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.