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

@article{saitoh2026mediating,
  title = {{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}},
  author = {Kaori Saitoh and Mohamed Lajnef and Marion Leboyer and Myrtille Andre and Christelle Andrieu and Bruno Aouizerate and Maud Apavou and Caroline Barau and Jeremy Bernard and Jihène Bouassida and Delphine Capdevielle and Isabelle Chereau and Julie Clauss-Kobayashi and Jean-Michel Dorey and Caroline Dubertret and Eric Fakra and Guillaume Fond and Tudi Goze and Sylvain Leignier and Pierre-Michel Llorca and David Misdrahi and Nicolas Oriol and Baptiste Pignon and Romain Rey and Paul Roux and Jasmina Mallet and Franck Schürhoff and Benoit Schorr and Mathieu Urbach and Etienne Very and Ching-Lien Wu and M. Andre and M. Andre and C. Andrieu-Haller and B. Aouizerate and F. Berna and O. Blanc and D. Capdevielle and M. Cléry and I. Chereau-Boudet and J. Clauss-Kobayashi and N. Coulon and R. Dassing and J.M. Dorey and C. Dubertret and T. D'Amato and A. Esselin and E. Fakra and G. Fond and F. Gabayet and T. Goze and M. Jarroir and D. Lacelle and M. Leboyer and S. Leignier and P.M. Llorca and J. Mallet and Z. Marongiu and E. Metairie and T. Michel},
  journal = {Brain, Behavior, \& Immunity - Health},
  year = {2026},
  month = oct,
  doi = {10.1016/j.bbih.2026.101391},
  url = {https://doi.org/10.1016/j.bbih.2026.101391},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - 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
AU  - Kaori Saitoh
AU  - Mohamed Lajnef
AU  - Marion Leboyer
AU  - Myrtille Andre
AU  - Christelle Andrieu
AU  - Bruno Aouizerate
AU  - Maud Apavou
AU  - Caroline Barau
AU  - Jeremy Bernard
AU  - Jihène Bouassida
AU  - Delphine Capdevielle
AU  - Isabelle Chereau
AU  - Julie Clauss-Kobayashi
AU  - Jean-Michel Dorey
AU  - Caroline Dubertret
AU  - Eric Fakra
AU  - Guillaume Fond
AU  - Tudi Goze
AU  - Sylvain Leignier
AU  - Pierre-Michel Llorca
AU  - David Misdrahi
AU  - Nicolas Oriol
AU  - Baptiste Pignon
AU  - Romain Rey
AU  - Paul Roux
AU  - Jasmina Mallet
AU  - Franck Schürhoff
AU  - Benoit Schorr
AU  - Mathieu Urbach
AU  - Etienne Very
AU  - Ching-Lien Wu
AU  - M. Andre
AU  - M. Andre
AU  - C. Andrieu-Haller
AU  - B. Aouizerate
AU  - F. Berna
AU  - O. Blanc
AU  - D. Capdevielle
AU  - M. Cléry
AU  - I. Chereau-Boudet
AU  - J. Clauss-Kobayashi
AU  - N. Coulon
AU  - R. Dassing
AU  - J.M. Dorey
AU  - C. Dubertret
AU  - T. D'Amato
AU  - A. Esselin
AU  - E. Fakra
AU  - G. Fond
AU  - F. Gabayet
AU  - T. Goze
AU  - M. Jarroir
AU  - D. Lacelle
AU  - M. Leboyer
AU  - S. Leignier
AU  - P.M. Llorca
AU  - J. Mallet
AU  - Z. Marongiu
AU  - E. Metairie
AU  - T. Michel
PY  - 2026
DA  - 2026/10/17
JO  - Brain, Behavior, & Immunity - Health
DO  - 10.1016/j.bbih.2026.101391
UR  - https://doi.org/10.1016/j.bbih.2026.101391
AB  - 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: Two hundred and sixty-one patients with SZ were genotyped for two NR3C1 polymorphisms (rs41423247, G > C and rs6198, T > C) and one GLCCI1 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: No significant association was observed between NR3C1 polymorphisms and outcomes studied. In contrast, multivariate analysis showed that the GLCCI1 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: The GLCCI1 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.
SN  - 2666-3546
ER  -