Community outcome in cognitively normal schizophrenia patients.

Recent reports suggest that cognition is relatively preserved in some schizophrenia patients. However, little is known about the functional advantage these patients may demonstrate. The purpose of this study was to identify cognitively normal patients with a recently developed test battery and to determine the functional benefit of this normality relative to cognitively impaired patients. Average-range cognitive ability was defined by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) composite score (T≥40) and applied to 100 patients with schizophrenia or schizoaffective disorder and to 81 non-psychiatric research participants. With group assignment adjusted for demographic variables, this procedure yielded 14 cognitively normal patients, 21 cognitively impaired patients, and 21 healthy adults with normal-range MCCB scores. Cognitively normal patients were indistinguishable from controls across all MCCB scales. Furthermore, their performance was superior to impaired patients on all scales except Social Cognition. Cognitively normal patients were also superior to impaired patients on a summary index of simulated life skills and functional competence. Nevertheless, both patient groups were equally disadvantaged relative to controls in independent community living. These findings suggest that normal-range cognition exists in schizophrenia, but fails to translate into enhanced community outcome.

Preserved, deteriorated, and premorbidly impaired patterns of intellectual ability in schizophrenia.

OBJECTIVE: The main purpose of this investigation was to identify patterns of intellectual performance in schizophrenia patients suggesting preserved, deteriorated, and premorbidly impaired ability, and to determine clinical, cognitive, and functional correlates of these patterns. METHOD: We assessed 101 patients with schizophrenia or schizoaffective disorder and 80 non-psychiatric control participants. The "preserved" performance pattern was defined by average-range estimated premorbid and current IQ with no evidence of decline (premorbid-current IQ difference <10 points). The "deteriorated" pattern was defined by a difference between estimated premorbid and current IQ estimates of 10 points or more. The premorbidly "impaired" pattern was defined by below average estimated premorbid and current IQ and no evidence of decline greater than 10 points. Preserved and deteriorated patterns in healthy controls were also identified and studied in comparison to patient findings. The groups were compared on demographic, neurocognitive, clinical and functionality variables. RESULTS: Patients with the preserved pattern outperformed those meeting criteria for deteriorated and compromised intellectual ability on a composite measure of neurocognitive ability as well as in terms of functional competence. Patients demonstrating the deteriorated and compromised patterns were equivalent across all measures. However, "preserved" patients failed to show any advantage in terms of community functioning and demonstrated cognitive impairments relative to control participants. CONCLUSIONS: Our results suggest that proposed patterns of intellectual decline and stability exist in both the schizophrenia and general populations, but may not hold true across other cognitive abilities and do not translate into differential functional outcome.

Stability and change in symptoms, cognition, and community outcome in schizophrenia.

It has been well established that neurocognitive deficits are a core feature in schizophrenia and predict difficulties in functional independence. However, few studies have assessed the longitudinal stability of cognition and key aspects of functional outcome concurrently. Even less attention has been directed at the contingency of cognitive change on real world outcome changes. Accordingly, this study will assess the extent to which significant changes in cognition and community status are independent or related. As a point of comparison, the stability of clinical symptom status and the relationship between symptom and outcome change are evaluated. Symptoms, cognitive abilities, and community outcome was assessed in 128 patients with schizophrenia at baseline and again one year later. Intraclass correlation coefficients were used to index stability and reliable change index analyses quantified the prevalence of significant improvement or deterioration in each of the three illness features. Results from these analyses revealed that symptom status, cognitive functioning, and community outcome are similarly stable in treated schizophrenia outpatients. A small proportion of the sample demonstrated significant improvement or deterioration in these domains, with only weak evidence that such change was predicted by changes in symptoms or cognition. Further, there was no strong evidence of a preferential relationship for cognition relative to symptoms in relation to functional outcome. These results shed light on the strength and nature of the cognition-real world outcome relationship in schizophrenia and have implications for pharmacological and behavioral interventions aimed at improving real world outcome.

WAIS-IV profile of cognition in schizophrenia.

The Wechsler Adult Intelligence Scale (WAIS) has been used extensively to study impairment across a range of cognitive domains in schizophrenia. However, cognitive performance among those with the illness has yet to be examined using the newest edition of this measure. Hence, the current study aims first, to provide WAIS-IV normative data for Canadian individuals with schizophrenia of low average intelligence; second, to examine schizophrenia performance on all WAIS-IV subtest, index and general intelligence scores relative to healthy comparison subjects; and third, to revalidate the pattern of impairment identified in this clinical group using the WAIS-III, where processing speed (PS) was most affected, followed by working memory (WM), perceptual reasoning (PR) and verbal comprehension (VC). The WAIS-IV was administered to outpatients with schizophrenia and their performance compared with age, gender, and education matched controls. WAIS-IV schizophrenia performance data are provided. Analyses revealed significant impairment on several tasks, including the new Cancellation subtest and the VC supplemental subtest, Comprehension. At the index score level, group differences in PS were significantly larger than those observed in all other cognitive domains. Impairments were also observed in WM amid relatively preserved performance in VC, thereby confirming the pattern of impairment identified using the WAIS-III.

