Remediation of Working Memory in Schizophrenia

The primary aim of the study is to test the efficacy of a novel cognitive remediation intervention that targets working memory-related functions. To accomplish this goal, 80 volunteer patients with schizophrenia will be enrolled and randomized to either a cognitive remediation condition that targets working memory or a computer skills training intervention that teaches computer applications. In both conditions participants will receive computer training three times a week for 4 months. The investigators hypothesize that patients who receive the cognitive remediation intervention will demonstrate significantly greater change on neuropsychological measures of working memory and executive abilities than patients who receive the computer skills course. In addition, the investigators hypothesize that the intervention-induced cognitive change will be associated with concurrent improvements in functional capacity and psychosocial functioning in the community. A second study goal is to examine the stability of the intervention-induced changes in cognition. Cognition and psychosocial functioning will be reassessed 4 and 8 months after treatment termination to examine the stability of treatment effects and to assess whether a less intense maintenance training (once a week sessions) provides any additional benefit to participants. Lastly, this study will examine in an exploratory manner whether there are individual differences in treatment response. The Val158Met polymorphism of the COMT gene has been found to be associated with working memory and prefrontal dysfunction in schizophrenia. The study will test whether the COMT polymorphism is predictive of response to cognitive remediation.

A 48-session working memory focused cognitive remediation program is conducted. Training tasks have been selected from 3 software programs, PSS CogRehab, BrainTrain, and custom made N-back tasks.

This is a 48-session, time matched comparison group in which participants practice keyboarding skills and the fundamentals of Microsoft Office Word, Powerpoint, and Excel programs.

This is an adaptive, computer-based cognitive training intervention. Participants will complete 3 1-hour cognitive training sessions focused on attention and working memory processes weekly for 4 months.

This is a computer-based course in which participants will be taught how to use Microsoft Office applications and typing skills. Participants will attend a 1-hour course three times a week four 4-months.

The Working Memory and Attention indexes of the MATRICS Consensus Cognitive Battery was used to assess near generalization of training with untrained tasks that were conceptually similar to training tasks. Each scale provide an age and gender corrected T-score. Thus, scores can range from 0-100, with a higher score indicating better performance.

The UPSA is a measure of the ability to apply cognitive skills to functional tasks. The total score from this scale was used. Scores may range from 0 - 100, with higher scores being better.

Inclusion Criteria: Veterans with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder No hospitalizations in the previous 4 weeks No antipsychotic medication changes in the previous 4 weeks Age 18-60 Does not meet DSM-IV criteria for substance dependence in the previous 6 months or substance abuse in the previous month Exclusion Criteria: History of clinically significant head injury or neurological disease Poor comprehension of the English language History of diagnosis of mental retardation or pervasive developmental disorder Unable to give informed consent

Ramsay IS, Nienow TM, Marggraf MP, MacDonald AW. Neuroplastic changes in patients with schizophrenia undergoing cognitive remediation: triple-blind trial. Br J Psychiatry. 2017 Mar;210(3):216-222. doi: 10.1192/bjp.bp.115.171496. Epub 2017 Feb 2.