Biomedical subjects

Susan R McGurk

Publications and source records attributed to Susan R McGurk.

At least 19 recordsLinked to original sources

PubMed2006

Cognitive and clinical predictors of work outcomes in clients with schizophrenia receiving supported employment services: 4-year follow-up.

In a prior study we showed that cognitive functioning was a modest predictor of work and supported employment services over 2-years in 30 clients with schizophrenia, whereas symptoms were not (McGurk et al. (2003). Psychiatric Services, 58, 1129-1135). In order to evaluate whether the long-term provision of supported employment services reduced the impact of cognitive functioning on work, we examined the relationships between cognitive functioning and symptoms assessed after the initial 2 years of the program, and work and vocational services over the following 2 years (3-4 years after joining the program). Cognitive functioning was more predictive of work during the latter 2 years of the study than the first 2 years, and a similar but weaker pattern was present for the prediction of employment services. Symptoms remained weak predictors for both time periods. In addition, learning and memory and executive functions were strongly correlated with job task complexity during the 3-4 year follow-up, but not the 1-2 year follow-up, suggesting that employment specialists were able to improve their ability to match clients to jobs based on their cognitive skills. Furthermore, the specific associations between cognitive functioning, services, and work outcomes changed from years 1-2 to years 3-4, suggesting a dynamic interplay between these factors over the long-term, rather than static and unchanging relationships. The findings indicate that rather than supported employment services reducing the impact of cognitive functioning on long-term competitive work, the impact actually increases over time, suggesting that efforts to improve cognitive functioning (e.g., cognitive rehabilitation) may optimize employment outcomes in schizophrenia.

Adult↗

PubMed2006

Validity and stability of performance-based estimates of premorbid educational functioning in older patients with schizophrenia.

This paper presents the results of two studies of the validity of word-recognition reading as an indicator of premorbid functioning in schizophrenia. The first examined the stability over a 6-year follow-up period of word recognition reading compared to other aspects of cognitive functioning, including verbal learning and delayed recall, verbal fluency, constructional skills, and naming ability. The second study examined the relative predictive power of indicators of premorbid functioning as compared to current cognitive functioning for the prediction of current social and self-care skills. In the first study 218 patients with chronic schizophrenia participated. For the second study, 231 male veterans with schizophrenia were assessed for cognitive functioning, indicators of premorbid adjustment, and current functional status. Analyses of the differences between correlations indicated that word recognition reading ability was significantly more stable than other aspects of cognitive functioning over a six-year period during which decline in some other aspects of performance was found. In the second study, premorbid educational and social attainment, word recognition reading skill, and current cognitive functioning were all significantly related to current functional status, defined by correlations with ratings of current functional status. Path analyses indicated, however, that current cognitive functioning was the only significant predictor of current functional status when the intercorrelations of the variables were considered. In sum, Premorbid functioning estimated with word-recognition reading was stable over time (study 1) and correlated with both current cognitive and functional status (study 2). The results of these two studies suggest that word-recognition reading skills are useful screening instruments to estimate premorbid functioning even in deteriorated patients with schizophrenia.

Achievement↗

PubMed2006

Strategies for coping with cognitive impairments of clients in supported employment.

OBJECTIVE: This study evaluated the strategies used by employment specialists to help clients in supported employment programs manage cognitive impairments that interfered with obtaining and keeping jobs. METHODS: Twenty-five supported employment specialists were surveyed to identify strategies they used to help their clients cope with cognitive problems in the domains of attention, psychomotor speed, memory, and problem solving. Then, 50 employment specialists were surveyed to determine whether they used each of the different coping strategies generated in the first part of the study. For each strategy used, they rated how effective it was. RESULTS: Employment specialists reported using a total of 76 different strategies for helping their clients cope with cognitive difficulties. The specialists reported using an average of 48 different coping strategies, which they rated on average as just below effective. Strategies for dealing with attention problems were rated as more effective than strategies used in the other three domains. The number of coping strategies that they reported using was significantly correlated with the perceived effectiveness of the strategies and the proportion of clients in their caseload who were working. CONCLUSIONS: Supported employment specialists were actively involved in helping clients cope with their cognitive impairments. Use of more strategies was correlated with specialists' greater perceived effectiveness of the strategies and with higher rates of working clients on their caseloads, although the reasons for these associations are unclear. Further research is needed to evaluate whether employment specialists' use of more strategies to help clients cope with cognitive problems contributes to better work outcomes.

