.

Prediction of Real World Functional Disability in Chronic Mental Disorders: A Comparison of Schizophrenia and Bipolar Disorder

OBJECTIVE Schizophrenia and bipolar disorder are associated with multidimensional disability. This study examined differential predictors of functional deficits in the two disorders. METHOD Community-dwelling individuals with schizophrenia (N=161) or bipolar disorder (N=130) were assessed with neuropsychological tests, symptom measures, and performance-based social and adaptive (i.e., everyday living skills) functional competence measures as well as three domains of real-world functioning: community and household activities; work skills; and interpersonal relationships. The authors used confirmatory path analysis to find the best-fitting models to examine the direct and indirect (as mediated by competence) prediction of the three domains of real-world functioning. RESULTS In all models for both groups, neurocognitions relationship with outcomes was largely mediated by competence. Symptoms were negatively associated with outcomes but unassociated with competence, with the exception of depression, which was a direct and mediated (through social competence) predictor in bipolar disorder. In both groups, neurocognition was related to activities directly and through a mediated relationship with adaptive competence. Work skills were directly and indirectly (through mediation with social competence) predicted by neurocognition in schizophrenia and entirely mediated by adaptive and social competence in bipolar disorder. Neurocognition was associated with interpersonal relationships directly in the schizophrenia group and mediated by social competence in both groups. CONCLUSIONS Although there was greater disability in schizophrenia, neurocognition predicted worse functioning in all outcome domains in both disorders. These results support the shared role of neurocognition in bipolar disorder and schizophrenia in producing disability, with predictive differences between disorders in domain-specific effects of symptoms and social and adaptive competence.

Combined Cognitive Remediation and Functional Skills Training for Schizophrenia: Effects on Cognition, Functional Competence, and Real-World Behavior

OBJECTIVE Cognitive remediation is an efficacious treatment for schizophrenia and, when used within broader psychosocial treatments, improves transfer to real-world behavior change. The authors examined whether cognitive remediation effectively generalizes to functional competence and real-world functioning as a standalone treatment and when combined with a functional skills treatment. METHOD Outpatients with schizophrenia (N=107) were randomly assigned to receive cognitive remediation, functional adaptation skills training, or combined treatment, with cognitive remediation preceding functional skills training. Clinical symptoms, neurocognition, social competence, functional competence, and case-manager-rated real-world behavior were assessed at baseline, at end of treatment, and at a 12-week durability assessment. RESULTS Neurocognition improved, with durable effects, after cognitive remediation but not after functional skills training. Social competence improved both with functional skills training and with combined treatment but not with cognitive remediation alone. Improvements in functional competence were greater and more durable with combined treatment. Cognitive remediation alone did not produce significant improvements in real-world behavior, but when combined with functional skills training, statistically significant improvements from baseline to end of treatment and follow-up were observed in community or household activities and work skills. Number-needed-to-treat analyses suggest that as few as three cases are required for treatment to induce a meaningful improvement in functional skills. CONCLUSIONS In a short intervention, cognitive remediation produced robust improvements in neurocognition. Generalization to functional competence and real-world behavior was more likely when supplemental skills training and cognitive remediation were combined.

Determinants of everyday outcomes in schizophrenia: The influences of cognitive impairment, functional capacity, and symptoms

Deficits in everyday living skills and social skills are associated with the pervasive disability seen in schizophrenia. Cognitive impairments are determinants of these skills deficits and it is known that positive and negative symptoms add to the influence of cognitive impairments for prediction of real-world outcomes. This study examined the relative importance of cognitive impairments measured with a neuropsychological battery, performance-based measures of social and everyday living skills, and positive and negative symptoms for the prediction of real-world outcomes in social and residential domains. In contrast to most previous studies, we examined the importance of individual symptoms, as well as total subscale scores, for predicting clinician rated outcomes in 194 older outpatients with schizophrenia. Symptoms were rated with the Positive and Negative Syndrome Scale; everyday living skills were measured by the UCSD Performance-based Skills Assessment; and social skills were measured with the Social Skills Performance Assessment. For prediction of real-world social outcomes, blunted affect and passive-apathetic social withdrawal accounted for all of the predicted variance, while social competence and cognitive impairments did not enter the final equation. For residential functioning, everyday living skills were the most important predictor, followed by lack of spontaneity. The positive symptoms of hallucinatory behavior and suspiciousness also predicted real-world residential outcomes. These results suggest that real-world disability is the product of a complex array of ability deficits and symptoms, indicating interventions will need to be carefully targeted. For social and everyday living outcomes, variance accounted for by the entire array of predictive variables was less than 40%, suggesting that other factors, such as social and cultural influences, are involved as well.

