A novel commentary: Investigation of the role of a balance between neurotrophic and apoptotic proteins in the pathogenesis of psychosis via the tPA-BDNF pathway

J Psychiatr Res. 2021 Oct:142:160-166. doi: 10.1016/j.jpsychires.2021.07.056. Epub 2021 Aug 1.

Abstract

Objective: Many hypotheses have put forward to better understand the pathogenesis of schizophrenia (SZ), such as synaptic pruning, stress-diathesis, neurodevelopment, neurodegeneration and neurotransmitter hypothesis; nonetheless, this pathogenesis still remains a mystery. The current study was designed with the hypothesis that impairment of a balance between pro-BDNF/mature BDNF and their receptors p75NTRK/TrkB may cause synaptic pruning in the pathogenesis of psychotic disorders.

Methods: Sixty-five drug-naïve patients with first-episode psychosis (FEP) who applied to outpatient clinics and were diagnosed according to DSM-5 as well as 65 healthy controls (HC) were included in the study. Symptoms at the time of evaluation were assessed with the PANSS scale by an experienced psychiatrist. Blood samples were collected from all participants to determine BDNF, pro-BDNF, TrkB and p75NTR, PAI1, tPA, ACTH and cortisol levels.

Results: Mature BDNF, TrkB and PAI-1, tPA levels were significantly lower while the levels of ACTH and cortisol were significantly higher in FEP patients compared to HC. No significant difference was found in pro-BDNF and p75NTR levels between the two independent groups. The pro-BDNF/mature BDNF and the p75NTR/TrkB ratios were significantly higher in FEP patients compared to HC. Moreover, the pro-BDNF/mature BDNF and the p75NTR/TrkB ratios were found to be significantly associated with the pathogenesis of SZ in a hierarchical regression model.

Discussion: Imbalance between neurotrophic and apoptotic proteins such as pro-BDNF/mature BDNF and p75NTR/TrkB may be take part pathogenesis of synaptic pruning in psychotic disorders.

Keywords: Apoptosis; BDNF; Neurotrophin; Schizophrenia; Synaptic pruning; proBDNF.

MeSH terms

  • Brain-Derived Neurotrophic Factor*
  • Case-Control Studies
  • Humans
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Plasminogen Activator Inhibitor 1
  • Psychotic Disorders*
  • Receptor, trkB
  • Receptors, Nerve Growth Factor
  • Tissue Plasminogen Activator

Substances

  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • NGFR protein, human
  • Nerve Tissue Proteins
  • Plasminogen Activator Inhibitor 1
  • Receptors, Nerve Growth Factor
  • SERPINE1 protein, human
  • BDNF protein, human
  • Receptor, trkB
  • tropomyosin-related kinase-B, human
  • Tissue Plasminogen Activator