Language

English

Publication Date

4-1-2024

Journal

l Neuropsychopharmacology

DOI

10.1038/s41386-023-01760-8

PMID

37903861

PMCID

PMC10948781

PubMedCentral® Posted Date

10-30-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Chronic low-grade peripheral and central nervous system inflammation may have a role in the pathogenesis of schizophrenia (SCZ). Inhibition of cyclooxygenase-2 (COX2), the arachidonic acid pathway, may inhibit cytokine responses and minimize inflammation. In this study, we added the COX2 inhibitor celecoxib to risperidone monotherapy to examine its efficacy on clinical symptoms and cognitive deficits in drug-naïve first episode (DNFE) SCZ patients. First, we genotyped two polymorphisms (rs5275 and rs689466) in the COX-2 gene in a case-control study of 353 SCZ patients and 422 healthy controls. Ninety patients participated in a 12-week, double-blind, randomized, placebo-controlled trial of celecoxib 400 mg/day. We used the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess clinical symptoms and cognition. Our results show that the COX2 rs5275 polymorphism was significantly correlated with SCZ and positive symptoms. After 12-week treatment, celecoxib significantly improved the PANSS total and three subscale scores of SCZ patients. Furthermore, patients with the rs5275 TT genotype had greater improvement in PANSS total score than patients carrying the C allele. However, no significant difference in RBANS total and subscale scores existed between the celecoxib and placebo groups at week 12. Our findings suggest that COX2 inhibitors may be promising therapeutics for clinical symptoms rather than cognitive impairment in first episode SCZ patients. COX2 rs5275 gene polymorphism may be implicated in the development and the efficacy of treating clinical symptoms in SCZ.

Keywords

Humans, Schizophrenia, Celecoxib, Cyclooxygenase 2, Antipsychotic Agents, Case-Control Studies, Pharmacogenetics, Treatment Outcome, Psychiatric Status Rating Scales, Cognitive Dysfunction, Inflammation, Double-Blind Method

Comments

Trial Registration Number: The trial was registered with www.clinicaltrials.gov (NCT00686140).

Published Open-Access

yes

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