This study will evaluate the effectiveness of intensive computerized cognitive training in preventing the onset of psychotic disorder and improving adaptive functioning in adolescents at high risk of schizophrenia.

Schizophrenia is a severe mental disorder that is marked by significant disruption in a person's thought and emotional processes, frequently involving psychotic features. Identifying behavioral changes and symptoms that indicate the beginning stages of schizophrenia is important for early intervention and prevention of a full psychotic episode. These initial symptoms, known as the prodromal symptoms of psychosis, may include odd behaviors, increased social withdrawal, difficulty concentrating, inappropriate emotional responses, suspicion of others, and dramatic sleep and appetite changes. Common treatments for adolescents demonstrating prodromal symptoms include forms of psychotherapy, nutritional training, and low doses of medication. As a form of psychotherapy, neuroadaptive cognitive training exercises delivered on a computer may be the most effective means of remediating the thinking difficulties of adolescents who are experiencing prodromal symptoms and are at risk for developing a first psychotic episode. This study will evaluate the effectiveness of intensive computerized neuroadaptive cognitive training exercises in preventing the onset of psychotic disorder and improving adaptive functioning in adolescents at high risk of schizophrenia.

Participation in this study will last 6 months and will involve both healthy participants and participants at high risk of schizophrenia. All participants will undergo baseline assessments that will include an interview, written tests, blood draws, and electroencephalogram (EEG) and magnetic resonance imaging (MRI) scans. Participants at high risk of schizophrenia will then be assigned randomly to receive treatment with either computerized neuroadaptive cognitive training or commercially available computer games. Healthy participants will receive treatment with computerized neuroadaptive cognitive training only. All participants will be asked to complete 60-minute sessions of their assigned treatments 5 days per week for 16 weeks. For participants receiving cognitive training, exercises will focus on improving speed and accuracy in the perception of and response to verbal and visuospatial targets. The first 8 weeks of treatment will focus on targeted cognitive training (TCT) and the second 8 weeks will focus on visuospatial training. Participants assigned to practice computer games will play standard, commercially available games, with no targeted response.

Participants will repeat baseline assessments at Weeks 8 and 16 of treatment and Month 6 of follow-up. The EEG and MRI will be repeated only at the Week 16 assessment visit. There will be a blood draw at Week 2 of treatment as well. After the Month 6 assessment, participants will be offered an opportunity to complete an additional 8 to 16 weeks of computer training with different modules.

• Behavioral: Neuroadaptive cognitive training
• Behavioral: Computer games

• Active Comparator: Participants will use commercially available computer games.
• Experimental: Participants will receive targeted cognitive training with neuroplasticity-based software created by Posit Science Corporation.
• Active Comparator: Healthy participants will receive targeted cognitive training with neuroplasticity-based software created by Posit Science Corporation.

Inclusion Criteria:

• Meets criteria from the Structured Interview of Prodromal Syndromes for the diagnosis of a prodromal syndrome
• Good general physical health
• English is first language
• Clinically stable (e.g., outpatient status for at least 8 weeks before study entry;on stable doses of medications for at least 1 month before study entry)

Exclusion Criteria:

• Confirmed neurological disorder