Effectiveness of Neuroadaptive Cognitive Training in Adolescents at Risk for Psychosis

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 24 months and will involve both healthy participants
and participants at high risk of schizophrenia. Healthy participants will only participate
for 12 months. 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 8 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 treatment
will focus on targeted cognitive training (TCT). Participants assigned to practice computer
games will play standard, commercially available games, with no targeted response.

Participants will repeat baseline assessments at post treatment and Month 6 of follow-up. The
EEG and MRI will be repeated only at the Week 8 assessment visit. There will be a blood draw
at Week 2 of treatment as well. After the Month 6 assessment, healthy controls will be
complete, and the at risk participants will continue to be followed up out to 24 months.

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