Mediating effect of inflammation on the association between glucocorticoid response-related polymorphism and metabolic syndrome in patients with schizophrenia: Evidence from the FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) cohort
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and impaired glucocorticoid sensitivity may contribute to the inflammatory and metabolic abnormalities observed in schizophrenia (SZ), including metabolic syndrome (MetS), a major contributor to excess morbidity and premature mortality. However, the contribution of glucocorticoid response-related genetic variants to these abnormalities remains underexplored. Method: polymorphism (rs37972, C > T). Logistic regression analyses were used to assess associations between genotypes and inflammation, evaluated by high-sensitivity C-reactive protein (hsCRP), and clinical features, including early-onset SZ (EOS), treatment-resistant SZ (TRS), suicidal attempts (SA) and MetS. Mediation analysis was used to evaluate the role of inflammation in genotype-MetS associations. Results: rs37972 TT genotype was significantly associated with an increased likelihood of inflammation and MetS compared with TC/CC genotypes (inflammation: OR = 3.51, 95% CI 1.55-7.96, pFDR = 0.009; MetS: OR = 3.06, 95% CI 1.26-7.43, pFDR = 0.027). Additionally, mediation analysis revealed a significant indirect effect of the rs37972 TT genotype on MetS through inflammation, whereas the direct effect was not significant. Conclusion: rs37972 polymorphism may be associated with altered glucocorticoid sensitivity, systemic inflammation, and MetS in SZ. These findings suggest a potential genetic-inflammatory pathway underlying the relationship between stress regulation and metabolic comorbidity in SZ. Given the cross-sectional design and the absence of a control group, the results should be considered exploratory and warrant replication in larger independent cohorts.
Authors: Kaori Saitoh, Mohamed Lajnef, Marion Leboyer, Myrtille Andre, Christelle Andrieu, Bruno Aouizerate, Maud Apavou, Caroline Barau, Jeremy Bernard, Jihène Bouassida, Delphine Capdevielle, Isabelle Chereau, Julie Clauss-Kobayashi, Jean-Michel Dorey, Caroline Dubertret, Eric Fakra, Guillaume Fond, Tudi Goze, Sylvain Leignier, Pierre-Michel Llorca, David Misdrahi, Nicolas Oriol, Baptiste Pignon, Romain Rey, Paul Roux, Jasmina Mallet, Franck Schürhoff, Benoit Schorr, Mathieu Urbach, Etienne Very, Ching-Lien Wu, M. Andre, C. Andrieu-Haller, B. Aouizerate, F. Berna, O. Blanc, D. Capdevielle, M. Cléry, I. Chereau-Boudet, J. Clauss-Kobayashi, N. Coulon, R. Dassing, J.M. Dorey, C. Dubertret, T. D'Amato, A. Esselin, E. Fakra, G. Fond, F. Gabayet, T. Goze, M. Jarroir, D. Lacelle, M. Leboyer, S. Leignier, P.M. Llorca, J. Mallet, Z. Marongiu, E. Metairie, T. Michel, D. Misdrahi, N. Oriol, C. Passerieux, B. Pignon, P. Peri, C. Portalier, A. Couturier, P. Carrillo, R. Rey, C. Roman, P. Roux, B. Schorr, F. Schürhoff, A. Szöke, A. Tessier, M. Urbach, E. Very, A. Zinetti-Bertschy, Ophélia Godin, Wahid Boukouaci
Institutions: Inserm, Université Paris-Est Créteil, Fondation FondaMental, Institut Mondor de Recherche Biomédicale, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Henri-Mondor, Centre Hospitalier Universitaire de Montpellier, Université Montpellier 1, Hôpital Sainte-Marguerite, Université de Bordeaux, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, NutriNeuro, Centre Hospitalier Charles Perrens, Oslo University Hospital, Centre National de la Recherche Scientifique, University of Oslo, Sorbonne Université, Pitié-Salpêtrière Hospital, Centre d'Immunologie et des Maladies Infectieuses, University of Toronto, Institut Pascal, Université Clermont Auvergne, Clermont Auvergne INP, Hôpitaux Universitaires de Strasbourg, Neuroscience et Psychiatrie Translationnelle de Strasbourg, Université de Strasbourg, Lyon 1 Université, Centre de Recherche en Neurosciences de Lyon, Centre Hospitalier Le Vinatier, Université Paris Cité, Hôpital Louis-Mourier, Sorbonne Paris Cité, Centre Hospitalier Universitaire de Saint-Étienne, Centre Hospitalier Universitaire de Toulouse, Université Toulouse - Jean Jaurès, Université de Toulouse, Equipe de Recherche sur les Rationalités Philosophiques et les Savoirs, Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, Université de Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, Centre de recherche en Epidémiologie et Santé des Populations, Centre Hospitalier de Versailles, Université d'Orléans, Centre hospitalier universitaire d'Orléans
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,890
Funder: Agence Nationale de la Recherche
OpenAlex ID: W7222839391