title: BDNF and NGF Signalling in Early Phases of Psychosis: Relationship With Inflammation and Response to Antipsychotics After 1 Year.
abstract: 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.
authors.affiliation: These authors have contributed equally to the article. monica.martinezcengotitabengoa@osakidetza.net.
authors.forename: M
authors.initials: M
authors.lastname: Martinez-Cengotitabengoa
authors.affiliation: Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain; Department of Pharmacology, Faculty of Medicine, Universidad Complutense de Madrid, & Research Institute of Hospital 12 de Octubre (i+12), Madrid, Spain; These authors have contributed equally to the article.
authors.forename: K S
authors.initials: KS
authors.lastname: MacDowell
authors.affiliation: Araba University Hospital, Bioaraba Research Institute, Vitoria, Spain; Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain; These authors have contributed equally to the article.
authors.forename: S
authors.initials: S
authors.lastname: Alberich
authors.affiliation: Department of Biostatistics, The University of Kansas Medical Center, Kansas City, KS;
authors.forename: F J
authors.initials: FJ
authors.lastname: Diaz
authors.affiliation: Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain; Department of Pharmacology, Faculty of Medicine, Universidad Complutense de Madrid, & Research Institute of Hospital 12 de Octubre (i+12), Madrid, Spain;
authors.forename: B
authors.initials: B
authors.lastname: Garcia-Bueno
authors.affiliation: Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain; Research Institute of Hospital 12 de Octubre (i+12), Madrid, Spain;
authors.forename: R
authors.initials: R
authors.lastname: Rodriguez-Jimenez
authors.affiliation: Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain; Barcelona Clínic Schizophrenia Unit, Neuroscience Institute, Hospital Clínic de Barcelona, Spain; Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain;
authors.forename: M
authors.initials: M
authors.lastname: Bioque
authors.affiliation: Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain; Department of Psychology, Psychobiology Area, Group of Research in Neuropsychopharmacology and Psychobiology (CTS-510), University of Cádiz, Spain;
authors.forename: E
authors.initials: E
authors.lastname: Berrocoso
authors.affiliation: Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain; Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, Madrid, Spain;
authors.forename: M
authors.initials: M
authors.lastname: Parellada
authors.affiliation: Department of Psychiatry, Instituto de Investigación Sanitaria Aragón and University of Zaragoza, Spain;
authors.forename: A
authors.initials: A
authors.lastname: Lobo
authors.affiliation: Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain; Department of Psychiatry, Faculty of Medicine, University of Oviedo. Instituto Universitario de Neurociencias del Principado de Asturias (INEUROPA), Oviedo, Spain;
authors.forename: P A
authors.initials: PA
authors.lastname: Saiz
authors.affiliation: University of the Basque Country (UPV-EHU), Bilbao, Spain; CIBERNED Neuroscience, Zamudio, Vizcaya, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Matute
authors.affiliation: Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain; Barcelona Clínic Schizophrenia Unit, Neuroscience Institute, Hospital Clínic de Barcelona, Spain; Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain;
authors.forename: M
authors.initials: M
authors.lastname: Bernardo
authors.affiliation: Araba University Hospital, Bioaraba Research Institute, Vitoria, Spain; Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain; University of the Basque Country (UPV-EHU), Bilbao, Spain; These authors have contributed equally to the article.
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez-Pinto
authors.affiliation: Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain; Department of Pharmacology, Faculty of Medicine, Universidad Complutense de Madrid, & Research Institute of Hospital 12 de Octubre (i+12), Madrid, Spain; These authors have contributed equally to the article.
authors.forename: J C
authors.initials: JC
authors.lastname: Leza
mesh_terms: D000293:Adolescent; D000328:Adult; D000341:Affective Disorders, Psychotic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism; D020033:Protein Isoforms; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism*; D012044:Regression Analysis; D015398:Signal Transduction; D055815:Young Adult
chemical_list: C477819:15-deoxyprostaglandin J2; D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D016328:NF-kappa B; C502240:NGF protein, human; D020033:Protein Isoforms; C579455:BDNF protein, human; D020932:Nerve Growth Factor; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020917:Receptor, trkA; D020813:Receptor, trkB; D015230:Prostaglandin D2
keywords: BDNF; NGF; antipsychotic; first-episode psychosis; inflammation; schizophrenia