Study recruitment milestones were not met.

The purpose of this research is to use specialized brain imaging techniques, Positron Emission Tomography (PET) scan and Magnetic Resonance Imaging (MRI), to learn more about the brain chemistry, e.g., how neurotransmitters and receptors in the brain function in people with schizophrenia compared to healthy controls.

Abnormalities in brain chemistry can be responsible for the hallucinations and delusions; thus, by treating these abnormalities, physicians can reduce symptoms of schizophrenia. In this study, investigators aim to examine the characteristics of two investigational radiotracers, [18F]AZAN and [18F]ASEM, in the brains of people with schizophrenia and healthy controls. Radiotracers are drugs in which one or more atoms are "labeled" with a small amount of radioactivity that allows investigators to see how the drug works in humans using PET and MRI brain imaging techniques.

Inclusion Criteria:

Inclusion Criteria for Healthy Subjects

• Between 18-55 years old (inclusive)men and women.
• Black/African-American or non Hispanic White/Caucasian
• Healthy as determined by medical history, physical examination, clinical laboratory test results, vital signs, and ECG within the reference ranges for the population or results within acceptable deviations that are not clinically significant as determined by study physician.
• Have sufficient arterial or venous access, as determined by Interventional neuroradiologist or anesthesiologist.
• Able to sign written informed consent and to comply with the study restrictions.
• No DSM-5diagnosis on axes I, II, III, and no currently active psychiatric diagnoses or substance use disorders as determined by [SCID]
• If Tobacco or Nicotine user-willing to abstain from products at least 3 hours prior to all PET scans until completion of the scan.

Inclusion Criteria for Patients with Schizophrenia

• Subjects with known chronic SCZ or acute psychotic episodes where suspicion of SCZ is high
• Patients who are drug naïve or nonadherent based on patient report or collateral information OR: a. Subjects on stable (3-months) doses of antipsychotics including risperidone, aripiprazole, ( Part 1 ) Note: if the results of Part 2 ( Aim 4 ) support the null hypothesis for olanzapine effects then investigators will include subjects with schizophrenia on chronic olanzapine. b. Subjects off and then on olanzapine only ( Part 2 )
• 3.18-55 years old (inclusive).
• 4.Male and female subjects meeting DSM-5 diagnostic criteria for a schizophrenia spectrum disorder, verified by SCID-1/P and schizophreniform (<1 year of symptoms5.Black/African-American or non-hispanic White/Caucasian

Exclusion Criteria:

Exclusion Criteria for Healthy Subjects

• Are currently enrolled in or discontinued within the last 30 days from a clinical trial involving an investigational drug or device (other than the study drug) or are currently enrolled in any other type of medical research.
• Have participated in other research protocols specifically regulated under 21 CFR 361.1 in the last year such that radiation exposure would exceed the annual limits.
• Pregnant or nursing women.
• History of head trauma with prolonged loss of consciousness (>10 minutes) or any neurological condition including stroke or seizure (excluding childhood febrile seizure) or history of migraine headache.
• Abnormal vital signs, ECG or clinical laboratory evaluations which are considered clinically significant by the clinical investigator.
• Suffer from claustrophobia and would be unable to undergo MRI or PET scanning.
• Clinically significant abnormal MRI.
• Subject has implanted or embedded metal objects, prostheses, or fragments in the head or body that would present a risk during the MRI scanning procedure, or have worked with ferrous metals either as a vocation or hobby (for example, as a sheet metal worker, welder, or machinist) in such a way that might have led to unknown, indwelling metal fragments that could cause injury if they moved in response to placement in the magnetic field.
• Currently uses prescription medications, over-the-counter drugs or herbal remedies such as St. Johns Wort) which cannot be discontinued 14 days (or <5 half-lives, whichever is longer), prior to the PET scan and throughout the study. Exceptions include daily multiple vitamins.
• Currently a user (including "recreational use") of any illicit drugs or alcohol abuse, or has a positive drug screen.
• Patients undergoing active use of medications that would influence radiotracer binding, including certain 5-HT3 antiemetics, acetylcholine (ACh) receptor agonists (nicotine) or antagonists, and acetylcholinesterase inhibitors.
• History of substance use disorder (DSM-V); or positive alcohol breath test.
• Are currently experiencing neuropsychiatric illness or severe systemic disease based on history and physical exam.

Exclusion Criteria for Patients with Schizophrenia

• Are currently enrolled in or discontinued within the last 30 days from a clinical trial involving an investigational drug or device (other than the study drug) or are currently enrolled in any other type of medical research.
• Have participated in other research protocols specifically regulated under 21 CFR 361.1 in the last year such that radiation exposure would exceed the annual limits.
• Pregnant or nursing women.
• Patients undergoing active use of medications that would influence radiotracer binding, including certain 5-HT3 antiemetics, acetylcholine (ACh) receptor agonists (nicotine) or antagonists, and acetylcholinesterase inhibitors.
• History of head trauma with prolonged loss of consciousness (>10 minutes) or any neurological condition including stroke or seizure (excluding childhood febrile seizure) or history of migraine headache.
• Abnormal vital signs, ECG or clinical laboratory evaluations which are considered clinically significant by the clinical investigator.
• Suffer from claustrophobia and would be unable to undergo MRI or PET scanning.
• Clinically significant abnormal MRI.
• Subject has implanted or embedded metal objects, prostheses, or fragments in the head or body that would present a risk during the MRI scanning procedure, or have worked with ferrous metals either as a vocation or hobby (for example, as a sheet metal worker, welder, or machinist) in such a way that might have led to unknown, indwelling metal fragments that could cause injury if they moved in response to placement in the magnetic field.
• Active substance or alcohol use disorder (including "recreational use") of any illicit drugs meeting criteria for current substance use disorder
• Any subject who has a positive Urine Drug Screen test unless in the Investigator's (Principal Investigator or Sub-Investigator) documented opinion, the positive test does not signal a clinical condition that would impact the safety of the subject or interpretation of the trial results.
• Any subject who has an Alcohol Breathalyzer test result deemed positive by the Investigator (Principal Investigator or Sub-Investigator unless in the Investigator's (Principal Investigator or Sub-Investigator) documented opinion, the positive test does not signal a clinical condition that would impact the safety of the subject or interpretation of the trial results.
• Current treatment with clozapine.
• Current treatment with typical antipsychotics, but not haloperidol.
• Current treatment with antiemetic or smoking cessation medications.

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