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A double-blind, randomized controlled study of the effects of celecoxib on clinical symptoms and cognitive impairment in patients with drug-naïve first episode schizophrenia: pharmacogenetic impact of cyclooxygenase-2 functional polymorphisms

Neuropsychopharmacology volume 49, pages 893–902 (2024)Cite this article

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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.

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

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Fig. 1: Effect of 12 weeks of celecoxib treatment on clinical symptoms and cognitive function.

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Data availability

The data that support the findings of this study are available from the corresponding author, [ZXY], upon reasonable request.

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Funding

Funding for this study was provided by grants from CAS International Cooperation Research Program (153111KYSB20190004).

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Authors and Affiliations

  1. CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Science, Beijing, China

    Dong-Mei Wang, Li Wang & Xiang-Yang Zhang

  2. Department of Psychology, University of Chinese Academy of Sciences, Beijing, China

    Dong-Mei Wang, Li Wang & Xiang-Yang Zhang

  3. Beijing HuiLongGuan hospital, Peking University, Beijing, China

    Da-Chun Chen & Mei-Hong Xiu

  4. Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA

    Thomas R. Kosten

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Contributions

DMW and X-YZ were responsible for study design, statistical analysis, and manuscript preparation. DC and MX was responsible for recruiting the patients, performing the clinical rating and collecting the samples. LW and TRK were involved in evolving the ideas and editing the manuscript. DMW and X-YZ were responsible for providing the funding for the study. All authors contributed to and have approved the final manuscript.

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Correspondence to Xiang-Yang Zhang.

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Wang, DM., Chen, DC., Xiu, MH. et al. A double-blind, randomized controlled study of the effects of celecoxib on clinical symptoms and cognitive impairment in patients with drug-naïve first episode schizophrenia: pharmacogenetic impact of cyclooxygenase-2 functional polymorphisms. Neuropsychopharmacol. 49, 893–902 (2024). https://doi.org/10.1038/s41386-023-01760-8

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