Tryptophan-Kynurenine Pathway Metabolism in the Pathophysiology of Cognitive Impairment in Schizophrenia.

NCT07162467 | Enrolling By Invitation DMC

• 1 other identifier: FESW-TKAH
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Schizophrenia is a common, long-term mental illness. It causes problems with thoughts, feelings, and behavior, including positive symptoms (hallucinations, delusions), negative symptoms (lack of emotion, motivation), and cognitive impairment (trouble with thinking, memory, and attention). While antipsychotic drugs effectively treat positive symptoms, they don't help much with cognitive impairment.This study will examine how the tryptophan-kynurenine pathway in the brain contributes to cognitive problems in people having their first episode of schizophrenia and treated with a single antipsychotic. Our goal is to create models for early detection of cognitive impairment in schizophrenia and find potential targets for new treatments to improve thinking and memory.

Conditions

Schizophrenia

Keywords

schizophrenia; cognitive funciton; tryptophan-kynurenine pathway

Outcome Measures

Primary Outcomes (3)

• TRP-KYN pathway candidate plasma metabolite levels

  Plasma levels of tryptophan-kynurenine (TRP-KYN) pathway candidate metabolites, including kynurenine, kynurenic acid, kynurenic quinolinic acid, quinolinic acid, tryptophan, indole-3-acetic acid, and indole-3-propionic acid, were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample information was registered in MetLIMS software, with designated positions for samples of interest, blanks, standards, and quality control samples. Samples were added to corresponding wells in a 96-well plate provided in the kit. Subsequently, derivatization was performed by adding a 5% phenylisothiocyanate solution. Finally, target analytes were extracted with an organic solvent and diluted. The pre-processed sample extracts underwent High-Performance Liquid Chromatography-Mass Spectrometry detection. Each sample was analyzed in two parts: the first involved signal acquisition in flow injection analysis mode, and the second in liquid chromatography-mass spectrometry mode.

  Baseline, week8

• Cognitive Function

  All participants underwent cognitive function assessment based on the MATRICS Consensus Cognitive Battery (MCCB). The MCCB is a standardized instrument for assessing cognitive function in schizophrenia. It comprises nine subtests primarily evaluating seven cognitive domains: processing speed, attention/alertness, working memory, verbal learning, visual memory, reasoning and problem-solving, and social cognition. The MCCB scoring procedure generates standardised T-scores that are corrected for age, gender, and educational level. Higher T-scores indicate better cognitive function.

  Baseline, week8

• Candidate gene mRNA expression levels

  Whole blood was collected in BD PAXgene® Blood RNA tubes (2.5 mL from antecubital veins) and gently inverted to mix. Samples were incubated vertically at room temperature for 2 hours, then stored at -20°C overnight before transfer to -80°C for RNA extraction. Extracted RNA was reverse transcribed to synthesize cDNA. Gene expression levels of TDO, IDO, KMO, KAT-II, KYNU, and 3HAO were determined by RT-qPCR with gel electrophoresis for product validation and densitometric scanning using a gel imaging system.

  Baseline, week8

Secondary Outcomes (4)

• Psychiatric Symptoms

  Baseline, week8

• Depressive Symptoms

  Baseline, week8

• Anxiety Symptoms

  baseline, week 8

• Clinical Global Impression of Efficacy

  baseline, week 8

Study Arms (2)

Schizophrenic Patients

100 eligible individuals will meet DSM-5 criteria for schizophrenia or schizoaffective disorder, be Han Chinese aged 18-55 years, presenting with a first episode of illness ≤ 5 years duration. Prior antipsychotic exposure must be ≤ 4 weeks cumulatively, or patients must be treatment-naïve. Informed consent will be obtained from patients and their families.

Healthy Control

100 healthy, age-, gender-, and education-matched Han Chinese volunteers, with informed consent.

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

This study will recruit 100 Han Chinese adults aged 18-55 years for two cohorts: patients and healthy controls. The patient cohort will comprise individuals experiencing their first episode of schizophrenia or schizophreniform disorder with a duration of ≤ 5 years, who have either never received antipsychotic treatment or have received it for a cumulative duration of ≤ 4 weeks prior to enrollment. Recruitment will be conducted from the outpatient and inpatient services of Tianjin Anding Hospital and surrounding communities in Tianjin, China. The healthy control cohort will consist of 100 Han Chinese adults matched to the patient group for sex, age, and education. These individuals must have no personal or family history of major psychiatric disorders and demonstrate no cognitive impairment on formal testing.

You may qualify if:

• Healthy volunteers matched to the patient group on sex, age, and education level;
• Ethnic Han Chinese;
• Able and willing to provide written informed consent.

You may not qualify if:

• Significant comorbid medical or neurological conditions;
• Any DSM-5-defined psychiatric disorder;
• Family history of psychiatric illness spanning three or more generations;
• Current use of psychoactive medications;
• Refusal to provide informed consent/participate.

Sponsors & Collaborators

• Tianjin Anding Hospital: lead

Study Sites (1)

Tianjin Anding Hospital

Tianjin, China

Location

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 8 Weeks
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2025
• First Posted: September 9, 2025
• Study Start: February 19, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

CN (1)