Introduction Only about one third of patients at high risk for psychosis based on current clinical criteria convert to a psychotic disorder within a 2.5-year follow-up period. Targeting clinical high-risk (CHR) individuals for preventive interventions could expose many to unnecessary treatments, underscoring the need to enhance predictive accuracy with non-clinical measures. Candidate measures include event-related potential (ERP) components with established sensitivity to schizophrenia. Here we examined the mismatch negativity (MMN) component of the ERP elicited automatically by auditory deviance in CHR and early illness schizophrenia (ESZ) patients. We also examined whether MMN predicted subsequent conversion to psychosis in CHR patients. Method MMN to auditory deviants (duration, frequency, and duration+frequency “double deviant”) were assessed in 44 healthy controls (HC), 19 ESZ, and 38 CHR patients. Within CHR patients, 15 converters to psychosis were compared to 16 non-converters with at least 12 months of clinical follow-up. Hierarchical Cox regression examined the ability of MMN to predict time to psychosis onset in CHR patients. Results Irrespective of deviant type, MMN was significantly reduced in ESZ and CHR patients relative to HC, and in CHR converters relative to non-converters. MMN did not significantly differentiate ESZ and CHR patients. The duration+frequency double deviant MMN, but not the single deviant MMNs, significantly predicted the time to psychosis onset in CHR patients. Conclusions Neurophysiological mechanisms underlying automatic processing of auditory deviance, as reflected by the duration+frequency double deviant MMN, are compromised prior to psychosis onset, and can enhance the prediction of psychosis risk among CHR patients.

The error-related negativity (ERN), an event-related potential component elicited by error responses in cognitive tasks, has been shown to be abnormal in most, but not all, studies of obsessive–compulsive disorder or obsessive–compulsive symptoms (OCD/S); these inconsistencies may be due to task selection, symptom subtype, or both. We used meta-analysis to further characterize the ERN in OCD/S, and pooled data across studies to examine the ERN in OCD/S with hoarding. We found an enhanced ERN in OCD/S relative to controls, as well as heterogeneity across tasks. When stratified, OCD/S showed a significantly enhanced ERN only in response conflict tasks. However, OCD/S + hoarding showed a marginally larger ERN than OCD/S–hoarding, but only for probabilistic learning tasks. These results suggest that abnormal ERN in OCD/S is task-dependent, and that OCD/S + hoarding show different ERN activity from OCD/S - hoarding perhaps suggesting different pathophysiological mechanisms of error monitoring.

Response monitoring abnormalities have been reported in chronic schizophrenia patients, but it is unknown whether they predate the onset of psychosis, are present in early stages of illness, or are late-developing abnormalities associated with illness progression. Response-synchronized event-related potentials (ERP) recorded during a picture-word matching task yielded error-related negativity (ERN), correct-response negativity (CRN), and error positivity (Pe) from 84 schizophrenia patients (SZ), 48 clinical high risk patients (CHR), and their age-matched healthy controls (HC; n = 110 and 88, respectively). A sub-sample of 35 early illness schizophrenia patients (ESZ) was compared to 93 age-matched HC and the CHR patients (after statistically removing the effects of normal aging). Relative to HC, 1) SZ, ESZ, and CHR had smaller ERNs, and 2) SZ and ESZ had larger CRNs and smaller Pes. Within the SZ, longer illness duration was associated with larger CRNs but was unrelated to ERN or Pe. CHR and ESZ did not differ on ERN or CRN, although Pe was smaller in ESZ than CHR. These results indicate that while ERN, CRN, and Pe abnormalities are present early in the illness, only the ERN abnormality is evident prior to psychosis onset, and only the CRN abnormality appears to worsen progressively over the illness course. Brain regions subserving response monitoring may be compromised early in the illness and possibly during its clinical prodrome.