Evaluating Two Types of Cognitive Training in Veterans With Schizophrenia

Cognitive dysfunction is a major contributor to the poor community outcome of individuals with schizophrenia. Developing more effective cognitive remediation interventions is imperative to improve the daily lives of affected subjects and reduce the disability of this illness. The goal of this clinical trial is to evaluate two types of cognitive training approaches to determine which one is more beneficial for individuals with schizophrenia. This study also uses electrophysiological techniques to gain a better understanding of the mechanisms involved in cognitive remediation. Findings from this study will provide information about how to design the most optimally efficient cognitive training intervention to improve the cognitive and social functioning of patients with severe mental illness.

Schizophrenia is a disorder that affects both higher-level neurocognitive operations (e.g., verbal memory, executive functioning) and lower-level perceptual processes (e.g., auditory processing). These deficits contribute to the poor community outcome and severe functional disability seen in patients. Effectively treating the cognitive dysfunction associated with this illness is important to achieve improvements in daily functioning. Recent meta-analytic studies report that cognitive training in schizophrenia has a moderate effect-size impact on cognitive functioning and a lower impact on daily functioning. However, most training interventions for schizophrenia have only targeted higher-order cognitive processes. A few recent interventions have targeted basic perceptual processing and shown that auditory and visual perceptual abilities can be trained and improved in patients with schizophrenia. These findings suggest that basic perceptual processing may be an ideal target for intervention. At this point, it is still unclear whether a neuroplasticity-based, bottom-up intervention is more effective than an intervention that targets top-down functions like attention, working memory, and executive functioning.

This clinical trial will contrast a bottom-up intervention targeting basic auditory processes and a top-down intervention targeting higher-order cognitive functions, compared with a control condition, in Veterans with schizophrenia. These interventions will be assessed by their effects on representative measures from three outcome domains: 1) neurocognition, 2) electroencephalography (EEG), and 3) functional capacity. Participants will be randomly assigned to the bottom-up auditory training, top-down cognitive training, or control treatment (commercial computer games). All treatments will be administered three times a week (1 hour each) for 12 weeks. A comprehensive battery of cognitive, electrophysiological, and functional measures will be administered at baseline, 6 weeks, and at completion of treatment. The investigators will enroll 120 Veterans with schizophrenia or schizoaffective disorder across the 5 years of the study.

This study will determine which training approach leads to the largest magnitude of improvement in neurocognition, functional capacity, and neural functioning measured with EEG. Moreover, it will shed light on the neural mechanisms underlying the response to training. By determining whether it is more beneficial to treat lower-level perceptual processes or higher-level cognitive functions, the results of this project will inform future recovery-based cognitive remediation interventions for Veterans with schizophrenia.

Eligibility Criteria:
Inclusion Criteria:

* Veterans with a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder
* Between 25 and 65 years of age
* Estimated premorbid inteIligence quotient (IQ) \> 70 (based on reading ability)
* Understand spoken English sufficiently to comprehend the consent form
* Clinically stable (i.e., no inpatient hospitalization in the 3 months, no changes in psychiatric medications in the 6 weeks, and no changes in housing in the 2 months, prior to enrollment)

Exclusion Criteria:

* Documented history of mental retardation or severe learning disability
* Clinically significant neurological disease as determined by medical history (e.g., epilepsy, stroke)
* History of serious head injury with loss of consciousness greater than 1 hour and concomitant neuropsychological sequelae
* Meeting DSM-IV criteria for drug or alcohol dependence during the 6 months, or abuse during the month preceding study enrollment