Persons with schizophrenia, despite receiving optimal doses of antipsychotic medications that reduce or entirely obliterate psychotic symptoms still fail to fully recover function. Research has shown that it is the cognitive dysfunction along with the negative symptoms that account for persistent psychosocial dysfunction. The field has recently taken on the task of identifying, testing, and developing new treatments for cognitive dysfunction in schizophrenia through the NIMH-sponsored MATRICS and TURNS projects (www.MATRICS.ucla.edu). The work of these groups is partially completed and they have defined for us (1) the nature of the cognitive dysfunction, (2) a battery of recommended neuropsychological tests to assess these cognitive features, and (3) likely molecular targets for cognitive enhancement (Psychopharmacology, June, 2004). Based on a considerable basic literature, we have been impressed that it may not only be a drug treatment (e.g., atomoxetine in this application) but also psychological approaches (e.g., cognitive remediation, in this application) that are needed to work together to optimally improve cognition in schizophrenia. Therefore, we have developed the hypothesis that the use of cognitive remediation in the context of a cognitive enhancing medication will be necessary for optimal cognitive improvement in schizophrenia. But, little direct preliminary data exist to suggest which drug and which cognitive approach may be effective, nor what the parameters of response to expect (e.g., effect size; response rate; attrition). Therefore, we are applying for a R34 grant to pilot the medication atomoxetine (to target one of MATRICS's highest-scored molecular targets: the D1 dopamine receptor in prefrontal cortex) along with a cognitive remediation routine (one that is already developed and has shown promise by itself in preliminary studies) for the treatment of cognitive dysfunction in schizophrenia. We will apply each putative treatment alone and combined, in a standard four cell design, and evaluate neuropsychological function as the primary outcome measure, and we will collect preliminary data on psychosocial improvements occurring with treatment, to determine its time course. [unreadable] [unreadable] [unreadable]