Deborah P. Greenwald

Neuroprotective Effects of Cognitive Enhancement Therapy Against Gray Matter Loss in Early Schizophrenia Results From a 2-Year Randomized Controlled Trial

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 < .04) compared with those who received 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.

Cognitive-behavioral treatment of agoraphobia: paradoxical intention vs self-statement training.

Abstract Twenty-six agoraphobics were randomly assigned to either Paradoxical Intention (PI) or Self-Statement Training (SST) which consisted of 12 weekly 90-min group sessions with 4–5 patients per group. Major assessments were carried out at pre-treatment, 6th week and 12th week of treatment, and at 1- and 6-month follow-ups. Measures included clinical ratings of severity of condition, phobia, anxiety and depression. Furthermore, a behavioral test was administered during which changes in subjective units of discomfort and cognitions were assessed. The results indicated statistically-significant improvement over time with both treatments. ANCOVAs performed revealed superior effects on several agoraphobia measures for the PI condition at post-treatment. However, by the 6-month follow-up assessment, the groups were equivalent due to marked improvement during the follow-up phase in the SST condition. Cognitive changes were marked by a decrease in self-defeating statements without concomitant increase in coping statements. These results and recommendations for future research are discussed.

One-year durability of the effects of cognitive enhancement therapy on functional outcome in early 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 2 years of either CET or an Enriched Supportive Therapy (EST) control were followed-up 1 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.

Commonalities in social and non-social cognitive impairments in adults with autism spectrum disorder and 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 remain 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.

Mechanisms of functional improvement in a 2-year trial of cognitive enhancement therapy for early schizophrenia.

BACKGROUND Cognitive rehabilitation has emerged as an effective treatment for addressing cognitive impairments and functional disability in schizophrenia; however, the degree to which changes in various social and non-social cognitive processes translate into improved functioning during treatment remains unclear. This research sought to identify the neurocognitive and social-cognitive mechanisms of functional improvement during a 2-year trial of cognitive enhancement therapy (CET) for early-course schizophrenia. METHOD Patients in the early course of schizophrenia were randomly assigned to CET (n=31) or an enriched supportive therapy control (n=27) and treated for up to 2 years. A comprehensive neurocognitive assessment battery and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) were completed annually, along with measures of functioning. Mediator analyses using mixed-effects growth models were conducted to examine the effects of neurocognitive and social-cognitive improvement on functional change. RESULTS Improvements over 2 years in neurocognition and the emotion management branch of the MSCEIT were found to be significantly related to improved functional outcome in early-course schizophrenia patients. Neurocognitive improvement, primarily in executive functioning, and social-cognitive change in emotion management also mediated the robust effects of CET on functioning. CONCLUSIONS Improvements in neurocognition and social cognition that result from cognitive rehabilitation are both significant mediators of functional improvement in early-course schizophrenia. Cognitive rehabilitation programs for schizophrenia may need to target deficits in both social and non-social cognition to achieve an optimal functional response.

Effects of Cognitive Enhancement Therapy on Employment Outcomes in Early Schizophrenia: Results from a 2-Year Randomized Trial.

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.

A broad cortical reserve accelerates response to cognitive enhancement therapy in early course schizophrenia

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.

Negative symptom improvement during cognitive rehabilitation: Results from a 2-year trial of Cognitive Enhancement Therapy

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.

Is cognitive enhancement therapy equally effective for patients with schizophrenia and schizoaffective disorder

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.

Cognitive Enhancement Therapy in substance misusing schizophrenia: Results of an 18-month feasibility trial

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.