P50 inhibitory sensory gating in schizophrenia: analysis of recent studies

Introduction: Inhibitory sensory gating of the P50 cerebral evoked potential to paired auditory stimuli (S1, S2) is a widely used paradigm for the study of schizophrenia and related conditions. Its use to measure genetic, treatment, and developmental effects requires a metric with more stable properties than the simple ratio of the paired responses.

Methods: This study assessed the ratio P50_S2μV/P50_S1μV and P50_S2μV co-varied for P50_S1μV in all 27 independent published studies that compared schizophrenia patients with healthy controls from 2000 to 2019. The largest study from each research group was selected. The Colorado research group's studies were excluded to eliminate bias from the first report of the phenomenon.

Results: Across the 27 studies encompassing 1179 schizophrenia patients and 1091 healthy controls, both P50_S2μV co-varied for P50_S1μV and P50_S2μV/P50_S1μV significantly separated the patients from the controls (both P < 0.0001). Effect size for P50_S2μV co-varied for P50_S1μV is d' = 1.23. The normal distribution of P50_S2μV co-varied for P50_S1μV detected influences of maternal inflammation and effects on behavior in a recent developmental study, an emerging use for the P50 inhibitory gating measure. P50_S2μV/P50_S1μV was not normally distributed. Results from two multi-site NIMH genetics collaborations also support the use of P50_S2μV as a biomarker.

Conclusion: Both methods detect an abnormality of cerebral inhibition in schizophrenia with high significance across multiple independent laboratories. The normal distribution of P50_S2μV co-varied for P50_S1μV makes it more suitable for studies of genetic, treatment, and other influences on the development and expression of inhibitory deficits in schizophrenia.