Meta-Analysis of the Association Between Cognitive Abilities and Everyday Functioning in Bipolar Disorder

Depp CA, Mausbach BT, Harmell AL, Savla GN, Bowie CR, Harvey PD, Patterson TL. Meta‐analysis of the association between cognitive abilities and everyday functioning in bipolar disorder. Bipolar Disord 2012: 14: 217–226.

Correlations of functional capacity and neuropsychological performance in older patients with schizophrenia: evidence for specificity of relationships?

BACKGROUND Neuropsychological (NP) performance is a consistent correlate of everyday functioning in schizophrenia, but it is unclear whether relationships between individual NP ability areas and domains of everyday functioning are general or specific. Assessments of real-world everyday functioning may be influenced by environmental and social factors (e.g., social security, disability status, opportunities and restrictions in living situations). This study examined the specificity of the relationships between different NP abilities and performance-based measures of social and living skills. METHODS 181 ambulatory older (age>50) patients with schizophrenia were examined with NP tests measuring episodic and working memory, executive functioning, verbal fluency, and processing speed. All subjects performed tasks examining social (Social Skills Performance Assessment: SSPA) and everyday living (UCSD Performance Based Skills Assessment: UPSA) skills. RESULTS Using canonical analysis, the NP variables were used to predict the functional capacity measures. The analysis found that 37% of the variance in the functional capacity and NP measures was shared, X(2) (54)=106.29, p<.001. Two canonical roots described the cognitive variables and the roots were differentially associated with everyday living and social skills. The root loading on processing speed, episodic memory, and executive functions were associated with UPSA scores, while the root loading on working and episodic memory and verbal fluency were associated most strongly with social competence. IMPLICATIONS Social and everyday living skills deficits in patients with schizophrenia may reflect generally independent domains of functional outcome, linked through cognitive performance. The data suggest that somewhat different cognitive processes are associated with these two domains of functional capacity, although there appears to be some overlap, which may be due to the nature of the NP tests employed.

Neurocognition: clinical and functional outcomes in schizophrenia.

Schizophrenia is characterized by significant heterogeneity in outcome. The last decades have witnessed a significant interest in identifying factors that can moderate or influence clinical and functional outcomes in people with schizophrenia. One factor of particular interest is neurocognition, as performance on various measures of cognitive abilities, such as memory, attention, and executive functions, have been consistently related to functional outcome and, to a lesser extent, clinical outcome. This review aims to provide an up-to-date description of recent studies examining the association between neurocognition and clinical and (or) functional outcomes. In the first section, studies examining neurocognitive performance in relation to clinical outcome are examined. When clinical outcome is defined dichotomously (for example, comparing remitted and nonremitted), verbal memory performance consistently exhibits a strong association with clinical status, with the poor outcome group showing the largest deficits. In the second section, studies exploring the relation between neurocognition and various dimensions of functional outcome are reviewed. These dimensions include independent living, social functioning, and vocational functioning, among others. Again, a strong link between neurocognitive deficits and impairments in several aspects of functioning clearly emerges from this review. Finally, several measurement issues are discussed that pertain to the need to standardize definitions of clinical and (or) functional outcomes, the importance of defining cognitive domains consistently across studies, and distinguishing between ones competence to perform tasks and what one actually does in everyday life. Addressing these measurement issues will be key to studies examining the development of effective interventions targeting neurocognitive functions and their impact on clinical and functional outcomes.

Functional implications of neuropsychological normality and symptom remission in older outpatients diagnosed with schizophrenia: A cross-sectional study

Cognitive impairments in schizophrenia are well documented and correlated with functional disability. Although some patients demonstrate normal neuropsychological (NP) functioning, little is known about their functional disability. We examined the cross-sectional functional implications of NP normality and symptomatic remission in older outpatients diagnosed with schizophrenia or schizoaffective disorder, who were administered a NP battery and performance-based measures of functional and social competence, with their real-world functioning rated by case managers. NP status was classified by the General Deficit Score (GDS) and remission status was based on the Positive and Negative Syndrome Scale (PANSS), yielding four subsamples of patients: NP normal-remitted (n = 21), NP normal-symptomatic (n = 22), NP impaired-remitted (n = 90), and NP impaired-symptomatic (n = 97). NP normal patients demonstrated better functional and social competence and better ratings of real world functioning, after controlling for premorbid abilities. However, compared to normative date, NP normal patients manifested disability in several real-world domains, including residential status. These results suggest that NP status is a better predictor of functional outcome then symptom status or the interaction of the two factors. The disability seen in NP normal cases indicates that factors other than cognitive impairments may determine aspects of everyday outcomes in schizophrenia.