Cognitive Enhancement Therapy for Early-Stage 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.

Inclusion Criteria:

- DSM-IV diagnosis of schizophrenia, schizoaffective or schizophreniform disorder at
the time of initial assessment

- Pre-treatment illness duration an average of 5 years, not to exceed 8 years

- Stable positive symptoms (e.g., if present do not grossly interfere with behavior
such as command hallucinations or delusions)

- Currently maintained and compliant with prescribed antipsychotic medication

- Socially and cognitively disabled, e.g., meet criteria on a Cognitive Style Scale
(score greater than or equal to 7), and Social Cognition Disability Scale (score
greater than or equal to 12).

Exclusion Criteria:

- Alcohol/drug abuse or dependence that has significantly interfered with adjustment in
the past two months (e.g., patients currently undergoing D and A treatment must
successfully complete their recovery program prior to referral)

- Organic brain syndrome, including HIV illness (due to its effect on CNS function)

- IQ below 80 or language skills below the sixth grade level

- Medical contraindications that preclude an appropriate antipsychotic medication

- Persistent suicidality