Improving the understanding of the link between cognition and functional capacity in schizophrenia and bipolar disorder.

OBJECTIVE: Deficits in cognitive functioning are related to functional disability in people with serious mental illness. Measures of functional capacity are commonly used as a proxy for functional disabilities for cognitive remediation programs, and robust linear relationships between functional capacity and cognitive deficits are frequently observed. This study aimed to determine whether a curvilinear relationship better approximates the association between cognitive functioning and functional capacity. METHOD: Two independent samples were studied. Study 1: participants with schizophrenia (n=435) and bipolar disorder (n=390) aged 18-83 completed a neuropsychological battery and a performance-based measure of functional capacity. Study 2: 205 participants with schizophrenia (age range=39-72) completed a brief neuropsychological screening battery and a performance-based measure of functional capacity. For both studies, linear and quadratic curve estimations were conducted with cognitive performance predicting functional capacity scores. RESULTS: Significant linear and quadratic trends were observed for both studies. Study 1: in both the schizophrenia and bipolar participants, when cognitive composite z-scores were >0 (indicating normal to above normal performance), cognition was not related to functional capacity. Study 2: when neuropsychological screening battery z-scores were >-1 (indicating low average to average performance), cognition was not related to functional capacity. CONCLUSIONS: These results illustrate that in cognitively normal adults with serious mental illness, the relationship between cognitive function and functional capacity is relatively weak. These findings may aid clinicians and researchers determine who may optimally benefit from cognitive remediation programs, with greater benefits possibly being achieved for individuals with cognitive deficits relative to individuals with normal cognition.

Association of obesity and treated hypertension and diabetes with cognitive ability in bipolar disorder and schizophrenia.

OBJECTIVES: People with bipolar disorder or schizophrenia are at greater risk for obesity and other cardio-metabolic risk factors, and several prior studies have linked these risk factors to poorer cognitive ability. In a large ethnically homogenous outpatient sample, we examined associations among variables related to obesity, treated hypertension and/or diabetes and cognitive abilities in these two patient populations. METHODS: In a study cohort of outpatients with either bipolar disorder (n = 341) or schizophrenia (n = 417), we investigated the association of self-reported body mass index and current use of medications for hypertension or diabetes with performance on a comprehensive neurocognitive battery. We examined sociodemographic and clinical factors as potential covariates. RESULTS: Patients with bipolar disorder were less likely to be overweight or obese than patients with schizophrenia, and also less likely to be prescribed medication for hypertension or diabetes. However, obesity and treated hypertension were associated with worse global cognitive ability in bipolar disorder (as well as with poorer performance on individual tests of processing speed, reasoning/problem-solving, and sustained attention), with no such relationships observed in schizophrenia. Obesity was not associated with symptom severity in either group. CONCLUSIONS: Although less prevalent in bipolar disorder compared to schizophrenia, obesity was associated with substantially worse cognitive performance in bipolar disorder. This association was independent of symptom severity and not present in schizophrenia. Better understanding of the mechanisms and management of obesity may aid in efforts to preserve cognitive health in bipolar disorder.

Determinants of occupational and residential functioning in bipolar disorder.

BACKGROUND: Bipolar disorder is associated with reduced rates of employment and residential independence. The influence of cognitive impairment and affective symptoms on these functional attainments has received little previous attention and is the focus of this study. METHOD: A total of 229 adult outpatients with bipolar disorder without active substance use disorders and with an average of mild severity of affective symptoms were included in the analyses. After adjusting for sociodemographic and illness history covariates, univariate and multivariate analyses were used to evaluate the independent and interactive associations of neurocognitive ability, performance-based functional capacity, and affective symptom severity with residential independence, occupational status and number of hours worked. RESULTS: A total of 30% of the sample was unemployed and 18% was not independently residing. Neurocognitive ability was the strongest predictor of any employment, but depressive symptom severity was the only variable significantly related to hours worked. The strongest predictor of residential independence was performance-based functional capacity. Affective symptoms and neurocognitive ability were independent (non-interactive) predictors of occupational and residential status. LIMITATIONS: This is a cross-sectional study and thus causal direction among variables is unknown. The sample was ethnically homogeneous and thus the results may not generalize to ethnically diverse samples. CONCLUSIONS: This study confirmed elevated rates of unemployment and residential non-independence in adults with bipolar disorder. Interventions targeting cognitive deficits and functional capacity may increase the likelihood of any employment or residential independence, respectively. Interventions targeting depressive symptoms may be most influential on work outcomes among those already employed.

