Tryptophan MRI in People With Schizophrenia and Healthy Controls

• Status: Completed
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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). They will test people using tryptophan and also using a placebo to look for differences. The investigators will test healthy controls and people with schizophrenia to look for differences.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Maryland; University of Maryland, Baltimore
• Collaborators: Mitsubishi Tanabe Pharma Corporation; National Institute of Mental Health (NIMH)
• Treatments: Tryptophan

Criteria

Inclusion Criteria (Schizophrenia:

• Males and females between the ages of 18 and 55 years

• Has met DSM-IV-TR/DSM-5 Criteria for schizophrenia, schizoaffective disorder or schizophreniform disorder

• 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)

• Women must be in the first half of their menstrual cycle at the time of the 2 challenge visits

Inclusion Criteria (Healthy Controls):

• Males and females between the ages of 18 and 55 years

• No DSM-IV-TR/DSM-5 Axis I Disorder (documented by SCID)

• Women must be in the first half of their menstrual cycle at the time of the 2 challenge visits

Exclusion Criteria:

• DSM-IV-TR/DSM-5 substance abuse in the last month or substance dependence in the last 6 months (documented by SCID)

• Calgary Depression Scale total score ≥ 10 at baseline

• Current smoker (expired CO ≥ 10 ppm)

• Current use of nicotine replacement therapy or other nicotine products

• Pregnancy or breast feeding

• Post-menopausal women will not be included due to changes in the HPA axis expression and hormonal effects on cognition. In women over the age of 45, menopausal status will be evaluated clinically

• Excessive self-reported daily caffeine intake, defined as intake exceeding 1000 mg or the equivalent of 8 cups of coffee

• 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

• History of an organic brain disorder; mental retardation; or a medical condition, whose pathology or treatment could alter cognition

• Claustrophobia

• Metal in body that will interfere with MR imaging

• Treatment with monoamine oxidase inhibitors, migraine headache medications (triptans) and dextromethorphan