Adaptation, Psychological↗

PubMed2005

Donepezil effects on mood in patients with schizophrenia and schizoaffective disorder.

Donepezil, 5 mg/d for 6 wk then 10 mg/d for 6 wk, and placebo daily for 12 wk in a double-blind cross-over paradigm, was added to the therapeutic regimen of 13 patients with schizophrenia or schizoaffective disorders, clinically stable on atypical antipsychotic medications. Patients had varying degrees of depressive symptoms, ranging from no depression to clinically significant depression. There was no worsening or induction of depression in individual patients or the group as a whole. In addition there was a statistically significant antidepressant effect in the group as a whole during the donepezil condition and a clinically significant antidepressant effect in the patients with clinically significant depressive symptoms, although there were not enough depressed patients in the group to conclude that donepezil may have antidepressant effects. Thus, in this study, donepezil did not induce or worsen depressive symptoms in schizophrenic and schizoaffective disorder patients.

Adult↗

PubMed2005

Cognitive training and supported employment for persons with severe mental illness: one-year results from a randomized controlled trial.

This study examined the effectiveness of cognitive training (the Thinking Skills for Work Program) for improving competitive employment outcomes in persons with severe mental illness who have a history of job failure. Forty-four clients receiving services at 2 inner-city community mental health agencies were randomly assigned (within each site) to receive either cognitive training and supported employment (CT + SE) or supported employment only (SE Only). Retention in the CT + SE program was high (91%). Baseline to 3-month assessments showed significantly greater improvements in neurocognitive functioning, depression, and autistic preoccupation on the Positive and Negative Syndrome Scale for the CT + SE set compared to the SE Only group. Employment outcomes over 1 year showed that clients who received CT + SE were significantly more likely to work (69.6 versus 4.8%, respectively), worked more jobs, worked more hours, and earned more wages than clients with SE Only. The findings provide support for the feasibility of implementing the Thinking Skills for Work Program in the context of supported employment and its beneficial effects on cognitive functioning and competitive employment in persons with severe mental illness.

Adult↗

PubMed2005

mRNA expression of AMPA receptors and AMPA receptor binding proteins in the cerebral cortex of elderly schizophrenics.

L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate the majority of the fast excitatory transmission in the CNS. To determine whether gene expression of AMPARs and/or AMPAR binding proteins, which control response/sensitivity of AMPAR-bearing neurons to glutamate, are altered in schizophrenia, mRNA expression and abundance of AMPAR subunits (GluR1-4) and several AMPAR binding proteins (SAP97, PICK1, GRIP, ABP) were measured in the dorsolateral prefrontal cortex (DLPFC) and the occipital cortex of elderly schizophrenia patients (n = 36) and matched normal controls (n = 26) by quantitative real-time PCR. The mRNA expression of GluR1, GluR4, and GRIP in the DLPFC and expression of the GluR4, GRIP, and ABP in the occipital cortex were significantly elevated in schizophrenics. GluR1 and ABP mRNA expression in the occipital cortex and GluR2, GluR3, SAP97, and PICK1 expression in either cortical area were not significantly altered. The data also demonstrated significant differences in the abundances of mRNAs encoding GluR1-4 subunits (GluR2 > GluR3 > GluR1 > GluR4) and of AMPAR binding proteins (SAP97 > PICK1 > GRIP > ABP) in both diagnostic groups. GluR2 (58-64%) and GluR3 (24-29%) were the major components of the AMPAR mRNA in both cortical areas, implying that the major AMPAR complexes in the human cortex are probably those containing GluR2 and GluR3 subunits. Small but significant differences in the amounts of GluR2, GluR3, and GRIP mRNAs were detected between the two cortical areas: more GluR3 and GRIP but less GluR2 were detected in the DLPFC than in the occipital cortex.

