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Randomized-controlled trials of Cognitive Enhancement Therapy (CET) reveal its impact on cognitive and functional improvements in schizophrenia and serve as an opportunity for causal claims of potential mediational relationships. In order to examine cognitive gains during CET as a mechanism for improving functional capacity, this secondary analysis included 86 outpatients in the early course of schizophrenia from an 18-month randomized-controlled trial of CET. Functional capacity was measured using the Brief UCSD Performance-Based Skills Assessment (UPSA-B) and cognitive performance by the MATRICS Consensus Cognitive Battery (MCCB) and additional measures of social cognition. Mixed-effects models were used to examine the effects of treatment on the UPSA-B changes and mediation through cognitive improvements. Changes in overall cognition proved to be a significant mediator of CET-related gains in functional capacity at mid-treatment and treatment completion. Exploratory models examining separable cognitive domains further found that improvements in attention, theory of mind, and emotion processing significantly mediated CET effects on functional capacity. This study suggests that CET has potential for improving functional capacity in individuals with schizophrenia, and that cognitive improvements partially mediate this relationship. This evidence can be beneficial for guiding more targeted approaches for rehabilitation in this population.

Cognitive enhancement therapy (CET) is an 18-month comprehensive cognitive remediation intervention designed to improve cognition and functioning among patients with schizophrenia. The current study sought to confirm previously observed benefits of CET on cognitive and behavioral outcomes in the early course of the condition in a large multisite trial.Overall, 102 outpatients with early-course schizophrenia were randomly assigned to 18 months of CET (N=58) or enriched supportive therapy (EST; N=44). Participants completed cognitive, social adjustment, and symptom assessments at baseline and at 9 and 18 months. Composite indices were calculated for these outcomes. Mixed-effects models investigated differential changes in outcomes between CET and EST. Because of a high attrition rate, sensitivity analyses of data from treatment completers (N=49) were conducted.The effects of CET on improved overall cognition were confirmed and tentatively confirmed for social cognition in both intent-to-treat and completer analyses, and beneficial effects on attention/vigilance were also observed. An effect of CET on social adjustment was not confirmed in the analyses, because both CET and EST groups had considerably improved social adjustment. Although not statistically significant, the between-group effect size for CET's effect on social adjustment doubled from the intent-to-treat (Cohen's d=0.23) to completer analyses (Cohen's d=0.51) (p=0.057). Both groups displayed similar symptom improvements.CET effectively improved cognition among patients with early-course schizophrenia. The functional benefits of CET appeared to increase with treatment retention. Further research is needed to understand predictors of attrition and mechanisms of change during CET for this population.

OBJECTIVE: Cognitive remediation is a promising approach to treating core cognitive deficits in adults with autism, but rigorously controlled trials of comprehensive interventions that target both social and non-social cognition over a sufficient period of time to impact functioning are lacking. This study examined the efficacy of Cognitive Enhancement Therapy (CET) for improving core cognitive and employment outcomes in adult autism. METHOD: Verbal adult outpatients with autism spectrum disorder (N = 54) were randomized to an 18-month, single-blind trial of CET, a cognitive remediation approach that integrates computer-based neurocognitive training with group-based training in social cognition, or an active Enriched Supportive Therapy (EST) comparison focused on psychoeducation and condition management. Primary outcomes were composite indexes of neurocognitive and social-cognitive change. Competitive employment was a secondary outcome. RESULTS: Intent-to-treat analyses indicated that CET produced significant differential increases in neurocognitive function relative to EST (d = .46, P = .013). Both CET and EST were associated with large social-cognitive improvements, with CET demonstrating an advantage at 9 (d = .58, p = .020), but not 18 months (d = .27, p = .298). Effects on employment indicated that participants treated with CET were significantly more likely to gain competitive employment than those in EST, OR = 6.21, p = .023, which was mediated by cognitive improvement. CONCLUSIONS: Cognitive Enhancement Therapy is a feasible and potentially effective treatment for core cognitive deficits in adult autism spectrum disorder. The treatment of cognitive impairments in this population can contribute to meaningful improvements in adult outcomes. LAY SUMMARY: Cognitive Enhancement Therapy (CET), an 18-month cognitive remediation intervention designed to improve thinking and social understanding, was found to be more effective than supportive therapy at improving mental quickness, attention, and employment in adults living with autism. Social understanding was equally improved in CET and supportive therapy. Cognitive remediation interventions are feasible and may confer significant functional benefits to adults with autism. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00902798