The Canadian Objective Assessment of Life Skills (COALS): a new measure of functional competence in schizophrenia.

This study examined the reliability and validity of a new performance-based measure of functional competence for individuals with serious mental illness, the Canadian Objective Assessment of Life Skills (COALS). The COALS assesses both routinized procedural knowledge routines (PKR) and executive operations (EXO) in order to capture functional outcome variance. The COALS was administered to 101 outpatients with schizophrenia and schizoaffective disorder and 80 non-psychiatric controls. One month later, 95 patients and 63 controls completed a follow-up assessment. Measures of psychopathology, neurocognition, functionality and community adjustment were also administered. Results indicated that the COALS summary scores had good test-retest reliability for patient data. Further, the COALS correlated with other measures of functionality and with negative symptoms, but was independent of positive symptoms, demonstrating concurrent and discriminant validity. The overall COALS summary score added incremental validity to the prediction of community independence over and above the contribution of symptoms, intellectual ability and neurocognitive performance. Inclusion of EXO scores provided incremental validity not available with PKR scores alone. The COALS increases the number of functional competence instruments and offers the advantage of specific validity while incorporating important distinctions in cognitive performance.

"Real world" functioning in schizophrenia patients and healthy adults: assessing validity of the Multidimensional Scale of Independent Functioning.

As treatment efforts to enhance cognitive abilities in schizophrenia increase, so too does the need for a critical appraisal of instruments that measure functionality and adjustment to community living. The Multidimensional Scale of Independent Functioning (MSIF; Jaeger et al., 2003) is a promising instrument that assesses functionality in relation to different life settings, performance levels, responsibilities and environmental supports. However, its applicability to the schizophrenia population has been questioned because relevant data are scarce. This study provides descriptive and validity-related information by reporting MSIF scores in healthy community-dwelling adults (n=71) and in schizophrenia outpatients (n=156). Results show that healthy adults performed within defined "normal" ranges in most MSIF domains in comparison to schizophrenia patients who showed moderate to severe impairments. Moreover, the MSIF distinguished between the two groups with accuracy rates as high as 98% and effect sizes (standardized mean group difference) above 2.0 in almost all domains. Accordingly, the MSIF is a potentially valuable measure of community independence that can inform treatment initiatives and may be adaptable to the evaluation of functionality changes over time. The unique structure and content of information obtained by the MSIF makes it a candidate for inclusion in studies aimed at developing a new generation of instruments for the assessment of real world functioning in schizophrenia.

An investigation of 3 neurocognitive subtypes in schizophrenia.

The purpose of this investigation was to identify patients with cognitively impaired, cognitively normal and verbal memory-impaired subtypes of schizophrenia and to examine their clinical and functional validity as distinct forms of the disorder. These subtypes occurred in 73 of 154 patients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder. A control group comprised of 18 healthy participants was also analyzed. Patient subtype and healthy groups were compared on adjunct cognitive as well as clinical and functional measures. The data support the cognitive validity and differentiation of these subtypes, with evidence that the generalized cognitive normality/impairment distinction associates with important aspects of symptom severity and functional outcome. Support for the clinical and functional validity of the verbal memory subtype was more equivocal. Overall, cognitively-based subtyping merits additional attention in efforts to organize the heterogeneity of the schizophrenia syndrome.

Interactions between the effects of early isolation rearing and complex housing on adult locomotor activity and sensitivity to amphetamine in rats involve noradrenergic neurotransmission.

Increased sensitivity to the locomotor-activating effects of amphetamine in rats with a history of early-life social isolation is commonly attributed to alteration of the dopamine system. The locomotor response to amphetamine may also be due to effects on the noradrenergic system and particularly alpha-adrenergic receptors. The present study examined whether noradrenergic neurotransmission mediates the increased sensitivity to the locomotor effects of amphetamine resulting from early social isolation and whether this effect can be reversed by later-life social housing experience. Rats reared in complete social isolation (artificially reared, AR) exhibited higher levels of locomotor activity than maternally reared (MR) rats in response to amphetamine (0.25mg/kg). Increased sensitivity to the locomotor effects of amphetamine in AR rats was reduced by the alpha-adrenergic receptor antagonist prazosin (0.5mg/kg). Prazosin alone reduced activity in AR rats to the level of MR rats. Group housing in cages that were more complex than standard laboratory cages reduced activity in both AR and MR rats. Group housing did not decrease the sensitivity of AR rats to the locomotor effects of either amphetamine or prazosin. Differences in activity between rats in standard and complex housing conditions were not altered by drug treatments. These findings indicate that pre-weaning social experience alters the responsiveness of the noradrenergic system to drug challenges, whereas post-weaning housing experience may not, even though ongoing activity is affected. Increased activity and sensitivity to amphetamine resulting from social isolation in early life may be mediated by changes in noradrenergic alpha-receptor mediated neurotransmission.

Cognitive performance and functional competence as predictors of community independence in schizophrenia.

Measures of functional competence have been introduced to supplement standard cognitive and neuropsychological evaluations in schizophrenia research and practice. Functional competence comprises skills and abilities that are more relevant to daily life and community adjustment. However, it is unclear whether relevance translates into significantly enhanced prediction of real-world outcomes. The aim of this study was to assess the specific contribution of functional competence in predicting a key aspect of real-world outcome in schizophrenia: community independence. Demographic, clinical, cognitive, and functional competence data were obtained from 127 patients with schizophrenia or schizoaffective disorder and used to predict community independence concurrently and longitudinally after 10 months. Hierarchical regression analyses indicated that demographic, clinical, and cognitive predictors accounted jointly for 35%-38% of the variance in community independence across assessment points. Functional competence data failed to add significantly to this validity. Considered separately from demographic and clinical predictors, cognitive and functional competence data accounted for significant amounts of outcome variance. However, the addition of functional competence to standard cognitive test data yielded a significant increase in validity only for concurrent and not for longitudinal prediction of community independence. The specific real-world validity of functional competence is modest, yielding information that is largely redundant with standard cognitive performance.

Psychopathology and cognition in divergent functional outcomes in schizophrenia.

Cognitive performance rather than symptoms, especially positive symptoms, is regarded as the primary predictor of functional outcome in schizophrenia. However, contradictory evidence exists and many studies fail to sample from the extremes of outcome measures. This study tested whether the differential importance assigned to symptoms and cognitive impairment is supportable in patients with high and low levels of community independence. Schizophrenia patients with highly unfavorable (n=24) and highly favorable (n=28) functional outcomes as defined by community support requirements were studied. Standard cognitive and psychopathology measures were analyzed using independent groups comparisons and outcome prediction with logistic regression methods. Symptom severity and cognitive data separately accounted for significant amounts of variance in community independence. Positive as well as negative symptoms, non-psychotic psychopathology and cognition generated large effect sizes between highly unfavorable and favorable outcome groups. The conditional validity of both overall psychopathology and positive symptoms was significant over and above the contribution of cognition to outcome prediction. Results suggest researchers may have underestimated the role of psychopathology in general and positive symptoms in particular as potential determinants of functional status in schizophrenia.

Cognitive, clinical, and functional characteristics of verbally superior schizophrenia patients.

The existence of small numbers of schizophrenia patients with superior ability in specific cognitive domains is implied by meta-analytic evidence as well as by occasional empirical reports. The authors identified 25 patients with superior (i.e., > or =90th percentile) ability on the Vocabulary subtest of the Wechsler Adult Intelligence Scale 3rd edition (Wechsler, 1997). These cognitively advantaged patients were compared with 22 healthy participants performing at the superior level and with 126 schizophrenia patients and 50 healthy participants scoring below the superior range. Verbally superior schizophrenia patients and verbally superior healthy participants had similar cognitive profiles and life skills performance, but diverged markedly in terms of independent "real-world" functioning. Verbally superior patients significantly outperformed more typical patients in other aspects of cognitive performance, life skills, and support requirements. However, severity of positive and negative symptoms was equivalent in the patient groups. Detailed biobehavioral study of cognitively exceptional patients may offer new insights into mechanisms mediating psychotic disorders.

Are schizophrenia and schizoaffective disorder neuropsychologically distinguishable?

This study sought to objectify the distinction between schizophrenia and schizoaffective disorder in terms of standard tasks measuring verbal and non-verbal cognitive ability, auditory working memory, verbal declarative memory and visual processing speed. Research participants included 103 outpatients with a diagnosis of schizophrenia, 48 with schizoaffective disorder, and 72 non-patients from the community. Schizophrenia patients were impaired on all cognitive measures relative to schizoaffective patients and non-psychiatric participants. Regression-based prediction models revealed that cognitive measures classified schizophrenia patients accurately (91%), but not patients with schizoaffective disorder (35%). In addition, there was no statistical evidence for the unique predictive validity of any specific cognitive task. Patients with schizophrenia were significantly more symptomatic and had greater community support requirements than those with schizoaffective disorder. However, group differences in cognitive performance are insufficient to separate these syndromes of psychotic illness.