BDNF and NGF Signalling in Early Phases of Psychosis: Relationship with Inflammation and Response to Antipsychotics after 1 Year

Martinez-Cengotitabengoa, M. ; Macdowell, K.S. ; Alberich, S. ; Diaz, F.J. ; Garcia-Bueno, B. ; Rodriguez-Jimenez, R. ; Bioque, M. ; Berrocoso, E. ; Parellada, M. ; Lobo, A. (Universidad de Zaragoza) ; Saiz, P.A. ; Matute, C. ; Bernardo, M. ; Gonzalez-Pinto, A. ; Leza, J.C.

Resumen: Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor BDNF] and nerve growth factor NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEPs.

Idioma: Inglés

DOI: 10.1093/schbul/sbv078

Año: 2016

Publicado en: SCHIZOPHRENIA BULLETIN 42, 1 (2016), 142-151
ISSN: 0586-7614

Factor impacto JCR: 7.575 (2016)

Categ. JCR: PSYCHIATRY rank: 6 / 139 = 0.043 (2016) - Q1 - T1
Categ. JCR: PSYCHOLOGY, EXPERIMENTAL rank: 8 / 142 = 0.056 (2016) - Q1 - T1

Factor impacto SCIMAGO: 4.121 - Psychiatry and Mental Health (Q1)

Financiación: info:eu-repo/grantAgreement/ES/MINECO-FEDER/PI10-01746
Financiación: info:eu-repo/grantAgreement/ES/MINECO-FEDER/PI11-01977
Financiación: info:eu-repo/grantAgreement/ES/MINECO-FEDER/PI11-02708
Financiación: info:eu-repo/grantAgreement/ES/MINECO-FEDER/PI12-02077
Financiación: info:eu-repo/grantAgreement/ES/MINECO-ISCIII/CIBERSAM

Tipo y forma: Article (Published version)

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