Substance use problems are common among people with schizophrenia, as are significant cognitive impairments. Because of potential shared neurobiological pathways, it is possible that cognitive remediation interventions may be associated with improvements in both substance use and cognition. This study examined the impact of cognitive remediation on alcohol and cannabis use and the cognitive correlates of changes in substance use among outpatients with schizophrenia.Individuals with schizophrenia who were receiving outpatient services at a psychiatric clinic and had moderate or higher addiction severity scores (N = 31) were randomized to 18 months of cognitive enhancement therapy (n = 22) or usual care (n = 9). Cognitive enhancement therapy is a cognitive remediation approach that integrates computer-based training in attention, memory, and problem solving with a group-based social cognition curriculum. Usual care was provided to all participants and consisted of routine psychiatric care. Primary outcomes included days of alcohol and cannabis use, assessed with the Timeline Followback method every six months and modeled using penalized quasi-likelihood growth curves.Participants were on average 38.23 (SD = 13.44) years of age, had been ill for 14.19 (SD = 11.28) years, and were mostly male (n = 22, 71%), and about half were Caucasian (n = 16, 52%). Temporal patterns of substance use days were highly variable and followed nonlinear trajectories. Intent-to-treat analyses indicated that, compared to patients only receiving usual care, those receiving cognitive enhancement therapy were significantly less likely to use alcohol (OR = .22; 95% CI: .05, .90; p = .036), but not cannabis (OR = 1.89; 95% CI: .02, 142.99; p = .774) over time, and they reduced their alcohol use at significantly accelerated rates (OR = 1.02; 95% CI: 1.01, 1.03; p = .003). Changes in cognition were variably associated with substance use outcomes, although improvements in visual learning and reasoning and problem solving were both consistently related to reduced alcohol and cannabis use.Cognitive remediation may be effective for improving some substance use problems in schizophrenia. Visual learning and problem-solving deficits may be particularly important targets of such interventions, given their association with reduced alcohol and cannabis use. This study is registered at clinicaltrials.gov under #NCT01292577.

Substance use is a frequent problem in schizophrenia, and although many substance misusing patients with the disorder also experience considerable cognitive impairments, such individuals have been routinely excluded from clinical trials of cognitive remediation that could support their functional and addiction recoveries. This study conducted a small-scale feasibility trial of Cognitive Enhancement Therapy (CET) in substance misusing schizophrenia patients to assess the feasibility and efficacy of implementing comprehensive neurocognitive and social-cognitive remediation in this population. A total of 31 schizophrenia outpatients meeting addiction severity criteria for alcohol and/or cannabis use were randomized to 18months of CET or usual care. Feasibility findings indicated high degrees of satisfaction with CET, but also presented significant challenges in the recruitment and retention of substance misusing patients, with high levels of attrition (50%) over the study period, primarily due to positive symptom exacerbation. Intent-to-treat efficacy analyses showed large and significant improvements in neurocognition (d=.86), social cognition (d=1.13), and social adjustment (d=.92) favoring CET. Further, individuals treated with CET were more likely to reduce alcohol use (67% in CET vs. 25% in usual care) during treatment (p=.021). These results suggest that once engaged and stabilized, CET is a feasible and potentially effective treatment for cognitive impairments in patients with schizophrenia who misuse alcohol and/or cannabis. Substance misusing patients who are able to engage in treatment may be able to benefit from cognitive remediation, and the treatment of cognitive impairments may help improve substance use outcomes among this underserved population.

