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BDNF as a biomarker in psychiatry
Carlino, Davide
2012-03-30
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 and major depression (SZ) especially in relation to cognitive deficits. However, analysis of serum BDNF as a potential biomarker in psychiatry 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).
Because of these discrepancies, we decided to perform a systematic review and a meta-analysis of studies measuring serum concentrations of BDNF to elucidate whether or not this neurotrophin is abnormally produced in patients with schizophrenia. Additionally, we were interested in identifying factors that might contribute to the different findings in literature, as to improve the design of future investigations in this field. In the second part of thesis, 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, perceptualmotor skills, processing speed and memory. Using an ELISA assay, we found a slight reduction in serum BDNF levels in SZ patients (n ¼ 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 ¼ 67.5%, specificity ¼ 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. Finally, future perspectives on the use of proBDNF as a novel biomarker for psychiatric disorders will be discussed.
Because of these discrepancies, we decided to perform a systematic review and a meta-analysis of studies measuring serum concentrations of BDNF to elucidate whether or not this neurotrophin is abnormally produced in patients with schizophrenia. Additionally, we were interested in identifying factors that might contribute to the different findings in literature, as to improve the design of future investigations in this field. In the second part of thesis, 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, perceptualmotor skills, processing speed and memory. Using an ELISA assay, we found a slight reduction in serum BDNF levels in SZ patients (n ¼ 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 ¼ 67.5%, specificity ¼ 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. Finally, future perspectives on the use of proBDNF as a novel biomarker for psychiatric disorders will be discussed.
Publisher
Università degli studi di Trieste
Languages
en
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