Mechanisms of Response to Therapeutic Intervention in Clinical High Risk (CHR) for Psychosis

Inclusion criteria

• Clinical High Risk (CHR):
• Male or female between 15 and 35 years old.
• Can understand and sign an informed consent (or assent for minors) document.
• Must meet the substance use criteria:
• No Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) Alcohol or Drug Dependence in the past 3 months;
• No use on the day of assessment, clearly not intoxicated or hung-over.
• Must meet diagnostic criteria for a prodromal syndrome. If under the age of 19 and meet diagnostic criteria for Schizotypal Personality Disorder or meet the diagnostic criteria called the Criteria for Prodromal Syndromes (COPS), which are operationalized as follows (a-c below):
• Genetic Risk and Deterioration Syndrome (GRDS): First degree biological relative with psychosis or subject with Schizotypal Personality Disorder and a 30% drop in Global Assessment of Functioning (GAF) score compared to one year ago, sustained over the past month.
• Attenuated Positive Symptoms Syndrome (APSS): Severity rating of moderate (rating of 3), moderately severe (4) or severe but not psychotic (5) on any one of the five Symptoms of Psychotic Disorders (SOPS) positive symptoms; symptom occurs at or above moderate severity level at an average frequency of at least once per week in the past month; symptom must have begun in the past year or currently rates at least one scale point higher than rated 12 months previously.
• Brief Intermittent Psychotic Syndrome (BIPS): Severity rating of psychotic intensity (6) on any of the 5 SOPS positive symptoms; symptom is present at least several minutes per day at a frequency of at least once per month; symptom(s) must have reached a psychotic intensity in the past 3 months; symptom is not seriously disorganizing or dangerous; symptom(s) do not last for more than 1 hour/day at an average frequency of 4 days/week over 1 month.
• . Participant may be remitted from the CHR syndrome or may have converted to a full psychotic disorder since study entry and either is acceptable - they remain eligible to participate in follow-up procedures.

Exclusion criteria

• Meet criteria for current or lifetime Axis I psychotic disorder, including affective psychoses and psychosis Not Otherwise Specified (NOS) at the baseline assessment
• Impaired intellectual functioning (i.e., Intelligence Quotient (IQ)\<70) at baseline.
• Past history of or current clinically significant central nervous system disorder that may contribute to prodromal symptoms or confound their assessment.
• Traumatic Brain Injury that is rated as 7 or above on the Traumatic Brain Injury screening instrument (signifying a significant brain injury with persistent sequelae) or current concussion that interferes with any assessment measures.
• Diagnostic prodromal symptoms that are clearly caused by one or more other psychiatric disorders, including substance use disorders, in the judgment of the evaluating clinician. Other non-psychotic Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) disorders will not be exclusionary (e.g., substance abuse disorder, major depression, anxiety disorders, personality disorders), as long as the disorder does not account for the diagnosis of prodromal symptoms.
• Healthy Controls (HC):
• Must meet subject inclusion criteria 1-2 and exclusion criteria 1-5. Must not meet criteria for any prodromal syndrome, any current or past psychotic disorder or Cluster A personality disorder diagnosis and must not be receiving any current treatment with psychotropic medication at the baseline assessment.
• Must not have a family history (in first-degree relatives) of schizophrenia, schizoaffective disorder, schizotypal personality disorder, or any other disorder involving psychotic symptoms.