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 females, Framingham correction(3)), with repeat measurement showing the same abnormality. * Current mood episode meeting criteria for a major depressive episode or a manic or hypomanic episode. * History of electroconvulsive therapy (ECT) or treatment with neurostimulation in the past 6 months, or with plans to begin either such treatment during the study. * History of ADHD pre-morbid to the onset of psychosis or other psychiatric illnesses that may be accompanied by cognitive impairments. * Meeting SCID-5 moderate or severe substance use disorder for any substance other than nicotine within the 3 months prior to the initial assessment. * Positive urine toxicology testing for any substance other than marijuana or those prescribed for medical reasons at Visits 1-6. * Pregnancy or intention to become pregnant during the study. * Lactating/breast-feeding or intending to do so during the study * Any non-MRI compatible metal in the body or other contraindication to MR imaging. A copper IUD is allowable if permitted by local MRI practices. * Severe claustrophobia, back pain, morbid obesity, or other condition that may make an extended MR session difficult or lead to excessive movement during the imaging session. * Color blindness, strabismus or other uncorrectable visual problems. Those wearing glasses would be asked to use MRI-safe glasses. * Daily use of the following medication within 10 days prior to the initial visit or during the study: Long-acting nighttime or daytime gamma aminobutyric acid-A (GABA-A) receptor facilitators; anticonvulsant medications used at high doses or for seizure control, or psychostimulants or medical cannabis. Participants can be re-assessed for eligibility once they have been free of daily use of these medications for \>10 days. Participants may take non-GABAergic sleep medications, short-acting GABA receptor facilitators (benzodiazepine, non-benzodiazepine) prior to and during the study. * Any change in type or dose of psychotropic medications within 3 weeks prior to initial visit or during study to avoid transient effects of medication regimen change. Medication type and dose will be carefully recorded and used as a covariate in analyses. Participants can be re-assessed for eligibility once they have been on a stable dose of medication for \>3 weeks. * CVL-562 is metabolized by P450 CYP3A4. In order to avoid pharmacokinetic interactions, medications or substances that induce (barbiturate, carbamazepine, etc.) or are moderate-strong inhibitors (ketoconazole, etc.; grapefruit juice) are excluded if used within 10 days prior to or during study. Participants can be re-assessed for eligibility once they have been free of these medications/substances for \>10 days. * Active attempts to discontinue smoking, vaping or other nicotine products within the 3 weeks prior to study or during the study. Participants can be re-assessed once quit attempt is stable. * Diastolic blood pressure \>95 or \<50 mmHg or systolic blood pressure \> 170 or \<80 mmHg with repeat measurement showing the same abnormality. * History of allergy or other contraindication to the proposed pharmacotherapy. * Other medication treatment with which proposed pharmacotherapy is contraindicated, in the opinion of study psychiatrists or of a subject's prescribing psychiatrist.