Neurotrophin blood-based gene expression and social cognition analysis in patients with autism spectrum disorder

Neurogenetics. 2015 Apr;16(2):123-31. doi: 10.1007/s10048-014-0434-9. Epub 2014 Dec 24.


Autism spectrum disorders (ASD) comprise neurodevelopmental disorders with clinical onset during the first years of life. The identification of peripheral biomarkers could significantly impact diagnosis and an individualized, early treatment. Although the aetiology of ASD remains poorly understood, there is increasing evidence that neurotrophins and their receptors represent a group of candidate genes for ASD pathophysiology and biomarker research. Total messenger RNA (mRNA) from whole blood was obtained from adolescents and adults diagnosed as ASD (n = 21) according to DSM-IV criteria and confirmed by the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R) algorithms, as well as healthy controls (n = 10). The mRNA expression of neurotrophins (BDNF, NT3 and NT4) and their receptors (TrkA, TrkB and p75 (NTR) ) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, social cognition abilities of ASD patients and controls were determined according to three Theory of Mind (ToM) tests (Reading the Mind in the Eyes, Faux pas, and Happé stories). The NT3 and NT4 mRNA expression in the whole blood was significantly lower in ASD compared to healthy controls, while p75(NTR) was higher (P < 0.005). In addition, lower scores in three of the ToM tests were observed in ASD subjects compared to controls. A significant (P < 0.005) ToM impairment in Happé stories test was demonstrated in ASD. Nevertheless, no correlations were observed between neurotrophins and their receptors expressions and measures of ToM. Given their potential as peripheral blood-based biomarkers, NT3, NT4 and p75 (NTR) mRNA expression patterns may be useful tools for a more personalized diagnostics and therapy in ASD. Further investigations with larger numbers of samples are needed to verify these results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autism Spectrum Disorder / blood*
  • Biomarkers / blood
  • Brain-Derived Neurotrophic Factor / genetics
  • Child
  • Female
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • Nerve Growth Factors / genetics*
  • Nerve Tissue Proteins / genetics*
  • Neurotrophin 3 / genetics
  • RNA, Messenger / blood
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor, trkA / genetics
  • Receptor, trkB / genetics
  • Receptors, Nerve Growth Factor / genetics*
  • Theory of Mind*
  • Young Adult


  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • NGFR protein, human
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Neurotrophin 3
  • RNA, Messenger
  • Receptors, Nerve Growth Factor
  • BDNF protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA
  • Receptor, trkB
  • neurotrophin 4