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.