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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-3β 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. Conclusions: Decreased neuregulin 1-induced activation of the PI3K/AKT system is associated with impaired sensory gating in first-episode schizophrenia. [ABSTRACT FROM AUTHOR]