Sensitivity and specificity of the UCSD Performance-based Skills Assessment (UPSA-B) for identifying functional milestones in schizophrenia.

Schizophrenia is a highly debilitating illness that often results in disruption to independent living and employment. However, "gold standard" methods of assessing functional abilities to achieve these milestones are still lacking. In a sample of 367 individuals with schizophrenia, we examined the sensitivity and specificity of the Brief UCSD Performance-based Skills Assessment (UPSA-B) to predict both residential and employment status. Of all individuals residing independently, 75.9% scored 78 or above on the UPSA-B, and of all individuals not residing independently, 59% scored below 78 on the UPSA-B. Of individuals who were employed, 73.9% scored above 82 on the UPSA-B, and of those not employed, 57.8% scored below 82. These results expand upon both the population base and functional milestones with which the UPSA-B is validated, although future work should examine whether the UPSA-B can be used as a decision aid in the likelihood of success in a longitudinal study, such as at critical transitions (post-hospitalization, cessation of supported housing).

Social competence and observer-rated social functioning in bipolar disorder.

OBJECTIVE: Impairment in social functioning appears to be common in bipolar disorder, although estimates have been derived largely from self-report measures. We examined performance-based and observer-based ratings of social competence and functioning and assessed the contribution of symptoms and neurocognitive ability to social functioning in bipolar disorder. METHODS: In this cross-sectional study, 164 subjects with bipolar disorder were administered the performance-based Social Skills Performance Assessment (SSPA), rated by an informant on the Specific Level of Functioning (SLOF)-Interpersonal subscale, received clinical ratings of depression and manic symptoms, and performed neurocognitive tests. We assessed the proportion of patients exhibiting social deficits and examined the associations between composite measures of neurocognitive ability, depression and manic symptoms, and SSPA scores with informant-rated, real-world social functioning. RESULTS: Mean age of the sample was 47.6 years (SD = 14.1). Subjects were experiencing, on average, mild levels of depression and minimal manic symptoms. A total of 29% exhibited norm-referenced impairment on the SSPA, and 64% registered at least one impairment on SLOF items; unemployed subjects had lower SSPA and SLOF ratings. Neurocognitive performance correlated with both performance-based and observer-rated social functioning, whereas depressive and manic symptoms correlated only with observer-rated social impairments. In multivariate models, depression was the most potent association with social functioning, and impairment in social competence (i.e., capacity) increased the strength of the relationships between depression and neurocognitive impairment and social functioning (i.e., real-world functioning). CONCLUSIONS: Our study confirmed the negative relationship of bipolar depression with social functioning. A subgroup of outpatients with bipolar disorder has impaired social competence, which, when present, worsened the impact of depression and cognitive impairment on social functioning.

Relationship of the Brief UCSD Performance-based Skills Assessment (UPSA-B) to multiple indicators of functioning in people with schizophrenia and bipolar disorder.

