Novel evidence for enhanced stem cell trafficking in antipsychotic-naïve subjects during their first psychotic episode

J Psychiatr Res. 2014 Feb:49:18-24. doi: 10.1016/j.jpsychires.2013.10.016. Epub 2013 Nov 5.

Abstract

In this study, we tested the novel hypothesis that stem cells and those factors that modulate their trafficking may be biological markers for acute psychosis. Twenty-eight subjects during their first nonaffective psychotic episode were investigated before and after antipsychotic treatment and were compared with 35 healthy controls (CG); the psychotic group (PG) was divided into "schizophrenic" (SG) and "non-schizophrenic" (NG) subgroups. We examined the number of circulating Lin(-)/CD45(-)/CD34(+) and Lin(-)/CD45(-)/CD133(+) very small embryonic-like stem cells (VSELs), which express markers of the neural lineage, and also the plasma levels of factors that modulate their trafficking: the C3a, C5a, and C5b-9 activated complement cascade components, stromal-derived factor 1, and sphingosine-1-phosphate (S1P). We found that the mean numbers of Lin(-)/CD45(-)/CD34(+) VSELs and the plasma levels of S1P prior to treatment differ between the CG and PG and that these cells express markers of neural lineage. The number of Lin(-)/CD45(-)/CD133(+) VSELs in peripheral blood differed between the SG and NG prior to treatment. Using logistic regression analysis, we found that C3a and S1P are the best predictors of risk and are potential markers for the first psychotic episode. Furthermore, in the SG, the number of circulating Lin(-)/CD45(-)/CD34(+) VSELs and the S1P plasma level are the best predictors of risk and are proposed as novel markers for the first "schizophrenic" episode of psychosis.

Keywords: Complement cascade; First episode of psychosis; Schizophrenia; Sphingosine-1-phosphate; VSEL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biomarkers / blood
  • Complement System Proteins / genetics
  • Complement System Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Oligodendrocyte Transcription Factor 2
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism
  • Psychiatric Status Rating Scales
  • Psychotic Disorders / blood
  • Psychotic Disorders / drug therapy
  • Psychotic Disorders / pathology*
  • Stem Cells / drug effects*
  • Stromal Interaction Molecule 1
  • Young Adult

Substances

  • Antigens, CD
  • Antipsychotic Agents
  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • OLIG1 protein, human
  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • Complement System Proteins
  • sphingosine-1-phosphate phosphatase
  • Phosphoric Monoester Hydrolases