Cognitive rehabilitation has shown beneficial effects on cognition in patients with schizophrenia, which may also help to improve negative symptoms due to overlapping pathophysiology between these two domains. To better understand the possible relationship between these areas, we conducted an exploratory analysis of the effects of Cognitive Enhancement Therapy (CET) on negative symptoms. Early course schizophrenia outpatients ( n =58) were randomized to 2 years of CET or an Enriched Supportive Therapy (EST) control condition. Results revealed significant and medium-sized ( d =0.61) differential improvements favoring CET in overall negative symptoms, particularly social withdrawal, affective flattening, and motor retardation. Neurocognitive improvement was associated with reduced negative symptoms in CET, but not EST patients. No relationships were observed between improvements in emotion processing aspects of social cognition, as measured by the Mayer–Salovey–Caruso Emotional Intelligence Test, and negative symptoms. CET represents an effective cognitive rehabilitation intervention for schizophrenia that may also have benefits to negative symptoms. Future studies specifically designed to examine negative symptoms during the course of cognitive rehabilitation are needed.

Adults with autism experience significant impairments in social and non-social information processing for which few treatments have been developed. This study conducted an 18-month uncontrolled trial of Cognitive Enhancement Therapy (CET), a comprehensive cognitive rehabilitation intervention, in 14 verbal adults with autism spectrum disorder to investigate its feasibility, acceptability, and initial efficacy in treating these impairments. Results indicated that CET was satisfying to participants, with high treatment attendance and retention. Effects on cognitive deficits and social behavior were also large (d = 1.40 to 2.29) and statistically significant (all p < .001). These findings suggest that CET is a feasible, acceptable, and potentially effective intervention for remediating the social and non-social cognitive impairments in verbal adults with autism.

Individuals with schizophrenia who misuse substances are burdened with impairments in emotion regulation. Cognitive enhancement therapy (CET) may address these problems by enhancing prefrontal brain function. A small sample of outpatients with schizophrenia and alcohol and/or cannabis substance use problems participating in an 18-month randomized trial of CET (n = 10) or usual care (n = 4) completed posttreatment functional neuroimaging using an emotion regulation task. General linear models explored CET effects on brain activity in emotional neurocircuitry. Individuals treated with CET had significantly greater activation in broad regions of the prefrontal cortex, limbic, and striatal systems implicated in emotion regulation compared to usual care. Differential activation favoring CET in prefrontal regions and the insula mediated behavioral improvements in emotional processing. Our data lend preliminary support of CET effects on neuroplasticity in frontolimbic and striatal circuitries, which mediate emotion regulation in people with schizophrenia and comorbid substance misuse problems.

Objectives Cognitive rehabilitation can improve cognition in schizophrenia and prevent disability. It is unknown, however, whether a greater neurobiologic reserve, as measured by cortical volumes, will predict a favorable response to rehabilitation. We investigated this question in early course schizophrenia patients treated with Cognitive Enhancement Therapy (CET). Methods Outpatients in the early course of schizophrenia or schizoaffective disorder were randomly assigned to CET (n = 29) or an Enriched Supportive Therapy control (n = 21) and treated for two years. Cortical surface area and gray matter volume data were collected before treatment using structural magnetic resonance imaging. Neurocognition and social cognition were assessed before, and after one and two years of treatment. Moderator analyses examined the impact of pre-treatment cortical surface area and gray matter volume on differential neurocognitive and social-cognitive response to CET. Results Pre-treatment, whole brain cortical surface area and gray matter volume significantly moderated the effects of CET on social cognition, but not neurocognition. Greater neurobiologic reserve predicted a rapid social-cognitive response to CET in the first year of treatment; patients with less neurobiologic reserve achieved a comparable social-cognitive response by the second year. While nearly every regional measurement significantly contributed to this accelerated social-cognitive treatment response, effects were the strongest in the temporal cortex. Conclusions A broad cortical surface area and gray matter reserve is associated with an accelerated social-cognitive response to CET in early schizophrenia, yet the benefits of cognitive rehabilitation are achieved in those with less initial cognitive resources after a longer duration of treatment.

