Comparison of Black and White participants with severe mental illness in response to cognitive remediation as an augmentation of vocational rehabilitation.

PURPOSE: Despite evidence that cognitive remediation improves cognitive and employment outcomes in persons with severe mental illnesses (SMI), its effects have not been systematically compared between Black and White participants. Considering that Black adults have more negative experiences receiving mental health treatment, providers may have greater difficulty engaging and retaining Black Americans in cognitive remediation. Due to the effects of structural racism on reducing employment opportunities for Black Americans, it is unclear whether Black participants will reap the same benefits of cognitive remediation on work outcomes as White Americans. This paper addressed this question. METHODS: A secondary analysis was conducted of five randomized controlled trials comparing cognitive remediation (the Thinking Skills for Work program: TSW) and vocational rehabilitation vs. vocational rehabilitation only in 137 Black and 147 White Americans (64.2% schizophrenia-schizoaffective disorder) who were followed up for two years. RESULTS: Comparable proportions of Black and White participants were engaged and retained in TSW (>75%). Participants who received TSW improved significantly more in cognition than those receiving vocational services alone, with no racial differences in benefit. Participants in TSW obtained more work, earned more wages, and worked more weeks than those receiving vocational services alone, with no differences between the races. CONCLUSIONS: The findings indicate that Black Americans with SMI receiving vocational services could be successfully engaged in and benefit from cognitive remediation, highlighting the vital role of healthcare service systems in giving credence to structural racism to more effectively mitigate racial disparities in treatment outcomes.

Supported employment for persons with serious mental illness: current status and future directions.

The individual placement and supported (IPS) model of supported employment is the most empirically validated model of vocational rehabilitation for persons with schizophrenia or another serious mental illness. Over 18 randomized controlled trials have been conducted throughout the world demonstrating the effectiveness of supported employment at improving competitive work compared to other vocational programs: IPS supported employment is defined by the following principles: 1) inclusion of all clients who want to work; 2) integration of vocational and clinical services; 3) focus on competitive employment; 4) rapid job search and no required prevocational skills training; 5) job development by the employment specialist; 6) attention to client preferences about desired work and disclosure of mental illness to prospective employers; 7) benefits counseling; and 8) follow-along supports after a job is obtained. Supported employment has been successfully implemented in a wide range of cultural and clinical populations, although challenges to implementation are also encountered. Common challenges are related to problems such as the failure to access technical assistance, system issues, negative beliefs and attitudes of providers, funding restrictions, and poor leadership. These challenges can be overcome by tapping expertise in IPS supported employment, including standardized and tested models of training and consultation. Efforts are underway to increase the efficiency of training methods for supported employment and the overall program, and to improve its effectiveness for those clients who do not benefit. Progress in IPS supported employment offers people with a serious mental illness realistic hope for achieving their work goals, and taking greater control over their lives.

Performance of subjects with and without severe mental illness on a clinical test of problem solving.

Severe mental illness is associated with impairments in executive functions, such as conceptual reasoning, planning, and strategic thinking all of which impact problem solving. The present study examined the utility of a novel assessment tool for problem solving, the Rapid Assessment of Problem Solving Test (RAPS) in persons with severe mental illness. Subjects were 47 outpatients with severe mental illness and an equal number healthy controls matched for age and gender. Results confirmed all hypotheses with respect to how subjects with severe mental illness would perform on the RAPS. Specifically, the severely mentally ill subjects (1) solved fewer problems on the RAPS, (2) when they did solve problems on the test, they did so far less efficiently than their healthy counterparts, and (3) the two groups differed markedly in the types of questions asked on the RAPS. The healthy control subjects tended to take a systematic, organized, but not always optimal approach to solving problems on the RAPS. The subjects with severe mental illness used some of the problem solving strategies of the healthy controls, but their performance was less consistent and tended to deteriorate when the complexity of the problem solving task increased. This was reflected by a high degree of guessing in lieu of asking constraint questions, particularly if a category-limited question was insufficient to continue the problem solving effort.

The convergence of neuropsychological testing and clinical ratings of cognitive impairment in patients with schizophrenia.

