Error monitoring dysfunction across the illness course of schizophrenia

Abstract

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.

Figures

Figure 1

Behavioral performance in the picture-word verification task across the illness course of schizophrenia and their age-matched control groups. In (a), error rates are shown as percent error (%), revealing increased error rates in all patient groups; (b), increased response time across all patient groups is shown in median reaction time (RT) values (ms) for correct and incorrect trials; (c), post-error slowing is displayed (ms), revealing intact strategic adjustment in all groups. Bars = standard error. Significant values are displayed as *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 2

Grand average ERP waveforms for response-locked error (solid) and correct (dashed) trials for age-matched healthy control participants and schizophrenia, early illness schizophrenia, and clinical high risk patients. Data shown in waveforms are from Fz, FCz, Cz, and Pz channels. The x-axis presents time in milliseconds from -100 ms (pre-response) to 750 ms (post-response) relative to the button press (0 ms). The y-axis presents amplitude in microvolts (μV). ERN and CRN peaks are signified by arrows at Fz, FCz and Cz, and the Pe time window (200 to 500 ms) is depicted by the gray bar at FCz, Cz and Pz in (a). (a) age-matched healthy control participants (left) and schizophrenia patients (right); (b) age-matched healthy control participants (left) and early illness schizophrenia patients (right); (c) age-matched healthy control participants (left) and clinical high risk patients (right).

Figure 3

(a), Group mean (± standard error) ERN and CRN amplitudes at Cz for each patient group and their age-matched healthy controls. (b), Group mean (± standard error) Pe amplitudes at Cz for each patient group and their age-matched healthy controls. (c) Mean (± standard error) age-corrected ERN, CRN, and Pe z-scores at Cz, reflecting the degree of deviation of each patient group from the healthy control (HC) group, are plotted for Clinical High Risk (CHR) and Early Illness Schizophrenia (ESZ) patients. Significant patient differences are shown for age-corrected Pe waveforms, while patient groups show statistical equivalence to each other on age-corrected ERN and CRN waveforms. Error bars indicate standard error. Significant values are displayed as *p < 0.05. **p < 0.01. ***p < 0.001.