Impact of relapse in BDNF receptors expression in patients with a first episode of schizophrenia

Bioque, Miquel ; Llorca-Bofí, Vicent ; MacDowell, Karina S ; Amoretti, Sílvia ; Mezquida, Gisela ; Cuesta, Manuel J. ; Díaz-Caneja, Covadonga M. ; Ibáñez, Ángela ; Segarra, Rafael ; González-Pinto, Ana ; Roldán, Alexandra ; Sáiz, Pilar A. ; Mané, Anna ; Lobo, Antonio (Universidad de Zaragoza) ; Martínez-Pinteño, Albert ; Cano-Escalera, Guillermo ; Berrocoso, Esther ; Bernardo, Miquel ; 2EPs Group

Resumen: Background and Hypothesis
Relapsing after a first episode of schizophrenia (FES) is a main predictor of clinical and functional prognosis. Brain-derived neurotrophic factor (BDNF) plays a critical role in neuronal development and plasticity, and its signaling may be altered by successive relapses.

Design
We assessed the impact of first relapse in the expression of the 2 isoforms of the BDNF tropomyosin-related kinase B (TrkB) receptor (active full-length TrkB-F and inactive truncated TrkB-T) in peripheral blood mononuclear cells from 53 FES patients in clinical remission followed up for 3 years.

Results
The group of participants that relapsed (n = 24) during the follow-up presented a significant decrease in the expression of the active TrkB-F receptor compared to baseline (M = 100 ± 28.13 vs. M = 83.42 ± 33.84, t = 2.5, P = .02), with no changes in the inactive TrkB-T receptor expression nor in BDNF plasma levels. This decrease also led to a significant decline in the F/T ratio (M = 1.13 ± 0.38 vs. 0.94 ± 0.36, t = 2.17, P = .041). No significant differences were found in the receptors’ expression nor in plasma levels in the group of cases that remained in remission (n = 29). These results were not associated with baseline differences between the groups in terms of the BDNF signaling pathway biomarkers, clinical or treatment variables.
Conclusions
These findings highlight the biological impact that a relapse produces over the systemic BDNF-TrkB signaling pathway, potentially undermining crucial neuronal functions. Identifying the actors involved can help design specific interventions for relapse prevention and improve the functional prognosis of people in the early stages of schizophrenia.

Idioma: Inglés

DOI: 10.1093/schbul/sbaf012

Año: 2025

Publicado en: Schizophrenia bulletin (2025), [12 pp.]
ISSN: 0586-7614

Financiación: info:eu-repo/grantAgreement/ES/ISCIII-FEDER/PI17-01066
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/JR19-00024
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI08-0208
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI11-00325
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI14/00612
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI17-00481
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI20-00721
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI22-01183
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI23-00625
Financiación: info:eu-repo/grantAgreement/ES/MICIU-ISCIII-FEDER/PI18-01055
Financiación: info:eu-repo/grantAgreement/ES/MICIU-ISCIII-FEDER/PI21-00713

Tipo y forma: Artículo (PostPrint)

Área (Departamento): Area Psiquiatría (Dpto. Medicina, Psiqu. y Derm.)