This study examined the relationship between clinical rating of cognitive symptoms and performance on neuropsychological tests in acute and chronic samples of patients with schizophrenia. Two separate studies examined patients who varied widely in their lifetime functional outcome, including 263 elderly poor-outcome inpatients and 20 acutely admitted patients. In the first study, six cognitive performance measures were collected, and in the second study, five different measures were collected. Correlations with different symptom models of cognitive and negative symptoms were examined. In both samples, cognitive symptoms were never more highly correlated with cognitive test performance than with negative symptoms. When cognitive and negative symptom ratings were combined, they never accounted for as much as half of the variance in performance on the cognitive tests in both samples. These data suggest that clinical assessment of symptoms is not a viable alternative to neuropsychological testing to obtain information about cognitive functioning in schizophrenia. These results may also be specific to the clinical rating scale used, the Positive and Negative Syndrome Scale (PANSS).

The role of cognition in vocational functioning in schizophrenia.

Schizophrenia is associated with long-term unemployment. Cognitive dysfunction, rather than clinical symptoms, may be the most important factor in the ability to work for patients with this disorder. To evaluate the relationship of clinical symptoms and cognitive functioning to work status, thirty patients with schizophrenia, who were participants in a vocational rehabilitation program, were evaluated with a comprehensive neuropsychological battery and assessment of psychopathology. Subjects were classified as being in stable full-time, part-time or unemployed work status for at least a year. Univariate analysis indicated that patients who were working full-time were significantly better educated, more likely to be treatment-resistant, more likely to be treated with an atypical antipsychotic medication, had more positive symptoms, and were engaged in work tasks which were more cognitively complex than the part-time employed and unemployed work groups. An ANCOVA controlling for education demonstrated that the full-time employed group performed significantly better than the unemployed group on measures of executive functioning, working memory and vigilance; and significantly better than the part-time group on measures of vigilance and executive functioning. Although negative symptoms did not significantly relate to work status in the univariate analysis, a multiple regression indicated that negative symptoms, level of education, and executive functioning differentiated the work groups. These results suggest that poor premorbid function, negative symptoms and cognitive dysfunction are significantly associated with unemployment in schizophrenia.

Relationship of cognitive functioning, adaptive life skills, and negative symptom severity in poor-outcome geriatric schizophrenia patients.

The authors assessed whether cognitive functioning and negative symptoms are related to functional outcome across severity of negative symptoms and examined relationships between symptom domains in patients with high versus low negative symptom severity. The interrelationships between cognitive functioning and functional skills in poor-outcome geriatric schizophrenic patients were compared between those who were in the first (n = 81) and the fourth quartiles (n = 127) of negative symptom severity based on the normative data in the Positive and Negative Syndrome Scale. It was found that negative symptoms and cognitive functioning were the strongest correlates of functional status in geriatric poor-outcome schizophrenic patients--regardless of negative symptom severity. Interestingly, the greater the severity of negative symptoms, the less strongly negative symptoms were related to functional outcome. The present findings demonstrate that the relationship of cognitive functioning to social and adaptive functioning remains significant despite differing levels of negative symptom severity.

The longitudinal relationship of clinical symptoms, cognitive functioning, and adaptive life in geriatric schizophrenia.

Cognitive dysfunction is increasingly being recognized as a major contributor to the adaptive impairment seen in most patients with schizophrenia. Reported here is a prospective longitudinal evaluation of the relationship between cognitive and adaptive functioning in elderly patients with schizophrenia. It was hypothesized that baseline cognitive and negative, but not positive symptoms, would be predictive of cross-sectional impairment and longitudinal outcome. Subjects were 168 elderly patients with schizophrenia, free of major neurological disorders, who were residents of a long-term psychiatric facility. Subjects were assessed at baseline and again an average of 15months later. The PANSS was used to assess the severity of symptoms of schizophrenia. Cognitive symptoms were assessed using the components of the CERAD cognitive battery. Social and adaptive functioning was assessed using the SAFE scale. Spearman correlations were determined among clinical variables, and the rank ordering of prediction of SAFE scale scores at follow-up was determined using a stepwise regression procedure. At follow-up, adaptive life skills correlated with cognitive performance and negative symptoms (Spearman rho values 0. 41-0.57, all p values <0.0001), but not positive symptoms (r=0.09, n. s.). Among cognitive tasks, verbal learning and memory were most highly correlated with adaptive skills at follow-up. These results confirm and extend previous studies that indicate that cognitive impairments are predictive, both cross-sectionally and longitudinally, of adaptive life skills in persons with schizophrenia. Negative symptoms, but not positive symptoms, were correlated with impaired adaptive skills. Taken together, these results underscore the need to develop more effective treatments for cognitive and negative symptoms in schizophrenia.

Neurocognition as a determinant of employment status in schizophrenia.

Chronic unemployment is a major problem faced by many persons with schizophrenia. In this article, the author first reviews reasons why employment is an important goal for patients with schizophrenia. Employment appears to improve the clinical symptoms of schizophrenia. Employment also reduces the economic costs of the illness to society. The author then discusses predictors of positive employment outcomes in schizophrenia. Clinical symptoms, especially positive symptoms, do not appear to play a large role in predicting occupational functioning in schizophrenia. The author than reviews the evidence for the role of cognitive impairment in unemployment in patients with schizophrenia. In seven of the eight studies reviewed, significant relationships between cognitive functioning and work status/work behaviors were reported. These studies provide the basis for identifying those patients most at risk for the poorest occupational outcomes as well as those most likely to benefit from focused intervention.

Risperidone versus haloperidol on secondary memory: can newer medications aid learning?

The introduction of the new generation of antipsychotic medications for the treatment of schizophrenia has been accompanied by a growing interest in the neurocognitive effects of these drugs. The present study compared the effects of risperidone and haloperidol on secondary memory in a group of treatment-resistant schizophrenia patients. The study design included a baseline phase and two double-blind phases in which patients were randomly assigned to medication under two different dose conditions (fixed dose and flexible dose). Secondary memory was assessed at baseline, fixed-dose, and flexible-dose phases, using the California Verbal Learning Test (CVLT). Six measures were selected, which formed three factors (general verbal learning ability, retention, and learning strategy). Risperidone-treated patients showed greater improvement than haloperidol-treated patients in general verbal learning ability, a finding characterized by significant treatment effects on CVLT measures of learning acquisition, recall consistency, and recognition memory. After controlling for benztropine status, differences on the measures of learning acquisition and recall consistency remained significant, and differences in recognition memory weakened slightly (p = 0.07). No significant treatment effects were noted on retention or learning strategy. These findings suggest that risperidone may exert a facilitating effect on the acquisition of new verbal information, an effect that does not appear to be due to the activation of semantic encoding strategies.

The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia.

Cognitive function is markedly impaired in most patients with schizophrenia. Antecedents of this impairment are evident in childhood. The cognitive disability is nearly fully developed at the first episode of psychosis in most patients. The contribution of cognitive impairment to outcome in schizophrenia, especially work function, has been established. Preliminary results indicate that cognitive function, along with disorganization symptoms, discriminate schizophrenia patients who are able to work full-time from those who are not. Typical neuroleptic drugs lack the ability to improve the various domains of cognitive function impaired in schizophrenia. Atypical antipsychotic drugs pharmacologically related to clozapine-quetiapine, olanzapine, risperidone, sertindole, and ziprasidone--share the ability to produce fewer extrapyramidal symptoms than typical neuroleptic drugs and more potent antagonism of serotonin2a relative to dopamine2 receptors. However, they have a number of different clinical effects. We have identified all the studies of clozapine, olanzapine, and risperidone that provide data on their effects on cognition in schizophrenia. Data for each drug are reviewed separately in order to identify differences among them in their effects on cognition. Twelve studies that report cognitive effects of clozapine are reviewed. These studies provide (1) strong evidence that clozapine improves attention and verbal fluency and (2) moderate evidence that clozapine improves some types of executive function. However, results of the effects of clozapine on working memory and secondary verbal and spatial memory were inconclusive. Risperidone has relatively consistent positive effects on working memory, executive functioning, and attention, whereas improvement in verbal learning and memory was inconsistent. Preliminary evidence presented here suggests that olanzapine improves verbal learning and memory, verbal fluency, and executive function, but not attention, working memory, or visual learning and memory. Thus, atypical antipsychotic drugs as a group appear to be superior to typical neuroleptics with regard to cognitive function. However, available data suggest that these drugs produce significant differences in specific cognitive functions. These differences may be valuable adjunctive guides for their use in clinical practice if cognitive improvements reach clinical significance. The effects of the atypical antipsychotic drugs on cholinergic and 5-HT2a-mediated neurotransmission as the possible basis for their ability to improve cognition are discussed. It is suggested that the development of drugs for schizophrenia should focus on improving the key cognitive deficits in schizophrenia: executive function, verbal fluency, working memory, verbal and visual learning and memory, and attention.

The effects of clozapine on cognitive functioning in schizophrenia.

Cognitive function may be markedly impaired in patients with schizophrenia; however, it has only recently been recognized as an important factor in determining patient outcome. Research has shown that improvements in cognitive functioning occur independently of improvements in positive or negative clinical symptoms, and whereas typical antipsychotics may improve clinical symptoms, they have little or no efficacy in improving cognitive dysfunction. However, there is evidence that the atypical antipsychotic clozapine may improve this core deficit of schizophrenia. This review summarizes 12 published studies that assessed the effect of clozapine on cognitive functioning. As a group, these studies suggest that psychomotor speed, verbal fluency, and verbal learning and memory may be improved by treatment with clozapine. Such cognitive improvements with clozapine treatment may offer an advantage to patients with schizophrenia by enhancing the possibility of better vocational functioning and quality of life.

Utilization of a school-based clinic for identification and treatment of adolescent sexual abuse.

Implementation of a mental health facet of a school-based clinic provided a special opportunity to gain more detailed information about the nature and scope of sexual abuse among Hispanic adolescents. A system was implemented to gather ongoing data on the number identified as having been sexually abused. Over the 16-month period covered by this report, in-depth semi-structured interviews were conducted with 22 Hispanics, and 50% were seen in therapy. Findings are reported regarding the abuse and its consequences, as well as implications for research and practice.

Dopaminergic drugs reverse the impairment of radial-arm maze performance caused by lesions involving the cholinergic medial pathway.

Pharmacological studies have shown that both cholinergic and dopaminergic transmitter systems are crucial for optimal choice accuracy in the radial-arm maze and that these systems interact in a complex fashion. Lesion studies have provided evidence that the basal nuclear complex of the forebrain, the origin of cholinergic projections to the cerebral mantle, may be critical for the cholinergic modulation of learning and memory. We have shown that knife-cut lesions of the medial cholinergic pathway significantly impair radial-arm maze choice accuracy performance. The current study examined the effectiveness of D1 and D2 ligands in counteracting this lesion-induced deficit. The adverse effects of medial cholinergic pathway lesions were diminished or reversed by daily treatment with a D1 agonist (SKF 38393), a D2 agonist (LY 171555) or a D1 antagonist (SCH 23390), but were not affected by treatment with a D2 antagonist (raclopride). The three beneficial treatments have previously been found to attenuate the adverse effects of nictonic or muscarinic blockade on choice accuracy performance in the radial-arm maze. The finding that these dopaminergic drugs ameliorate the memory deficit caused by lesions involving the cholinergic medial pathway suggests the importance of interactions between cholinergic and dopaminergic systems in radial-arm maze performance. These results may provide leads for the development of novel therapeutic approaches for treating human disorders thought to result from cholinergic hypofunction.

Impairment of radial-arm maze performance in rats following lesions involving the cholinergic medial pathway: reversal by arecoline and differential effects of muscarinic and nicotinic antagonists.

Pharmacologic studies have indicated that accurate performance on the radial-arm maze depends upon the integrity of both nicotinic and muscarinic cholinergic neurotransmitter systems and that these systems interact in a complex fashion. Although numerous studies have suggested that pathways deriving from the basal nuclear complex of the forebrain are critical for the cholinergic modulation of learning and memory, most have focussed on the septohippocampal projection, and none have specifically targeted the medial or lateral systems. In Experiment 1, cortical knife cuts interrupting the medial cholinergic pathway were made at the level of the caudate-putamen nucleus. Such transections produced a robust but temporary disruption of choice accuracy performance in the radial-arm maze. Recovery of this behavior occurred within 10 days and before cholinergic fiber regeneration, suggesting that compensatory changes could have taken place in non-ablated neuronal circuits. In Experiment 2, daily postsurgical administration of arecoline, an agonist with predominantly muscarinic actions, was found to virtually eliminate the adverse behavioral effects of medial pathway transections, indicating that the deficit could be attributable, in part, to disruption of cholinergic projections. In Experiment 3, the effects of scopolamine, a muscarinic antagonist, and mecamylamine, a nicotinic antagonist, were examined in rats with medial cholinergic pathway transections after behavior had returned postsurgically to control levels. Although both drugs attenuated radial-arm maze performance before knife cuts, only scopolamine reduced choice accuracy following surgery. We conclude that the medial cholinergic pathway, particularly its nicotinic actions, plays an important role in cognitive function, at least as exemplified by radial-arm maze performance. Muscarinic mechanisms associated with other telencephalically projecting cholinergic networks, as well as possibly with the medial pathway itself, appear to operate interactively with nicotinic influences.

Cholinergic-dopaminergic interactions in cognitive performance.

Both acetylcholinergic (ACh) and dopaminergic (DA) systems have been found to be crucial for the maintenance of accurate cognitive performance. In a series of studies examining those aspects of cognitive function revealed by the radial-arm maze, we have found that these two neurotransmitter systems interact in a complex fashion. Choice accuracy deficits in the radial-arm maze can be induced by blockade of either muscarinic- or nicotinic-ACh receptors. The choice accuracy deficit induced by blockade of muscarinic receptors with scopolamine can be reversed by the DA receptor blocker, haloperidol. The specific DA D1 blocker SCH 23390 also has this effect, whereas the specific D2 blocker raclopride does not, implying that it is D1 blockade that is critical for reversing the scopolamine effect. On the other hand, the choice accuracy deficit induced by nicotinic blockade with mecamylamine is potentiated by haloperidol. This effect is also seen with the D2 antagonist raclopride, but not with the D1 antagonist SCH 23390, implying that it is the D2 receptor which is important for the potentiation of the mecamylamine effect. The relevance of the D2 receptor for nicotinic actions on cognitive function is emphasized by the finding that the selective D2 agonist LY 171555 reverses the choice accuracy deficit caused by mecamylamine. Nicotinic and muscarinic blockade are synergistic in the deficit they produce. Antagonist doses subthreshold when given alone produce a pronounced impairment when given together. This latter deficit can be reversed by the D2 agonist LY 171555. These studies have outlined the complex nature of ACh-DA interactions with regard to cognitive function. Possible neural circuits for these interactions are discussed. The effectiveness of these selective DA treatments in reversing cognitive deficits due to ACh underactivation suggests a novel approach to treating cognitive dysfunction in syndromes such as Alzheimer's disease.

Characterization of the cognitive effects of combined muscarinic and nicotinic blockade.

Choice accuracy performance in the radial-arm maze is dependent upon the integrity of both the nicotinic and muscarinic cholinergic receptors. Pharmacological blockade of either of these subtypes of cholinergic receptors with mecamylamine or scopolamine impairs choice accuracy in the radial-arm maze. We have previously demonstrated that the performance deficit caused by muscarinic blockade is exacerbated in at least an additive fashion by coadministration of the nicotinic antagonist, mecamylamine. In the present study, it was found that mecamylamine and scopolamine act together in a greater than additive fashion in disrupting radial-arm maze choice accuracy. When doses of these drugs which do not by themselves cause significant impairments in choice accuracy are given together, they induce a pronounced impairment. Previous results have shown that the adverse effects of nicotinic blockade could be reversed by the dopaminergic D2 agonist LY 171555. In this study, this drug was found to attenuate the cognitive impairment caused by combined nicotinic and muscarinic blockade. On the other hand, the dopaminergic D1 antagonist SCH 23390 which has previously been shown to reverse the adverse effects of muscarinic blockade was not found in this study to attenuate the impairment of combined nicotinic and muscarinic blockade. Since combined nicotinic and muscarinic blockade approximates generalized cholinergic underactivation, treatments like LY 171555, which attenuate the adverse effects of this combined blockade, may be useful in treating syndromes like Alzheimer's disease, which are characterized by generalized cholinergic loss.

Reversal of a mecamylamine-induced cognitive deficit with the D2 agonist, LY 171555.

