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.

Background: Deficits in social cognition and neurocognition are believed to underlie schizophrenia disability. Attempts at rehabilitation have had circumscribed effects on cognition, without concurrent improvement in broad aspects of behavior and adjustment.Objective: To determine the differential effects of cognitive enhancement therapy (a recovery-phase intervention) on cognition and behavior compared with stateof-the-art enriched supportive therapy.Design: A 2-year, randomized controlled trial with neuropsychological and behavioral assessments completed at baseline and at 12 and 24 months.

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.

Most effects of the highly efficacious CET were sustained one year after treatment. Early improvement in processing speed (and perhaps other unassessed aspects of attention) seems to be the principal mediator of CET effects.