Community-Based Cognitive Training in Early Schizophrenia

The purpose of this study is to perform a double-blind randomized controlled trial (RCT) in
young patients with recent-onset (RO) schizophrenia to target improvement in cognitive
functioning within real-world treatment settings. This multi-site study will be performed in
4 community mental health centers with specialized Early Intervention Services (EIS). We will
compare the effects of web-based targeted cognitive training (TCT) vs. web-based general
cognitive exercises (GCE), both delivered via portable laptop computers. We will investigate
the behavioral and functional changes seen immediately after the intervention as well as at
6-month follow-up, compared to a no-training control group (NTC). This will be the first
study to investigate cognitive enhancement for young RO schizophrenia patients in community
mental health settings, using scalable interactive neurotechnology, and the first to compare
two distinct cognitive training approaches. This study will generate high impact data on the
potential for targeted pre-emotion of the downward spiral of in cognitive and functional
disability that often characterizes psychotic illness. It will also generate valuable data on
the relative effects of two distinct cognitive training approaches in schizophrenia, each
derived from a very different theoretical rationale, providing much-needed information on the
efficacy of a targeted "distributed neural system" training model derived from systems
neuroscience vs. a "general cognitive stimulation" training model derived from
neuropsychological rehabilitation approaches.

The aims of this project are based on the current state of early psychosis research, as well
as our own experience successfully applying neuroscience-informed cognitive training in
schizophrenia. It is now abundantly clear that cognitive/neural system dysfunction represents
a significant risk factor for schizophrenia as well as a poor prognostic indicator.
Functional outcome in RO schizophrenia is predicted by level of cognitive impairment and
baseline cognitive reserve, and recent findings suggest that specialized EIS programs
focusing only on symptom reduction and psychosocial support may not robustly improve
long-term outcomes— indicating that critical treatment targets are not being addressed at
present in early psychosis interventions. Cognitive dysfunction and underlying neural system
inefficiency should therefore be one of the primary targets for pre-emptive intervention in
early psychosis. In this study, we will determine whether we can achieve this goal using
cognitive training delivered via a portable computer, in order to improve functional outcome
in young individuals with RO schizophrenia.

Inclusion Criteria:

- Clinical diagnosis of schizophrenia, schizoaffective disorder, psychosis Not Otherwise
Specified (NOS), Unspecified Schizophrenia Spectrum Disorder, Schizophrenia Spectrum
Disorder, Specified, or schizophreniform disorder with onset of first psychotic
episode within the last 2 years.

- Good general physical health

- Between 18 and 35 years of age

- Is fluent and proficient in the English language

- Currently enrolled in PREP/BEAM services

- Achieved clinical stability (e.g., outpatient status for at least 1 month before study
entry)

Exclusion Criteria:

- Any neurological disorder

- If clinically significant substance abuse occurs that is impeding the subject's
ability to participate fully during recruitment, assessment, or training, the subject
will be dropped from the study.

- Being treated with benztropine, diphenhydramine, or high doses of clozapine (>500 mg
po qd) or olanzapine(to be determined on a case by case basis)