Adaptor Proteins, Signal Transducing↗

PubMed2005

The effects of clozapine and risperidone on spatial working memory in schizophrenia.

OBJECTIVE: The purpose of this investigation was to evaluate the effects of clozapine and risperidone on spatial working memory in patients with schizophrenia. METHOD: Spatial working memory performance was evaluated at baseline and after 17 and 29 weeks in 97 patients with schizophrenia participating in a multisite trial. RESULTS: Compared with baseline performance while receiving conventional antipsychotic medication, risperidone improved, and clozapine worsened, spatial working memory performance. CONCLUSIONS: The differential effects of these medications on spatial working memory may be due to the anticholinergic effects of clozapine and prefrontal dopamine-enhancing effects of risperidone.

Adult↗

PubMed2004

Cognitive functioning, symptoms, and work in supported employment: a review and heuristic model.

OBJECTIVE: Supported employment has been shown to improve the employment outcomes of clients with severe mental illness (SMI), but many clients who receive this service still fail to achieve their vocational goals. There is a need to better understand how illness-related impairments interfere with work, and how supported employment services deal with those impairments in order to improve the employment outcomes of clients with SMI. METHOD: We conducted a review of research on the relationship between cognitive functioning, symptoms, and competitive employment in clients with SMI. Based on this review, we developed a heuristic model of supported employment that proposes specific interactions between cognitive factors, symptoms, vocational services, and employment outcomes. RESULTS: The review indicated that cognitive functioning and symptoms were strongly related to work in studies of general psychiatric samples. In studies of clients participating in vocational rehabilitation programs, associations between cognitive functioning, symptoms, and work were also present, but were attenuated, suggesting that vocational rehabilitation compensates for the effects of some cognitive impairments and symptoms on work. We describe a heuristic model of supported employment that posits specific and testable effects of cognitive domains and symptoms on vocational services and employment outcomes. CONCLUSIONS: Supported employment appears to work by compensating for the effects of cognitive impairment and symptoms on work. The model may serve as a guide for research aimed at understanding how supported employment works, and for developing supplementary strategies designed to improve the effectiveness and cost-effectiveness of supported employment services.

Cognition Disorders↗

PubMed2004

Schizophrenia.

Schizophrenia is a mental illness that is among the world's top ten causes of long-term disability. The symptoms of schizophrenia include psychosis, apathy and withdrawal, and cognitive impairment, which lead to problems in social and occupational functioning, and self-care. About 1% of the population is affected by schizophrenia, with similar rates across different countries, cultural groups, and sexes. The illness tends to develop between the ages of 16 and 30 years, and mostly persists throughout the patient's lifetime. The cause of schizophrenia is unknown, but evidence suggests that genetic factors, early environmental influences (eg, obstetric complications), and social factors (eg, poverty) contribute. No biological alterations are pathognomonic of schizophrenia, although several pathophysiological differences exist in a wide range of brain structures. Antipsychotic medications are the mainstay for managing schizophrenia. A range of psychosocial treatments are also helpful, including family intervention, supported employment, cognitive-behaviour therapy for psychosis, social skills training, teaching illness self-management skills, assertive community treatment, and integrated treatment for co-occurring substance misuse.

Antipsychotic Agents↗

PubMed2004

Antipsychotic and anticholinergic effects on two types of spatial memory in schizophrenia.

