Suppression of the P50 evoked response and neuregulin 1-induced AKT phosphorylation in first-episode schizophrenia

Am J Psychiatry. 2010 Apr;167(4):444-50. doi: 10.1176/appi.ajp.2009.09050723. Epub 2010 Jan 4.


Objective: Diminished suppression of the P50 auditory evoked potential is a widely used sensory gating phenotype in the molecular genetic studies of schizophrenia. The aim of this study was to explore the relationship between this phenotype and neuregulin 1-related intracellular signaling processes.

Method: The P50 evoked potential was recorded in 30 first-episode, never-medicated patients with schizophrenia and in 30 healthy comparison volunteers. Neuregulin 1-induced activation of the phosphoinositide 3'-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3beta system was characterized by the measurement of the phosphorylated AKT to total AKT ratio in peripheral B lymphoblasts.

Results: Relative to comparison subjects, patients with first-episode schizophrenia displayed diminished P50 suppression and decreased neuregulin 1-induced AKT phosphorylation. There was a significant relationship between P50 suppression and AKT phosphorylation.

Conclusion: Decreased neuregulin 1-induced activation of the PI3K/AKT system is associated with impaired sensory gating in first-episode schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cognition Disorders / diagnosis
  • Evoked Potentials, Auditory / drug effects*
  • Female
  • Hippocampus / drug effects
  • Humans
  • Male
  • Neuregulin-1 / pharmacology*
  • Nucleus Accumbens / drug effects
  • Phosphorylation / drug effects
  • Phosphotransferases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Schizophrenia* / drug therapy
  • Schizophrenia* / metabolism
  • Schizophrenia* / physiopathology
  • Sensory Gating
  • Severity of Illness Index
  • Signal Transduction / drug effects
  • Wechsler Scales


  • Neuregulin-1
  • Phosphotransferases
  • Proto-Oncogene Proteins c-akt