Schizophrenia is an often chronic mental disorder that is characterized by significant impairments in cognition and functioning. Marked deficits have been observed in social and non-social cognitive domains (Heinrichs & Zakzanis, 1998; Penn, Corrigan, Bentall, Racenstein, & Newman, 1997), which cross-sectional and longitudinal studies have found to be significant and consistent predictors of functional outcome (Couture, Penn, & Roberts, 2006; Green, Kern, Braff, & Mintz, 2000). Such findings have fueled arguments for the treatment of cognitive impairments in schizophrenia as a key mechanism for improving functioning in the disorder (Green & Nuechterlein, 1999; Hogarty & Flesher, 1992). While the pharmacologic treatment of cognitive impairments in schizophrenia has produced limited improvements (Keefe et al., 2007; Sergi et al., 2007), a number of psychosocial cognitive rehabilitation approaches have emerged as effective methods for addressing cognitive deficits in the disorder (McGurk, Twamley, Sitzer, McHugo, & Mueser, 2007). One integrated approach to the remediation of social and non-social cognitive impairments in schizophrenia that has been shown to be particularly effective at improving cognition and functioning in the disorder is Cognitive Enhancement Therapy (CET; Hogarty & Greenwald, 2006). In the initial CET study with chronically ill patients, we demonstrated that CET resulted in marked improvements in processing speed, neurocognition, and social cognition, as well as social adjustment (Hogarty et al., 2004). A one-year follow-up study also showed that these improvements could be maintained after the completion of treatment (Hogarty, Greenwald, & Eack, 2006). Recently, we tested the effects of CET as an early intervention approach with 58 early course schizophrenia outpatients, and again found substantial improvements in neurocognition (d = .46) and social cognition (d = 1.55), but not processing speed, which was relatively preserved among early course patients. In addition, large (d = 1.53) and broad functional improvements were observed in vocational functioning, activities of daily living, and other domains of social adjustment (Eack et al., 2009; Eack et al., in press). The effects of CET and other cognitive rehabilitation approaches on functional outcome strongly support the treatment of cognition as a critical mechanism for functional improvement in schizophrenia. Unfortunately, few studies have explicitly tested the degree to which improvements in cognition contribute to functional improvement. In the initial CET study with chronically ill patients, we found that improvements in processing speed served as a significant partial mediator of CET effects on social adjustment (Hogarty, Greenwald, & Eack, 2006). Wykes and colleagues studied Cognitive Remediation Therapy among early-onset patients and found that improvements in executive functioning, working memory, and planning were related to improved social behavior (Wykes et al., 2007); however, previous studies of that intervention with chronic patients did not demonstrate a link between changes in neurocognitive domains and functioning (Reeder et al., 2004; Reeder et al., 2006). To date, no studies have examined the effect of both improved neurocognition and social cognition on functional outcome during cognitive rehabilitation in schizophrenia. Having recently found substantial functional benefits of CET in early schizophrenia during a two year randomized trial (Eack et al., 2009), we now examine the degree to which social-cognitive and neurocognitive enhancement during this trial served as active mechanisms of functional improvement in these early course patients. It was hypothesized that both improved neurocognition and social cognition would contribute to improvements in functioning, and mediate the differential effects of CET on functional outcome. Unlike our initial CET study (Hogarty, Greenwald, & Eack, 2006), the mediational effects of improved processing speed were not investigated, as this sample of early course patients demonstrated relatively preserved performance in processing speed that did not change with treatment (Eack et al., 2009).