Spatial memory is of interest in schizophrenia because of widespread impairments in adaptive functioning, including independent living skills. Short-term spatial memory is impaired in this disease, whereas spatial reference memory, a longer-term spatial memory, has not been evaluated. Animal studies have demonstrated that anticholinergics impair short-term spatial memory but not spatial reference memory. The effects of haloperidol and risperidone on these two types of spatial memory were evaluated in a double-blind randomized comparison in inpatients with schizophrenia. It was predicted that risperidone would have a greater beneficial effect on spatial working memory than haloperidol. Computerized measures of spatial working memory and spatial reference memory were developed based on animal assessment of these functions. Subjects with schizophrenia were assessed during a medication-free period and again following 4 weeks of fixed-dose treatment. Risperidone, compared to haloperidol, improved spatial working memory performance, an effect that became nonsignificant when benztropine co-treatment was controlled. There were no treatment effects on spatial reference memory performance. Consistent with animal studies, benztropine impaired spatial working memory but not spatial reference memory. The relative benefits of risperidone on spatial working memory performance were largely explained by differential benztropine treatment for the haloperidol-treated subjects.

Adult↗

PubMed2004

GAD67 and GAD65 mRNA and protein expression in cerebrocortical regions of elderly patients with schizophrenia.

Gamma-Aminobutyric acid (GABA), the principal inhibitory neurotransmitter of CNS, has been consistently implicated in the pathophysiology of schizophrenia. GABA is synthesized from glutamate by the enzyme glutamic acid decarboxylase (GAD). Two isoforms of GAD have been identified and have been named GAD65 and GAD67 based on their apparent molecular weights. In this study, GAD65 and GAD67 mRNA and protein levels were measured by using real-time RT-PCR and immunoblotting, respectively, in post-mortem brain tissue from the dorsolateral prefrontal cortex (DLPFC) and the occipital cortex of the elderly persons with schizophrenia and matched normal controls. In addition, the mRNA expression of GAT-1, one of the principal transporters of GABA, was also studied in the same subjects. Expression of GAD65 and GAD67 mRNA in the DLPFC and in the occipital cortex was significantly elevated in patients with schizophrenia, whereas the expression of the corresponding proteins and GAT-1 mRNA was unchanged. Although the levels of GAD65 and GAD67 messages were increased in schizophrenia subjects, the proportion of the two GAD isoforms remained constant in controls and schizophrenics. In the human DLPFC, GAD65 mRNA was found to be expressed significantly less than the message for GAD67, approximately 16% of that observed for GAD67. On the contrary, the abundance of GAD65 protein in the DLPFC was about 350% of that observed for GAD67. The results suggest a substantial dysregulation of GAD mRNA expression in schizophrenia and, taken together with the results of protein expression studies, raise the possibility that both cortical and subcortical GABA function may be compromised in the disease.

Aged↗

PubMed2004

Cognitive effects of olanzapine treatment in schizophrenia.

Improvement in some but not all domains of cognition during treatment with the atypical antipsychotic drugs clozapine, quetiapine, olanzapine, and risperidone has been reported in some but not all studies. It has been recently suggested that these reports are an artifact, related to lessening of the impairment due to typical neuroleptic drugs and anticholinergic agents. The purpose of this study was to further test the hypothesis that olanzapine, an atypical antipsychotic drug reported to have anticholinergic properties, improves cognition in patients with schizophrenia, including domains of cognition related closely to work and social function (ie, verbal learning and memory) and that this improvement is independent of improvement in psychopathology. Thirty-four patients with schizophrenia who were partial responders to typical antipsychotic drug treatment were evaluated with a comprehensive neurocognitive battery, including measures of executive functioning; verbal and visual learning and memory; working memory; immediate, selective, and sustained attention; perceptual/motor processing; and motor skills prior to and following treatment with olanzapine for 6 weeks. The Brief Psychiatric Rating Scale (BPRS) was used to assess psychopathology in patients treated with typical antipsychotic drugs. Subjects were switched to olanzapine (average dose 13.4 mg, range 5-20 mg) and reassessed following 6 weeks and 6 months of treatment. Significant improvement was noted in 9 of 19 cognitive tests, including measures of selective attention, verbal learning and memory, and verbal fluency. No cognitive test was worsened by olanzapine treatment. Improvements in the BPRS Total and Positive Symptom Subscale scores were noted. Improvements in verbal learning and memory, sustained attention, and psychomotor tracking were independent of improvement in psychopathology. These data suggest that olanzapine improved some but not all cognitive deficits in schizophrenia, including verbal memory, a cognitive domain impaired by anticholinergic drugs. The basis for the improvement in cognitive scores, which should lead to improvement in role functioning if real, is discussed.

