title: Low serum truncated-BDNF isoform correlates with higher cognitive impairment in schizophrenia.
abstract: Brain-derived neurotrophic factor (BDNF) is a key factor in learning and memory. Altered BDNF-signalling is thought to contribute to the pathogenesis of schizophrenia (SZ) especially in relation to cognitive deficits. However, analysis of serum BDNF as a potential biomarker in schizophrenia has provided controversial data. We hypothesized that these confounding results might be due to a differential regulation of BDNF precursor pro-BDNF (32 KDa) and proteolytic products mature (mat-BDNF; 14 KDa), and truncated-BDNF (28 KDa). Accordingly, we investigated the serum abundance of these BDNF isoforms and its relationship with cognitive impairment in schizophrenia. Schizophrenia was diagnosed with PANSS test. Abbreviated cognitive assessment included tests for attention, perceptual-motor skills, processing speed and memory. Using an ELISA assay, we found a slight reduction in serum BDNF levels in SZ patients (n = 40) with respect to healthy controls (HC, n = 40; p = 0.018). Western-blot analysis revealed increased serum pro-BDNF and mat-BDNF and reduced truncated-BDNF (p < 0.001) in SZ with respect to HC. Patients with an increase in pro-BDNF (n = 15/40) or mat-BDNF (n = 9/40) higher than the HC mean + 2 Standard Deviations (SD) also had >2SD reduction of truncated-BDNF (n = 27/40). Reduced truncated-BDNF correlated significantly with higher positive and lower negative PANNS scores and a worst performance in all cognitive assays but not with antipsychotic type. Measurement of serum truncated-BDNF abundance predicted for high cognitive deficits with sensitivity = 67.5%, specificity = 97.5%, Negative Predictive Value = 75% and Positive Predictive Value = 96.4%. These results suggest deficiency in pro-BDNF processing as a possible biological mechanism underlying schizophrenia with cognitive impairment.
authors.affiliation: Dipartimento Clinico di Scienze Mediche, Tecnologiche e Traslazionali, Unita' Clinica Operativa di Clinica Psichiatrica, University of Trieste, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Carlino
authors.forename: Emiliano
authors.initials: E
authors.lastname: Leone
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Cola
authors.forename: Gabriele
authors.initials: G
authors.lastname: Baj
authors.forename: Raffaella
authors.initials: R
authors.lastname: Marin
authors.forename: Giacomo
authors.initials: G
authors.lastname: Dinelli
authors.forename: Enrico
authors.initials: E
authors.lastname: Tongiorgi
authors.forename: Maurizio
authors.initials: M
authors.lastname: De Vanna
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D003072:Cognition Disorders / Q000097:blood* / Q000209:etiology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009483:Neuropsychological Tests; D020033:Protein Isoforms / Q000097:blood*; D012559:Schizophrenia / Q000150:complications*; D013223:Statistics as Topic
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020033:Protein Isoforms