Randomized Clinical Trial of Intensive Computer-based Cognitive Remediation in Recent-onset Schizophrenia

This study employs two computerized programs: TARA (the treatment program), and a set of
ordinary computer games (the active control program). Participants will be asked to use
their assigned program (treatment or active control) for one hour per session, for four-five
sessions per week, over 8-10 weeks (40 total sessions). Several elements of flexibility are
allowed in the schedule to accommodate the challenges that people with ASD can face.

Inclusion Criteria:

- The investigators will study outpatient volunteer subjects who have schizophrenia,
schizophreniform disorder or schizoaffective disorder and have experienced their
first psychotic episode within the past 5 years, who are clinically stable, and who
are between the ages of 18 and 35 years. Approximately 35-40% of the subjects
recruited will be female, approximately 50-60% of potential subjects will be
Euro-American, 10-20% will be Asian-American, 15-20% Latino, 15-20% African-American.
The subject sample will reflect the racial and ethnic diversity of Northern
California and the prevalence of schizophrenia across gender in this age period.

- The investigators will study volunteer subjects at high risk for psychosis who are
clinically stable, and who are between the ages of 12-35. Approximately 35-40% of the
subjects recruited will be female, approximately 50-60% of potential subjects will be
Euro-American, 10-20% will be Asian-American, 15-20% Latino, 15-20% African-American.
Our subject sample will reflect the racial and ethnic diversity of the San Francisco
Bay Area.

- The study will have volunteer healthy controls matched by age and gender to our
subjects at high risk for psychosis.

- The study subjects will not have their medications changed by the study researchers.
If a subject's personal doctor changes a medication, the change will simply be
documented by the study researchers.

- Investigators will recruit subjects with a clinical diagnosis of schizophrenia,
schizophreniform or schizoaffective disorder with first psychotic episode within the
last 5 years, good general physical health; age between 12 and 35 years; Is fluent
and proficient in the English language; no neurological disorder. In addition, all
subjects must have achieved clinical stability, defined as outpatient status for at
least 3 months prior to study participation, plus stable doses of psychiatric
medications for at least one month prior to study participation using the following
operationalized definition: stable low to moderate dose of antipsychotic medication
(<1000 mg. chlorpromazine equivalents) for at least 4 weeks prior to study, plus
stable doses of all other psychotropic medications (anticholinergics,
benzodiazepines) for at least 4 weeks prior to entry. However, subjects are not
required to be on medications during participation. Minors must have parental/legal
guardian consent to participate. Although investigators request that a family member
also participate in the clinical assessments, this is not required for a participant
to be eligible.

This study will also recruit subjects who meet criteria for a Prodromal Syndrome as
defined on the SIPS:

- Attenuated Positive Prodromal Syndrome: Ideas of reference, odd beliefs or magical
thinking, paranoid ideation, odd thinking and speech, odd behavior and appearance
that are at a prodromal level of intensity that is rated at the level of 3-5 on the
Scale of Prodromal Symptoms (SOPS). Symptoms must occur at an average frequency of at
least once per week in the past month.

- Brief Intermittent Psychotic Syndrome: Positive symptoms rated at psychotic intensity
as a score of 6 on the SOPS that are not disorganizing or dangerous, do not last more
than 1 hour per day at an average frequency of four days per week over one month, and
have begun in the past three months, currently present at least several minutes a day
at a frequency of at least once per month.

- Genetic Risk and Deterioration Syndrome: Schizotypal personality disorder OR first
degree relative with a DSM-IV psychotic disorder, PLUS significant decrease in
functioning defined as 30% or greater drop in GAF score during the last month
compared to 12 months ago.

- High Risk Syndromes: Individuals who experience subthreshold psychotic symptoms
without restrictions on frequency of onset, functional impairment, or family history
of psychosis.

- Investigators will recruit age and gender matched healthy comparison subjects who do
not meet criteria for any Axis I diagnosis on the SCID. They cannot meet prodromal
criteria on the Prodromal Questionnaire administered during the screening.

- All subjects must be in good general physical health; Fluent and proficient in the
English language.

- Minors must have parental/legal guardian consent to participate. Although
investigators request that a family member also participate in the clinical
assessments, this is not required for a proband to be eligible.

- Individuals with a diagnosis of schizophrenia do not need to be within the 5 years of
onset, as that might have passed while in the first part of the study. Also, they
must be at least 18 years of age due to the developmental considerations for the
social cognition software of someone who is under the age of 18. The 16 healthy
controls also run in this part of the study will be age and gender matched to the
individuals with a diagnosis of schizophrenia.

Exclusion Criteria:

- Recent Onset Schizophrenia Subjects: Investigators will exclude subjects with a
history of psychoactive substance abuse in past 6 months determined by DSM-IV
criteria from the SCID interview.

- Prodromal Subjects: Psychotic disorder previously diagnosed as schizophrenia or
schizoaffective disorder or psychotic syndrome as defined by the SIPS: Fully
psychotic symptoms have occurred at least one hour per day at a minimum average
frequency of 4 days per week over one month OR the psychotic symptom is seriously
disorganizing or dangerous.

- Healthy Control Subjects: Criteria is met for any Axis I diagnosis on the SCID.
Healthy controls cannot have any first or second degree relative with a diagnosis of
schizophrenia, schizoaffective disorder, or bipolar disorder. Any previous
psychiatric hospitalizations will exclude a healthy control from the study.

- Any subject presenting a significant danger to self or others who requires inpatient
treatment will be referred for that treatment and evaluated for study eligibility
only after acute care treatment is no longer necessary.

- Subjects will also be excluded if they have a neurological disorder, or mental
retardation (IQ < 70 previously documented, or by intellectual testing, if
necessary), or autism.

- Physical disability that prohibits testing (deafness or blindness).

- Subjects will be excluded if they currently meet DSM-IV criteria for
alcohol/substance dependence or has met criteria within the last 6 months OR
prodromal symptoms are present only during use and withdrawal from alcohol/substances
OR subject is unable to attend assessments sober.

- Any contraindications to receiving an MRI scan, including having metal implants or
metal fragments in their body.

- Any history of head injury with loss of consciousness greater than 30 minutes.