Adult↗

PubMed2004

Cognitive functioning predicts outpatient service utilization in schizophrenia.

Aim of the study was to evaluate the cognitive and symptom predictors of outpatient service utilization in schizophrenia. The relationships between cognitive functioning (verbal learning and memory, executive functions), symptoms (positive symptoms, negative symptoms), and outpatient service utilization (case management, medication monitoring), were examined in 20 patients receiving outpatient services at a psychosocial clubhouse over a 12-month period. Executive functions, as measured on the Wisconsin Card Sorting Test (WCST), were the only significant predictor of outpatient service utilization, accounting for over 20% of the variance in total outpatient services used, with greater impairment associated with higher service utilization. Specifically, poorer performance on the WCST was associated with delivery of more case management services, but not medication management services. More case management services may be required to compensate for impairments in executive functioning in patients with schizophrenia.

Adult↗

PubMed2004

Working memory performance in poor outcome schizophrenia: relationship to age and executive functioning.

Performance on the Letter-Number Sequencing (LNS) and Wisconsin Card Sorting Tests (WCST) have been shown to be significantly correlated in patients with schizophrenia, a relationship postulated to be due to working memory demands of the two tests (Gold, Carpenter, Randolph, Goldberg, & Weinberger, 1997). An alternative explanation for the association between these two tests is their sorting demands, in that both require sorting of information albeit in slightly different ways. If the latter explanation is valid, then working memory tasks that do not require sorting or other conceptualization demands should be less predictive of WCST performance than LNS. These hypotheses were examined in 34 poor outcome patients with schizophrenia, one-half of whom were over the age of 65. Patients were evaluated on Digit Span Forward, spatial working memory, LNS, and the WCST. It was found that WCST performance was significantly associated with performance on the LNS but no other working memory task. Age related performance differences were greatest on the WCST Categories and floor effects were noted on this test in one-half of the subjects. Analyses predicting WCST Categories in subjects whose scores were greater than zero (n = 16) also demonstrated that LNS, but not Digit Span or spatial working memory (any delay) predicted WCST performance. These findings indicate that LNS may be an index of executive functioning, particularly in patients who cannot perform the WCST.

Adult↗

PubMed2003

Changes in cognitive functioning with risperidone and olanzapine treatment: a large-scale, double-blind, randomized study.

OBJECTIVE: The effects of risperidone and olanzapine on cognitive functioning in patients with schizophrenia were compared in a randomized, double-blind trial. METHOD: Three hundred and seventy-seven patients were randomly assigned to receive 2-6 mg/day of risperidone or 5-20 mg/day of olanzapine for 8 weeks. Cognitive function was assessed with a focused cognitive assessment battery; in addition, extrapyramidal symptoms were assessed using the extrapyramidal symptom rating scale (ESRS), and the positive and negative syndrome scale (PANSS) was rated for all patients. RESULTS: Treatment with these two atypical antipsychotic medications was associated with improved performance on the Wisconsin card sorting test, the trail-making test, the California verbal learning test, the continuous performance test, and some aspects of verbal fluency and spatial working memory. No differences in the effects of the drugs on any of the cognitive tests were noted. Correcting for the effects of anticholinergic treatment did not alter the magnitude of cognitive effects. CONCLUSIONS: Atypical antipsychotic treatment is associated with wide-ranging benefits on cognitive functioning. Previous reports of greater benefits of olanzapine over risperidone in a small-sample pilot study were not substantiated. These results are not due in general to changes in clinical symptoms or movement disorders, suggesting a direct effect of atypical antipsychotic medications on cognitive deficits in schizophrenia.

