Objective: To investigate which cognitive and affective features contribute most to responder/non-responder group separation during a switching trial with atypical antipsychotic. Design: A prospective open trial with an atypical antipsychotic (olanzapine). Patients: One hundred and thirty-four patients meeting diagnostic criteria for schizophrenia, schizophreniform or schizoaffective disorder began an 8-week open-label olanzapine treatment at a dose of 5mg/day which was increased to 10mg/day after one week. Interventions: Olanzapine during 8 weeks. Patients were considered as responders if their BPRS score decreased of at least 20% (n=96) and non-responders if it did not (n=38). Neuropsychological assessments were carried out at baseline, at four and at eight weeks. Results: Neurocognitive measures were analyzed for discriminate factors between responder and non-responder groups. A regression analysis was applied to explain the effects of depression on each cognitive variable. Depression was found to be a weak discriminant factor, however this finding could not firmly establish that depression is a potential factor in explaining deficits and improvements in cognition.