OBJECTIVE: This study assessed the relationship between multiple indicators of 'real-world' functioning and scores on a brief performance-based measure of functional capacity known as the Brief University of California San Diego (UCSD) Performance-based Skills Assessment (UPSA-B) in a sample of 205 patients with either serious bipolar disorder (n = 89) or schizophrenia (n = 116). METHODS: Participants were administered the UPSA-B and assessed on the following functional domains: (i) independent living status (e.g., residing independently as head of household, living in residential care facility); (ii) informant reports of functioning (e.g., work skills, daily living skills); (iii) educational attainment and estimated premorbid IQ as measured by years of education and Wide Range Achievement Test reading scores, respectively; and (iv) employment. RESULTS: Better scores on the UPSA-B were associated with greater residential independence after controlling for age, diagnosis, and symptoms of psychopathology. Among both bipolar disorder and schizophrenia patients, higher UPSA-B scores were significantly related to better informant reports of functioning in daily living skills and work skills domains. Greater estimated premorbid IQ was associated with higher scores on the UPSA-B for both schizophrenia and bipolar disorder participants. Participants who were employed scored higher on the UPSA-B when controlling for age and diagnosis, but not when controlling for symptoms of psychopathology. CONCLUSIONS: These data suggest the UPSA-B may be useful for assessing capacity for functioning in a number of domains in both people diagnosed with schizophrenia and bipolar disorder.

Familiality of novel factorial dimensions of schizophrenia.

CONTEXT: Factor analysis of the signs and symptoms of schizophrenia yields dimensional phenotypes that may relate to underlying genetic variation. Examination of familiality of factor scores can demonstrate whether they are likely to be of use in genetic research. OBJECTIVE: To produce a broader set of factorial phenotypes that are tested for familiality including core symptoms of schizophrenia and additional indicators of social, work, and educational dysfunction. DESIGN: The study used psychiatric assessment data collected from several large samples of individuals with schizophrenia who have participated in family or case-control genetic studies (1988-2006) in the Epidemiology-Genetics Program in Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Seventy-three signs and symptoms were selected from direct assessment interviews and consensus diagnostic ratings (integrating interview data, medical records, and informant reports). SETTING: Study participants were recruited from across the United States, and a few additional participants were recruited from Canada, Greece, Italy, Poland, and Israel. Assessments generally were performed in the individuals' homes. PARTICIPANTS: Forty-three percent of 1199 volunteers had largely white European backgrounds. The remaining individuals were recruited for family and case-control studies with focus on Ashkenazi Jews. All individuals had a consensus diagnosis of schizophrenia (including schizoaffective disorder) using DSM-III or DSM-IV criteria. MAIN OUTCOME MEASURES: The 73 indicators were subjected to principal components factor analysis, and factor scores representing 9 dimensions were analyzed for familiality. RESULTS: The 9 factors include the often-reported delusions, hallucinations, disorganization, negative, and affective factors; novel factors included child/adolescent sociability, scholastic performance, disability/impairment, and prodromal factors. All 9 factors demonstrated significant familiality (measured by a heritability statistic), with the highest scores for disability/impairment (0.61), disorganization (0.60), and scholastic performance (0.51). CONCLUSIONS: The factor scores show varying degrees of familiality and may prove useful as quantitative traits and covariates in linkage and association studies.

Five latent factors underlying schizophrenia: analysis and relationship to illnesses in relatives.

Clinical signs and symptoms in a sample of 1,043 individuals with schizophrenia or schizoaffective disorder were subjected to latent class factor analysis. Positive, negative, disorganized, and affective factors were similar in content to factors described in a number of other studies, while a fifth factor representing early onset/developmental signs provided a new area for investigation. The five sets of factor scores were logistically regressed on psychiatric illness indicators in first and second degree relatives. Relatives of probands with higher positive or negative symptom factor scores had a lower risk of depressive illness. Higher affective factor scores in probands predicted more mania and depression in relatives. Both the disorganized and the early onset/developmental factors were related to increased risk of psychiatric hospitalization in relatives, as well as increased risk of psychosis (marginally so for the disorganization factor). Increased early onset/developmental signs in the proband were also associated with increased risk for depression in relatives. These findings suggest a possible endophenotypic role for the factor scores in future studies.