Objective: To examine the effects of psychosocial cognitive rehabilitation on employment outcomes in a randomized controlled trial for individuals with early course schizophrenia. Method: Early course schizophrenia outpatients (N = 58) were randomly assigned to cognitive enhancement therapy (CET) or an enriched supportive therapy (EST) control and treated for 2 years. Comprehensive data on cognition and employment were collected annually. Results: Individuals treated with CET were significantly more likely to be competitively employed, had greater earnings from employment, and were more satisfied with their employment status by the end of treatment compared to EST recipients. Mediator analyses revealed that improvements in both social and nonsocial cognition mediated CET effects on employment. Conclusion: CET can help facilitate employment in early schizophrenia by addressing the cognitive impairments that limit functioning in the disorder. Inclusion of cognitive rehabilitation in social work practice can support more optimal functional recovery from schizophrenia.

Cognitive rehabilitation is an effective intervention for addressing cognitive impairments in patients with schizophrenia. Previous research has shown that the early application of Cognitive Enhancement Therapy (CET) can improve neurocognitive and-social cognitive deficits in the early course of the disorder, and ultimately reduce the substantial functional disability that these patients experience. However, the lasting effects of CET on functional outcome in early course schizophrenia patients remain unknown. In this study, 58 patients in the early course of schizophrenia or schizoaffective disorder treated with two years of either CET or an Enriched Supportive Therapy (EST) control were followed-up one year after the completion of treatment to examine the durability of CET effects on functional outcome. At one-year post-treatment, a high (72%) retention rate was observed in both treatments. Results from intent-to-treat analyses employing linear mixed-effects models indicated that CET effects on functional outcome were broadly maintained one-year post-treatment, and that patients receiving CET continued to demonstrate highly significant differential functional benefits compared to patients treated with EST. These findings support the durability of CET effects on functional outcome in the early course of schizophrenia, and point to the potential of cognitive rehabilitation to have a lasting impact on the early trajectory of the disorder.

This research examined the preliminary effects of Cognitive Enhancement Therapy (CET) on social cognition in early course schizophrenia, using an objective, performance-based measure of emotional intelligence. Individuals in the early course of schizophrenia were randomly assigned to either CET (n = 18) or Enriched Supportive Therapy (n = 20), and assessed at baseline and after one year of treatment with the Mayer-Salovey-Caruso Emotional Intelligence Test. A series of analyses of covariance showed highly significant (p = .005) and large (Cohen's d = .96) effects favoring CET for improving emotional intelligence, with the most pronounced improvements occurring in patients' ability to understand and manage their own and others' emotions. These findings lend preliminary support to the previously documented benefits of CET on social cognition in schizophrenia, and suggest that such benefits can be extended to patients in the early course of the illness (141 words).

Cognitive rehabilitation is an emerging set of potentially effective interventions for the treatment of autism spectrum disorder, yet the applicability of these approaches for "high functioning" adults who have normative levels of intelligence remains unexplored. This study examined the initial cognitive performance characteristics of 40 verbal adults with autism enrolled in a pilot trial of Cognitive Enhancement Therapy to investigate the need for cognitive rehabilitation in this population. Results revealed marked and broad deficits across neurocognitive and social-cognitive domains, despite above-average IQ. Areas of greatest impairment included processing speed, cognitive flexibility, and emotion perception and management. These findings indicate the need for comprehensive interventions designed to enhance cognition among verbal adults with autism who have intact intellectual functioning.

To examine the effects of psychosocial cognitive rehabilitation on employment outcomes in a randomized controlled trial for individuals with early course schizophrenia.Early course schizophrenia outpatients (Individuals treated with CET were significantly more likely to be competitively employed, had greater earnings from employment, and were more satisfied with their employment status by the end of treatment compared to EST recipients. Mediator analyses revealed that improvements in both social and non-social cognition mediated the CET effects on employment.CET can help facilitate employment in early schizophrenia, by addressing the cognitive impairments that limit functioning in the disorder. Inclusion of cognitive rehabilitation in social work practice can support more optimal functional recovery from schizophrenia.

Autism spectrum disorder (ASD) and schizophrenia are both conditions that are characterized by impairments in social and non-social cognition, yet commonalities in the magnitude and domains of cognitive deficits across these two conditions remains unclear. This study examined neurocognitive and social-cognitive functioning in 47 outpatients with schizophrenia, 43 verbal adults with ASD, and 24 healthy volunteers. A comprehensive neuropsychological battery assessing processing speed, attention, memory, and problem-solving domains was administered along with a social-cognitive battery of emotion processing. Results demonstrated large and significant impairments in emotion processing and neurocognition relative to healthy individuals in participants with autism (d = -.97 and -1.71, respectively) and schizophrenia (d = -.65 and -1.48, respectively). No significant differences were observed between those with ASD and schizophrenia on any cognitive domain assessed, and the areas of greatest impairment were identical across both disorders and included slowness in speed of processing and an inability to understand emotions. These findings indicate a high degree of similarity in the cognitive challenges experienced by verbal adults with autism and schizophrenia, and the potential need for trans-diagnostic remediation approaches to enhance cognition in these conditions.

Patients with schizoaffective disorder (SZA) experience significant deficits in cognitive functioning similar to those seen in patients with schizophrenia (SZ), which are associated with poor functional outcomes. Cognitive remediation (CR) has shown promise in improving cognitive and functional outcomes in patients with SZ: however, no studies have compared these effects across diagnoses. We compared patients with SZ and SZA after cognitive enhancement therapy (CET) or enriched supportive therapy (EST). Both patient groups improved in multiple domains after CET, and diagnosis did not significantly moderate this relationship. Extending CR to all patients in which cognitive dysfunction is a core feature may be indicated.

a School of Social Work, University of Pittsburgh, United States b Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, United States c Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States d Department of Psychiatry, University of Pittsburgh School of Medicine, United States e Department of Neurology, University of Pittsburgh School of Medicine, United States

Context Cognitive rehabilitation has shown efficacy in improving cognition in patients with schizophrenia but the underlying neurobiologic changes that occur during these treatments and support cognitive improvement are not well known. Objective To examine differential changes in brain morphology in early course schizophrenia during cognitive rehabilitation vs supportive therapy. Design Randomized controlled trial. Setting An outpatient research clinic at a university-based medical center that provides comprehensive care services for patients with severe mental illness. Patients A total of 53 symptomatically stable but cognitively disabled outpatients in the early course of schizophrenia or schizoaffective disorder. Interventions A 2-year trial with annual structural magnetic resonance imaging and cognitive assessments. Cognitive enhancement therapy is an integrated approach to the remediation of cognitive impairment in schizophrenia that uses computer-assisted neurocognitive training and group-based social-cognitive exercises. Enriched supportive therapy is an illness management approach that provides psychoeducation and teaches applied coping strategies. Main Outcome Measures Broad areas of frontal and temporal gray matter change were analyzed with longitudinal, voxel-based morphometry methods using mixed-effects models followed by volumetric analyses of regions that demonstrated significant differential changes between treatment groups. Results Patients who received cognitive enhancement therapy demonstrated significantly greater preservation of gray matter volume over 2 years in the left hippocampus, parahippocampal gyrus, and fusiform gyrus, and significantly greater gray matter increases in the left amygdala (all corrected P Conclusion Cognitive enhancement therapy may offer neurobiologic protective and enhancing effects in early schizophrenia that are associated with improved long-term cognitive outcomes. Trial Registration clinicaltrials.gov Identifier:NCT00167362 Published online May 3, 2010 (doi:10.1001/archgenpsychiatry.2010.63).

Nursing administrators cannot ignore the need for suicide precautions in the general hospital. Though the incidence of suicide might be low, the number of patients at risk remains high. Legal liability for the institution that fails to provide reasonable care can be considerable. The authors offer a model suicide precautions policy, specifically tailored to the general hospital, and describe procedures for its implementation.