Adolescent↗

PubMed2003

RNA editing and alternative splicing of human serotonin 2C receptor in schizophrenia.

Serotonin 2C receptor (5-HT2CR) heterogeneity in the brain occurs mostly from two different sources: (i) 5-HT2CR mRNA undergoes adenosine-to-inosine editing events at five positions, which leads to amino acid substitutions that produce receptor variants with different pharmacological properties; (ii) 5-HT2CR mRNA is alternatively spliced, resulting in a truncated mRNA isoform (5-HT2CR-tr) which encodes a non-functional serotonin receptor. 5-HT2CR mRNA editing efficiencies and the expression of the full-length and the truncated 5-HT2CR mRNA splice isoforms were analyzed in the prefrontal cortex of elderly subjects with schizophrenia vs. matched controls (ns = 15). No significant differences were found, indicating that there are no alterations in editing or alternative splicing of 5-HT2CRs that are associated with schizophrenia in persons treated with antipsychotic medications. Quantitation of 5-HT2CR and 5-HT2CR-tr mRNA variants revealed that the expression of 5-HT2CR-tr was approximately 50% of that observed for the full-length isoform.

Adenosine↗

PubMed2003

Cognitive functioning and employment in severe mental illness.

This study compared cognitive functioning and symptomatology of unemployed, supported employed, and independently employed clients with severe mental illness. Unemployed clients who wanted to work (N = 21) were compared with clients working in supported employment programs (N = 17) and clients who had been working independently for at least 1 year (N = 23) on a neuropsychological battery and the Positive and Negative Syndrome Scale. Clients who were unemployed had more severe symptoms and worse cognitive functioning on both positive and negative symptoms, and almost all domains of cognitive functioning. Supported employed clients had more severe psychotic symptoms and worse working memory than independently employed clients, but did not differ in negative symptoms or the other domains of cognitive functioning, including attention/concentration, psychomotor speed, verbal learning and memory, or executive functions. Finally, job complexity was correlated with impaired executive functions among clients working independently, but not in supported employment. Severe symptoms and cognitive impairment may interfere with the ability of some clients with severe mental illness to obtain competitive work. Supported employment programs appear to work by helping clients compensate for problematic symptoms and cognitive impairment and, to a lesser extent, by finding or developing environmental niches in which these impairments do not impede their ability to perform the necessary job tasks.

Adult↗

PubMed2003

Cognitive and symptom predictors of work outcomes for clients with schizophrenia in supported employment.

OBJECTIVES: This study examined the relationships of measures of cognitive functioning and psychiatric symptoms with work outcomes and use of vocational services for clients with schizophrenia in a supported employment program. METHODS: Thirty clients who were newly enrolled in a supported employment program were evaluated with cognitive and symptom measures at program entry and two years later. The clients' amounts of competitive work, wages earned, on-job support, and contact with employment specialists during the two-year follow-up period were documented. RESULTS: Predictors of clients' work outcomes included previous work history, amount of government entitlement income received, severity of negative symptoms, involvement in sheltered work activity at baseline, and level of cognitive functioning, including scores on measures of executive functioning and verbal learning and memory. The amounts of on-job support and contact with employment specialists were predicted by the cognitive domains of executive functioning, verbal learning, attention, and psychomotor speed as well as by the severity of psychotic symptoms. CONCLUSIONS: Clients with schizophrenia who have higher levels of cognitive impairment may require greater amounts of vocational support than those with lower levels of impairment. A variety of rehabilitation strategies may be required to improve vocational outcomes and reduce the amount of supported employment services needed by clients with schizophrenia.

Adult↗