Disturbances of Kynurenine Pathway of Trytophan Metabolism in Schizophrenia: A Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) Study

This study has been completed.
Sponsor:
Information provided by:
North Suffolk Mental Health Association
ClinicalTrials.gov Identifier:
NCT00573300
First received: December 13, 2007
Last updated: August 11, 2009
Last verified: August 2009
  Purpose

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.


Condition Intervention
Schizophrenia
Procedure: Phlebotomy

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Disturbances of Kynurenine Pathway of Trytophan Metabolism in Schizophrenia: A Quantitative RT-PCR Study

Resource links provided by NLM:


Further study details as provided by North Suffolk Mental Health Association:

Biospecimen Retention:   Samples Without DNA

Whole blood


Estimated Enrollment: 60
Study Start Date: January 2006
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Schizophrenia
Schizophrenia Patients
Procedure: Phlebotomy
Single blood draw
Healthy Controls
Healthy Controls
Procedure: Phlebotomy
Single blood draw

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Schizophrenia patients

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00573300

Locations
United States, Massachusetts
Freedom Trail Clinic
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
North Suffolk Mental Health Association
Investigators
Principal Investigator: Oliver Freudenreich, M.D. North Suffolk Mental Health Association
  More Information

No publications provided

Responsible Party: Oliver Freudenreich, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00573300     History of Changes
Other Study ID Numbers: CORRC#10-2005
Study First Received: December 13, 2007
Last Updated: August 11, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by North Suffolk Mental Health Association:
Schizophrenia
Immune System
Kynurenate
tryptophan metabolism
NMDA receptor
indolamine 2,3-deoxygenase (IDO)

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on April 17, 2014