Rehabilitation, Brain Function and Early Schizophrenia

In this study, we wish to determine the neurobiological predictors and the relative efficacy of Cognitive Enhancement Therapy (CET) in ameliorating specific cognitive abnormalities presumably mediated by PFC and related brain structures, among younger, early-course schizophrenia patients who potentially have a better prognosis. A series of recent-onset schizophrenic patients, whose psychotic symptoms have successfully been stabilized on an atypical antipsychotic drug for one year following initiation of treatment, will be randomized to CET combined with an enriched supportive therapy (EST) or EST alone, and treated for two years. Subjects will have been assessed on neurobehavioral and clinical indices immediately prior to beginning CET or EST (corresponding with the CNMD 1-year follow-up) and in the proposed study will again be assessed after 1 and 2 years of psychosocial treatment. In a smaller subset of patients, we will also seek to collect preliminary data on the efficacy of CET in reversing the neurobiological alterations in the PFC. The hypotheses of this study are:

1. The presence of relatively well preserved PFC structure and function (PFC volume, activation with fMRI, and metabolism as measured by proton MRS) at baseline will predict a better response to CET (Neurobiological Prediction Hypothesis).
2. CET combined with "enriched" supportive psychotherapy (EST) will be more effective than EST alone in ameliorating social and non-social cognitive deficits of patients with early schizophrenic illness whose psychotic symptoms have been stabilized on maintenance chemotherapy (The Treatment Efficacy Hypothesis).
3. CET will result in additive, positive effects on neurocognitive parameters that were not observed following one year of antipsychotic medication, using a "sequential" treatment design in a subset of patients in whom we have pre-neuroleptic baseline data from CNMD studies (The Treatment Specificity Hypothesis).

Study Design: Subjects will be randomly assigned, once stabilized clinically, to CET plus EST (n = 30) or EST alone (n = 30) and then treated for up to two years. Clinical, neuropsychological, neurological and functional neuroimaging assessments will be administered at baseline and at two annual follow-ups. At the end of CET or EST treatment, subjects will be asked to come back quarterly to meet informally with either their Cognitive Enhancement Therapy clinicians and former group members, or with their Enriched Supportive Therapy clinician. The purpose of these visits is for us to learn more about the successes that patients have had, or about the difficulties that they might have had since leaving the program. Clinician(s) will also share information obtained during this follow-up which might help patient in overcoming these difficulties. At the end of the one-year period post EST or CET treatment, subjects will be assessed on all measures, except for diagnostic, imaging and blood studies.