Clinical trial NCT00573300: Disturbances of Kynurenine Pathway of Trytophan Metabolism in Schizophrenia: A Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) Study
Official title: Disturbances of Kynurenine Pathway of Trytophan Metabolism in Schizophrenia: A Quantitative RT-PCR Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Schizophrenia
Keywords: Schizophrenia
Immune System
Kynurenate
tryptophan metabolism
NMDA receptor
indolamine 2,3-deoxygenase (IDO)
Lead sponsor: North Suffolk Mental Health Association
Sponsor class: OTHER
First posted: 2007-12-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Schizophrenia patients

Brief summary: In this pilot study, the investigators propose to characterize the pattern of activation of the kynurenine pathway of tryptophan metabolism in peripheral macrophages of patients with schizophrenia. To do this, the investigators will measure the gene expression of several major enzymes in this pathway in macrophages, including the key enzyme involved in tryptophan to kynurenine metabolism, IDO, by means of quantitative reverse-transcription polymerase chain reaction (RT-PCR). The focus on enzyme mRNA expression as opposed to serum or cerebrospinal fluid levels of metabolites provides a possibly more sensitive characterization of the activation of this metabolic pathway.

Detailed description: In this pilot study, we propose to characterize the pattern of activation of the kynurenine pathway of tryptophan metabolism in peripheral macrophages of patients with schizophrenia. To do this, we will measure the gene expression of several major enzymes in this pathway in macrophages, including the key enzyme involved in tryptophan to kynurenine metabolism, IDO, by means of quantitative reverse-transcription polymerase chain reaction (RT-PCR). The focus on enzyme mRNA expression as opposed to serum or cerebrospinal fluid levels of metabolites provides a possibly more sensitive characterization of the activation of this metabolic pathway.

Primary hypotheses: We hypothesize that patients with schizophrenia will differ in their expression of macrophage IDO mRNA, reflecting activation of this pathway compared to normals. We further hypothesize that patients with deficit syndrome will have higher degrees of enzyme activation.

Secondary hypotheses: Serum tryptophan levels will be lower in patients with schizophrenia compared to controls, and they will correlate with measures of dysphoria. Serum kynurenine levels will be elevated in patients with schizophrenia, particularly in deficit syndrome patients. mRNA expression levels of enzymes downstream from IDO will differ between patients and controls. Measures of immune activation will be influenced by medical disease burden (medical comorbidities).

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of Schizophrenia, any subtype or schizoaffective disorder
2. Ages 18-65 years
3. Males or females
4. English speaking with ability to complete symptom ratings
5. Ability to provide informed consent

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Freedom Trail Clinic
state: Massachusetts
Study officials:
affiliation: North Suffolk Mental Health Association
name: Oliver Freudenreich, M.D.
role: PRINCIPAL_INVESTIGATOR
References: