The Effects of Kynurenine Aminotransferase Inhibition in People With Schizophrenia

HP-00086009

Kynurenic acid (KYNA) is a naturally occurring chemical in the brain. Studies with rodents indicate that levels of KYNA can impact levels of the neurotransmitters glutamate and dopamine. One way to reliably increase KYNA levels is by ingesting the amino acid tryptophan. Tryptophan is a normal part of the human diet. Tryptophan gets metabolized/changed to other chemicals in the body- including KYNA. By giving people 6 grams of tryptophan, the investigators will be able to increase the KYNA level in a controlled way. The investigators will then be able to study the effects of KYNA on neurotransmitters by using cognitive tests and magnetic resonance imaging techniques (measuring brain activity and brain chemistry using the MRI magnet). The overall goal of the study is to examine how the medication N-acetylcysteine (NAC), when added to tryptophan, affects various cognitive functions, such as verbal and visual memory. The investigators will also use magnetic resonance imaging (MRI) to examine how NAC affects brain activity and chemicals.

2020-01-20

2024-06-30

2024-06-30

Recruiting

Early phase I

75

Inclusion Criteria: * Males and females * Age: 18 to 55 years * DSM-5 Criteria for schizophrenia, schizoaffective disorder or schizophreniform disorder (documented by SCID) * Prescription of antipsychotic medication for at least 60 days and constant dose for 30 days prior to study entry (either first or second generation antipsychotics permitted) * Female participants must agree to use a medically accepted means of contraception Exclusion Criteria: * DSM-5 alcohol or substance misuse disorder in the last 3 months (documented by SCID) * History of an organic brain disorder; mental retardation; or a medical condition, whose pathology or treatment could alter cognition * Active disorders that have been reported to affect tryptophan metabolism or interfere with absorption will be excluded (Acute Intermittent Porphyria, Celiac Disease, Crohn's Disease, Irritable Bowel Syndrome; Brune and Pflughaupt 1975; Torres et al 2007). * Excessive self-reported daily caffeine intake, defined as intake exceeding 1000mg or the equivalent of 8 cups of coffee * Pregnancy or lactation * No metal in body that will interfere with MR imaging * Monoamine oxidase inhibitors, migraine headache medications (triptans) and dextromethorphan * Forensic or legal issues

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2023-12-15