Low serum truncated-BDNF isoform correlates with higher cognitive impairment in schizophrenia
- PMID: 20630543
- DOI: 10.1016/j.jpsychires.2010.06.012
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.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Similar articles
-
Cognitive function and serum levels of brain-derived neurotrophic factor in patients with bipolar disorder.Bipolar Disord. 2009 Sep;11(6):663-71. doi: 10.1111/j.1399-5618.2009.00733.x. Bipolar Disord. 2009. PMID: 19689509
-
Altered serum content of brain-derived neurotrophic factor isoforms in multiple sclerosis.J Neurol Sci. 2012 Sep 15;320(1-2):161-5. doi: 10.1016/j.jns.2012.07.016. Epub 2012 Jul 24. J Neurol Sci. 2012. PMID: 22836016
-
Low serum levels of brain-derived neurotrophic factor in patients with schizophrenia do not elevate after antipsychotic treatment.Prog Neuropsychopharmacol Biol Psychiatry. 2004 Jul;28(4):709-13. doi: 10.1016/j.pnpbp.2004.05.008. Prog Neuropsychopharmacol Biol Psychiatry. 2004. PMID: 15276697 Clinical Trial.
-
Is altered BDNF biosynthesis a general feature in patients with cognitive dysfunctions?Neuroscientist. 2013 Aug;19(4):345-53. doi: 10.1177/1073858412469444. Epub 2012 Dec 14. Neuroscientist. 2013. PMID: 23242909 Review.
-
Brain-derived neurotrophic factor and electroconvulsive therapy in a schizophrenic patient with treatment-resistant paranoid-hallucinatory symptoms.J ECT. 2011 Mar;27(1):e44-6. doi: 10.1097/YCT.0b013e318205e1c0. J ECT. 2011. PMID: 21206369 Review.
Cited by
-
Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients.PLoS One. 2016 Oct 5;11(10):e0162619. doi: 10.1371/journal.pone.0162619. eCollection 2016. PLoS One. 2016. PMID: 27706235 Free PMC article.
-
Selective Noradrenergic Activation of BDNF Translation by Mirtazapine.Mol Neurobiol. 2024 Nov 18. doi: 10.1007/s12035-024-04619-1. Online ahead of print. Mol Neurobiol. 2024. PMID: 39557799
-
Exploring the association between brain-derived neurotrophic factor levels and longitudinal psychopathological and cognitive changes in Sardinian psychotic patients.Eur Psychiatry. 2022 Oct 25;65(1):e71. doi: 10.1192/j.eurpsy.2022.2333. Eur Psychiatry. 2022. PMID: 36281033 Free PMC article.
-
Elucidating the impact of neurofibromatosis-1 germline mutations on neurofibromin function and dopamine-based learning.Hum Mol Genet. 2015 Jun 15;24(12):3518-28. doi: 10.1093/hmg/ddv103. Epub 2015 Mar 18. Hum Mol Genet. 2015. PMID: 25788518 Free PMC article.
-
Altered balance of proteolytic isoforms of pro-brain-derived neurotrophic factor in autism.J Neuropathol Exp Neurol. 2012 Apr;71(4):289-97. doi: 10.1097/NEN.0b013e31824b27e4. J Neuropathol Exp Neurol. 2012. PMID: 22437340 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical