A Translational and Neurocomputational Evaluation of a Dopamine Receptor 1 Partial Agonist for Schizophrenia

Inclusion Criteria

• Between the ages of 18 (including 18 years of age) and 45 (up to 45 years and 11 months) at the time of baseline study visit.
• Able to provide informed consent (as established by consent interview), and voluntary, signed informed consent prior to the performance of any study-specific procedures
• Willing and able to perform study-relevant clinical assessments and Magnetic Resonance Imaging (MRI) as assessed by research staff.
• Meet Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder on the basis of the Structured Clinical Interview for DSM-5 (SCID-5).
• Be within 10 years of the onset of psychosis based on clinical assessment at the time of Visit 1.
• Treatment seeking and willing to accept the constraints on treatment entailed by the study.
• Able to demonstrate a basic ability to follow spatial working memory task instructions and perform necessary related motor functions.
• Demonstrate a premorbid IQ of ≥80 based on the Penn Reading Assessment (PRA). The PRA correlates with other measures of IQ including the Wide Range Achievement Test (WRAT), but is computerized, based in the laboratory of co-investigators Ruben C. Gur and Raquel E. Gur, and brief to administer, allowing us to lessen the assessment burden on an already lengthy first visit.
• Be fluent in English as assessed by research staff.
• Clinically stable treatment for at least two months prior to Visit 1 (no hospitalizations, or current suicidal/homicidal active ideation, intent, or plan).
• On a stable psychotropic medication regimen (can include no psychotropic medications) for at least 3 weeks prior to Visit 1, and willing to maintain an unchanged regimen during the study. If on depot antipsychotics, participants must have stable dosing for at least two consecutive injections (including the most recent one) as the most recent injections. If on Invega Trinza, there must be no plans to change dosing during the course of the study.
• For women of child bearing potential, no intention to become pregnant during the study period, and agreement to use a reliable method of birth control (e.g. Intra-Uterine Device (IUD), hormonal contraception, abstinence, condoms) during the study period. Women will be asked to continue their method of contraception for 1 month after receiving their final dose of medication. Any individual who becomes pregnant during the study will be immediately removed, and discussion of the risks and benefits of ongoing pharmacotherapy will proceed on purely clinical grounds.

Exclusion Criteria

• Any unstable medical, psychiatric, or neurological condition (including active or otherwise remarkable suicidal or homicidal ideation) that may necessitate urgent treatment. Active medical conditions that are minor or well controlled are not exclusionary if they do not affect risk to the patient, metabolism of study drug, or the study results (e.g. well-controlled type II diabetes or hypertension) as per the judgment of the investigator.
• Be currently treated with any of the following: olanzapine, clozapine, ziprasidone or asenapine, in order to avoid prominent D1 receptor effects.
• Any major neurological disease, brain injury, epilepsy, or history of severe head trauma, including concussion with loss of consciousness greater than or equal to > 15 minutes, or of psychosurgery.
• History of significant cardiac disease (ex: ischemia, arrhythmia).
• Any clinically significant abnormality on baseline medical screening tests (electrocardiogram (EKG), complete blood count with differential (CBC), complete metabolic profile (CMP).
• Hepatitis B or C (by report or testing) in the presence of abnormal liver function tests
• Human Immunodeficiency Virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS) (by report or by testing) due cognitive effects of HIV and AIDS.
• Baseline EKG showing prolonged QTc interval (>450 for males, >470 for female