Objective Although patients with schizophrenia exhibit impaired suppression of the P50 event-related brain potential (ERP) to the second of two identical auditory stimuli during a paired-stimulus paradigm, uncertainty remains over whether this deficit in inhibitory gating of auditory sensory processes has relevance for patients’ clinical symptoms or cognitive performance. We examined associations between P50 suppression deficits and several core features of schizophrenia to address this gap. Method P50 was recorded from 52 patients with schizophrenia and 41 healthy individuals during a standard auditory paired-stimulus task. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were used to assess clinical symptoms, and the MATRICS Cognitive Consensus Battery (MCCB) measured cognitive performance in a subsample of 39 patients. Correlation and regression analyses were used to examine P50 suppression in relation to clinical symptom and cognitive performance measures. Results Patients with schizophrenia demonstrated a deficit in P50 suppression when compared to healthy participants, replicating prior research. Within the patient sample, impaired P50 suppression covaried reliably with greater difficulties in attention, poorer working memory, and reduced processing speed. Conclusions Impaired suppression of auditory stimuli is associated with core pathological features of schizophrenia, increasing confidence that P50 inhibitory processing can inform the development of interventions that target cognitive impairments in this chronic and debilitating mental illness.

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Endophenotypes are quantitative, heritable traits that may help to elucidate the pathophysiologic mechanisms underlying complex disease syndromes, such as schizophrenia. They can be assessed at numerous levels of analysis; here, we review electrophysiological endophenotypes that have shown promise in helping us understand schizophrenia from a more mechanistic point of view. For each endophenotype, we describe typical experimental procedures, reliability, heritability, and reported gene and neurobiological associations. We discuss recent findings regarding the genetic architecture of specific electrophysiological endophenotypes, as well as converging evidence from EEG studies implicating disrupted balance of glutamatergic signaling and GABA-ergic inhibition in the pathophysiology of schizophrenia. We conclude that refining the measurement of electrophysiological endophenotypes, expanding genetic association studies, and integrating datasets are important next steps for understanding the mechanisms that connect identified genetic risk loci for schizophrenia to the disease phenotype.