Pharmacological blockade of either nicotinic or muscarinic cholinergic receptors has been found to impair choice accuracy in the radial-arm maze. Simultaneous blockade of both of these receptor types causes an additive impairment. However, despite these common effects, nicotinic and muscarinic receptors have been found to have differential involvement with dopamine receptors. The cognitive impairment caused by the muscarinic antagonist scopolamine is reversed by the D1 antagonist SCH 23390 but is unaffected by the D2 antagonist raclopride. In contrast, the cognitive impairment caused by the nicotinic antagonist mecamylamine is unaffected by SCH 23390 but is potentiated by raclopride. In the current study, the D2 agonist LY 171555 was found to be effective in reversing the radial-arm maze choice accuracy impairment caused by mecamylamine. In contrast, the D1 agonist SKF 38393 was not found to be effective. Thus, we have found selective dopaminergic D1 and D2 treatments which counteract the adverse cognitive effects of either nicotinic or muscarinic blockade. A combination of these treatments may be useful in treating the cognitive effects of generalized cholinergic underactivation.

Nicotinic-dopaminergic relationships and radial-arm maze performance in rats.

Accurate performance on the radial-arm maze is dependent upon the integrity of nicotinic-cholinergic, muscarinic-cholinergic, and dopaminergic systems. Pharmacological blockade of these systems with mecamylamine, scopolamine, or haloperidol impairs choice accuracy in the maze. We have previously demonstrated that the performance deficit caused by muscarinic blockade is enhanced by coadministration of the nicotinic antagonist, mecamylamine, and is diminished by coadministration of the dopamine antagonist, haloperidol. In the present study, it was found that the choice accuracy deficit produced by nicotinic blockade is enhanced, not antagonized, by coadministration of haloperidol. Thus, although both nicotinic and muscarinic cholinergic systems are involved in radial-arm maze performance and antagonists of these receptors are additive in the deficits they cause, nicotinic and muscarinic interactions with dopaminergic systems are opposite in nature.

Effects of combined muscarinic and nicotinic blockade on choice accuracy in the radial-arm maze.

Acetylcholine (ACh) systems have been found to be crucial for the maintenance of accurate cognitive performance. A great variety of studies have shown that the muscarinic ACh receptor blocker scopolamine impairs choice accuracy in the radial-arm maze. Recently, it has been found that the nicotinic ACh receptor blocker mecamylamine also impairs radial-arm maze choice accuracy. In the present study, we investigated the effects of combined administration of these two ACh blockers. Scopolamine (0.15 mg/kg) and mecamylamine (10 mg/kg) each moderately impaired choice accuracy. Combined treatment with scopolamine and mecamylamine significantly decreased choice accuracy relative to either drug alone. This combination treatment lowered choice accuracy to chance levels. These data show that nicotinic and muscarinic blockade have at least additive effects in producing an anterograde memory deficit. Concurrent blockade of these two components of ACh systems may provide a better animal model of cognitive impairments due to the loss of cholinergic neurons, such as Alzheimer's disease.

Radial-arm maze performance in rats is impaired by a combination of nicotinic-cholinergic and D2 dopaminergic antagonist drugs.

Performance on the radial-arm maze depends on the integrity of both cholinergic and dopaminergic systems. We have previously found that administration of either the nicotinic-cholinergic antagonist, mecamylamine, or the muscarinic-cholinergic antagonist, scopolamine, impairs choice accuracy in the radial-arm maze. Co-administration of the dopaminergic antagonist, haloperidol, ameliorated the performance deficit caused by scopolamine but exacerbated the deficit caused by mecamylamine. Furthermore, antagonism of the effect of scopolamine is due specifically to blockade of D1 receptors. In the present experiment behaviorally subthreshold doses of mecamylamine and the D2 antagonist raclopride impaired maze performance when administered together. No interactive effects were observed between mecamylamine and the D1 antagonist SCH 23390. Although several of the drug treatments studied significantly increased choice latency, an index of motor behavior, there was no perfect relationship between choice accuracy and choice latency. These data indicate that nicotinic-cholinergic and muscarinic-cholinergic systems interact selectively and differentially with D1 and D2 dopaminergic systems.