Deficits in P300 Amplitude Associated With Psychosis Risk Syndrome

It has been shown that deficits in P300 amplitude appear to precede the onset of psychosis, thus supporting the use of target P3b as a potential prognostic biomarker of clinical outcomes in patients with psychosis risk syndrome. In the current study, auditory P300 data were compiled as part of the multisite, case-control North American Prodrome Longitudinal Study at 8 university-based outpatient programs. Results of the analysis were published in JAMA Psychiatry.

The investigators sought to establish whether P300 event-related potential amplitude, which has been found to be deficient in patients with schizophrenia, is decreased in the psychosis risk syndrome and whether it is associated with clinical outcomes. The main study outcomes were baseline electroencephalography, which was recorded during an auditory oddball task. Additionally, 2 P300 components were measured: P3b, which is elicited by infrequent target stimuli, and P3a, which is generated by uncommon nontarget novel stimuli.

A total of 788 participants were included in the study — 552 individuals who met psychosis risk syndrome criteria (psychosis risk syndrome group) and 236 healthy controls with P300 data available (control group). Auditory data from the at-risk participants who converted to psychosis (n=73) were compared with data from nonconverters who were followed for 24 months and continued to exhibit symptoms (n=135) or who remitted from the PRS group (n=90). Data were obtained between May 27, 2009, and September 17, 2014, and were analyzed from December 3, 2015, through May 1, 2019.

The psychosis risk syndrome arm comprised 236 women and 316 men with a mean age of 19.21 ± 4.38 years. The control arm comprised 111 women and 125 men with a mean age of 20.44 ± 4.73 years. Study findings showed that target P3b and novelty P3a amplitudes were decreased among at-risk persons vs healthy controls (d =0.37). Moreover, target P3b, but not novelty P3a, was significantly decreased among psychosis converters compared with nonconverters (d =0.26). Additionally, smaller target P3b amplitude was associated with a significantly shorter time to onset of psychosis in at-risk persons (hazard ratio, 1.45; 95% CI, 1.04-2.0; P =.03).

Those participants with psychosis risk syndrome who went into remission had baseline target P3b amplitudes that were similar to those of healthy controls and were greater than the target P3b amplitudes of converters (d =0.5) and of those at-risk persons who remained symptomatic (d =0.4).

The investigators concluded that target P3b amplitudes may be sensitive to clinical outcomes in psychosis risk syndrome, including both conversion to psychosis and clinical remission. The use of auditory target P3b seems to be promising as a recognized prognostic biomarker of clinical outcome in psychosis risk syndrome.

Reference

Hamilton HK, Roach BJ, Bachman PM, et al. Association between P300 responses to auditory oddball stimuli and clinical outcomes in the psychosis risk syndrome [published online August 7, 2019]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.2135