COX-2 pathway is upregulated in ultra-high risk individuals for psychosis

Abstract

Background

The identification of Ultra-High Risk (UHR) individuals is thought to be useful for early intervention to improve psychosis outcomes. However, transition rates vary widely, and there is an effort to make these criteria more specific and accurate. Neuroinflammation has been discussed in the pathophysiology of psychosis. The metabolism of eicosanoids is a key process in inflammatory states. Therefore, we investigated whether the study of the inflammatory COX-2 pathway through the quantification of the eicosanoid levels can be a useful approach for the characterisation of UHR individuals.

Methods

One hundred and twenty-two individuals were included in this study (67 UHR and 55 controls) based on performance on the Prodromal Questionnaire. UHR status was assessed by Structured Interview for Prodromal Syndromes (SIPS). We determined the levels of Prostaglandin F_2α (PGF_2α), Prostaglandin E₂ (PGE₂), and Thromboxane B₂ (TxB₂) in plasma using ELISA assays.

Results

Concentrations of PGE₂ and TxB₂ were increased in UHR compared to controls (p = 0.01 and p < 0.05, respectively). PGE₂ and PGF_2α levels were correlated to negative symptoms (p < 0.01 and p < 0.05), whereas TxB₂ correlated with positive symptoms (p = 0.05) as assessed by the SIPS.

Conclusions

Our findings suggest that overactivation of the COX-2 pathway may be related to an increased risk for psychosis. However, our data do not allow us to draw conclusions related to the cause-effect mechanisms. Future studies should determine whether the levels of the eicosanoids have a predictive value for the transition of UHR to frank psychosis.

Keywords:

• Inflammation
• eicosanoids
• COX-2 pathway
• biomarker
• ultra-high risk for psychosis

Acknowledgements

None.

Statement of interest

None to declare.

Additional information

Funding

This work was supported by the CAPES, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação de Amparo à Pesquisa do Estado de São Paulo, and Associação Beneficente Alzira Denise Hertzog da Silva.