Decomposing P300 into correlates of genetic risk and current symptoms in schizophrenia: An inter-trial variability analysis

Background: The P300 event-related potential (ERP) component, which reflects cognitive processing, is a candidate biomarker for schizophrenia. However, the role of P300 in the pathophysiology of schizophrenia remains unclear because averaged P300 amplitudes reflect both genetic predisposition and current clinical status. Thus, we sought to identify which aspects of P300 are associated with genetic risk versus symptomatic status via an inter-trial variability analysis. Methods: Auditory P300, clinical symptoms, and neurocognitive function assessments were obtained from forty-five patients with schizophrenia, thirty-two subjects at genetic high risk (GHR), thirty-two subjects at clinical high risk (CHR), and fifty-two healthy control (HC) participants. Both conventional averaging and inter-trial variability analyses were conducted for P300, and results were compared across groups using analysis of variance (ANOVA). Pearson's correlation was utilized to determine associations among inter-trial variability for P300, current symptoms and neurocognitive status. Results: Average P300 amplitude was reduced in the GHR, CHR, and schizophrenia groups compared with that in the HC group. P300 inter-trial variability was elevated in the CHR and schizophrenia groups but relatively normal in the GHR and HC groups. Furthermore, P300 inter-trial variability was significantly related to negative symptom severity and neurocognitive performance results in schizophrenia patients. Conclusions: These results suggest that P300 amplitude is an endophenotype for schizophrenia and that greater inter-trial variability of P300 is associated with more severe negative and cognitive symptoms in schizophrenia patients.