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

Tianjin Anding Hospital

Status: Invitation-only

Conditions: Schizophrenia

Study type: Observational

Funder types: Other

Identifiers

NCT07162467

FESW-TKAH

Details and patient eligibility

About

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.

Full description

This single-center, prospective study will recruit 100 treatment-naïve, first-episode schizophrenia (SZ) patients at Tianjin Anding Hospital for an 8-week follow-up. All patients will receive monotherapy with risperidone and undergo baseline and week 8 assessments including clinical rating scales and the MATRICS Consensus Cognitive Battery (MCCB), along with peripheral blood sample collection. Concurrently, 100 age-, sex-, and education-matched healthy controls (HCs) will be recruited. Prior data from 300 medication-naïve SZ patients and 100 HCs will be selectively included in the final analysis (totaling 300 SZ patients and 200 HCs). We hypothesize that dysregulation of the tryptophan-kynurenine (TRP-KYN) pathway in SZ patients, leading to an imbalanced ratio of neuroprotective kynurenic acid (KYNA) to neurotoxic quinolinic acid (QUIN), affects inflammatory markers and NMDA receptor (NMDAR) levels, ultimately causing cognitive impairment. Specifically, we will analyze the association between cognitive function and plasma TRP-KYN pathway metabolites in medication-naïve FES patients; relationship between cognitive function and TRP-KYN pathway gene polymorphisms and mRNA expression in medication-naïve FES patients; and changes in cognitive function post-8-week treatment with plasma TRP-KYN pathway mRNA expression and metabolite levels.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

• 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.

Trial design

200 participants in 2 patient groups

Schizophrenic Patients

Description:

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

Description:

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