Context Cognitive rehabilitation has shown efficacy for 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 schizophrenia during cognitive rehabilitation versus supportive therapy. Design A 2-year, randomized-controlled trial with annual structural magnetic resonance imaging and cognitive assessments. Setting An outpatient research clinic at a university-based medical center providing 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 Cognitive enhancement therapy is an integrated approach to the remediation of cognitive impairments in schizophrenia that utilizes 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 using longitudinal voxel-based morphometry methods employing mixed-effects models, followed by volumetric analyses of regions demonstrating significant differential changes between treatment groups. Results Patients receiving cognitive enhancement therapy demonstrated significantly greater preservation of gray matter volume over the course of two years in the left hippocampus, parahippocampal gyrus, and fusiform gyrus, and significantly greater gray matter increases in the left amygdala (all corrected P < .040), compared with those receiving enriched supportive therapy. Less gray matter loss in the left parahippocampal and fusiform gyrus, and greater gray matter increases in the left amygdala were significantly related to improved cognition and mediated the beneficial cognitive effects of cognitive enhancement therapy. 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

Objective The early application of cognitive rehabilitation may afford long-term functional benefits to patients with schizophrenia. This study examined the two-year effects of an integrated neurocognitive and social-cognitive rehabilitation program, cognitive enhancement therapy (CET), on cognitive and functional outcomes in early course schizophrenia. Method Early course outpatients (mean illness duration = 3.19±2.24 years) with schizophrenia or schizoaffective disorder were randomly assigned to CET (n = 31) or enriched supportive therapy (EST) (n = 27), an illness management intervention utilizing psychoeducation and applied coping strategies, and treated for 2 years. Multivariate composite indexes of cognitive, social adjustment, and symptomatology domains were derived from assessment batteries administered annually by computer-based tests and raters not blind to treatment assignment. Results Of the 58 patients randomized and treated, 49 and 46 completed 1 and 2 years of treatment, respectively. Intent to treat analyses showed significant differential effects favoring CET on social cognition, cognitive style, social adjustment, and symptomatology composites during the first year of treatment. After two years, moderate effects (d = .46) were observed favoring CET at enhancing neurocognitive function. Strong differential effects (d > 1.00) on social cognition, cognitive style, and social adjustment composites remained at year 2, and also extended to measures of symptomatology, particularly negative symptoms. Conclusions CET appears to be an effective approach to the remediation of cognitive deficits in early schizophrenia that may help reduce disability among this population. The remediation of such deficits should be an integral component of early intervention programs treating psychiatrically stable schizophrenia outpatients.

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.

CET appears to be an effective approach to the remediation of cognitive deficits in early schizophrenia that may help reduce disability in this population. The remediation of such deficits should be an integral component of early intervention programs treating psychiatrically stable schizophrenia outpatients.

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 1 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.

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.

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.

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 recovery. 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 18 months 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% vs. 25%) 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.